¿Pueden los factores clínicopatológicos mejorar la predicción de metástasis en ganglios linfáticos no centinelas en pacientes con cáncer de mama?

Introduction: To determine whether clinicopathological characteristics can improve the prediction of metastasis to nonsentinel lymph nodes (NSLNs) over the use of only mRNA copy number in sentinel lymph node (SLN) biopsies. Methods: This was a retrospective, observational study that included a total of 824 patients with T1-3 breast cancer who had clinically negative, ultrasound-negative axilla without evidence of metastasis and who underwent one-step nucleic acid amplification in SLN biop-sies. Results: 118 required a complete axillary lymph node dissection (ALNhD). About 35.6% (42/118) had metastases to a NSLN, and 64.4% (76/118) had no metastasis to a NSLN. The ROC curve of the total tumor load (TTL) presented an area under the curve (AUC) of 0.651 (95%; CI: 0.552-0.751). The 7294 copies of CK19 mRNA were established as the optimal cutoff point, with sensitivity: 93%, specificity: 63%, positive predictive value: 44%, and negative predictive value: 91%. By as-sociating the clinicopathological parameters (multicentricity, pooled immunohistochemistry [IHC], and progesterone receptors), the AUC went up to 0.752 (95% CI: 0.663-0.841). Conclusions: Clinicopathological factors should be considered together with the total CK19 mRNA copy number (the TTL) of the SLNs to improve the predictive capacity of metastatic involvement of the NSLNs

Characterization of Gelidium corneum's (Florideophyceae, Rhodophyta) vegetative propagation process under increasing levels of temperature and irradiance

Climate change is affecting Gelidium corneum (Hudson) J.V. Lamouroux fields in the Bay of Biscay by reducing its cover and biomass. Understanding those changes requires a good characterization of the responses of this species to different stressors, particularly the effects on key processes such as the vegetative propagation. Here, we aimed to characterize the interactive effect of temperature (15, 20 and 25◦C) and irradiance (5-10, 55-60 and 95-100 μmol*m2*s- 1) on two phases of the vegetative propagation process: the re-attachment capacity and the survival of re-attached fragments. The study findings revealed significant effects of both temperature and irradiance in the re-attachment capacity of the species, with higher rates of attachment registered at 20 ◦C and 5-10 μmol*m- 2*s-1 after 10, 20 and 30 days of culture. However, the interaction effects were not significant at any time interval. At higher or lower temperatures and increasing irradiances, the attachment capacity was reduced. On the other hand, irradiance was demonstrated to be the main factor controlling the survival of rhizoids. In fact, higher levels of irradiance generated severe damage on rhizoids, and thus, conditioned the development of new plants. According to this, it seems clear that the vegetative propagation process of this species is expected to become more vulnerable as both variables are expected to rise due to climate change. An increased vulnerability of this species may have several implications from an ecological and economic perspective, so we encourage to continue exploring the factors and processes controlling its distribution in order to adopt better management actions in the future.This work was funded by the National Plan for Research in Science and Technological Innovation from the Spanish Government 2017–2020 [grant number C3N-pro project PID2019-105503RB-I00] and co-funded by the European Regional Development’s funds. Samuel Sainz-Villegas and Begoña Sánchez-Astráin acknowledge the financial support received under predoctoral grants from the Spanish Ministry of Science, Innovation and Universities [grant numbers: FPU18/03573 and PRE2020-096255, respectively]. This work is part of the PhD project of Samuel Sainz-Villegas

Clinical and Economic Evaluation after Adopting Contingent Cell-Free DNA Screening for Fetal Trisomies in South Spain.

Contingent cell-free (cf) DNA screening on the basis of the first-trimester combined test (FCT) results has emerged as a cost-effective strategy for screening of trisomy 21 (T21). Objectives: To assess performance, patients’ uptake, and cost of contingent cfDNA screening and to compare them with those of the established FCT. Methods: This is a prospective cohort study including all singleton pregnancies attending to their FCT for screening of T21 at 2 university hospitals in South Spain. When the FCT risk was ≥1:50, there were major fetal malformations, or the nuchal translucency was ≥3.5 mm, women were recommended invasive testing (IT); if the risk was between 1:50 and 1:270, women were recommended cfDNA testing; and for risks bellow 1:270, no further testing was recommended. Detection rate (DR), false-positive rate (FPR), patients’ uptake, and associated costs were evaluated. Results: We analyzed 10,541 women, including 46 T21 cases. DR of our contingent strategy was 89.1% (41/46) at 1.4% (146/10,541) FPR. Uptake of cfDNA testing was 91.2% (340/373), and overall IT rate was 2.0%. The total cost of our strategy was €1,462,895.7, similar to €1,446,525.7 had cfDNA testing not been available. Conclusions: Contingent cfDNA screening shows high DR, low IT rate, and high uptake at a similar cost than traditional screening.pre-print133 K

Gravity modeling of the lithosphere in the Calatrava Volcanic Province (Spain): geodynamic implications

The origin of the intraplate volcanism in the Calatrava Volcanic Province (CVP) is controversial. On the basis of its geochemical signature it has been ascribed to an “aborted” rift, implying lithospheric thinning. However, the volcanism occurred during the generalized Cenozoic NW−SE-oriented compressive tectonic regime. On the other hand, on the basis of evidence for its deep-seated origin, it has been linked to the existence of a baby-plume detached from an active megaplume below the Canary-Azores Islands and the western Mediterranean. In order to understand better the aforementioned geodynamic scenarios for the origin of the CVP, we address here the study of the lithosphere in the CVP and its vicinity by means of gravity analysis and 2+1/2D modeling. Gravity modeling results do not support the rifting model adopted for the intraplate volcanism occurred in the CVP because the crust shows a constant thickness. Density models suggest the existence of a sub-crustal, anomalous low-density block that could be underplated magmatic material at the base of the crust, suggesting that only a minor part of it intruded up into the crust and erupted. The localized magmatism of the CVP can be related to the combination of two factors: one active, the gentle folding of the Iberian lithosphere and associated uplifting of the Variscan basement due to the NW-directed transmission of compressive stresses in the upper plate yielded by the subduction/collision in the south Iberian margin. The formation of the lithospheric folding in the Calatrava region results in a decrease of the pressure beneath the swell of the antiform that is likely to bring about basaltic magmatism below the swell; and one passive, the existence of a Variscan right-lateral shear band, which yields a weakened  crust that facilitates the ascent of the magmatic materials. The relatively small volume, but large extension, of the volcanic outcrops could be associated with the preferential ascent of the magmas along the weakened crust of this NW−SE-trending Variscan shear band.El origen del volcanismo intraplaca en la Provincia Volcánica de Calatrava (CVP) es controvertido. En base a su signatura geoquímica se ha atribuido a la formación de un rift “abortado”, implicando un adelgazamiento litosférico. Sin embargo, el volcanismo se desarrolló durante un régimen tectónico compresivo orientado NW-SE que fue generalizado en la región de Calatrava durante el Cenozoico. Por otro lado, en base a las evidencias de su origen profundo, se le ha relacionado con la existencia de una mini-pluma desconectada de una mega-pluma activa debajo de los archipiélagos de Canarias y Azores, y en el Mediterráneo occidental. Con el propósito de contribuir a la discriminación entre los escenarios geodinámicos mencionados para el origen del volcanismo se ha abordado aquí el estudio de la litosfera en la CVP y en las zonas próximas mediante el análisis gravimétrico y la modelación 2+1/2D. Los modelos gravimétricos no apoyan el modelo de rifting adoptado para el volcanismo intraplaca ocurrido en la CVP porque el espesor de la corteza es cuasi-constante. Los modelos siguieren la existencia de un cuerpo anómalo sub-cortical de baja densidad que podría ser material magmático acrecionado y almacenado en la base de la corteza indicando que sólo una parte menor habría intruido en la corteza y producido erupciones. El volcanismo localizado de la CVP se puede relacionar con la combinación de dos factores: a) Un factor activo correspondiente a un amplio plegamiento de la litosfera (corteza) Ibérica y el consiguiente levantamiento asociado del basamento varisco debido a la transmisión hacia el NW de los esfuerzos compresivos en la placa superior de la subducción/colisión miocena en el margen meridional Ibérico. La formación del anticlinal a escala cortical en la región de Calatrava ha producido la disminución de la presión en el intrados del anticlinal y ha originado probablemente el magmatismo basáltico; b) Un factor pasivo correspondiente a la existencia de una banda de cizalla con dirección próxima a NW-SE, heredada de la deformación varisca, que localiza una zona de debilidad cortical favorecedora del ascenso del magmatismo

Predicting non-native seaweeds global distributions: The importance of tuning individual algorithms in ensembles to obtain biologically meaningful results

ABSTRACT: Modelling non-native marine species distributions is still a challenging activity. This study aims to predict the global distribution of five widespread introduced seaweed species by focusing on two mains aspects of the ensemble modeling process: (1) Does the enforcement of less complex models (in terms of number of predictors) help in obtaining better predictions? (2) What are the implications of tuning the configuration of individual algorithms in terms of ecological realism? Regarding the first aspect, two datasets with different number of predictors were created. Regarding the second aspect, four algorithms and three configurations were tested. Models were evaluated using common evaluation metrics (AUC, TSS, Boyce index and TSS-derived sensitivity) and ecological realism. Finally, a stepwise procedure for model selection was applied to build the ensembles. Models trained with the large predictor dataset generally performed better than models trained with the reduced dataset, but with some exceptions. Regarding algorithms and configurations, Random Forest (RF) and Generalized Boosting Models (GBM) scored the highest metric values in average, even though, RF response curves were the most unrealistic and non-smooth and GBM showed overfitting for some species. Generalized Linear Models (GLM) and MAXENT, despite their lower scores, fitted smoother curves (especially at intermediate complexity levels). Reliable and biologically meaningful predictions were achieved. Inspecting the number of predictors to include in final ensembles and the selection of algorithms and its complexity have been demonstrated to be crucial for this purpose. Additionally, we highlight the importance of combining quantitative (based on multiple evaluation metrics) and qualitative (based on ecological realism) methods for selecting optimal configurations.This work was funded by the National Plan for Research in Science and Technological Innovation from the Spanish Government 2017-2020 [grant number C3N-pro project PID2019-105503RB-I00] and co-funded by the European Regional Development’s funds. SS-V acknowledges financial support under a predoctoral grant from the Spanish Ministry of Education andVocational Training [grantnumber:FPU18/03573]. CH acknowledges the financial support from the Government of Cantabria through the Fénix Programme and under a postdoctoral grant from the University of Cantabria [grant number: POS-UC- 2020-07]. This work is part of the PhD project of SS-V

To den or not to den. Contributions to the taphonomic history of the Early Pleistocene site of Venta Micena 4 (Orce, Guadix-Baza Basin)

Venta Micena (Orce, Guadix-Baza Basin, Spain) is an Early Pleistocene locality renowned for the richness and quality of its palaeontological record. VM is spread over an area of 2.5 km2, where several exposed fossil outcrops are visible amidst its gorges and ravines. The best known of these sites, VM3, has been interpreted as a hyaena den. In addition, a new site, named VM4, has recently been the focus of fieldwork and taphonomic studies. The publication by Luz on et al. (2021) pointed out that VM4 presents a more complex history than VM3. First, two different sub-levels were identified: VM4-I and VM4-II. Secondly, the preliminary taphonomic analysis showed conspicuous differences with regard to VM3. Nevertheless, such interpretation has been challenged by Palmqvist et al. (2022) who proposed that VM3 and VM4 are both the result of a single depositional process, entailing the selective transport of skeletal parts by the giant extinct hyaena Pachycrocuta brevirostris back to its den. Using well-preserved faunal elements whose depositional context and provenance are reliable, in this paper we show that: 1) there are two clearly defined sub-levels in VM4 with some shared taphonomic characteristics as well as some notable differences; 2) VM3 and VM4 exhibit enough divergence to support differences in site formation processes; 3) The interpretation of both VM4-I and VM4-II is more consistent with their characterisation as open-air sites in which multiple agents and depositional processes contributed to its formation, rather than with hyaena dens. Nevertheless, excavations are still in progress at VM4 and therefore any results and interpretations ought to be considered as provisional.Consejeía de Cultura de la Junta de Andalucia through the General Research Project Primeras ocupaciones humanas y contexto paleoecologico a partir de los depositos Plio-pleistocenos de la cuenca Guadix-Baza BC.03.032/17Inside the Artefacts & Ecofacts" Excellence Unit (University of Granada) HUM-607 PID 2021.125098NB.I00 MCIN/AEI/10.13039/501100011033/FEDERUna manera de hacer Europa ProyExcel_00274 2021 SGR 01238Agencia de Gestio D'Ajuts Universitaris de Recerca Agaur (AGAUR) Generalitat de CatalunyaNational Health and Medical Research Council (NHMRC) of Australia PRE2020-094482 CEX2019-000945-M-20-1Spanish GovernmentArchaeometrical Studies. Inside the Artefacts & Ecofacts" Excellence Unit (University of Granad

Nuclear receptor NR5A2 and bone: gene expression and association with bone mineral density

ObjectiveThere is growing evidence for a link between energy and bone metabolism. The nuclear receptor subfamily 5 member A2 (NR5A2) is involved in lipid metabolism and modulates the expression of estrogen-related genes in some tissues. The objective of this study was to explore the influence of NR5A2 on bone cells and to determine whether its allelic variations are associated with bone mineral density (BMD).DesignAnalyses of gene expression by quantitative PCR and inhibition of NR5A2 expression by siRNAs were used to explore the effects of NR5A2 in osteoblasts. Femoral neck BMD and 30 single nucleotide polymorphisms (SNPs) were first analyzed in 935 postmenopausal women and the association of NR5A2 genetic variants with BMD was explored in other 1284 women in replication cohorts.ResultsNR5A2 was highly expressed in bone. The inhibition of NR5A2 confirmed that it modulates the expression of osteocalcin, osteoprotegerin, and podoplanin in osteoblasts. Two SNPs were associated with BMD in the Spanish discovery cohort (rs6663479, P=0.0014, and rs2816948, P=0.0012). A similar trend was observed in another Spanish cohort, with statistically significant differences across genotypes in the combined analysis (P=0.03). However, the association in a cohort from the United States was rather weak. Electrophoretic mobility assays and studies with luciferase reporter vectors confirmed the existence of differences in the binding of nuclear proteins and the transcriptional activity of rs2816948 alleles.ConclusionsNR5A2 modulates gene expression in osteoblasts and some allelic variants are associated with bone mass in Spanish postmenopausal women

Testing accuracy in 2D and 3D geometric morphometric methods for cut mark identification and classification

The analysis of bone surface modifications (BSMs) is a prominent part of paleoanthropological studies, namely taphonomic research. Behavioral interpretations of the fossil record hinge strongly upon correct assessment of BSMs. With the significant impact of microscopic analysis to the study of BSMs, multiple authors have discussed the reliability of these technological improvements for gaining resolution in BSM discrimination. While a certain optimism is present, some important questions are ignored and others overemphasized without appropriate empirical support. This specifically affects the study of cut marks. A diversity of geometric morphometric approaches applied to the study of cut marks have resulted in the coexistence (and competition) of different 2D and 3D methods. The present work builds upon the foundation of experiments presented by Maté-González et al. (2015), Courtenay et al. (2017) and Otárola-Castillo et al. (2018) to contrast for the first time 2D and 3D methods in their resolution of cut mark interpretation and classification. The results presented here show that both approaches are equally valid and that the use of sophisticated 3D methods do not contribute to an improvement in accuracy

Valor de la PET en la recurrencia del cáncer de próstata con PSA < 5 ng/ml

We intend to evaluate the usefulness of PET scans in diagnosing recurrent prostate cancer after a curative attempt using radical treatment. MATERIAL AND METHODS: 92 consecutive prostate cancer patients in biochemical progression following radical surgery (63) or radiation treatment (29) were studied with positron emission tomography (PET). In all cases two scans were performed in the same day (11C-choline and 18F-FDG). PET efficacy was evaluated both globally (by employing the results achieved with both 11C-choline and 18F-FDG) and using both radiotracers independently to detect recurrence in patients with biochemical progression. For this purpose, we used comparison of means for k-independent samples, 2 x 2 and 2 x X contingency tables and ROC curves. RESULTS: 1. Global PET: there is evidence of PET alteration regarding the PSA level (P=.003): the clinical stage (P=.01). There are no statistically significant PET alterations regarding the affected biopsy (uni or bilateral), surgical margins, pathological stage and time to progression. ROC curve PET-PSA is statistically significant (P< .0001) permitting calculation of different cut-off points, with a specificity of 91% (highest) for a PSA of 4.3 ng/ml. 2. PET 18FDG: the area under the ROC curve is statistically significant (P< .0001) with a specificity of 91% for a PSA of 6.51 ng/ml. 3. PET 11choline: the area under the ROC curve is statistically significant (P< .0001) with a specificity of 91% for a PSA of 5.15 ng/ml. CONCLUSIONS: PET is a useful tool for diagnosing prostate cancer recurrence after a curative attempt using radical treatment

An Evaluation of Landmark-Based Methods to Explore Tooth Score Morphology: A Case Study on Felids and Hyenids

Taphonomic studies aim to identify the modifying agents that intervene in bone assemblages found at archaeopaleontological sites. Carnivores may modify, accumulate, or scavenge skeletal parts inflicting tooth marks, including scores, on the cortical surface. Several works have studied tooth score morphology to discern which carnivore group modified the bone assemblages, achieving different results. In the present study, different methods based on the use of landmarks and semilandmarks have been tested to describe and analyze the score profile cross-sections of spotted and brown hyenas, leopards, and lions. According to our results, the already published seven-landmark method is useful in order to differentiate between carnivore species from different families (e.g., felids and hyenids). Meanwhile, felid species (e.g., leopards and lions) cannot be consistently distinguished using any of the methods tested here. In contrast, hyenid species can be morphologically differentiated. On the other hand, the use of semilandmarks does not generally improve morphological characterization and distinction, but low numbers of landmarks and the inclusion of the score’s deepest point might provide the best results when semi-automatic semilandmark models are preferred to avoid sampling biases.The grant IJC2020-043576-I funded by MCIN/AEI/10.13039/501100011033 and the “European Union NextGenerationEU/PRTR” has been awarded to M.C.A. The grant RYC2021-034813-I funded by MCIN/AEI/10.13039/501100011033 and the European Union “NextGenerationEU”/PRTR has been awarded to M.Á.M.-G. During the development of the present work, J.A. was funded by the Euskal Herriko Unibertsitatea [ESPDOC21/05]. L.A.C. is funded by the Spanish Ministry of Science, Innovation and Universities by an FPI Predoctoral grant PRE2019-089411 associated with project RTI2018-099850-B-I0