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Abstract Culturing and genomic sequencing of Mycobacterium tuberculosis (MTB) from tuberculosis (TB) cases is the basis for many research and clinical applications. The alternative, culture-free sequencing from diagnostic samples, is promising but poses challenges to obtain and analyse the MTB genome. Paradoxically, culture is assumed to impose a diversity bottleneck, which, if true, would entail unexplored consequences. To unravel this paradox we generate high-quality genomes of sputum-culture pairs from two different settings after developing a workflow for sequencing from sputum and a tailored bioinformatics analysis. Careful downstream comparisons reveal sources of sputum-culture incongruences due to false positive/negative variation associated with factors like low input MTB DNA or variable genomic depths. After accounting for these factors, contrary to the bottleneck dogma, we identify a 97% variant agreement within sputum-culture pairs, with a high correlation also in the variants’ frequency (0.98). The combined analysis from five different settings and more than 100 available samples shows that our results can be extrapolated to different TB epidemic scenarios, demonstrating that for the cases tested culture accurately mirrors clinical samples.

Abstract Genetic studies have identified the voltage‐gated sodium channel 1.7 (Nav1.7) as pain target. Due to the ineffectiveness of small molecules and monoclonal antibodies as therapeutics for pain, single‐domain antibodies (VHHs) are developed against the human Nav1.7 (hNav1.7) using a novel antigen presentation strategy. A 70 amino‐acid peptide from the hNav1.7 protein is identified as a target antigen. A recombinant version of this peptide is grafted into the complementarity determining region 3 (CDR3) loop of an inert VHH in order to maintain the native 3D conformation of the peptide. This antigen is used to isolate one VHH able to i) bind hNav1.7, ii) slow the deactivation of hNav1.7, iii) reduce the ability of eliciting action potentials in nociceptors, and iv) reverse hyperalgesia in in vivo rat and mouse models. This VHH exhibits the potential to be developed as a therapeutic capable of suppressing pain. This novel antigen presentation strategy can be applied to develop biologics against other difficult targets such as ion channels, transporters and GPCRs.

Abstract The strategic location of North Africa has led to cultural and demographic shifts, shaping its genetic structure. Historical migrations brought different genetic components that are evident in present-day North African genomes, along with autochthonous components. The Imazighen (plural of Amazigh) are believed to be the descendants of autochthonous North Africans and speak various Amazigh languages, which belong to the Afro-Asiatic language family. However, the arrival of different human groups, especially during the Arab conquest, caused cultural and linguistic changes in local populations, increasing their heterogeneity. We aim to characterize the genetic structure of the region, using the largest Amazigh dataset to date and other reference samples. Our findings indicate microgeographical genetic heterogeneity among Amazigh populations, modeled by various admixture waves and different effective population sizes. A first admixture wave is detected group-wide around the twelfth century, whereas a second wave appears in some Amazigh groups around the nineteenth century. These events involved populations with higher genetic ancestry from south of the Sahara compared to the current North Africans. A plausible explanation would be the historical trans-Saharan slave trade, which lasted from the Roman times to the nineteenth century. Furthermore, our investigation shows that assortative mating in North Africa has been rare.

The UV–Visible Working Group of the Network for the Detection of Atmospheric Composition Changes (NDACC) focuses on the monitoring of air-quality-related stratospheric and tropospheric trace gases in support of trend analysis, satellite validation and model studies. Tropospheric measurements are based on MAX-DOAS-type instruments that progressively emerged in the years 2010 onward. In the interest of improving the overall consistency of the NDACC MAX-DOAS network and facilitating its further extension to the benefit of satellite validation, the ESA initiated, in late 2016, the FRM4DOAS project, which aimed to set up the first centralised data processing system for MAX-DOAS-type instruments. Developed by a consortium of European scientists with proven expertise in measurements, data extraction algorithms and software design specialities, the system has now reached pre-operational status and has demonstrated its ability to deliver a set of quality-controlled atmospheric composition data products with a latency of one day. The processing system has been designed using a highly modular approach, making it easy to integrate new tools or processing updates. It incorporates advanced algorithms selected by community consensus for the retrieval of total ozone, lower tropospheric and stratospheric NO2 vertical profiles and formaldehyde profiles. The ozone and NO2 products are currently generated from a total of 22 stations and delivered daily to the NDACC rapid delivery (RD) repository, with an additional mirroring to the ESA Validation Data Centre (EVDC). Although it is still operated in a pre-operational/demonstrational mode, FRM4DOAS was already used for several validation and science studies, and it was also deployed in support of field campaigns for the validation of the TROPOMI and GEMS satellite missions. It recently went through a CEOS-FRM self-assessment process aiming at assessing the level of maturity of the service in terms of instrumentation, operations, data sampling, metrology and verification. Based on this evaluation, it falls under class C, which is a good rating but also implies that further improvements are needed to reach full compliance with FRM standards, i.e., class A.

Genetic differentiation between populations inhabiting ecologically different habitats might appear because of limited dispersal and gene flow, which may lead to patterns of phenotypic divergence and local adaptation. In this study, we use dispersal, genotypic (24 microsatellite loci) and phenotypic (body size and clutch size) data to analyse patterns of genetic structuring and phenotypic divergence in a blue tit (Cyanistes caeruleus) population inhabiting a continuous and heterogeneous woodland along a valley. The two slopes of the valley differ in their forest formations and environmental conditions. Findings showed that most blue tits reproduced within their natal slope. Accordingly, microsatellite analyses revealed that populations of blue tits established in the two slopes show subtle genetic differentiation. The two genetic populations diverged in clutch size, exceeding the level of differentiation expected based on genetic drift, hence suggesting divergent selection (or other processes promoting divergence) on this life-history trait. Our findings reveal that restricted dispersal and spatial heterogeneity may lead to genetic differentiation among bird populations at a surprisingly small scale. In this respect, it is worth highlighting that such differentiation occurs for an organism with high dispersal capacity and within a continuous woodland. Moreover, we show that small-scale ecological differences, together with limited gene flow, can result in selection favouring different phenotypes even within the same continuum population.

Abstract There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p

Abstract Mesospheric Green emissions from excited Oxygen in Sprite Tops (ghosts) are infrequent and faint greenish transient luminous events that remain for hundreds of milliseconds on top of certain energetic sprites. The main hypothesis to explain this glow persistence is the long lifetime of excited atomic oxygen at 557.73 nm, a well-known emission line in aurora and airglow. However, due to the lack of spectroscopic campaigns to analyse such events to date, the species involved in the process can not yet be identified. Here we report observational results showing the temporal evolution of a ghost spectrum between 500 nm and 600 nm. Besides weak -but certain- traces of excited atomic oxygen, our results show four main contributors related to the slow decay of the glow: atomic iron and nickel, molecular nitrogen and ionic molecular oxygen. Additionally, we are able to identify traces of atomic sodium, and ionic silicon, these observations being consistent with previous direct measurements of density profiles of meteoric metals in the mesosphere and lower thermosphere. This finding calls for an upgrade of current air plasma kinetic understanding under the influence of transient luminous events.

Cell spheroids are an important three-dimensional (3D) model for in vitro testing and are gaining interest for their use in clinical applications. More natural 3D cell culture environments that support cell–cell interactions have been created for cancer drug discovery and therapy applications, such as the scaffold-free 3D Petri Dish® technology. This technology uses reusable and autoclavable silicone micro-molds with different topographies, and it conventionally uses gelled agarose for hydrogel formation to preserve the topography of the selected micro-mold. The present study investigated the feasibility of using a patterned Poly(vinyl alcohol) hydrogel using the circular topography 12–81 (9 × 9 wells) micro-mold to form HeLa cancer cell spheroids and compare them with the formed spheroids using agarose hydrogels. PVA hydrogels showed a slightly softer, springier, and stickier texture than agarose hydrogels. After preparation, Fourier transform infrared (FTIR) spectra showed chemical interactions through hydrogen bonding in the PVA and agarose hydrogels. Both types of hydrogels favor the formation of large HeLa spheroids with an average diameter of around 700–800 µm after 72 h. However, the PVA spheroids are more compact than those from agarose, suggesting a potential influence of micro-mold surface chemistry on cell behavior and spheroid formation. This was additionally confirmed by evaluating the spheroid size, morphology, integrity, as well as E-cadherin and Ki67 expression. The results suggest that PVA promotes stronger cell-to-cell interactions in the spheroids. Even the integrity of PVA spheroids was maintained after exposure to the drug cisplatin. In conclusion, the patterned PVA hydrogels were successfully prepared using the 3D Petri Dish® micro-molds, and they could be used as suitable platforms for studying cell–cell interactions in cancer drug therapy.

Abstract Water and nitrogen (N) are the most limiting factors to plant productivity globally, but we lack a critical understanding of how water availability impacts N dynamics in agricultural systems. Plant N requirements are particularly uncertain when water is limited because of the interactive effect of water and N on plant growth, N demand, and plant uptake. We investigated impacts of N application and water availability on plant growth and N movement, including above and belowground growth, water productivity, N productivity, N uptake, N recovery, and greenhouse gas emissions within a semi-arid system in northeastern Colorado, USA. Moderately high soil N availability depressed grain yield and shoot growth under both limited and full water availability, despite no indication of physical toxicity, and came with additional risk of deleterious N losses. Under low N availability, plant N concentrations in aboveground tissues showed greater recovery of N than what was applied in the low N treatments under both full and limited water availability. This enhanced recovery underscores the need to better understand both plant soil foraging and processes governing resource availability under these conditions. Finally, limited water availability reduced N uptake across all N treatments and left 30% more soil nitrate (NO3 −) deep in the soil profile at the end of the season than under full water availability. Our results show that plant N needs are not linearly related to water use and emphasize the need for an integrated understanding of water and N interactions, plant foraging for these resources, and the dynamics of processes that make N available to plants.

Abstract Despite being enclosed between the Mediterranean Sea and the Sahara Desert, North Africa has been the scenario of multiple human migrations that have shaped the genetic structure of its present-day populations. Despite its richness, North Africa remains underrepresented in genomic studies. To overcome this, we have sequenced and analyzed 264 mitogenomes from the Algerian Chaoui-speaking Imazighen (a.k.a. Berbers) living in the Aurès region. The maternal genetic composition of the Aurès is similar to Arab populations in the region, dominated by West Eurasian lineages with a moderate presence of M1/U6 North African and L sub-Saharan lineages. When focusing on the time and geographic origin of the North African specific clades within the non-autochthonous haplogroups, different geographical neighboring regions contributed to the North African maternal gene pool during time periods that could be attributed to previously suggested admixture events in the region, since Paleolithic times to recent historical movements such as the Arabization. We have also observed the role of North Africa as a source of geneflow mainly in Southern European regions since Neolithic times. Finally, the present work constitutes an effort to increase the representation of North African populations in genetic databases, which is key to understand their history.

Abstract Because of its location, North Africa (NA) has witnessed continuous demographic movements with an impact on the genomes of present-day human populations. Genomic data describe a complex scenario with varying proportions of at least four main ancestry components: Maghrebi, Middle Eastern-, European-, and West-and-East-African-like. However, the footprint of positive selection in NA has not been studied. Here, we compile genome-wide genotyping data from 190 North Africans and individuals from surrounding populations, investigate for signatures of positive selection using allele frequencies and linkage disequilibrium-based methods and infer ancestry proportions to discern adaptive admixture from post-admixture selection events. Our results show private candidate genes for selection in NA involved in insulin processing (KIF5A), immune function (KIF5A, IL1RN, TLR3), and haemoglobin phenotypes (BCL11A). We also detect signatures of positive selection related to skin pigmentation (SLC24A5, KITLG), and immunity function (IL1R1, CD44, JAK1) shared with European populations and candidate genes associated with haemoglobin phenotypes (HPSE2, HBE1, HBG2), other immune-related (DOCK2) traits, and insulin processing (GLIS3) traits shared with West and East African populations. Finally, the SLC8A1 gene, which codifies for a sodium-calcium exchanger, was the only candidate identified under post-admixture selection in Western NA.

Abstract Familial hypercholesterolemia (FH) is an autosomal dominant disease that has a prevalence of approximately 1/250 inhabitants and is the most frequent cause of early coronary heart disease (CHD). We included 1.343.973 women and 1.210.671 men with at least one LDL-c measurement from the Catalan primary care database. We identified 14.699 subjects with Familial hypercholesterolemia-Phenotype (FH-P) based on LDL-c cut-off points by age (7.033 and 919 women, and 5.088 and 1659 men in primary and secondary prevention, respectively). Lipid lower therapy (LLT), medication possession ratio (MPR) as an indicator of adherence, and number of patients that reached their goal on lipid levels were compared by sex. In primary and secondary prevention, 69% and 54% of women (P = 0.001) and 64% and 51% of men (P = 0.001) were on low-to-moderate-potency LLT. Adherence to LLT was reduced in women older than 55 years, especially in secondary prevention (P = 0.03), where the percentage of women and men with LDL-c > 1.81 mmol/L were 99.9% and 98.9%, respectively (P = 0.001). Women with FH-P are less often treated with high-intensity LLT, less adherent to LLT, and have a lower probability of meeting their LDL-c goals than men, especially in secondary prevention.

Abstract The Roma are the largest ethnic minority in Europe. With a Northwestern Indian origin around ~ 1.5 kya, they travelled throughout West Asia until their arrival in Europe around the eleventh century CE. Their diaspora through Europe is characterized by population bottlenecks and founder events which have contributed to their present day genetic and cultural diversity. In our study, we focus on the effects of founder effects in the mitochondrial DNA (mtDNA) pool of Iberian Roma by producing and analyzing 144 novel whole mtDNA sequences of Iberian Roma. Over 60% of their mtDNA pool is composed by founder lineages of South Asian origin or acquired by gene flow during their diaspora in the Middle East or locally in Europe in Europe. The TMRCA of these lineages predates the historical record of the Roma arrival in Spain. The abundance of founder lineages is in contrast with ~ 0.7% of autochthonous founder lineages present in the non-Roma Iberian population. Within those founder lineages, we found a substantial amount of South Asian M5a1b1a1 haplotypes and high frequencies of West Eurasian founder lineages (U3b1c, J2b1c, J1c1b, J1b3a, H88, among others), which we characterized phylogenetically and put in phylogeographical context. Besides, we found no evidence of genetic substructure of Roma within the Iberian Peninsula. These results show the magnitude of founder effects in the Iberian Roma and further explain the Roma history and genetic diversity from a matrilineal point of view.

Urban agriculture is gaining attraction to become one of the pillars of the urban ecological transition and to increase food security in an urbanized planet. However, there is a lack of systematic quantification of the benefits provided by urban agriculture solutions. In this paper, we present an R package to estimate several indicators related to benefits of urban agriculture. The goal is to provide a tool for researchers and practitioners interested in the impacts of urban agriculture. The ediblecity package provides functions to calculate 8 indicators: urban heat island, runoff prevention, green areas accessibility, NO2 sequestration, jobs created in commercial gardens, volunteers involved in community gardens, green per capita and, finally, food production. Moreover, the package also provides a function to generate scenarios with different implementations of urban agriculture. We illustrate the use of the package by comparing three scenarios in a neighborhood of Girona (Spain), which is included in the package as an example dataset. There, we compare scenarios with an increasing amount of urban agriculture solutions. The ediblecity package is open-source software. This allows other R developers to contribute to the package, providing new functionalities or improving the existing ones.

Over 200 different SARS-CoV-2 lineages have been observed in Mexico by November 2021. To investigate lineage replacement dynamics, we applied a phylodynamic approach and explored the evolutionary trajectories of five dominant lineages that circulated during the first year of local transmission. For most lineages, peaks in sampling frequencies coincided with different epidemiological waves of infection in Mexico. Lineages B.1.1.222 and B.1.1.519 exhibited similar dynamics, constituting clades that likely originated in Mexico and persisted for >12 months. Lineages B.1.1.7, P.1 and B.1.617.2 also displayed similar dynamics, characterized by multiple introduction events leading to a few successful extended local transmission chains that persisted for several months. For the largest B.1.617.2 clades, we further explored viral lineage movements across Mexico. Many clades were located within the south region of the country, suggesting that this area played a key role in the spread of SARS-CoV-2 in Mexico.

Abstract There is an ongoing debate on the implementation of the COVID-19 passport throughout Europe. We sought to build and test a feasible prevention strategy to ensure low SARS-CoV transmission risk in public events. We conducted a non-randomised controlled study. The intervention group obtained a confidential digital certificate of very low capacity for transmitting SARS-CoV-2 and attended socio-cultural events in Girona (Spain) between 1 April and 21 May 2021. The primary care services and a network of pharmacies cooperated in providing the certification. A group of non-attendees was randomly selected from pseudonymised health records as controls. We estimated the incidences of SARS-CoV-2 infection and recorded the challenges in the process. Follow-up was complete for 1351 participants, who were matched with 4050 controls. Mean age of the study population was 31.1 years, and 53% of participants were women. Incidence rates of SARS-CoV infection at 14 days in the group of attendees and non-attendees were 15.9 and 17.7 per 100,000 person-days, respectively; the difference between incidences was − 1.8 (95% CI − 22.8, 19.3). Implementation problems were minor, and 89.2% of respondents to a survey were satisfied with the process. The incidence rate of SARS-CoV-2 infection was not different in the intervention and control groups. These results are in favour of establishing a COVID-19 certificate to attend public events, and connote feasibility of implementation at a population level.

Zika virus (ZIKV) was first isolated in 1947. From its isolation until 2007, symptoms of ZIKV-caused disease were limited (e.g., fever, hives, and headache); however, during the epidemic in Brazil in 2014, ZIKV infection caused Guillain-Barré syndrome in adults and microcephaly in fetuses and infants of women infected during pregnancy. The neurovirulence of ZIKV has been studied using neural progenitor cells (NPCs), brain organoids, neurons, and astrocytes. NPCs and astrocytes appear to be the most susceptible cells of the Central Nervous System to ZIKV infection. In this work, we aimed to develop a culture of astrocytes derived from a human NPC cell line. We analyze how ZIKV affects human astrocytes and demonstrate that 1) ZIKV infection reduces cell viability, increases the production of Reactive Oxygen Species (ROS), and results in high viral titers; 2) there are changes in the expression of genes that facilitate the entry of the virus into the cells; 3) there are changes in the expression of genes involved in the homeostasis of the glutamatergic system; and 4) there are ultrastructural changes in mitochondria and lipid droplets associated with production of virions. Our findings reveal new evidence of how ZIKV compromises astrocytic functionality, which may help understand the pathophysiology of ZIKV-associated congenital disease.

Abstract Human populations are genetically affected by their demographic history, which shapes the distribution of their functional genomic variation. However, the genetic impact of recent demography is debated. This issue has been studied in different populations, but never in North Africans, despite their relevant cultural and demographic diversity. In this study we address the question by analyzing new whole-exome sequences from two culturally different Tunisian populations, an isolated Amazigh population and a close non-isolated Arab-speaking population, focusing on the distribution of functional variation. Both populations present clear differences in their variant frequency distribution, in general and for putatively damaging variation. This suggests a relevant effect in the Amazigh population of genetic isolation, drift, and inbreeding, pointing to relaxed purifying selection. We also discover the enrichment in Imazighen of variation associated to specific diseases or phenotypic traits, but the scarce genetic and biomedical data in the region limits further interpretation. Our results show the genomic impact of recent demography and reveal a clear genetic differentiation probably related to culture. These findings highlight the importance of considering cultural and demographic heterogeneity within North Africa when defining population groups, and the need for more data to improve knowledge on the region’s health and disease landscape.

Aloe vera (Aloe barbadensis Miller) gel is a frequently used ingredient in many food pro-ducts, particularly beverages, due to its reported health benefits. Studies have identified acemannan, a polysaccharide rich in mannose units which are partially or fully acetylated, as the primary bioactive compound in Aloe vera gel. The acemannan content and its degree of acetylation (DA) were measured in 15 different commercial beverages containing Aloe vera at varying concentrations (from 30% to 99.8%) as listed on the label. Other biopolymers such as pectins, hemicelluloses, and cellulose were also evaluated. Flavoured beverages (seven samples labelled as containing from 30% to 77% Aloe vera) presented low levels of acemannan (

Transmission is a driver of tuberculosis (TB) epidemics in high-burden regions, with assumed negligible impact in low-burden areas. However, we still lack a full characterization of transmission dynamics in settings with similar and different burdens. Genomic epidemiology can greatly help to quantify transmission, but the lack of whole genome sequencing population-based studies has hampered its application. Here, we generate a population-based dataset from Valencia region and compare it with available datasets from different TB-burden settings to reveal transmission dynamics heterogeneity and its public health implications. We sequenced the whole genome of 785 Mycobacterium tuberculosis strains and linked genomes to patient epidemiological data. We use a pairwise distance clustering approach and phylodynamic methods to characterize transmission events over the last 150 years, in different TB-burden regions. Our results underscore significant differences in transmission between low-burden TB settings, i.e., clustering in Valencia region is higher (47.4%) than in Oxfordshire (27%), and similar to a high-burden area as Malawi (49.8%). By modeling times of the transmission links, we observed that settings with high transmission rate are associated with decades of uninterrupted transmission, irrespective of burden. Together, our results reveal that burden and transmission are not necessarily linked due to the role of past epidemics in the ongoing TB incidence, and highlight the need for in-depth characterization of transmission dynamics and specifically tailored TB control strategies.

Abstract Amyloid deposits in pancreatic islets, mainly formed by human islet amyloid polypeptide (hIAPP) aggregation, have been associated with loss of β-cell mass and function, and are a pathological hallmark of type 2 diabetes (T2D). Treatment with chaperones has been associated with a decrease in endoplasmic reticulum stress leading to improved glucose metabolism. The aim of this work was to investigate whether the chemical chaperone 4-phenylbutyrate (PBA) prevents glucose metabolism abnormalities and amyloid deposition in obese agouti viable yellow (Avy) mice that overexpress hIAPP in β cells (Avy hIAPP mice), which exhibit overt diabetes. Oral PBA treatment started at 8 weeks of age, when Avy hIAPP mice already presented fasting hyperglycemia, glucose intolerance, and impaired insulin secretion. PBA treatment strongly reduced the severe hyperglycemia observed in obese Avy hIAPP mice in fasting and fed conditions throughout the study. This effect was paralleled by a decrease in hyperinsulinemia. Importantly, PBA treatment reduced the prevalence and the severity of islet amyloid deposition in Avy hIAPP mice. Collectively, these results show that PBA treatment elicits a marked reduction of hyperglycemia and reduces amyloid deposits in obese and diabetic mice, highlighting the potential of chaperones for T2D treatment.

Polyclonal infections occur when at least two unrelated strains of the same pathogen are detected in an individual. Here, Moreno-Molina et al. analyse sputum and surgical resections from tuberculosis patients, showing that the magnitude of polyclonal infections can be underestimated when only testing sputum samples.

Abstract Respiratory syncytial virus (RSV) is a major cause of respiratory infections and is classified in two main groups, RSV-A and RSV-B, with multiple genotypes within each of them. For RSV-B, more than 30 genotypes have been described, without consensus on their definition. The lack of genotype assignation criteria has a direct impact on viral evolution understanding, development of viral detection methods as well as vaccines design. Here we analyzed the totality of complete RSV-B G gene ectodomain sequences published in GenBank until September 2018 (n = 2190) including 478 complete genome sequences using maximum likelihood and Bayesian phylogenetic analyses, as well as intergenotypic and intragenotypic distance matrices, in order to generate a systematic genotype assignation. Individual RSV-B genes were also assessed using maximum likelihood phylogenetic analyses and multiple sequence alignments were used to identify molecular markers associated to specific genotypes. Analyses of the complete G gene ectodomain region, sequences clustering patterns, and the presence of molecular markers of each individual gene indicate that the 37 previously described genotypes can be classified into fifteen distinct genotypes: BA, BA-C, BA-CC, CB1-THB, GB1-GB4, GB6, JAB1-NZB2, SAB1, SAB2, SAB4, URU2 and a novel early circulating genotype characterized in the present study and designated GB0.

Abstract Whole genome sequencing (WGS) has been shown to be superior to traditional procedures of genotyping in tuberculosis (TB), nevertheless, reports of its use in drug resistant TB (DR-TB) isolates circulating in Mexico, are practically unknown. Considering the above the main of this work was to identify and characterize the lineages and genomic transmission clusters present in 67 DR-TB isolates circulating in southeastern Mexico. The results show the presence of three major lineages: L1 (3%), L2 (3%) and L4 (94%), the last one included 16 sublineages. Sublineage 4.1.1.3 (X3) was predominant in 18 (27%) of the isolates, including one genomic cluster, formed by eleven multidrug resistant isolates and sharing the SIT 3278, which seems to be restricted to Mexico. By the use of WGS, it was possible to identify the high prevalence of L4 and a high number of sublineages circulating in the region, also was recognized the presence of a novel X3 sublineage, formed exclusively by multidrug resistant isolates and with restrictive circulation in Mexico for at least the past 17 years.

Marine Protected Areas (MPAs) require effective indicators to assess their performance, in compliance with the goals of relevant national and international commitments. Achieving and prioritizing shortlists of multidisciplinary indicators demands a significant effort from specialists to depict the multiple conservation and socioeconomic interests, and the large complexity of natural systems. The present paper describes a structured expert-based methodology (process and outputs) to co-define a list of multidisciplinary MPA performance indicators. This work was promoted by the management authority of coastal MPAs in mainland Portugal to gather a consensual and feasible list of indicators that would guide the design of a future national monitoring program. Hence, Portuguese coastal MPAs served as a case study to develop such a process between 2019 and 2020. In the end, participants (1) agreed on a shortlist of prioritized indicators (i.e., environmental, governance, and socioeconomic indicators) and (2) defined minimum monitoring frequencies for the indicators in this list, compatible with the potential replicability of the associated survey methods. The present approach recommends that management plans incorporate monitoring procedures and survey methods, with a validated list of indicators and associated monitoring periodicity, agreed among researchers, MPA managers and governance experts. The proposed methodology, and the lessons learned from it, can support future processes aiming to define and prioritize MPA performance indicators.

Every day important healthcare decisions are made with incomplete or outdated information about the effects of the healthcare interventions available, what delivers the best value for the health system and where more research is needed. It is necessary to invest in strategies that allow access to reliable and updated evidence on which to base health decisions. The objective is to develop and evaluate a strategy for building the capacity among different actors of a country’s health system to implement the model known as “Living Evidence” [LE] in the evidence synthesis and dissemination of knowledge transfer [KT] products to inform health decisions. The study will involve professional members of health system organizations in charge of developing KT products to inform health decisions. The project will be developed in three complementary phases: 1) LE-implementation framework development through review of the literature, brainstorming meetings, user testing, and expert consultation; 2) training in LE tools and strategies; 3) developing LE synthesis for KT products by applying the framework to real-life diverse situations. To achieve the capacity-building strategy assessment goal, several surveys and interviews will take place during the process to assess: 1) the LE-implementation framework for the incorporation of LE synthesis in the development of KT products; 2) the training workshops; 3) the whole capacity-building strategy used for health system organizations be able of implementing the LE as part of the KT products they regularly produce. The expected results are an effective capacity-building strategy for health system organizations to implement the living evidence model in different KT products; a LE-implementation framework to be applicable to any country or region to incorporate LE in the KT products; LE synthesis for KT products directly applicable to the real-setting situations; integration of Epistemonikos-L.OVE platform for keeping the LE process in the development and updating of KT products.

The two-dimensional morphology of molybdenum oxycarbide (2D-Mo2CO x ) nanosheets dispersed on silica is found vital for the dry reforming of methane. Here the authors show that the specific activity of 2D-Mo2CO x /SiO2 exceeds that of other Mo2C-based catalysts by ca. 3 orders of magnitude.

Abstract Carbonate cave deposits (speleothems) have been used widely for paleoclimate reconstructions; however, few studies have examined the utility of other speleothem-forming minerals for this purpose. Here we demonstrate for the first time that stable isotopes (δ17O, δ18O and δD) of structurally-bound gypsum (CaSO4·2H2O) hydration water (GHW) can be used to infer paleoclimate. Specifically, we used a 63 cm-long gypsum stalactite from Sima Blanca Cave to reconstruct the climate history of SE Spain from ~ 800 BCE to ~ 800 CE. The gypsum stalactite indicates wet conditions in the cave and humid climate from ~ 200 BCE to 100 CE, at the time of the Roman Empire apogee in Hispania. From ~ 100 CE to ~ 600 CE, evaporation in the cave increased in response to regional aridification that peaked at ~ 500–600 CE, roughly coinciding with the transition between the Iberian Roman Humid Period and the Migration Period. Our record agrees with most Mediterranean and Iberian paleoclimate archives, demonstrating that stable isotopes of GHW in subaerial gypsum speleothems are a useful tool for paleoclimate reconstructions.

Some strains of Mycobacterium tuberculosis seem to be able to avoid host defense systems. Here the authors stratify patients by severity of tuberculosis and find correlations with the level of IL-1β production by macrophages exposed to these isolates.

Background: Living evidence (LE) refers to the methodological processes that permit new research findings to be continually incorporated into evidence synthesis. This approach is of great value in the resolution of relevant and rapidly changing clinical questions. To date, the methods to carry out this type of synthesis are not completely defined, and great variability is observed in the approaches used by different groups of authors. Objective: To identify, evaluate and summarise the current methods used for living evidence synthesis Methods: We will conduct a methodological study based on a systematic literature search to identify any type of evidence synthesis such as systematic reviews, network metanalyses and overviews that used “living evidence synthesis” as part of their methods. The search will be conducted in Medline (via PubMed) and Epistemonikos databases. Additionally, we will search websites of the organisations publishing any living evidence synthesis retrieved in the two databases, in order to identify unpublished subsequent reports. Two reviewers will independently assess each article against the selection criteria, extract data on methods and procedures, and assess the methodological quality of each publication. Data will be analysed descriptively.

Bergmann’s and Allen’s rules were defined to describe macroecological patterns across latitudinal gradients. Bergmann observed a positive association between body size and latitude for endothermic species while Allen described shorter appendages as latitude increases. Almost two centuries later, there is still ongoing discussion about these patterns. Temperature, the common variable in these two rules, varies predictably across both latitude and elevation. Although these rules have been assessed extensively in mammals across latitude, particularly in regions with strong seasonality, studies on tropical montane mammals are scarce. We here test for these patterns and assess the variation of several other locomotory, diet-associated, body condition, and thermoregulatory traits across elevation in the Mountain Treeshrew (Tupaia montana) on tropical mountains in Borneo. Based on morphological measurements from both the field and scientific collections, we found a complex pattern: Bergmann’s rule was not supported in our tropical mountain system, since skull length, body size, and weight decreased from the lowest elevations (

Introducción. Los Sistemas de Información Geográfica (SIG) han adquirido gran relevancia, al aumentar el valor de la información geográfica para tomar decisiones. Mejorar la eficacia del procesamiento y la recuperación de información en SIG, teniendo en cuenta los grandes volúmenes de datos geográficos disponibles, su heterogeneidad, y la ausencia de significados semánticos formalizados, constituye un desafío y objetivo general de esta investigación. Métodos. Los enfoques basados en ontologías (ej. ontologías geográficas) constituye una alternativa muy prometedora para dotar de semántica a los datos y su procesamiento. Los paradigmas de acceso e integración de datos basados en ontologías permiten la administración de grandes ontologías y la interoperabilidad de datos heterogéneos, problemáticas también tratadas en la investigación. En el trabajo se presenta un nuevo método semiautomático para la generación de ontologías geográficas a partir de fuentes de datos espaciales heterogéneas y un modelo de gestión de datos basado en ontologías y Razonamiento Basado en Casos (RBC). Resultados. El método propuesto permite dotar a los SIG de recursos de conocimiento más robustos, incrementando sus capacidades de recuperar información y su eficacia. Además, el paradigma de ontologías basadas en bases de datos aplicado permite un mejor manejo del volumen de conocimiento generado. Este paradigma, aplicado también en el modelo de gestión de datos basado en ontologías propuesto, permitió resolver los problemas de interoperabilidad existentes en sistemas de la Unión Eléctrica entre datos geográficos y de dominio eléctrico, al mismo tiempo que se extendieron las capacidades de formulación de consultas y la recuperación de información con el RBC.

The coordinated efforts to stop the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) include massive immunization of the population at a global scale. The humoral immunity against COVID-19 is conferred by neutralizing antibodies (NAbs) that occur during the post-infection period and upon vaccination. Here, we provide robust data showing that potent neutralizing antibodies are induced in convalescent patients of SARS-CoV-2 infection who have been immunized with different types of vaccines, and patients with no previous history of COVID-19 immunized with a mixed vaccination schedule regardless of the previous infection. More importantly, we showed that a heterologous prime-boost in individuals with Ad5-nCoV (Cansino) vaccine induces higher NAbs levels in comparison to a single vaccination scheme alone.

Bergmann's and Allen's rules were defined to describe macroecological patterns across latitudinal gradients. Bergmann observed a positive association between body size and latitude for endothermic species while Allen described shorter appendages as latitude increases. Almost two centuries later, there is still ongoing discussion about these patterns. Temperature, the common variable in these two rules, varies predictably across both latitude and elevation. Although these rules have been assessed extensively in mammals across latitude, particularly in regions with strong seasonality, studies on tropical montane mammals are scarce. We here test for these patterns and assess the variation of several other locomotory, diet-associated, body condition, and thermoregulatory traits across elevation in the Mountain Treeshrew (Tupaia montana) on tropical mountains in Borneo. Based on morphological measurements from both the field and scientific collections, we found a complex pattern: Bergmann's rule was not supported in our tropical mountain system, since skull length, body size, and weight decreased from the lowest elevations (

Introducción: La habilidad de materiales arcillosos para albergar y liberar fármacos en un sitio específico, así como su potencialidad para absorber especies químicas de gran tamaño molecular y variedad de grupos funcionales, ha sido discutida pobremente en la literatura. El objetivo de la investigación es aportar nuevos conocimientos sobre el tema. Métodos: La interacción mineral arcilla-molécula orgánica (fármacos y colorantes) se realizó en fase líquida. Se monitoreó las concentraciones de compuestos orgánicos por espectroscopía UV-visible. Los materiales de partida y materiales compuestos se caracterizaron empleando difracción de rayos X (DRX) y espectroscopía infrarroja (FTIR). Se utilizaron dos métodos de simulación computacional, teoría de los funcionales de la densidad (DFT) y dinámica molecular (DM). Resultados y discusión: Se cuantificó la carga de fármaco o colorante en milígramo por gramo de material. Para ambos, se evaluó la cinética de liberación o desorción en función del pH. Se demostró la estabilidad estructural de los materiales compuestos y se precisaron los grupos funcionales de las moléculas orgánicas comprometidos en la interacción con los minerales. La liberación y desorción dependen de la fortaleza de la interacción. Los resultados de las simulaciones fueron coherentes con los obtenidos experimentalmente. En conclusiones, se demostró que los minerales arcillosos son capaces de albergar, y de liberar de forma controlada fármacos, cumpliendo con los estándares farmacéuticos. Se confirmó la potencialidad de arcillas naturales cubanas, en términos de remediación medioambiental. La combinación adecuada de cálculos teóricos permitió profundizar en la naturaleza de las interacciones.

A variety of biological differences exist between strains and phylogenetic lineages in the Mycobacterium tuberculosis complex (MTBC). Here, the authors perform RNAseq and methylome analysis of the main clades of the MTBC and show variation in transcriptional profiles is mainly due to mutations in transcriptional start sites.

δ18O of speleothems are a widely used paleoclimate proxy. Here, the authors conduct a global analysis of cave drip water δ18O compositions and find that drip waters from warmer climates have a seasonal bias toward precipitation δ18O of recharge periods, unlike in cooler climates where drip waters match well with recharge-weighted δ18O.

Horizontal gene transfer (HGT) by plasmid conjugation is a major driving force in the spread of antibiotic resistance among Enterobacteriaceae. Most of the conjugation studies are based on calculation of conjugation ratios (number of transconjugants/number of donors) after viable counting of transconjugant and donor cells. The development of robust, fast and reliable techniques for in situ monitoring and quantification of conjugation ratios might accelerate progress in understanding the impact of this cellular process in the HGT. The IncHI1 plasmids, involved in multiresistance phenotypes of relevant pathogens such as Salmonella and E. coli, are distinguished by the thermosensitivity of their conjugative transfer. Conjugation mediated by IncHI1 plasmids is more efficient at temperatures lower than 30 °C, suggesting that the transfer process takes place during the environmental transit of the bacteria. In this report, we described a methodology to monitor in situ the conjugation process during agar surface matings of the IncHI1 plasmid R27 and its derepressed derivative drR27 at different temperatures. A three-color-labeling strategy was used to visualize the spatial distribution of transconjugants within the heterogeneous environment by epifluorescence and confocal microscopy. Moreover, the fluorescent labelling was also used to quantify conjugation frequencies in liquid media by flow cytometry.

Background: Lineage 1 (L1) and 3 (L3) are two lineages of the Mycobacterium tuberculosis complex (MTBC) causing tuberculosis (TB) in humans. L1 and L3 are prevalent around the rim of the Indian Ocean, the region that accounts for most of the world’s new TB cases. Despite their relevance for this region, L1 and L3 remain understudied. Methods: We analyzed 2,938 L1 and 2,030 L3 whole genome sequences originating from 69 countries. We reconstructed the evolutionary history of these two lineages and identified genes under positive selection. Results: We found a strongly asymmetric pattern of migration from South Asia toward neighboring regions, highlighting the historical role of South Asia in the dispersion of L1 and L3. Moreover, we found that several genes were under positive selection, including genes involved in virulence and resistance to antibiotics. For L1 we identified signatures of local adaptation at the esxH locus, a gene coding for a secreted effector that targets the human endosomal sorting complex, and is included in several vaccine candidates. Conclusions: Our study highlights the importance of genetic diversity in the MTBC, and sheds new light on two of the most important MTBC lineages affecting humans.

Background: Lineage 1 (L1) and 3 (L3) are two lineages of the Mycobacterium tuberculosis complex (MTBC) causing tuberculosis (TB) in humans. L1 and L3 are prevalent around the rim of the Indian Ocean, the region that accounts for most of the world’s new TB cases. Despite their relevance for this region, L1 and L3 remain understudied. Methods: We analyzed 2,938 L1 and 2,030 L3 whole genome sequences originating from 69 countries. We reconstructed the evolutionary history of these two lineages and identified genes under positive selection. Results: We found a strongly asymmetric pattern of migration from South Asia toward neighboring regions, highlighting the historical role of South Asia in the dispersion of L1 and L3. Moreover, we found that several genes were under positive selection, including genes involved in virulence and resistance to antibiotics . For L1 we identified signatures of local adaptation at the esxH locus, a gene coding for a secreted effector that targets the human endosomal sorting complex, and is included in several vaccine candidates. Conclusions: Our study highlights the importance of genetic diversity in the MTBC, and sheds new light on two of the most important MTBC lineages affecting humans.

Climate change is projected to increase the incidence of severe drought in many regions, potentially requiring selection for different traits in crop species to maintain productivity under water stress. In this study, we identified a suite of hydraulic traits associated with high productivity under water stress in four genotypes of S. melongena L. We also assessed the potential for recovery of this suite of traits from drought stress after re-watering. We observed that two genotypes, PHL 4841 and PHL 2778, quickly grew into large plants with smaller, thicker leaves and increasingly poor hydraulic status (a water-spender strategy), whereas PHL 2789 and Mara maintained safer water status and larger leaves but sacrificed large gains in biomass (a water-saver strategy). The best performing genotype under water stress, PHL 2778, additionally showed a significant increase in root biomass allocation relative to other genotypes. Biomass traits of all genotypes were negatively impacted by water deficit and remained impaired after a week of recovery; however, physiological traits such as electron transport capacity of photosystem II, and proportional allocation to root biomass and fine root length, and leaf area recovered after one week, indicating a strong capacity for eggplant to rebound from short-term deficits via recovery of physiological activity and allocation to resource acquiring tissues. These traits should be considered in selection and breeding of eggplant hybrids for future agricultural outlooks.

This study analyzes the effects of COVID-19 confinement on the autonomous learning performance of students in higher education. Using a field experiment with 458 students from three different subjects at Universidad Autónoma de Madrid (Spain), we study the differences in assessments by dividing students into two groups. The first group (control) corresponds to academic years 2017/2018 and 2018/2019. The second group (experimental) corresponds to students from 2019/2020, which is the group of students that had their face-to-face activities interrupted because of the confinement. The results show that there is a significant positive effect of the COVID-19 confinement on students' performance. This effect is also significant in activities that did not change their format when performed after the confinement. We find that this effect is significant both in subjects that increased the number of assessment activities and subjects that did not change the student workload. Additionally, an analysis of students' learning strategies before confinement shows that students did not study on a continuous basis. Based on these results, we conclude that COVID-19 confinement changed students' learning strategies to a more continuous habit, improving their efficiency. For these reasons, better scores in students' assessment are expected due to COVID-19 confinement that can be explained by an improvement in their learning performance.

The aim of this proof-of-concept study was to evaluate if trained dogs could discriminate between sweat samples from symptomatic COVID-19 positive individuals (SARS-CoV-2 PCR positive) and those from asymptomatic COVID-19 negative individuals. The study was conducted at 2 sites (Paris, France, and Beirut, Lebanon), followed the same training and testing protocols, and involved six detection dogs (three explosive detection dogs, one search and rescue dog, and two colon cancer detection dogs). A total of 177 individuals were recruited for the study (95 symptomatic COVID-19 positive and 82 asymptomatic COVID-19 negative individuals) from five hospitals, and one underarm sweat sample per individual was collected. The dog training sessions lasted between one and three weeks. Once trained, the dog had to mark the COVID-19 positive sample randomly placed behind one of three or four olfactory cones (the other cones contained at least one COVID-19 negative sample and between zero and two mocks). During the testing session, a COVID-19 positive sample could be used up to a maximum of three times for one dog. The dog and its handler were both blinded to the COVID-positive sample location. The success rate per dog (i.e., the number of correct indications divided by the number of trials) ranged from 76% to 100%. The lower bound of the 95% confidence interval of the estimated success rate was most of the time higher than the success rate obtained by chance after removing the number of mocks from calculations. These results provide some evidence that detection dogs may be able to discriminate between sweat samples from symptomatic COVID-19 individuals and those from asymptomatic COVID-19 negative individuals. However, due to the limitations of this proof-of-concept study (including using some COVID-19 samples more than once and potential confounding biases), these results must be confirmed in validation studies.

In August 2018, a firefly (Coleoptera: Lampyridae) of American origin was observed in several localities in Girona (Catalonia, Spain) and was described as Photinus immigrans by Zaragoza-Caballero and Vinolas, 2018. Here, we show that this species dispersed very quickly throughout northeastern Spain and was, in 2020, observed in the French Pyrenees. The animal’s quick progress is documented, and part of its biology is described (dispersion speed, land use, phenology, identification of all life stages). An additional population was localized in Extremadura, and its special status is discussed. We were able to determine its Argentinian–Uruguayan origin and propose, therefore, to consider Photinus immigrans as a synonym of Photinus signaticollis (Blanchard, 1846) (=Photinus immigrans Zaragoza-Caballero and Viñolas, 2018, syn. nov.). Our data clearly show that at least the Catalan and French populations are spreading very quickly and are able to settle permanently if adequate ecosystems are found. The species is highly expansive and may well be invasive; our citizen science platforms are ideally suited to monitor their progress throughout Spain and France. This is important for avoiding future ecological problems with diverse native faunas, such as glow-worms, fireflies and earthworms. If no ways are found to stop the species’ progression, the animals will quite probably invade substantial areas of France, Spain and the rest of Europe in the years to come.

The mesospheric OH layer varies on several timescales, primarily driven by variations in atomic oxygen, temperature, density and transport (advection). Vibrationally excited OH airglow intensity, rotational temperature and altitude are closely interrelated and thus accompany each other through these changes. A correct interpretation of the OH layer variability from airglow measurements requires the study of the three variables simultaneously. Ground-based instruments measure excited OH intensities and temperatures with high temporal resolution, but they do not generally observe altitude directly. Information on the layer height is crucial in order to identify the sources of its variability and the causes of discrepancies in measurements and models. We have used SABER space-based 2002–2015 data to infer an empirical function for predicting the altitude of the layer at midlatitudes from ground-based measurements of OH intensity and rotational temperature. In the course of the analysis, we found that the SABER altitude (weighted by the OH volume emission rate) at midlatitudes decreases at a rate of 40 m decade−1, accompanying an increase of 0.7 % decade−1 in OH intensity and a decrease of 0.6 K decade−1 in OH equivalent temperature. SABER OH altitude barely changes with the solar cycle, whereas OH intensity and temperature vary by 7.8 % per 100 s.f.u. and 3.9 K per 100 s.f.u., respectively. For application of the empirical function to Sierra Nevada Observatory SATI data, we have calculated OH intensity and temperature SATI-to-SABER transfer functions, which point to relative instrumental drifts of −1.3 % yr−1 and 0.8 K yr−1, respectively, and a temperature bias of 5.6 K. The SATI predicted altitude using the empirical function shows significant short-term variability caused by overlapping waves, which often produce changes of more than 3–4 km in a few hours, going along with 100 % and 40 K changes in intensity and temperature, respectively. SATI OH layer wave effects are smallest in summer and largest around New Year's Day. Moreover, those waves vary significantly from day to day. Our estimations suggest that peak-to-peak OH nocturnal variability, mainly due to wave variability, changes within 60 days at least 0.8 km for altitude in autumn, 45 % for intensity in early winter and 6 K for temperature in midwinter. Plausible upper limit ranges of those variabilities are 0.3–0.9 km, 40–55 % and 4–7 K, with the exact values depending on the season.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Two billion people are infected with Mycobacterium tuberculosis, leading to 10 million new cases of active tuberculosis and 1.5 million deaths annually. Universal access to drug susceptibility testing (DST) has become a World Health Organization priority. We previously developed a software tool, Mykrobe predictor, which provided offline species identification and drug resistance predictions for M. tuberculosis from whole genome sequencing (WGS) data. Performance was insufficient to support the use of WGS as an alternative to conventional phenotype-based DST, due to mutation catalogue limitations. Here we present a new tool, Mykrobe, which provides the same functionality based on a new software implementation. Improvements include i) an updated mutation catalogue giving greater sensitivity to detect pyrazinamide resistance, ii) support for user-defined resistance catalogues, iii) improved identification of non-tuberculous mycobacterial species, and iv) an updated statistical model for Oxford Nanopore Technologies sequencing data. Mykrobe is released under MIT license at https://github.com/mykrobe-tools/mykrobe. We incorporate mutation catalogues from the CRyPTIC consortium et al. (2018) and from Walker et al. (2015), and make improvements based on performance on an initial set of 3206 and an independent set of 5845 M. tuberculosis Illumina sequences. To give estimates of error rates, we use a prospectively collected dataset of 4362 M. tuberculosis isolates. Using culture based DST as the reference, we estimate Mykrobe to be 100%, 95%, 82%, 99% sensitive and 99%, 100%, 99%, 99% specific for rifampicin, isoniazid, pyrazinamide and ethambutol resistance prediction respectively. We benchmark against four other tools on 10207 (=5845+4362) samples, and also show that Mykrobe gives concordant results with nanopore data. We measure the ability of Mykrobe-based DST to guide personalized therapeutic regimen design in the context of complex drug susceptibility profiles, showing 94% concordance of implied regimen with that driven by phenotypic DST, higher than all other benchmarked tools.

This paper proposes a UAV platform that autonomously detects, hunts, and takes down other small UAVs in GPS-denied environments. The platform detects, tracks, and follows another drone within its sensor range using a pre-trained machine learning model. We collect and generate a 58,647-image dataset and use it to train a Tiny YOLO detection algorithm. This algorithm combined with a simple visual-servoing approach was validated on a physical platform. Our platform was able to successfully track and follow a target drone at an estimated speed of 1.5 m/s. Performance was limited by the detection algorithm's 77% accuracy in cluttered environments and the frame rate of eight frames per second along with the field of view of the camera.

BACKGROUND:Colorectal cancer (CRC) screening has proven effective in reducing CRC mortality. This study aimed to systematically review, and evaluate the reporting quality, of the economic evidence regarding CRC screening in average-risk individuals. METHODS:Databases searched included Medline, EMBASE, National Health Service Economic Evaluation, Database of Abstracts of Reviews of Effects, Cost-Effectiveness Analysis registry, EconLit, and Health Technology Assessment database. Eligible studies were cost-effectiveness and cost-utility analyses comparing CRC screening strategies in average-risk individuals, published in English or Spanish, between January 2012 and November 2018. Reporting quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS:Of 1,993 publications initially retrieved, 477 were excluded by duplicate review, 1,449 by title/abstract review, and 34 by full-text review. Finally, 33 publications were included in the qualitative synthesis. Most studies were conducted in Europe (36,4%), followed by United States (24,2%) and Asia (24,2%). The main screening modalities considered were fecal immunochemical tests (70%), colonoscopy (67%), guaiac fecal occult blood test (42%) and flexible sigmoidoscopy (30%). In most studies, CRC screening was deemed cost-effective compared to no screening. Sensitivity analyses indicated that cost of CRC screening tests, adherence to screening, screening test sensitivity, and cost of CRC treatment had the greatest impact on cost-effectiveness results across studies. The majority of studies (73%) adequately reported at least 50% of the items included in the CHEERS checklist. Least well reported items included setting, study perspective, discount rate, model choice, and methods to identify effectiveness data or to estimate resource use and costs. CONCLUSIONS:CRC screening is an efficient alternative to no screening. Nevertheless, it is not possible to conclude which strategy should be preferred for population-based screening programs. Although we observed an overall good adherence to CHEERS recommendations, there is still room for improvement in economic evaluations reporting in this field.