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© 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/., The success of personalized medicine depends on the discovery of biomarkers that allow oncologists to identify patients that will benefit from a particular targeted drug. Molecular tests are mostly performed using tumor samples, which may not be representative of the tumor's temporal and spatial heterogeneity. Liquid biopsies, and particularly the analysis of circulating tumor DNA, are emerging as an interesting means for diagnosis, prognosis, and predictive biomarker discovery. In this study, the amplification refractory mutation system (ARMS) coupled with high-resolution melting analysis (HRMA) was developed for detecting two of the most relevant KRAS mutations in codon 12. After optimization with commercial cancer cell lines, KRAS mutation screening was validated in tumor and plasma samples collected from patients with pancreatic ductal adenocarcinoma (PDAC), and the results were compared to those obtained by Sanger sequencing (SS) and droplet digital polymerase chain reaction (ddPCR). The developed ARMS-HRMA methodology stands out for its simplicity and reduced time to result when compared to both SS and ddPCR but showing high sensitivity and specificity for the detection of mutations in tumor and plasma samples. In fact, ARMS-HRMA scored 3 more mutations compared to SS (tumor samples T6, T7, and T12) and one more compared to ddPCR (tumor sample T7) in DNA extracted from tumors. For ctDNA from plasma samples, insufficient genetic material prevented the screening of all samples. Still, ARMS-HRMA allowed for scoring more mutations in comparison to SS and 1 more mutation in comparison to ddPCR (plasma sample P7). We propose that ARMS-HRMA might be used as a sensitive, specific, and simple method for the screening of low-level mutations in liquid biopsies, suitable for improving diagnosis and prognosis schemes., This work is financed by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB. FCT-MCTES is also acknowledged for 2020.07660.BD for BBO. Open access funding provided by FCT|FCCN (b-on).

© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, The association of Parkinson's Disease (PD) with atrial fibrillation (AF) is not well established and previous studies' results were heterogeneous. This review aimed to evaluate if patients with PD are at increased risk of having AF. MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science, were searched from inception May 2021. Two reviewers independently selected observational studies with data allowing to estimate the risk of atrial fibrillation in PD patients compared with no-PD controls. Pooled estimates Odds Ratio (OR) and 95% confidence intervals (CIs) were derived through meta-analysis. Heterogeneity was assessed using I2 test. The risk of bias of individual studies was evaluated using the ROBINS-I tool. The study protocol was registered at PROSPERO: CRD42020216572. Seven studies were included: five case-control studies and two cohort studies. Three of the studies included were a population-based study. No significant difference was detected between PD and controls regarding atrial fibrillation (OR 1.10, 95% CI 0.81 to 1.49). Early PD present a significant higher risk of AF (OR 1.55, 95% CI 1.00 to 2.40, I2 98%). The overall risk of bias was serious, with only two studies being considered as having moderate risk. The best evidence available do not support that there is an increased risk of AF in PD patients. Further studies are needed to better conclude if there is a relation between AF and PD.

© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Objectives: We aimed to analyze the efficacy and safety of endoscopic sleeve gastroplasty at 3 months as well as to determine factors influencing post-procedural weight loss. Methods: Seventy-three patients with obesity classes I, II and III (BMI 31.1-46.6 kg/m2) underwent ESG between September 2021 and April 2022 at a tertiary care hospital using Overstitch (Apollo Endosurgery, Austin, TX). ESG's efficacy and safety was evaluated at 1 and 3 months post-procedure with regard to excess weight loss (EWL) and total weight loss (TWL). Categorical variables were expressed as percentages and compared with chi-square test while continuous variables were expressed as mean ± standard deviation and compared with paired t test and analysis of variance (ANOVA) as applicable. Pearson's correlation was used to determine association between factors at baseline and weight loss. Results: Mean age was 49.2 ± 9.7 years with 61 (83.6%) patients being female. Mean initial weight was 105.7 ± 15.7 kg, and mean BMI was 38.6 ± 3.5 kg/m2. Median hospitalization was 2.0 ± 1.8 days with 62 (84.9%) patients discharged after 24 h. One patient had accidental suturing of the stomach to the abdominal wall and diaphragm which was managed laparoscopically. Mean %EWL was 25.4 ± 7.1 and 36.3 ± 11.4, and %TBWL was 11.2 ± 2.6 and 15.8 ± 4.2 at 1 and 3 months, respectively. Significant excess weight loss at 3 months was only observed in patients with BMI < 40 kg/m2 (p = 0.001). Conclusions: ESG is safe and effective to manage obesity. Significant weight loss at 3 months was only observed in patients with obesity class I and class II.

International audience; Biomagnetic monitoring increasingly is applied to assess particulate matter (PM) concentrations, mainly using plant leaves sampled in small geographical area and from a limited number of species. Here, the potential of magnetic analysis of urban tree trunk bark to discriminate between PM exposure levels was evaluated and bark magnetic variation was investigated at different spatial scales. Trunk bark was sampled from 684 urban trees of 39 genera in 173 urban green areas across six European cities. Samples were analysed magnetically for the Saturation Isothermal Remanent Magnetisation (SIRM). The bark SIRM reflected well the PM exposure level at city and local scale, as the bark SIRM (i) differed between the cities in accordance with the mean atmospheric PM concentrations and (ii) increased with the cover of roads and industrial area around the trees. Furthermore, with increasing tree circumferences, the SIRM values increased, as a reflection of a tree age effect related to PM accumulation over time. Moreover, bark SIRM was higher at the side of the trunk facing the prevailing wind direction. Significant relationships between SIRM of different genera validate the possibility to 2 combine bark SIRM from different genera to improve sampling resolution and coverage in biomagnetic studies. Thus, the SIRM signal of trunk bark from urban trees is a reliable proxy for atmospheric coarse to fine PM exposure in areas dominated by one PM source, as long as variation caused by genus, circumference and trunk side is taken into account.

Humans have been altering the Mediterranean landscapes for millennia. To diminish the probability of encounters with domestic animals, humans and their activities, many species adjust their behavior to become more nocturnal. Even habitat-generalist species, such as red fox and stone marten that are somehow tolerant to environmental changes, might be affected by anthropic disturbances. Nevertheless, only a small number of studies were implemented in Iberia targeting these mesocarnivores’ activity patterns, and fewer have assessed the temporal ecology of these species in Eucalyptus plantations, the current main forest cover in Portugal. Based on camera traps, we aimed to analyze: 1) the temporal and spatio-temporal activity patterns of red fox and stone marten; and 2) how they are affected by distinct human disturbances (i.e., humans, livestock, dogs, plantations, and hunting). Foxes presented a higher crepuscular activity, while martens were entirely nocturnal, suggesting some avoidance behavior. Both mesocarnivores showed a higher overlap with dogs’ activity than with humans or livestock. Foxes’ activity patterns vary between seasons and habitats but were not influenced by the hunting period. Results suggest that both mesocarnivores, besides setting apart their activity from humans related disturbances, also show a tendency to temporally avoid each other. While the increase of nocturnality may indicate an anthropic disturbance impact, a reduction of activity overlap between mesocarnivores may be a strategy to reduce competition. These results may help support the sustainable management of landscapes by highlighting critical periods where activity overlaps may occur, and thus the anthropic impacts on wildlife are higher.

Silicon (Si) is a “quasi-essential” element, associated to stresses/limitations alleviation in crops. However, stressful situations are becoming the norm, due to climate change, human exhaustion of natural resources, land degradation and loss of soil biodiversity. In this context, Si becomes a critical element, capacitating crops to grow more and better with less. A total of 467 articles up to 2021 were selected, reporting 501 experiments (lab-oriented and field trials) resulting in 682 cases where different Si-based fertilizers were used to study crops/plants with agronomic value to evaluate its physiological and/or agronomic performance under a specific motivation. Results show that 63% of cases testing Si-fertilization show increase in productivity, while 13% refuted this observation and 24% did not evaluate plant growth. Crop physiological responses was registered in 42% of the cases and only 3% did not report any alteration, although 55% did not evaluate these indicators. Symptom alleviation, in cases where stresses/limitations were studied, was registered in 74% of the cases with a low number of negative outcomes (9%). Field trials where crop yield was measured after application of Si-fertilization show that 69% of different measurements (599) register a yield improvement ≥ 5%, while 18% of the measurements registered between 0 and 5% and only 14% reported yield loss. Si-fertilization is therefore and important factor to improve crop yield and capacitate crops with resilience to endure future limitations. Its inclusion in modern agriculture should be considered in larger scales to adapt crops to the current challenges of sustainable agriculture and food provision.

Variable trace metal concentrations in the Precambrian ocean were closely linked to oxygen availability, although less is known about the drivers of seawater trace metal chemistry after the spread of complex life into the Phanerozoic eon. A major phytoplankton succession took place at the transition from the Palaeozoic to the Mesozoic era (~250 Myr ago), from an ocean dominated by the green Archaeplastida to secondary endosymbiotic algae with red-algal-derived plastids. Here, our comparative genomic analysis of 26 complete proteomes and metal domain analysis of additional 608 partially complete sequences of phytoplankton reveal that groups with different evolutionary history have distinct metal-binding proteins and contrasting metal acquisition strategies, adapted to differing availability of trace metals. The secondary-endosymbiont-bearing lineages are better adapted to well-oxygenated, nutrient-poor environments. This is supported by an enhanced thiol-based binding affinity of their transporters, coupled with minimized proteomic requirement for trace elements such as iron, copper and zinc at both protein and domain levels. Such different metal requirements across these lineages suggest a drastic decline in open-ocean trace metal concentrations at the inception of the Mesozoic, contributing to the shifts in phytoplankton communities that drove major changes in ocean chemical buffering.

© Springer Nature Limited 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law., Heavy alcohol consumption is a major cause of morbidity and mortality. Globally, alcohol per-capita consumption rose from 5.5 litres in 2005 to 6.4 litres in 2016 and is projected to increase further to 7.6 litres in 2030. In 2019, an estimated 25% of global cirrhosis deaths were associated with alcohol. The global estimated age-standardized death rate (ASDR) of alcohol-associated cirrhosis was 4.5 per 100,000 population, with the highest and lowest ASDR in Africa and the Western Pacific, respectively. The annual incidence of hepatocellular carcinoma (HCC) among patients with alcohol-associated cirrhosis ranged from 0.9% to 5.6%. Alcohol was associated with approximately one-fifth of global HCC-related deaths in 2019. Between 2012 and 2017, the global estimated ASDR for alcohol-associated cirrhosis declined, but the ASDR for alcohol-associated liver cancer increased. Measures are required to curb heavy alcohol consumption to reduce the burden of alcohol-associated cirrhosis and HCC. Degree of alcohol intake, sex, older age, obesity, type 2 diabetes mellitus, gut microbial dysbiosis and genetic variants are key factors in the development of alcohol-associated cirrhosis and HCC. In this Review, we discuss the global epidemiology, projections and risk factors for alcohol-associated cirrhosis and HCC., R.L. receives funding support from the NIAAA (U01AA029019), the NIEHS (5P42ES010337), the NCATS (5UL1TR001442), the NIDDK (U01DK130190, U01DK061734, R01DK106419, P30DK120515, R01DK121378 and R01DK124318), the NHLBI (P01HL147835) and the DOD PRCRP (W81XWH-18-2-0026). D.Q.H. receives funding support from Singapore’s Ministry of Health’s National Medical Research Council under its NMRC Research Training Fellowship (MOH-000595-01). P.M. receives funding support from the Programme Hospitalier de Recherche Clinique (French Minister for Health). H.C.-P. receives funding support from the FCT: Projectos De Investigação Científica E Desenvolvimento, Portugal.

The scientifc exchange correspondence of the Dundo Museum Biology Laboratory (Angola), included in the archive of António de Barros Machado (1912–2002) and Dora Lustig (1907–1986), constitutes a valuable repository of information for the history of contemporary science, particularly in the feld of natural sciences— botany, entomology, mammals, ornithology, primates, reptiles, termites, zoogeography, zoology—and of biology. This paper describes the application of the Records in Contexts model to the correspondence collection, with the aim of representing two realities: its production context and the relationships between scientists. The exploration of the model sought to understand its fundamentals and, simultaneously, model the information, starting by identifying the entities, attributes and relations needed for the collection representation scheme. This study resulted in a modelling exercise of the relations between 11 correspondents and the director of the Dundo Museum Biology Laboratory, Barros Machado, regarding the work on the museum collections which culminated in the publication of scientifc articles in Publicações Culturais da Companhia de Diamantes de Angola [Cultural Publications of the Diamond Company of Angola]. In the future, it is proposed to apply the same scheme to the description of the remaining scientists in the epistolary collection.

Funding Information: We thank the organizers and funders of the ILTER Nitrogen Initiative Training Course and Workshop in Hokkaido, Japan in June 2016, which brought together many of the participants in this project. Templer was supported by a US National Science Foundation LTER grant NSF DEB 1637685. McDowell was supported by US National Science Foundation LTER grant NSF DEB 1831592. We are grateful to the EU Horizon 2020 funded eLTER PLUS project (Grand Agreement No. 871128) for financial support to Haase and Dirnböck. Dirnböck was also funded by the LTER-CWN project (FFG project number 858024). This study was partly supported by the Research Initiative Grants of the ILTER, Grants-in-Aid for Scientific Research (17H03833), and Research Institute for Humanity and Nature (RIHN; a constituent member of NIHU) Project No. 14200156. Sharif was supported by NRT-INFEWS: UMD Global STEWARDS (STEM Training at the Nexus of Energy, WAter Reuse and FooD Systems) that was awarded to the University of Maryland School of Public Health by the National Science Foundation National Research Traineeship Program, Grant number 1828910. The monitoring of the Svartberget site in Sweden was funded by the SITES program from the Swedish Research Council. The monitoring of the Volbu Nyhaga site in Norway was part of JOVA—The Norwegian Agricultural Environmental Monitoring Programme, financed by the Ministry of Agriculture and Food. Lajtha was supported by NSF grants DEB-1257032 and DEB-1440409 to the H. J. Andrews Long Term Ecological Research program. The data collection in the Wüstebach catchment was supported by TERENO (Terrestrial Environmental Observatories) funded by the Helmholtz-Gemeinschaft. We thank the “Hessisches Landesamt für Naturschutz, Umwelt und Geologie” for providing data from the Rhine-Main-Observatory. I.Kokorīte was supported by the University of Latvia grant No. AAp2016/B041//Zd2016/AZ03. We thank the Latvian Environment, Geology and Meteorology Center for providing the monitoring data for Latvian site. Anna Avila was supported by Spanish Ministry of Science projects CGL2017-84687-C2-2-R and CGL2009-13188-C03-01. We thank the Tyrolean Alps Long-Term Sociological Ecological and Research (LTSER, Austria) and R. Psenner and S. Morales for helping with data for Piburger See. Data from Hubbard Brook were supported by the National Science Foundation (DEB-1907683) and US Forest Service, Northern Research Station. A. Robison was supported by US National Science Foundation LTER grant NSF OCE 1637630. W. Dodds was supported by NSF DEB 2025849. Observations at Lange Bramke site were funded by the Ministry of Nutrition, Agriculture and Consumer Protection of Lower Saxony under the Permanent Soil Monitoring Programme. The Krofdorf site was funded by the Hessian Ministry of Environment, Climate Protection, Agriculture and Consumer Protection under the “Waldökosystemstudie Hessen”. SRM Lins was supported by the São Paulo Research Foundation—FAPESP, grant number 2012/20377-9. Long-term monitoring at Lake Maggiore (LTER site EU-IT08-001-A) was funded by the International Commission for the Protection of Swiss-Italian waters (CIPAIS). We thank Emma Conrad-Rooney for help with Fig. . Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG. Previous studies have evaluated how changes in atmospheric nitrogen (N) inputs and climate affect stream N concentrations and fluxes, but none have synthesized data from sites around the globe. We identified variables controlling stream inorganic N concentrations and fluxes, and how they have changed, by synthesizing 20 time series ranging from 5 to 51 years of data collected from forest and grassland dominated watersheds across Europe, North America, and East Asia and across four climate types (tropical, temperate, Mediterranean, and boreal) using the International Long-Term Ecological Research Network. We hypothesized that sites with greater atmospheric N deposition have greater stream N export rates, but that climate has taken a stronger role as atmospheric deposition declines in many regions of the globe. We found declining trends in bulk ammonium and nitrate deposition, especially in the longest time-series, with ammonium contributing relatively more to atmospheric N deposition over time. Among sites, there were statistically significant positive relationships between (1) annual rates of precipitation and stream ammonium and nitrate fluxes and (2) annual rates of atmospheric N inputs and stream nitrate concentrations and fluxes. There were no significant relationships between air temperature and stream N export. Our long-term data shows that although N deposition is declining over time, atmospheric N inputs and precipitation remain important predictors for inorganic N exported from forested and grassland watersheds. Overall, we also demonstrate that long-term monitoring provides understanding of ecosystems and biogeochemical cycling that would not be possible with short-term studies alone.

© The Author(s) 2022. 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/., Oocyte cryopreservation is one of the more recently established methods of assisted reproduction technologies (ART). Vitrifcation procedures have helped to overcome most technical difculties enabling better oocyte survival after warming. There are diferent indications for oocyte cryopreservation. The technology can be used if the partner fails to produce sperm for an IVF treatment on the day of oocyte collection. For patients at risk of ovarian hyperstimulation syndrome (OHSS), we could also opt not only for “freeze-all embryos” but possibly also for “freeze-all oocytes.” Also, women who may have no partner or may lose their fertility potential due to surgery, chemotherapy, radiotherapy, autoimmune diseases, medical conditions causing ovarian insuffciency, or hematopoietic stem cell transplantation could store their oocytes for future use. Planned oocyte cryopreservation can also be used as a tool to help mitigate age-related fertility decline regardless of whether a patient is partnered. All such procedures raise questions both to patients and healthcare professionals: Can we predict the chance for the parenthood from one medically assisted reproduction (MAR) cycle with cryopreserved oocytes? What is the minimal number of cryopreserved oocytes needed to have a reasonable likelihood of success? Is there an upper age limit for women to store their oocytes?, The paper is a part of research programme P3-0327 funded by the Slovenian Research Agency.

Co-production is now the gold standard in policymaking, characterised by national and international actors with different types of knowledge working together to contribute to a collaborative decision-making process. The benefits of co-production in policymaking can include improved knowledge generation that merges practice-centred, political and technical knowledge and incorporates local knowledges to provide complementary information and increase ownership over policymaking processes. Nevertheless, it can also present pitfalls such as multiple and diverging interests, incomplete and asymmetric information, and resource asymmetries and elite capture as highlighted by Bender in (Eur J Dev Res, 2022). By reviewing a case in the European periphery, we document and illustrate situations of collaboration and conflict, benefits and pitfalls resulting from policymaking co-production, throughout recent Portuguese history and in present-day participatory budget initiatives. From competing national actors to influences from the Global North and Global South, the final outcome reflects a learning process in collaboration but also underlying power struggles.La co-création est désormais la référence en matière d'élaboration des politiques. Elle est caractérisée par des acteurs nationaux et internationaux dotés de différents types de connaissances qui travaillent ensemble pour contribuer à un processus décisionnel collaboratif. Les avantages de la co-création dans l'élaboration des politiques peuvent inclure une meilleure création de connaissances qui permet de fusionner les connaissances politiques et techniques centrées sur la pratique et qui intègre les connaissances locales pour fournir des informations complémentaires et accroître l'appropriation des processus d'élaboration des politiques. Néanmoins, la co-création peut également présenter des écueils tels que des intérêts multiples et divergents, des informations incomplètes et asymétriques, des asymétries de ressources et une accaparation par les élites, comme le souligne Bender in in (Eur J Dev Res, 2022). Par le biais d’une étude de cas dans la zone européenne, nous documentons et illustrons des situations de collaboration et de conflit, ainsi que les avantages et les inconvénients résultant de la co-création de politiques, grâce à l'histoire portugaise récente et, actuellement, dans le cadre des initiatives budgétaires participatives. Qu’il soit question d’acteurs nationaux concurrents ou d’influences issues des pays du Nord et du Sud, le résultat final reflète un processus d'apprentissage collaboratif ainsi que des luttes de pouvoir sous-jacentes.

Some plants are able to accumulate on their leaves metals taken from the soil, using this as a defence against herbivorous arthropods. However, herbivore response to metal accumulation in plants is known to be variable. While some species and taxonomic groups are less affected than others, hormetic effects have also been observed in spider-mites, herbivorous crop pests. Still, knowledge on the range and causes of intraspecific variation in the response of herbivores to metal accumulation is lacking. Here, using two species of spider-mites, Tetranychus urticae and T. evansi , we tested the variation of 17 populations in response to cadmium-accumulating tomato plants and the drivers of such variation. We observed a non-linear, hormetic response of mites to plants with cadmium in some, but not all, populations. The same pattern was recaptured in artificial diets with different concentrations of cadmium but not in artificial diets with sugars, which change in the plant in response to cadmium. This indicates that herbivores on metal-accumulating plants respond to metals, not to the variations in leaf carbohydrates. Therefore, metals exert different effects on herbivores according to the amount accumulated, but independently of other plant traits. This knowledge is key to the understanding of the mechanisms underlying herbivore responses to metal-based plant defences and to pesticides containing heavy metals. Additionally, our findings draw attention to the need of considering intraspecific variation and non-linearities when studying the effects of metals and other contaminants on herbivorous arthropods.

Rainfall is considered the most important physical process for landslide triggering in Portugal. It is expected that changes in the precipitation regimes in the region, as a direct consequence of climate change, will have influence in the occurrence of extreme rainfall events that will be more frequently, throughout the century. The aim of this study relied on the assessment of the projected future changes in the extreme precipitation over Portugal mainland and quantifying the correlation between extreme rainfall events and landslide events through Rainfall Triggering Thresholds (RTTs). This methodology was applied for two specific locations within two Portuguese areas of great geomorphological interest. To analyze the past frequency of landslide events, we resorted to the DISASTER database. To evaluate the possible projected changes in the extreme precipitation, we used the Iberia02 dataset and the EURO-CORDEX models’ runs at a 0.11° spatial resolution. It was analyzed the models’ performance to simulate extreme values in the precipitation series. The simulated precipitation relied on RCM-GCM models’ runs, from EURO-CORDEX, and a multimodel ensemble mean. The extreme precipitation assessment relied on the values associated to the highest percentiles, and to the values associated to the RTTs’ percentiles. To evaluate the possible future changes of the precipitation series, both at the most representative percentiles and RTTs’ percentiles, a comparison was made between the simulated values from EURO-CORDEX historical runs (1971–2000) and the simulated values from EURO-CORDEX future runs (2071–2100), considering two concentration scenarios: RCP 4.5 and RCP 8.5. In the models’ performance, the multimodel ensemble mean appeared to be within the best representing models. As for the projected changes in the extreme precipitation for the end of the century, when following the RCP 4.5 scenario, most models projected an increase in the extreme values, whereas, when following the RCP 8.5 scenario, most models projected a decrease in the extreme values.

© 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data., The European rabbit (Oryctolagus cuniculus) populations of the Iberian Peninsula have been severely affected by the emergence of the rabbit haemorrhagic disease virus (RHDV) Lagovirus europaeus/GI.2 (RHDV2/b). Bushflies and blowflies (Muscidae and Calliphoridae families, respectively) are important RHDV vectors in Oceania, but their epidemiological role is unknown in the native range of the European rabbit. In this study, scavenging flies were collected between June 2018 and February 2019 in baited traps at one site in southern Portugal, alongside a longitudinal capture-mark-recapture study of a wild European rabbit population, aiming to provide evidence of mechanical transmission of GI.2 by flies. Fly abundance, particularly from Calliphoridae and Muscidae families, peaked in October 2018 and in February 2019. By employing molecular tools, we were able to detect the presence of GI.2 in flies belonging to the families Calliphoridae, Muscidae, Fanniidae and Drosophilidae. The positive samples were detected during an RHD outbreak and absent in samples collected when no evidence of viral circulation in the local rabbit population was found. We were able to sequence a short viral genomic fragment, confirming its identity as RHDV GI.2. The results suggest that scavenging flies may act as mechanical vectors of GI.2 in the native range of the southwestern Iberian subspecies O. cuniculus algirus. Future studies should better assess their potential in the epidemiology of RHD and as a tool for monitoring viral circulation in the field., This study was performed within the scope of project LAGMED (www.lagmed.eu), supported by Fundação para a Ciência e Tecnologia, FCT (PRIMA/0003/2018) and PRIMA programme, an Art.185 initiative supported and funded under Horizon 2020, the European Union’s Framework Programme for Research and Innovation. This work was also co-funded by the European Regional Development Fund (FEDER) and Norte Portugal Regional Operational Programme (NORTE2020), under the PORTUGAL 2020 Partnership Agreement, and by the project NORTE-01-0246-FEDER-000063. The authors also acknowledge FCT research support via the Junior Researcher grant of Ana M. Lopes (CEECIND/01388/2017), the PhD grant of João Vasco Côrte-Real (DFA/BD/4965/2020), the post-doctoral grant of Nuno Santos (SFRH/BPD/116596/2016), the Principal Researcher grant of Pedro J. Esteves (CEECIND/CP1601/CT0005), the Assistant Researcher grant of Joana Abrantes (CEECIND/00078/2017), and projects CIISA UIDB/00276/2020, LA/P/0059/2020-Al4AnimalS and CESAM UID/AMB/50017-POCI-01-0145-FEDER-007638.

© 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/., Background: Engaging in physical activity increases energy expenditure, reducing total body fat. Time spent in sedentary behaviours is associated with overweight and obesity, and adequate sleep duration is associated with improved body composition. This systematic review aimed to analyse the relationship between compliance with the 24-h movement guidelines and obesity indicators in toddlers, children and adolescents. Methods: A systematic review and meta-analysis was conducted. PubMed, Web of Science and Scopus were searched from inception to December 2021. Cross-sectional and prospective studies that analysed the relationship between 24-h movement guidelines and overweight and obesity written in English, French, Portuguese or Spanish were included. PROSPERO registration number is CRD42022298316. Results: The associations between meeting the 24-h movement guidelines and standardised body mass index were null in the two studies for toddlers. Seven studies analysed the relationship between compliance with the 24-h movement guidelines and overweight and obesity among preschool children. Of these seven studies, six found no association between compliance with 24-h movement guidelines and body composition. Among children and adolescents, 15 articles were analysed. Of these 15 studies, in seven, it was found that children and adolescents who meet the 24-h movement guidelines were more likely to have lower risks of overweight and obesity. The meta-analysis yielded a pooled OR = 0.80 (95% CI = 0.68 to 0.95, p = 0.012, I2 = 70.5%) in favour of compliant participants. Regarding participants' age groups, compliance with 24-h movement guidelines seems to exert greater benefits on overweight and obesity indicators among children-adolescents (OR = 0.62, p = 0.008) compared to participants at preschool (OR = 1.00, p = 0.931) and toddlers (OR = 0.91, p = 0.853). Conclusion: Most included studies have not observed a significant relationship between compliance with the 24-h movement guidelines and overweight and obesity in toddlers, children and adolescents.

© 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data., Background: Renal denervation (RDN) has emerged in recent years as a possible treatment for hypertension. The first sham-controlled trial showed a small magnitude and non-significant in the blood pressure (BP) lowering effect, also due to a substantial decrease of BP in sham arm. Considering this, we aimed to quantify the magnitude of BP decrease within the sham arm of Randomized Controlled Trials (RCT) with RDN in patients with hypertension. Methods: Electronic databases were searched since inception until January 2022 for randomized sham-controlled trials which assessed the efficacy in lowering BP of the sham intervention for catheter-based RDN in adult patients with hypertension. The outcomes were change in ambulatory/office systolic and diastolic BP. Results: A total of 9 RCT were included in the analysis enrolling a total of 674 patients. Sham intervention showed a decrease in all evaluated outcomes. Office systolic BP had a reduction of -5.52 mmHg [95%CI -7.91, -3.13] and office diastolic BP of -2.13 mmHg [95%CI -3.08, -1.17]. Sham procedure for RDN also showed a reduction of -3.41 mmHg [95%CI -5.08, -1.75] in ambulatory systolic BP and - 2.44 mmHg [95%CI -3.31, -1.57] in ambulatory diastolic BP. Conclusion: Despite recent data indicating that RDN might be an effective treatment for patients with resistant hypertension when compared to a sham intervention, our results indicate that the sham intervention for RDN also has a significant effect on lowering Office and Ambulatory (24-h) Blood Pressure in adult patients with hypertension. This highlights that BP itself might be sensitive to placebo-like effect and also brings further difficulties in establishing the BP lowering efficacy of invasive interventions due to the magnitude of the sham effect., This work was supported by national funds, Fundação para a Ciência e a Tecnologia, reference number UIDB/00306/2020.

© The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR) 2023, Introduction/objectives: The study aims to define the clinical and subclinical calcinosis prevalence, the sensitivity of radiographed site and clinical method for its diagnosis, and the phenotype of Portuguese systemic sclerosis (SSc) patients with calcinosis. Method: A cross-sectional multicenter study was conducted with SSc patients fulfilling Leroy/Medsger 2001 or ACR/EULAR 2013 classification criteria, registered in the Reuma.pt. Calcinosis was assessed through clinical examination and radiographs of hands, elbows, knees, and feet. Independent parametric or non-parametric tests, multivariate logistic regression, and sensitivity calculation of radiographed site and clinical method for calcinosis detection were performed. Results: We included 226 patients. Clinical calcinosis was described in 63 (28.1%) and radiological calcinosis in 91 (40.3%) patients, of which 37 (40.7%) were subclinical. The most sensitive location to detect calcinosis was the hand (74.7%). Sensitivity of the clinical method was 58.2%. Calcinosis patients were more often female (p = 0.008) and older (p < 0.001) and had more frequently longer disease duration (p < 0.001), limited SSc (p = 0.017), telangiectasia (p = 0.039), digital ulcers (p = 0.001), esophageal (p < 0.001) and intestinal (p = 0.003) involvements, osteoporosis (p = 0.028), and late capillaroscopic pattern (p < 0.001). In multivariate analysis, digital ulcers (OR 2.63, 95% CI 1.02-6.78, p = 0.045) predicted overall calcinosis, esophageal involvement (OR 3.52, 95% CI 1.28-9.67, p = 0.015) and osteoporosis (OR 4.1, 95% CI 1.2-14.2, p = 0.027) predicted hand calcinosis, and late capillaroscopic pattern (OR 7.6, 95% CI 1.7-34.9, p = 0.009) predicted knee calcinosis. Anti-nuclear antibody positivity was associated with less knee calcinosis (OR 0.021, 95% CI 0.001-0477, p = 0.015). Conclusions: Subclinical calcinosis high prevalence suggests that calcinosis is underdiagnosed and radiographic screening might be relevant. Multifactorial pathogenesis may explain calcinosis predictors' variability. Key Points • Prevalence of subclinical calcinosis in SSc patients is substantial. • Hand radiographs are more sensitive to detect calcinosis than other locations or clinical method. • Digital ulcers were associated with overall calcinosis, esophageal involvement and osteoporosis were associated with hand calcinosis, and late sclerodermic pattern in nailfold capillaroscopy was associated with knee calcinosis. • Anti-nuclear antibody positivity may be a protective factor for knee calcinosis.

© The Author(s) 2023, Purpose: Theory-based interventions aimed at promoting health behavior change in cancer survivors seem to be effective but remain scarce. More information on intervention features is also needed. This review aimed to synthesize the evidence from randomized controlled trials evaluating the efficacy of theory-based interventions (and its features) on physical activity (PA) and/or diet behaviors in cancer survivors. Methods: A systematic search in three databases (PubMed, PsycInfo, and Web of Science) identified studies that (i) targeted adult cancer survivors and (ii) included theory-based randomized controlled trials designed to influence PA, diet, or weight management. A qualitative synthesis of interventions' effectiveness, extensiveness of theory use, and applied intervention techniques was conducted. Results: Twenty-six studies were included. Socio-Cognitive Theory was the most used theory, showing promising results in PA-only trials and mixed findings in multiple-behavior interventions. Mixed findings were observed for interventions based on the Theory of Planned Behavior and Transtheoretical Model. Limited findings were found in diet-only interventions. A large variability in the extensiveness of theory use, and in intervention techniques was found. Further research is required to understand how and why these interventions offer promise for improving behavior. Conclusions: Theory-based interventions seem to improve PA and diet behaviors in cancer survivors. Further studies, including thorough intervention descriptions, are needed to confirm these findings and identify the optimal features and content of lifestyle theory-based interventions for cancer survivors. Implications for cancer survivors: This systematic review can contribute to the development of more effective interventions to promote long-term adherence to healthy lifestyle behaviors., Open access funding provided by FCT|FCCN (b-on). This work was supported by the PAC-WOMAN scientific project, funded by the Portuguese Foundation for Science and Technology [grant numbers: PTDC/SAU-DES/2865/2020].

Background COVID-19 caused the largest pandemic of the twenty-first century forcing the adoption of containment policies all over the world. Many studies on COVID-19 health determinants have been conducted, mainly using multivariate methods and geographic information systems (GIS), but few attempted to demonstrate how knowing social, economic, mobility, behavioural, and other spatial determinants and their effects can help to contain the disease. For example, in mainland Portugal, non-pharmacological interventions (NPI) were primarily dependent on epidemiological indicators and ignored the spatial variation of susceptibility to infection. Methods We present a data-driven GIS-multicriteria analysis to derive a spatial-based susceptibility index to COVID-19 infection in Portugal. The cumulative incidence over 14 days was used in a stepwise multiple linear regression as the target variable along potential determinants at the municipal scale. To infer the existence of thresholds in the relationships between determinants and incidence the most relevant factors were examined using a bivariate Bayesian change point analysis. The susceptibility index was mapped based on these thresholds using a weighted linear combination. Results Regression results support that COVID-19 spread in mainland Portugal had strong associations with factors related to socio-territorial specificities, namely sociodemographic, economic and mobility. Change point analysis revealed evidence of nonlinearity, and the susceptibility classes reflect spatial dependency. The spatial index of susceptibility to infection explains with accuracy previous and posterior infections. Assessing the NPI levels in relation to the susceptibility map points towards a disagreement between the severity of restrictions and the actual propensity for transmission, highlighting the need for more tailored interventions. Conclusions This article argues that NPI to contain COVID-19 spread should consider the spatial variation of the susceptibility to infection. The findings highlight the importance of customising interventions to specific geographical contexts due to the uneven distribution of COVID-19 infection determinants. The methodology has the potential for replication at other geographical scales and regions to better understand the role of health determinants in explaining spatiotemporal patterns of diseases and promoting evidence-based public health policies.

© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Cryoballoon ablation (CBA) has been increasingly used for atrial fbrillation (AF) ablation. The presence of pulmonary vein (PV) anatomical variants, particularly left common pulmonary trunk (LCPT), may limit the cryoballoon adaptability and performance. To evaluate the impact of the presence of LCPT in CBA, we compared the success, safety, and procedure characteristics in consecutive patients referred for a frst-ever PVI attempt, irrespective of AF type and PV anatomy.

© 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).

Funder: CIBERNED, Funder: Lemaire Family Foundation, Funder: Swedish Frontotemporal Dementia Initiative Schorling Foundation, Funder: Swedish Alzheimer Foundation, Funder: Karolinska Institutet; doi: http://dx.doi.org/10.13039/501100004047, Funder: Weston Brain Institute; doi: http://dx.doi.org/10.13039/100012479, Funder: Miriam Marks Brain Research UK, BACKGROUND: Behavioural variant fronto-temporal dementia (bvFTD) is characterised by a progressive change in personality in association with atrophy of the frontal and temporal lobes. Whilst language impairment has been described in people with bvFTD, little is currently known about the extent or type of linguistic difficulties that occur, particularly in the genetic forms. METHODS: Participants with genetic bvFTD along with healthy controls were recruited from the international multicentre Genetic FTD Initiative (GENFI). Linguistic symptoms were assessed using items from the Progressive Aphasia Severity Scale (PASS). Additionally, participants undertook the Boston Naming Test (BNT), modified Camel and Cactus Test (mCCT) and a category fluency test. Participants underwent a 3T volumetric T1-weighted MRI, with language network regional brain volumes measured and compared between the genetic groups and controls. RESULTS: 76% of the genetic bvFTD cohort had impairment in at least one language symptom: 83% C9orf72, 80% MAPT and 56% GRN mutation carriers. All three genetic groups had significantly impaired functional communication, decreased fluency, and impaired sentence comprehension. C9orf72 mutation carriers also had significantly impaired articulation and word retrieval as well as dysgraphia whilst the MAPT mutation group also had impaired word retrieval and single word comprehension. All three groups had difficulties with naming, semantic knowledge and verbal fluency. Atrophy in key left perisylvian language regions differed between the groups, with generalised involvement in the C9orf72 group and more focal temporal and insula involvement in the other groups. Correlates of language symptoms and test scores also differed between the groups. CONCLUSIONS: Language deficits exist in a substantial proportion of people with familial bvFTD across all three genetic groups. Significant atrophy is seen in the dominant perisylvian language areas and correlates with language impairments within each of the genetic groups. Improved understanding of the language phenotype in the main genetic bvFTD subtypes will be helpful in future studies, particularly in clinical trials where accurate stratification and monitoring of disease progression is required.

Patterns of detectability and occupation of the jaguar (Panthera onca) vary throughout its distribution, being determined primarily by vegetation cover, prey availability, and anthropogenic factors. However, there is still a large knowledge gap regarding what determines jaguar occupancy, especially in the Amazon. This knowledge gap is even more pronounced for oceanic islands, which represent unique and very sensitive ecosystems, such as the Maracá-Jipioca Islands of the Northeastern Brazilian Amazon. Our study aimed to establish the spatial ecology of jaguars in this insular ecosystem and to provide information to facilitate sustainable management of the population there. We assessed how different factors (vegetation type and prey availability) potentially influence detectability and occupancy patterns of the jaguars of the Maracá-Jipioca Islands. We found that greater wetland (beach-sea and lagoon-channel) cover was the main driver of jaguar detectability and occupancy. We revealed factors driving the population and spatial ecology of jaguars in an insular system. Despite imminent threats to the region, the knowledge we present can inform the sustainable management of jaguars to ensure that the fundamental and unique ecosystem services provided by this top predator are maintained.

Lichens are one of the most responsive components of the ecosystem to reactive forms of nitrogen. In this work, we selected the lichen genera Cladonia and Usnea, composed of terricolous and epiphytic lichens respectively, and described as sensitive to nitrogen, to test the effects of different doses of nitrogen on lichen physiological parameters (photobiont and mycobiont vitality, chitin quantification, nitrogen content and stable isotopes analysis). The main objectives were to check if the activation of protective mechanisms could be stimulated in case of chronic stress (low nitrogen increase for prolonged time), and, if so, if a toxicity threshold could be identified above which these mechanisms fail. The two lichen genera were generally affected by prolonged exposure to increased nitrogen availability. However, Cladonia rangiformis was able to maintain physiological functioning at the lowest nitrogen doses used, whereas thalli of Usnea become overwhelmed. Moreover, the mycobiont appeared to be more sensitive than the photobiont responding to lower nitrogen doses. Although only studies of longer duration and testing more nitrogen doses will be able to determine an accurate toxicity threshold, these results give important clues on the use of lichens as biomonitors for the establishment of environmental policies.

Humans have negatively impacted most ecosystems on Earth, altering how species use habitats and resources available to them, but also their circadian rhythms. Among many factors affecting animal activity patterns, conversion of native habitat into production forests and hunting are critical, and their impacts may be exacerbated by seasonal weather conditions. Both these factors are issues in Mediterranean Europe, especially in Portugal. Nevertheless, their impact on native species behavior remains largely unknown, even for generalist species often resilient to human disturbance such as wild boar (Sus scrofa). Therefore, we assessed temporal activity patterns of wild boar in Portugal to explore differences between habitats (native forest versus Eucalyptus plantations), hunting and non-hunting periods, or between seasons. We found that wild boars were primarily nocturnal, with greater nighttime activity more evident during the dry season and within plantations. Furthermore, they appeared to avoid dusk during the hunting season. Together, these patterns indicate that even a species typically resilient to disturbance and environmental change, such as wild boar, tends to avoid adverse weather conditions and disturbance factors, namely high daytime temperatures in summer and probability of encountering forestry workers or hunters. Accordingly, other more sensitive or resource-demanding mammals may also be affected, so evaluating the impacts of the studied anthropic drivers on other mammals should be prioritized to provide information for sustainable plantation management and hunting.

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial 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-nc/4.0/., Introduction: Cancer care providers have faced many challenges in delivering safe care for patients during the COVID-19 pandemic. This cross-sectional survey-based study investigated the impact of the pandemic on clinical practices of Portuguese medical oncologists caring for patients with breast cancer. Methods: An anonymous online survey comprising 42 questions gathered information regarding COVID-19 testing, treatment in (neo)adjuvant and metastatic settings, and other aspects of breast cancer management. Practices before and during the pandemic were compared, and potential differences in outcomes according to respondents' regions, case volumes, and practice type were explored. Results: Of 129 respondents, 108 worked in the public health system, giving a representative national picture of the impact of the COVID-19 pandemic on breast cancer management. Seventy-one percent of respondents reported a reduction in visits for new cases of breast cancer, and there was a shift towards increased use of telemedicine. Clinical decision-making was largely unaffected in the most aggressive indications (i.e., triple-negative, HER2-positive, visceral crisis). The use of neoadjuvant therapy increased when access to surgery was difficult, whereas dose-dense regimens decreased, and cyclin-dependent kinase 4/6 inhibitor treatment decreased for less aggressive disease and increased for more aggressive disease. The use of oral formulations and metronomic chemotherapy regimens increased, and clinical trial participation decreased. Some differences by respondents' region and case volume were noted. Conclusion: Medical oncologists in Portugal implemented many changes during the COVID-19 pandemic, most of which were logical and reasonable responses to the current healthcare emergency; however, the true impact on patient outcomes remains unknown.

This study measures the output (start-ups) of an entrepreneurial ecosystem and estimates the moderating effect of institutional transparency on the relationship between entrepreneurial ecosystem and start-ups, applied to the context of Portuguese municipalities. Using factor analysis, a composite index of entrepreneurial ecosystem is constructed. The empirical results reveal that institutional transparency catalyzes the positive effect of entrepreneurial ecosystem index on the start-ups. Nevertheless, when the individual effects of entrepreneurial ecosystem’s elements on start-ups are analyzed, the composite index of institutional transparency reveals to be non-linearly related with the output of the entrepreneurial ecosystem, denoting a negative coefficient, in the linear form, and a positive coefficient, in the quadratic form. In addition, increases in financial and economic transparency and the transparency in urban planning deter the new business formation in a municipality, whereas the municipalities where public procurement is relatively transparent are found to be attracting more start-ups. Results also suggest that by increasing the transparency in public procurement, the government can raise the number of start-ups in a municipality. The empirical findings also corroborate the thesis that the presence of higher education institutions in a municipality help to attract more start-ups.

© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, The microenvironment of pituitary adenomas (PAs) includes a range of non-tumoral cells, such as immune and stromal cells, as well as cell signaling molecules such as cytokines, chemokines and growth factors, which surround pituitary tumor cells and may modulate tumor initiation, progression, invasion, angiogenesis and other tumorigenic processes. The microenvironment of PAs has been actively investigated over the last years, with several immune and stromal cell populations, as well as different cytokines, chemokines and growth factors being recently characterized in PAs. Moreover, key microenvironment-related genes as well as immune-related molecules and pathways have been investigated, with immune check point regulators emerging as promising targets for immunotherapy. Understanding the microenvironment of PAs will contribute to a deeper knowledge of the complex biology of PAs, as well as will provide developments in terms of diagnosis, clinical management and ultimately treatment of patients with aggressive and/or refractory PAs.

This article dwells on the case study of José Rosado, a fake translator of his own books to Portuguese (never written in any other language), and his interaction between 1942 and 1957 with Romano Torres, a twentieth century Portuguese publishing house, within the crime fiction collection Grandes Mistérios, Grandes Aventuras [Great Mysteries, Great Adventures]. Exploring José Rosado’s relationship with his publisher, centered on the process of authorial invention of fake foreign books, draws attention to the manifold processes involved in the creation of the translated texts—or the idea of translated text—as literary agency. It also illustrates the tensions within the heterogeneous framework of print production, circulation and appropriation of the translated text.

© 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/., Erythrocytes are deformable cells that undergo progressive biophysical and biochemical changes affecting the normal blood flow. Fibrinogen, one of the most abundant plasma proteins, is a primary determinant for changes in haemorheological properties, and a major independent risk factor for cardiovascular diseases. In this study, the adhesion between human erythrocytes is measured by atomic force microscopy (AFM) and its effect observed by micropipette aspiration technique, in the absence and presence of fibrinogen. These experimental data are then used in the development of a mathematical model to examine the biomedical relevant interaction between two erythrocytes. Our designed mathematical model is able to explore the erythrocyte-erythrocyte adhesion forces and changes in erythrocyte morphology. AFM erythrocyte-erythrocyte adhesion data show that the work and detachment force necessary to overcome the adhesion between two erythrocytes increase in the presence of fibrinogen. The changes in erythrocyte morphology, the strong cell-cell adhesion and the slow separation of the two cells are successfully followed in the mathematical simulation. Erythrocyte-erythrocyte adhesion forces and energies are quantified and matched with experimental data. The changes observed on erythrocyte-erythrocyte interactions may give important insights about the pathophysiological relevance of fibrinogen and erythrocyte aggregation in hindering microcirculatory blood flow., This work was supported by Fundação para a Ciência e a Tecnologia – Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal) projects PTDC/EMD-TLM/7289/2020 (all authors), PTDC/BBB-BMD/6307/2014 and UID/BIM/50005/2019 (CSL, FAC, NCS), through Fundos do Orçamento de Estado. JC and RT also thank the support of FEDER funds through the Operational Programme Competitiveness Factors – COMPETE and Fundação para a Ciência e a Tecnologia through the strategic projects UIDB/04564/2020 and UIDP/04564/2020. CSL also acknowledges FCT-MCTES fellowships PD/BD/135045/2017 and COVID/BD/151823/2021, General Programme of the European Molecular Biology Conference – EMBO Short-Term Fellowship 8350, and an EBSA Bursary for a working visit to the University of Southern Denmark to perform the micropipette aspiration technique experiments, as well as Erasmus+ mobility – ERASMUS SMT Student Mobility for Traineeships. AH-M acknowledges support from Ministerio de Ciencia e Innovación (Spain) under project PID2019-106063GB-100 and AGAUR (Generalitat de Catalunya) under project 2017 SGR-1061.

© 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/., Short nighttime sleep duration impairs the immune response to virus vaccination, and long nighttime sleep duration is associated with poor health status. Thus, we hypothesized that short (9 h) nighttime sleepers have a higher post-COVID risk than normal nighttime sleepers, despite two doses of mRNA vaccine (which has previously been linked to lower odds of long-lasting COVID-19 symptoms). Post-COVID was defined as experiencing at least one core COVID-19 symptom for at least three months (e.g., shortness of breath). Multivariate logistic regression adjusting for age, sex, BMI, and other factors showed in 9717 respondents (age span 18-99) that two mRNA vaccinations lowered the risk of suffering from post-COVID by about 21% (p < 0.001). When restricting the analysis to double-vaccinated respondents (n = 5918), short and long sleepers exhibited a greater post-COVID risk than normal sleepers (adjusted OR [95%-CI], 1.56 [1.29, 1.88] and 1.87 [1.32, 2.66], respectively). Among respondents with persistent sleep duration patterns during the pandemic compared to before the pandemic, short but not long sleep duration was significantly associated with the post-COVID risk (adjusted OR [95%-CI], 1.59 [1.24, 2.03] and 1.18 [0.70, 1.97], respectively). No significant association between sleep duration and post-COVID symptoms was observed in those reporting positive SARS-CoV-2 test results (n = 538). Our findings suggest that two mRNA vaccinations against SARS-CoV-2 are associated with a lower post-COVID risk. However, this protection may be less pronounced among those sleeping less than 6 h per night. Our findings warrant replication in cohorts with individuals with confirmed SARS-CoV-2 infection., CB’s research is financially supported by the Swedish Brain Research Foundation [FO2022-0254]. PX’s research is financially supported by the Åke Wiberg Foundation [M22-0081]. MP’s research is is financially supported by Signe and Arne Gyllenberg Foundation.

© 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data., Background: Excess weight is increasing worldwide, and in Latin America more than half of the population is excess weight. One of the reasons for this increase has been excessive sitting time. Still, it remains to be seen whether there is an excessive amount of that time in Latin American adults. This study aimed to associate different sitting time cut-off points with the excess weight. Methods: Data from the Latin American Study of Nutrition and Health (ELANS), a cross-sectional population-based survey conducted in eight Latin American countries, were used. The excess weight indicators used were body mass index, and waist and neck circumferences. Sitting time was obtained using questionnaires and categorized at different cut-off points. Differences between sitting time categories (< 4 or ≥ 4; < 6 or ≥ 6; and < 8 or ≥ 8 hours/day) and excess weight were obtained by Student's t test for independent samples and the association between sitting time categories and different indicators of excess weight were obtained by logistic regression. Results: The median of the sitting time was 420 min/day (IQR: 240-600). There were no significant differences between body mass index (kg/m2) and waist circumference (cm) with categories of sitting time. The mean values of neck circumference (cm) were significantly higher in ≥4, ≥6 and ≥ 8 hours/day than < 4, < 6, and < 8 hours/day of sitting time in the pooled sample. Some distinct differences by country were observed. There were significant differences among excess weight by body mass index (63.2% versus 60.8) with < 8 vs ≥8 hours/day of sitting time. The proportion of excess weight by neck circumference was higher in participants who reported ≥4, ≥6, and ≥ 8 hours/day compared to < 4, < 6, and < 8 hours/day of sitting time. Considering ≥8 hours/day of sitting time, higher odds of excess weight were found evaluated by body mass index (OR: 1.10; 95% CI: 1.01, 1.20) and neck circumference (OR: 1.13; CI 95%: 1.03, 1.24) overall. Conclusions: Sitting time above 8 hours/day was associated with higher odds of excess weight, even though there were no differences in waist circumference between sitting time categories.

© 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data., Background: Psychotic spectrum features in borderline personality disorder (PD) are a long-standing phenomenon, but remarkably, to date, they have not been the focus of many empirical studies. Moreover, the comparative studies that acknowledge their links to affective psychoses are even more scarce. Likewise, the contributions of empirical research on the DSM-5 dimensional approach to this topic are also uncommon. This study seeks to identify the best set of pathological personality traits and/or symptoms that are predictors of psychotic features (psychoticism and ideation paranoid symptoms) in borderline PD and in bipolar disorder, based on the framework of the DSM-5 section III personality traits. Methods: A cross-sectional study of two clinical samples: 1) Borderline PD group of 63 participants; 2) Bipolar disorder group of 65 participants. Self-reported assessment: Personality Inventory for DSM-5 (PID-5); Brief Symptom Inventory (BSI). A series of linear and logistic regression analyses were computed. Results: Overall, the data emerging as common predictors are detachment, negative affectivity, psychoticism, depressivity, grandiosity, suspiciousness and interpersonal sensitivity symptoms. Borderline PD has the highest score in BSI paranoid ideation which emerges as its discriminating trait (Nagelkerke R2 = .58): cognitive and perceptual dysregulation (OR: 13.02), restricted affectivity (OR: 12.09), withdrawal (OR: 11.70), anhedonia (OR: 10.98) and emotional lability (OR: 6.69). Conclusions: Besides the commonality that appears to overlap both disorders with a psychosis superspectrum, the patterns of the pathological personality-symptoms underlying the psychotic features appear to reinforce a position between schizophrenia and bipolar disorders that borderline PD may occupy, highlighting the possibility of its intersection with schizoaffective/psychosis spectra. The pathological personality nature of the psychotic features emerges as a potential comprehensive trait of the phenomenological dimensions., This work received national funding from FCT – Fundação para a Ciência e a Tecnologia, I. P [Foundation for Science and Technology] through the Research Center for Psychological Science of the Faculty of Psychology, University of Lisbon (UIDB/04527/2020; UIDP/04527/2020).

© The Author(s) 2022. 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data., Background: Machine learning algorithms have recently been developed to enable the automatic and real-time echocardiographic assessment of left ventricular ejection fraction (LVEF) and have not been evaluated in critically ill patients. Methods: Real-time LVEF was prospectively measured in 95 ICU patients with a machine learning algorithm installed on a cart-based ultrasound system. Real-time measurements taken by novices (LVEFNov) and by experts (LVEFExp) were compared with LVEF reference measurements (LVEFRef) taken manually by echo experts. Results: LVEFRef ranged from 26 to 80% (mean 54 ± 12%), and the reproducibility of measurements was 9 ± 6%. Thirty patients (32%) had a LVEFRef < 50% (left ventricular systolic dysfunction). Real-time LVEFExp and LVEFNov measurements ranged from 31 to 68% (mean 54 ± 10%) and from 28 to 70% (mean 54 ± 9%), respectively. The reproducibility of measurements was comparable for LVEFExp (5 ± 4%) and for LVEFNov (6 ± 5%) and significantly better than for reference measurements (p < 0.001). We observed a strong relationship between LVEFRef and both real-time LVEFExp (r = 0.86, p < 0.001) and LVEFNov (r = 0.81, p < 0.001). The average difference (bias) between real time and reference measurements was 0 ± 6% for LVEFExp and 0 ± 7% for LVEFNov. The sensitivity to detect systolic dysfunction was 70% for real-time LVEFExp and 73% for LVEFNov. The specificity to detect systolic dysfunction was 98% both for LVEFExp and LVEFNov. Conclusion: Machine learning-enabled real-time measurements of LVEF were strongly correlated with manual measurements obtained by experts. The accuracy of real-time LVEF measurements was excellent, and the precision was fair. The reproducibility of LVEF measurements was better with the machine learning system. The specificity to detect left ventricular dysfunction was excellent both for experts and for novices, whereas the sensitivity could be improved.

The existence of crime-related racial stereotypes has been well documented. People tend to associate certain groups with specifc crimes, which, in turn, impacts criminal-sentencing decisions through the perceptions of crime severity. This evidence calls for regular updating of rating norms combining these variables. With this objective, and given that most of the normative studies provide norms for a small number of crimes and/or with an insufcient number of participants, a new norming study was conducted. Furthermore, norms from European countries are absent, and the existing ones (mostly with USA-based populations) do not simultaneously examine crime stereotypicality and crime severity. The Crime Stereotypicality and Severity Database (CriSSD) presents normative ratings for a set of 63 crimes on three dimensions: White stereotypicality, Black stereotypicality, and crime severity. The crimes were selected according to a comprehensive procedure. A total of 340 Portuguese participants (72.6% female; Mage=26.86, SD=7.65) answered an online survey. Each crime was evaluated by a range of 46–60 participants. Data allowed us to identify a crime typology with three clusters. We present descriptive data (means, standard deviations, and 95% confdence intervals) for each crime. Crime evaluations were associated with sociodemographic characteristics. Additionally, this study gives input regarding the understudied link between crime stereotypes and crime severity, showing that crime severity is predicted by ratings of both Black and White stereotypicality. The CriSSD (available at osf.io/gkbrm) provides a valuable resource for researchers in the feld of social psychology to conduct studies with controlled materials on potential disparities in criminal-sentencing decisions. Fundação para a Ciência e Tecnologia - FCT info:eu-repo/semantics/publishedVersion

© The Author(s) 2022. 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/., When Trypanosoma brucei parasites, the causative agent of sleeping sickness, colonize the adipose tissue, they rewire gene expression. Whether this adaptation affects population behavior and disease treatment remained unknown. By using a mathematical model, we estimate that the population of adipose tissue forms (ATFs) proliferates slower than blood parasites. Analysis of the ATFs proteome, measurement of protein synthesis and proliferation rates confirm that the ATFs divide on average every 12 h, instead of 6 h in the blood. Importantly, the population of ATFs is heterogeneous with parasites doubling times ranging between 5 h and 35 h. Slow-proliferating parasites remain capable of reverting to the fast proliferation profile in blood conditions. Intravital imaging shows that ATFs are refractory to drug treatment. We propose that in adipose tissue, a subpopulation of T. brucei parasites acquire a slow growing behavior, which contributes to disease chronicity and treatment failure., The project leading to this application has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 771714). This work was also supported by IC&DT Programa de Actividades Conjuntas – ref. 016417 “Oneida”, PTDC/BIMMET/4471/2014 and PTDC/CVT-CVT/29161/2017 (FCT). SFRH/BPD/89833/2012 and DL 57/2016/CP1451/CT0019 (FCT) to S.T, LT000047/2019-L (HFSP) and ALTF 1048-2016 (EMBO) to M.D.N, MSCA ITN Cell2Cell fellowship to L.LE and CEECIND/03322/2018 (FCT) to L.M.F. FBr is supported by the Agence National de Recherche (ANR, grant number ANR19-CE15-0004-01: ADIPOTRYP), the Fondation pour le Recherche Médicale (FRM, grant n°EQU201903007845: “Equipe FRM”) and the Laboratoire d’Excellence (grant number ANR-11-LABX-0024:ParaFrap).

The golden-striped salamander is a streamside species endemic to the northwestern corner of the Iberian Peninsula. In the first half of the twentieth century, an undisclosed number of individuals of this species were reportedly captured in Buçaco, Central Portugal, and deliberately introduced in Sintra Mountains, 170 km south of its native distribution range. The discovery of a breeding population of this salamander in Sintra during 2015 prompted this work: we used neutral genetic markers, the mitochondrial DNA cytochrome b (cytb), and seven microsatellite loci to elucidate on the relict/human-introduced nature of Sintra population, identify the potential source population, and infer the severity of founder effect. Our results support a human-mediated introduction. First, sequencing analysis of cytb showed the presence of a unique haplotype (h31) in Sintra, which was detected only in Buçaco and in two additional populations located close to Mondego river. Second, microsatellite analysis showed that Sintra is more closely related to populations in between Douro and Mondego rivers (Central Portugal), instead of its geographically closest populations (southernmost), as would be expected if Sintra was a relict population isolated in an interglacial refuge. Third, Sintra presents both reduced levels of genetic variability and effective population size when compared to native populations, particularly to those of Central Portugal. Consistent with an isolated population funded by a small number of individuals (inferred herein to be ca. 10–11 salamanders), Sintra forms a geographically coherent genetic unit that is significantly differentiated from the extant native C. lusitanica populations. Although our data provide supporting evidence for Buçaco as a likely source population, as documented in the literature, overall, we cannot unequivocally exclude other populations close to Mondego river as a potential source of the introduced individuals in Sintra.

Copyright © 2023, Springer Nature Limited, DNMT3A is best known for its de novo DNA methyltransferase activity. But a new study shows that the protein also has a role in RNA splicing during activation of embryonic and haematopoietic stem cells. This introduces a new perspective for approaching diseases associated with DNMT3A mutations.

© International League of Associations for Rheumatology (ILAR) 2021, Evidence for the role of sex in the clinical manifestations of systemic sclerosis (SSc) patients is emerging. Some multicenter cohorts have shown that male SSc patients have more severe disease and worse survival. To assess the differences in clinical manifestations and survival in Portuguese SSc patients according to gender. Data from male and female adult SSc patients included in the Rheumatic Diseases Portuguese Register (Reuma.pt) were analysed and compared. Survival was calculated for patients included in Reuma.pt. within the first two years of diagnosis (inception cohort). In total, 1054 adult patients with SSc were included, 12.5% males. No differences in demographic features and comorbidities were found between the sexes, except for a higher rate of cigarette smokers among men. Diffuse cutaneous SSc and anti-topoisomerase antibodies were more prevalent in males than females. Additionally, male patients presented significantly more myositis, interstitial lung disease and gastric involvement. There were no differences in the patterns of drug use between the sexes. During follow-up, more deaths were reported in men than women (12.1% vs 7.3%, p = 0.04). The overall 1-, 3-, and 5-year survivals from diagnosis of the inception cohort (N = 469) for men vs women were 96.4% vs 98.2%, 93% vs 95.9%, and 75.8% vs 93.2%, respectively, with statistically significant differences (p < 0.01). This study confirms the existence of gender differences in clinical and immunological SSc features. Although SSc is less common in men than women, men have a more severe expression of skin and internal organ involvement and worse survival. Key Points • There are differences in SSc disease manifestations between sexes. • Males more commonly have diffuse cutaneous SSc, anti-topoisomerase antibodies, pulmonary and musculoskeletal involvement. • In the inception cohort, men had worse survival rates than women.

Eucalyptus globulus Labill. is one of the most widely planted hardwood species worldwide. This species occupies a quarter of the country's forested area in Portugal, so there is a growing concern about its post-fire dispersal. Although it is generally recognised that fire promotes E. globulus natural regeneration and that precipitation and topography influence recruitment, little is known about the role of post-fire conditions on the establishment of the species following off-season fires. We examine how post-fire conditions affect E. globulus natural regeneration and invasive potential. Sapling establishment was assessed in plantations and under old and large isolated eucalyptus trees (seed-trees) following two off-season fire events (2017 June and October fires). Abiotic and biotic local factors affected differently sapling establishment in plantations and under seed-trees. In plantations, sapling cover was more influenced by tree-related traits (age and height), whereas the conditions beneath seed-trees mitigated the impact of harsh conditions on saplings. In both cases, post-fire climatic conditions constrained natural regeneration, with less impact under seed-trees, reinforcing their importance in establishment success. Thus, isolated seed-trees should be considered while managing the species’ unplanned spread.

Whether ethnoarcheological models of hunter-gatherer mobility, landscape use, and structuration of the inhabited space are relevant to the archeology of Neandertals and the Middle Paleolithic remains controversial. The thin lenses of hearth-associated stone tools and faunal remains excavated in sub-complex AS5 of Cueva Antón (Murcia, Spain) significantly advance these debates. Dated to 77.8–85.1 ka, these living floors are interstratified in river-accumulated sands and were buried shortly after abandonment by low-energy inundation events, with minimal disturbance and negligible palimpsest formation. Stone tools were made and ergonomically modified to fit tasks; their spatial distributions and use-wear reveal hearth-focused activities and a division of the inhabited space into resting and working areas. Site function varied with season of the year: units III-i/j1 and III-i/j2-3 record winter visits focused on filleting and hide processing, while woodworking predominated in unit III-b/d, which subsumes visits to the site over the course of at least one winter, one spring, and one summer. These snapshots of Neandertal behavior match expectations derived from the ethnographic and Upper Paleolithic records for the lifeways of hunter-gatherers inhabiting temperate regions with a markedly seasonal climate.

© The Author(s) 2022. 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/., SARS-CoV-2 transmission occurs mainly indoors, through virus-laden airborne particles. Although the presence and infectivity of SARS-CoV-2 in aerosol are now acknowledged, the underlying circumstances for its occurrence are still under investigation. The contamination of domiciliary environments during the isolation of SARS-CoV-2-infected patients in their respective rooms in individual houses and in a nursing home was investigated by collecting surface and air samples in these environments. Surface contamination was detected in different contexts, both on high and low-touch surfaces. To determine the presence of virus particles in the air, two sampling methodologies were used: air and deposition sampling. Positive deposition samples were found in sampling locations above the patient's height, and SARS-CoV-2 RNA was detected in impactation air samples within a size fraction below 2.5 μm. Surface samples rendered the highest positivity rate and persistence for a longer period. The presence of aerosolized SARS-CoV-2 RNA occurred mainly in deposition samples and closer to symptom onset. To evaluate the infectivity of selected positive samples, SARS-CoV-2 viability assays were performed, but our study was not able to validate the virus viability. The presented results confirm the presence of aerosolized SARS-CoV-2 RNA in indoor compartments occupied by COVID-19 patients with mild symptoms, in the absence of aerosol-generating clinical procedures., This Project has been partially supported by Portuguese national funds via Fundação para a Ciência e a Tecnologia—Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES), under Project 679 Research4Covid19, UIDB/04539/2020 and UIDP/04539/2020.

© The Author(s) 2022. 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data., Background: By 2016, signs of emergence of Plasmodium falciparum resistance to artemisinin and partner drugs were detected in the Greater Mekong Subregion. Recently, the independent evolution of artemisinin resistance has also been reported in Africa and South America. This alarming scenario calls for the urgent development of new antimalarials with novel modes of action. We investigated the interference with protein aggregation, which is potentially toxic for the cell and occurs abundantly in all Plasmodium stages, as a hitherto unexplored drug target in the pathogen. Results: Attempts to exacerbate the P. falciparum proteome's propensity to aggregation by delivering endogenous aggregative peptides to in vitro cultures of this parasite did not significantly affect their growth. In contrast, protein aggregation inhibitors clearly reduced the pathogen's viability. One such compound, the bis(styrylpyridinium) salt YAT2150, exhibited potent antiplasmodial activity with an in vitro IC50 of 90 nM for chloroquine- and artemisinin-resistant lines, arresting asexual blood parasites at the trophozoite stage, as well as interfering with the development of both sexual and hepatic forms of Plasmodium. At its IC50, this compound is a powerful inhibitor of the aggregation of the model amyloid β peptide fragment 1-40, and it reduces the amount of aggregated proteins in P. falciparum cultures, suggesting that the underlying antimalarial mechanism consists in a generalized impairment of proteostasis in the pathogen. YAT2150 has an easy, rapid, and inexpensive synthesis, and because it fluoresces when it accumulates in its main localization in the Plasmodium cytosol, it is a theranostic agent. Conclusions: Inhibiting protein aggregation in Plasmodium significantly reduces the parasite's viability in vitro. Since YAT2150 belongs to a novel structural class of antiplasmodials with a mode of action that potentially targets multiple gene products, rapid evolution of resistance to this drug is unlikely to occur, making it a promising compound for the post-artemisinin era., This work was supported by grants (i) PCIN-2017-100, RTI2018-094579-B-I00 and PID2021-128325OB-I00 (XF-B), and SAF2017-82771-R and PID2020-118127RB-I00 (DM-T), funded by Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación (MCIN/AEI/10.13039/501100011033 for grants PID2021- and PID2020-), which for grants RTI2018-, PID2021-, and SAF2017- included FEDER funds; (ii) ERA-NET Cofund EURONANOMED (http://euronanomed.net/), grant number 2017-178 (XF-B); and (iii) Generalitat de Catalunya, Spain (http://agaur.gencat.cat/), grant numbers 2017-SGR-908 (XF-B) and 2017-SGR-106 (DM-T). Work at Pompeu Fabra University was supported by the “La Caixa” Banking Foundation (https://fundacionlacaixa.org/, grant HR17-00409), and by grant AGL2017-84097-C2-2-R and the “María de Maeztu” Program for Units of Excellence in R&D from the Spanish Ministry of Science, Innovation and Universities.

Reciprocal migration—which we define as the mutual exchange of origin and destination by two different migrating groups—is hardly acknowledged in the migration literature. In terms of the temporalities of migration, which are usually seen as sequences or transitions, reciprocal migrations are simultaneous. We analyse the reciprocal migrations between Angola and Portugal over the time-frame of the past 10–15 years. In-depth interviews were carried out with Portuguese migrants in Angola, most of whom moved there in the wake of the post-2008 financial crisis, and with Angolan third-level students and recent graduates in Portugal. A key operational concept in our analysis is the plastic notion of skill and its differential racialisation. Portuguese migrants in Angola are automatically regarded as ‘skilled’ even when they are not, whereas Angolan students and graduates in Portugal, when they seek work, are often viewed as ‘unskilled African migrant workers’. We thus distinguish and deconstruct the geographical binary between transnational origin and destination spaces and the social binary between ‘skilled white bodies’ and ‘unskilled black bodies’. These racialised embodied tropes draw on histories of Portuguese colonisation and the contested notion of ‘Lusotropicalism’, as well as the so-called Lusophone migration system involving complex transnational relations and two-way migration flows. Theoretically we frame this asymmetrical system of reciprocal migration within a modified version of core–periphery relations, as well as the coloniality of power and its enduring influence over the racialisation of skill, education, culture and language across the Portuguese–Angolan transnational space.

How and at what pace bacteria evolve when colonizing healthy hosts remains unclear. Here, by monitoring evolution for more than six thousand generations in the mouse gut, we show that the successful colonization of an invader Escherichia coli depends on the diversity of the existing microbiota and the presence of a closely related strain. Following colonization, two modes of evolution were observed: one in which diversifying selection leads to long-term coexistence of ecotypes and a second in which directional selection propels selective sweeps. These modes can be quantitatively distinguished by the statistics of mutation trajectories. In our experiments, diversifying selection was marked by the emergence of metabolic mutations, and directional selection by acquisition of prophages, which bring their own benefits and costs. In both modes, we observed parallel evolution, with mutation accumulation rates comparable to those typically observed in vitro on similar time scales. Our results show how rapid ecotype formation and phage domestication can be in the mammalian gut.

Fluvial flooding continues to be a process that has a major impact on society, the environment and the economy. Although its natural triggering factors, the spatial configuration of exposure and vulnerability is expected to play a relevant role in explaining the damage records. The starting point of this research is the use of existing flood susceptibility, exposure and social vulnerability mapping, produced at the parish level, as input data in a Classification and Regression Trees' (CART) model. Two models were ran, autonomously, that use two databases of flood damage as dependent variables: one including the human damages (fatalities, missing, injured, displaced and evacuated people) from flood events-the DISASTER database; another one that sums the DISASTER cases and the lower impact damages (damages to roads, railroads and buildings). The results show a quite distinct classification of parishes, whether one database is used or the other. The DISASTER database reveals susceptibility as the most relevant flood risk driver in explaining the damage patterns, while the database with all the flood cases identifies exposure as the more relevant driver. In the end, the degree of damages as documented in databases is conditioned by the geographical distribution and overlay configuration of the three flood risk drivers. Finally, the CART classification groups are analyzed at the light of the European Union's Floods Directive areas of significant potential flood risk. This analysis showed that the Directive's parishes are interpreted differently-in terms of their positioning in face of the risk drivers-which is explained by the use of distinct impacting-criteria in the construction of the flood damage databases.

© The Author(s) 2022 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/., Reprogramming of somatic cells into induced Pluripotent Stem Cells (iPSCs) is a major leap towards personalised approaches to disease modelling and cell-replacement therapies. However, we still lack the ability to fully control the epigenetic status of iPSCs, which is a major hurdle for their downstream applications. Epigenetic fidelity can be tracked by genomic imprinting, a phenomenon dependent on DNA methylation, which is frequently perturbed in iPSCs by yet unknown reasons. To try to understand the causes underlying these defects, we conducted a thorough imprinting analysis using IMPLICON, a high-throughput method measuring DNA methylation levels, in multiple female and male murine iPSC lines generated under different experimental conditions. Our results show that imprinting defects are remarkably common in iPSCs, but their nature depends on the sex of donor cells and their response to culture conditions. Imprints in female iPSCs resist the initial genome-wide DNA demethylation wave during reprogramming, but ultimately cells accumulate hypomethylation defects irrespective of culture medium formulations. In contrast, imprinting defects on male iPSCs depends on the experimental conditions and arise during reprogramming, being mitigated by the addition of vitamin C (VitC). Our findings are fundamental to further optimise reprogramming strategies and generate iPSCs with a stable epigenome., Work in S.T.d.R.’s team was supported by Fundação para a Ciência e Tecnologia (FCT) Ministério da Ciência, Tecnologia e Ensino Superior (MCTES), Portugal [IC&DT projects PTDC/BEX-BCM/2612/2014 and PTDC/BIA-MOL/29320/2017 as well as projects UIDB/04565/2020 and UIDP/04565/2020 of the Research Unit Institute from Bioengineering and Biosciences – iBB and LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy – i4HB]; S.T.d.R. and A.-V.G. are supported by assistant research contracts from FCT/MCTES (CEECIND/01234/2017 and CEECIND/02085/2018, respectively); M.A and A.C.R. are supported, respectively, by SFRH/BD/151251/2021 and SFRH/BD/137099/2018 PhD fellowships from FCT/MCTES. J.V.G.L is supported by COVID/BD/152624/2022 from FCT/MCTES. MAE-M was supported by a BBSRC Discovery Fellowship (BB/T009713/1) and is now supported by a Snow Medical Fellowship. F.K. is supported by the Babraham Institute Strategic Core Funding and A.M. by BBSRC BBS/E/B/000C0421. B.B.J. work was funded by Fundação para a Ciência e Tecnologia (FCT), and FEDER, LISBOA-01-0145-FEDER-028534, project co-funded by FEDER, through POR Lisboa 2020—Programa Operacional Regional de Lisboa. T.K. is supported by Janko Jamnik Doctoral Scholarship from National Institute of Chemistry.

Funder: The Bluefield Project, Funder: UK Dementia Research Institute; doi: http://dx.doi.org/10.13039/501100017510, Funder: Alzheimer's Society; doi: http://dx.doi.org/10.13039/501100000320, Funder: schorling foundation, Funder: Swedish brain foundation, Funder: swedish alzheimer foundation, Funder: Stockholm Council ALF, Funder: Demensfonden; doi: http://dx.doi.org/10.13039/501100021594, Funder: Gun och Bertil Stohnes Stiftelse; doi: http://dx.doi.org/10.13039/100009673, Funder: Stiftelsen för Gamla Tjänarinnor; doi: http://dx.doi.org/10.13039/100010815, Funder: Karolinska Institutet; doi: http://dx.doi.org/10.13039/501100004047, Funder: Stratneuro, Funder: Mady Browaeys Fonds, Funder: Knut och Alice Wallenbergs Stiftelse; doi: http://dx.doi.org/10.13039/501100004063, BACKGROUND: Neuroinflammation is emerging as an important pathological process in frontotemporal dementia (FTD), but biomarkers are lacking. We aimed to determine the value of complement proteins, which are key components of innate immunity, as biomarkers in cerebrospinal fluid (CSF) and plasma of presymptomatic and symptomatic genetic FTD mutation carriers. METHODS: We measured the complement proteins C1q and C3b in CSF by ELISAs in 224 presymptomatic and symptomatic GRN, C9orf72 or MAPT mutation carriers and non-carriers participating in the Genetic Frontotemporal Dementia Initiative (GENFI), a multicentre cohort study. Next, we used multiplex immunoassays to measure a panel of 14 complement proteins in plasma of 431 GENFI participants. We correlated complement protein levels with corresponding clinical and neuroimaging data, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). RESULTS: CSF C1q and C3b, as well as plasma C2 and C3, were elevated in symptomatic mutation carriers compared to presymptomatic carriers and non-carriers. In genetic subgroup analyses, these differences remained statistically significant for C9orf72 mutation carriers. In presymptomatic carriers, several complement proteins correlated negatively with grey matter volume of FTD-related regions and positively with NfL and GFAP. In symptomatic carriers, correlations were additionally observed with disease duration and with Mini Mental State Examination and Clinical Dementia Rating scale® plus NACC Frontotemporal lobar degeneration sum of boxes scores. CONCLUSIONS: Elevated levels of CSF C1q and C3b, as well as plasma C2 and C3, demonstrate the presence of complement activation in the symptomatic stage of genetic FTD. Intriguingly, correlations with several disease measures in presymptomatic carriers suggest that complement protein levels might increase before symptom onset. Although the overlap between groups precludes their use as diagnostic markers, further research is needed to determine their potential to monitor dysregulation of the complement system in FTD.