Expert-based collaborative analysis of the situation and prospects of biomarker test implementation in oncology in Spain / Análisis colaborativo de expertos de la situación y perspectivas de la implementación de pruebas de biomarcadores en oncología en España

Purpose: Biomarkers as screening for precision medicine is a fundamental step. The purpose of this article is twofold. First, to highlight the existing barriers in the implementation of Precision Medicine in Spain, with a special emphasis on barriers in access to the determination of biomarkers. Second, to provide a Roadmap that can help implement Precision Medicine equitably at the national level and optimize the use of biomarkers. Methods: A systematic review of literature (SRL) and a focus group (FG) with multidisciplinary experts has been carried out in 2023. Participants were contacted individually, and discourse analysis was processed anonymously. Results: We carried out a quantitative (SRL) and a qualitative approach (FG). The discourse analysis and roadmap were sent individually to each expert for approval. Conclusions: The potential of Precision Medicine has not been fulfilled in Spain. While several regional initiatives are in place, a national plan or strategy around Precision Medicine and use of biomarkers is lacking. In a general context of rapid progress at a global and European level, including the 2021 Europe’s Beating Cancer Plan, it is time to define and implement a National Plan to make the promise come true. While some comparable countries within Europe – such as the UK or France – are mature enough to adopt such strategies, in Spain there is still a long way to go. We consider that the different strands of work outlined in the Roadmap can be used as basis for such purpose.(AU)

One sixth of Amazonian tree diversity is dependent on river floodplains.

Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.

Expert-based collaborative analysis of the situation and prospects of biomarker test implementation in oncology in Spain.

PURPOSE: Biomarkers as screening for precision medicine is a fundamental step. The purpose of this article is twofold. First, to highlight the existing barriers in the implementation of Precision Medicine in Spain, with a special emphasis on barriers in access to the determination of biomarkers. Second, to provide a Roadmap that can help implement Precision Medicine equitably at the national level and optimize the use of biomarkers. METHODS: A systematic review of literature (SRL) and a focus group (FG) with multidisciplinary experts has been carried out in 2023. Participants were contacted individually, and discourse analysis was processed anonymously. RESULTS: We carried out a quantitative (SRL) and a qualitative approach (FG). The discourse analysis and roadmap were sent individually to each expert for approval. CONCLUSIONS: The potential of Precision Medicine has not been fulfilled in Spain. While several regional initiatives are in place, a national plan or strategy around Precision Medicine and use of biomarkers is lacking. In a general context of rapid progress at a global and European level, including the 2021 Europe's Beating Cancer Plan, it is time to define and implement a National Plan to make the promise come true. While some comparable countries within Europe - such as the UK or France - are mature enough to adopt such strategies, in Spain there is still a long way to go. We consider that the different strands of work outlined in the Roadmap can be used as basis for such purpose.

HIV-1 Tat Induces Dysregulation of PGC1-Alpha and Sirtuin 3 Expression in Neurons: The Role of Mitochondrial Biogenesis in HIV-Associated Neurocognitive Disorder (HAND).

During the antiretroviral era, individuals living with HIV continue to experience milder forms of HIV-associated neurocognitive disorder (HAND). Viral proteins, including Tat, play a pivotal role in the observed alterations within the central nervous system (CNS), with mitochondrial dysfunction emerging as a prominent hallmark. As a result, our objective was to examine the expression of genes associated with mitophagy and mitochondrial biogenesis in the brain exposed to the HIV-1 Tat protein. We achieved this by performing bilateral stereotaxic injections of 100 ng of HIV-1 Tat into the hippocampus of Sprague-Dawley rats, followed by immunoneuromagnetic cell isolation. Subsequently, we assessed the gene expression of Ppargc1a, Pink1, and Sirt1-3 in neurons using RT-qPCR. Additionally, to understand the role of Tert in telomeric dysfunction, we quantified the activity and expression of Tert. Our results revealed that only Ppargc1a, Pink1, and mitochondrial Sirt3 were downregulated in response to the presence of HIV-1 Tat in hippocampal neurons. Interestingly, we observed a reduction in the activity of Tert in the experimental group, while mRNA levels remained relatively stable. These findings support the compelling evidence of dysregulation in both mitophagy and mitochondrial biogenesis in neurons exposed to HIV-1 Tat, which in turn induces telomeric dysfunction.

Mapping density, diversity and species-richness of the Amazon tree flora.

Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution.

More than 10,000 pre-Columbian earthworks are still hidden throughout Amazonia.

Indigenous societies are known to have occupied the Amazon basin for more than 12,000 years, but the scale of their influence on Amazonian forests remains uncertain. We report the discovery, using LIDAR (light detection and ranging) information from across the basin, of 24 previously undetected pre-Columbian earthworks beneath the forest canopy. Modeled distribution and abundance of large-scale archaeological sites across Amazonia suggest that between 10,272 and 23,648 sites remain to be discovered and that most will be found in the southwest. We also identified 53 domesticated tree species significantly associated with earthwork occurrence probability, likely suggesting past management practices. Closed-canopy forests across Amazonia are likely to contain thousands of undiscovered archaeological sites around which pre-Columbian societies actively modified forests, a discovery that opens opportunities for better understanding the magnitude of ancient human influence on Amazonia and its current state.

Micronuclei and nuclear buds in amniotic tissue of rats treated with cyclophosphamide.

Fetal development can be altered by DNA damage caused by maternal exposure to chemical, physical, or biological agents during gestation. One method of assessing genotoxicity is to detect micronuclei (MNs) and/or nuclear abnormalities. This can be performed in vivo and requires only frequently dividing tissues, such as amniotic tissue (AT), which is in contact with the fetal environment and is composed of very thin layers of cells. This study evaluated the presence of MNs, nucleoplasmic bridges, and nuclear buds (NBs) in the fetal AT following maternal exposure to cyclophosphamide (CP) during pregnancy. Pregnant Wistar rats were divided into a negative control group and an experimental group that was orally administered CP (10 mg/kg). Daily blood smears were obtained from pregnant rats on days 14-19 of gestation. The rats were dissected, and fetal ATs were obtained on the 19th day of gestation. The MN and NB frequencies in AT cells were analyzed using a fluorescence microscope (100 ×). Micronucleated erythrocytes in the peripheral blood of the control rats were also assessed. Micronucleated polychromatic erythrocyte frequencies were significantly higher than those in the controls. Polychromatic erythrocyte frequencies were lower in CP-treated rats than in controls at 48-120 h. Fetuses in the CP-treated group also showed a significant increase in MNs and NBs in AT cells. In conclusion, AT could be used for analyzing MNs and NBs in rats following maternal exposure to a genotoxic agent and as a viable alternative for analyzing the integrity of fetal DNA during gestation.

Niche breadth of Amazonian trees increases with niche optimum across broad edaphic gradients.

Understanding how biotic interactions and environmental filtering mediated by soil properties shape plant community assembly is a major challenge in ecology, especially when studying complex and hyperdiverse ecosystems like tropical forests. To shed light on the influence of both factors, we examined how the edaphic optimum of species (their niche position) related to their edaphic range (their niche breadth) along different environmental gradients and how this translates into functional strategies. Here we tested four scenarios describing the shape of the niche breadth-niche position relationship, including one neutral scenario and three scenarios proposing different relative influences of abiotic and biotic factors on community assembly along a soil resource gradient. To do so, we used soil concentration data for five key nutrients (N, P, Ca, Mg, and K), along with accurate measurements of 14 leaf, stem, and root traits for 246 tree species inventoried in 101 plots located across Eastern (French Guiana) and Western (Peru) Amazonia. We found that species niche breadth increased linearly with species niche position along each soil nutrient gradient. This increase was associated with more resource acquisitive traits in the leaves and the roots for soil N, Ca, Mg, and K concentration, while it was negatively associated with wood density for soil P concentration. These observations agreed with one of our hypothetical scenarios in which species with resource conservation traits are confined to the most nutrient-depleted soils (abiotic filter), but they are outperformed by faster-growing species in more fertile conditions (biotic filter). Our results refine and strengthen support for niche theories of species assembly while providing an integrated approach to improving forest management policies.

Evolutionary genomics of oceanic island radiations.

A recurring feature of oceanic archipelagos is the presence of adaptive radiations that generate endemic, species-rich clades that can offer outstanding insight into the links between ecology and evolution. Recent developments in evolutionary genomics have contributed towards solving long-standing questions at this interface. Using a comprehensive literature search, we identify studies spanning 19 oceanic archipelagos and 110 putative adaptive radiations, but find that most of these radiations have not yet been investigated from an evolutionary genomics perspective. Our review reveals different gaps in knowledge related to the lack of implementation of genomic approaches, as well as undersampled taxonomic and geographic areas. Filling those gaps with the required data will help to deepen our understanding of adaptation, speciation, and other evolutionary processes.

Unraveling Amazon tree community assembly using Maximum Information Entropy: a quantitative analysis of tropical forest ecology.

In a time of rapid global change, the question of what determines patterns in species abundance distribution remains a priority for understanding the complex dynamics of ecosystems. The constrained maximization of information entropy provides a framework for the understanding of such complex systems dynamics by a quantitative analysis of important constraints via predictions using least biased probability distributions. We apply it to over two thousand hectares of Amazonian tree inventories across seven forest types and thirteen functional traits, representing major global axes of plant strategies. Results show that constraints formed by regional relative abundances of genera explain eight times more of local relative abundances than constraints based on directional selection for specific functional traits, although the latter does show clear signals of environmental dependency. These results provide a quantitative insight by inference from large-scale data using cross-disciplinary methods, furthering our understanding of ecological dynamics.

Climate Constrains Photosynthetic Strategies in Darwin's Daisies: A Test of the Climatic Variability and Jack-of-All-Trades Hypotheses.

AbstractEmpirical evidence for the climate variability and performance trade-off hypotheses is limited to animals, and it is unclear whether climate constrains the photosynthetic strategies of plants. The plant genus Scalesia Arn. ex Lindl (family Asteraceae), endemic to the Galápagos archipelago, provides an ideal study system to test these hypotheses because of its species with markedly different leaf morphologies that occupy distinct climatic zones. In this study we tested the classic hypotheses that (1) climate constrains leaf size, (2) high climatic temperature variability selects for thermal generalists (i.e., the climate variability hypothesis), and (3) there is a trade-off between the breadth and rate of photosynthetic performance (i.e., jack-of-all-trades but master of none hypothesis). To do this we measured the leaf morphologies and photosynthetic temperature response curves of 11 Scalesia species. In support of a priori predictions, we found that small-leaved Scalesia species were more likely to occupy hotter and drier climates than large-leaved species, there was a positive relationship between climatic temperature variability and the breadth of photosynthetic performance, and photosynthetic performance was negatively correlated with photosynthetic breadth. Our study is among the first to provide evidence for the performance-breadth trade-off hypothesis in photosynthesis, suggesting that climate change may select for photosynthetic thermal generalists.

Low-cost homemade cocktails for enzymatic conversion of sugarcane and cassava bagasses.

The agricultural industries generate lignocellulosic wastes that can be modified by fungi to generate high value-added products. This work aimed to analyze the efficiency and the cost-effectiveness of the bioconversion of sugarcane and cassava bagasses using low-cost homemade enzymatic cocktails from Aspergillus niger LBM 134. Both bagasses were pretreated with a soft alkaline solution without any loss of polysaccharides. After the hydrolysis, a 28% of conversion to glucose and 42% to xylose were reached in the hydrolysis of sugarcane bagasse while an 80% of saccharification yield, in the hydrolysis of cassava bagasse using the homemade enzymes. Furthermore, a more disorganised surface and no starch granules were observed in the sugarcane and cassava bagasses, respectively. The bioethanol yield from sugarcane and casava bagasses was predicted to be 4.16 mg mL-1 and 2.57 mg mL-1, respectively. A comparison of the cost of the homemade and the commercial enzymes was carried out. Similar hydrolysis percentages were achieved employing any enzyme; however, it was 1000-2000 times less expensive using the homemade cocktails than using the commercial enzymes. Therefore, the cost of obtaining glucose from bagasses was most expensive when applying the commercial enzymes. Moreover, the hydrolysis of the cassava bagasse was most efficient with the homemade cocktails. The importance and novelty of this work lie in the similar performance and the lower cost of the homemade cocktails from the fungus A. niger LBM 134 compared with the commercial enzymes on the hydrolysis of the sugarcane and cassava bagasses.

Accelerating the discovery of rare tree species in Amazonian forests: integrating long monitoring tree plot data with metabolomics and phylogenetics for the description of a new species in the hyperdiverse genus Inga Mill.

In species-rich regions and highly speciose genera, the need for species identification and taxonomic recognition has led to the development of emergent technologies. Here, we combine long-term plot data with untargated metabolomics, and morphological and phylogenetic data to describe a new rare species in the hyperdiverse genus of trees Inga Mill. Our combined data show that Inga coleyana is a new lineage splitting from their closest relatives I. coruscans and I. cylindrica. Moreover, analyses of the chemical defensive profile demonstrate that I. coleyana has a very distinctive chemistry from their closest relatives, with I. coleyana having a chemistry based on saponins and I. cylindrica and I. coruscans producing a series of dihydroflavonols in addition to saponins. Finally, data from our network of plots suggest that I. coleyana is a rare and probably endemic taxon in the hyper-diverse genus Inga. Thus, the synergy produced by different approaches, such as long-term plot data and metabolomics, could accelerate taxonomic recognition in challenging tropical biomes.

Diagnostic Potential of the Serological Response to Synthetic Peptides from Mycobacterium tuberculosis Antigens for Discrimination Between Active and Latent Tuberculosis Infections.

Diagnosis and treatment of active tuberculosis (ATB) as well as latent tuberculosis infection (LTBI) are required for effective tuberculosis (TB) control, especially in TB endemic area. The usefulness of conventional tests to distinguish between ATB and LTBI has remained challenging. The present study was aimed to demonstrate the usefulness of the serological response to synthetic peptides from Mycobacterium tuberculosis (Mtb) antigens for discrimination between ATB and LTBI in Warao Amerindians. Serum IgG antibody levels were measured by the indirect ELISA assay using 22 designed and synthesized peptides derived from immunogenic Mtb ESAT-6 and Ag85A proteins. A total of 211 adult Warao Amerindians were included; cases with active TB (ATB, n = 75), latent TB infection (LTBI, n = 85) and non-infected (NI, n = 51). The approach's diagnostic information was compared using receiver operating characteristic (ROC) curves. For ATB diagnostic performance between ATB and NI; ESAT-6; P-12037 had 100% of sensitivity (AUC = 0.812; 0.733 to 0.891 95% CI); and Ag85A; P-10997 had 100% of specificity (AUC = 0.691; 0.597 to 0.785 95% CI); and ATB and LTBI; Ag85A; P-29878 had 100% of sensitivity (AUC = 0.741; 0.666-0.817 95% CI), and P-29879 had 99% of specificity (AUC = 0.679; 0.593-0.765 95% CI). While that ESAT-6 P-12037 also allowed differentiation between LTBI and NI or healthy ones. It had 98.8% of sensitivity and 98.0% of specificity (AUC = 0.640; 0.545-0.735 95% CI). The potential of combination-antigen immunoassays with peptides could discriminate between Warao Amerindians with ATB, LTBI and NI. Further validation of this approach could lead to developing a complementary tool for rapid diagnosis of TB infections.

Rediscovery of Gasteranthusextinctus L.E.Skog & L.P.Kvist (Gesneriaceae) at multiple sites in western Ecuador.

We report the rediscovery of the Critically Endangered cloud forest herb Gasteranthusextinctus, not seen since 1985. In 2019 and 2021, G.extinctus was recorded at five sites in the western foothills of the Ecuadorian Andes, 4-25 km from the type locality at the celebrated Centinela ridge. We describe the species' distribution, abundance, habitat and conservation status and offer recommendations for further research and conservation efforts focused on G.extinctus and the small, disjunct forest remnants it occupies.

Los costes indirectos de la cefalea tensional. Una revisión sistemática de la literatura / The indirect costs of tension type headache. A systematic literature review

Objetivo: El objetivo de este trabajo fue revisar sistemáticamente la literatura publicada con relación a los costes indirectos estimados asociados al TTH.DiseñoEsta revisión sistemática siguió la declaración de elementos de informes preferidos para revisiones sistemáticas y metaanálisis (PRISMA).Fuentes de datosLa revisión se realizó en dos bases de datos principales, PubMed y EconLit, y fue completada con la búsqueda de literatura gris.Selección de estudiosEl criterio básico para la inclusión de estudios fue que presentaran al menos una medida de costes indirectos específicos del TTH.Extracción de datosSe seleccionaron finalmente 12 estudios para la extracción de la información. De todos los artículos seleccionados se sintetizaron las características del diseño del estudio, los tipos de coste incluidos, así como el instrumento de medida, y los resultados principales.ResultadosLa búsqueda arrojó en total 568 estudios. Se encontró heterogeneidad en los diseños y muestras/poblaciones de los estudios incluidos. Sólo dos estudios estimaron costes directos e indirectos para el TTH. Entre los resultados más destacables, encontramos un impacto moderado estimado de la discapacidad por TTH (entre 0,037 y 0,15 por persona, 0,06-0,09% para la población). Las pérdidas de productividad y eficiencia se observaron y fueron muy heterogéneas. La disposición a pagar por un tratamiento efectivo oscilaría entre $1,32 y $9,20 mensuales. La calidad de vida es baja, entre 28,2 y 28,4 puntos sobre 100, y la calidad de vida relacionada con la salud, parece mejorar significativamente con un tratamiento.ConclusionesA pesar de la elevada heterogeneidad de los resultados, podemos concluir que la cefalea tensional se caracteriza por un impacto moderado en la discapacidad, en la productividad y eficiencia en el trabajo o la escuela, y en la calidad de vida de quien la sufre.

Objective: The objective of this work was to systematically review the published literature in relation to the estimated indirect costs associated with TTH.DesignThis systematic review followed the Preferred Reporting Items Statement for Systematic Reviews and Meta-analyzes (PRISMA).Data sourcesThe review was performed in two main databases, PubMed and EconLit, and was completed with the gray literature search.Study selectionThe basic criterion for the inclusion of studies was that they present at least one measure of indirect costs specific to TTH.Data extraction12 studies were finally selected for information extraction. Of all the selected articles, the characteristics of the study design, the types of costs included, as well as the measurement instrument, and the main results were synthesized.ResultsThe search yielded a total of 568 studies. Heterogeneity was found in the designs and samples/populations of the included studies. Only two studies estimated direct and indirect costs for TTH. Among the most notable results, we find an estimated moderate impact of disability due to TTH (between 0.037 and 0.15 per person, 0.06–0.09% for the population). Productivity and efficiency losses were observed and were very heterogeneous. The willingness to pay for effective treatment would range from $1.32 to $9.20 per month. Quality of life is low, between 28.2 and 28.4 points out of 100, and health-related quality of life seems to improve significantly with treatment.ConclusionsDespite the high heterogeneity of the results, we can conclude that tension headache is characterized by a moderate impact on disability, on productivity and efficiency at work or school, and on the quality of life of those who suffer it.

Diagnostic agreement of quantitative flow ratio with fractional flow reserve in a Latin-American population.

Quantitative flow ratio (QFR) is a recently proposed angiographic index that allows to assess the pressure loss in coronary arteries in a similar fashion as the fractional flow reserve (FFR). The purpose of this study was to evaluate the diagnostic performance of QFR as compared to FFR, in a Latin-American population of patients with suspected ischaemic heart disease. QFR was retrospectively derived from coronary angiograms. The association, diagnostic performance, and continuous agreement of fixed-flow QFR (fQFR) and contrast-flow QFR (cQFR) with FFR was assessed by continuous and dichotomous methods. 90 vessels form 66 patients were finally included. The study comprised coronary stenoses of intermediate severity, both angiographically (diameter stenosis: 46.6 ± 12.8%) and physiologically [median FFR = 0.83 (quartile 1-3, 0.76-0.89)]. The correlation of FFR with both fQFR [ρ = 0.841, (95% CI 0.767 to 0.893), p < 0.001] and cQFR [ρ = 0.833, (95% CI 0.755 to 0.887), p < 0.001] was strong. The diagnostic performance of cQFR was good [area under the ROC curve of 0.92 (95% CI 0.86 to 0.97, p < 0.001)], with 0.80 as the optimal cQFR cut-off against FFR ≤ 0.80. This 0.80 cQFR cut-off classified correctly 83.3% of total stenoses, with a sensitivity of 85.2% and specificity of 80.6%. QFR was strongly associated with FFR and exhibited a high diagnostic performance in this Latin-American population.