Intraspecific niche models for the invasive ambrosia beetle Xylosandrus crassiusculus suggest contrasted responses to climate change.

Xylosandrus crassiusculus is an invasive ambrosia beetle comprising two differentiated genetic lineages, named cluster 1 and cluster 2. These lineages invaded different parts of the world at different periods of time. We tested whether they exhibited different climatic niches using Schoener's D and Hellinger's I indices and modeled their current potential geographical ranges using the Maxent algorithm. The resulting models were projected according to future and recent past climate datasets for Europe and the Mediterranean region. The future projections were performed for the periods 2041-2070 and 2071-2100 using 3 SSPs and 5 GCMs. The genetic lineages exhibited different climate niches. Parts of Europe, the Americas, Sub-Saharan Africa, Asia, and Oceania were evaluated as suitable for cluster 1. Parts of Europe, South America, Central and South Africa, Asia, and Oceania were considered as suitable for cluster 2. Models projection under future climate scenarios indicated a decrease in climate suitability in Southern Europe and an increase in North Eastern Europe in 2071-2100. Most of Southern and Western Europe was evaluated as already suitable for both clusters in the early twentieth century. Our results show that large climatically suitable regions still remain uncolonized and that climate change will affect the geographical distribution of climatically suitable areas. Climate conditions in Europe were favorable in the twentieth century, suggesting that the recent colonization of Europe is rather due to an increase in propagule pressure via international trade than to recent environmental changes.

Enfermedad mínima residual en leucemia mieloide aguda no promielocítica: Resultados preliminares de un estudio colaborativo internacional / Minimal residual disease in non-myelocytic acute myeloid leukemia: preliminary results of an international collaborative study

A pesar de los avances en los protocolos de tratamiento y en las medidas de soporte en pacientes con Leucemia Mieloide Aguda (LMA), 27% presentan recaídas de la enfermedad. Esto se debe, entre otras causas, a la persistencia de pequeñas cantidades de células malignas (blastos) resistentes a la terapia. Estas pequeñas cantidades de blastos remanentes se denominan Enfermedad Mínima Residual (EMR). La determinación de EMR requiere de técnicas no solo muy sensibles, sino también específicas, y permite evaluar la respuesta individual a la terapia. La introducción de la EMR como parámetro de respuesta y estratificación está bien definida en Leucemia Linfoblástica Aguda (LLA). Por el contrario, aunque existen publicaciones sobre el impacto pronóstico de la EMR en LMA, aún no se encuentra incluida en forma sistemática en los protocolos nacionales actuales, entre otros motivos, por lo laborioso de la determinación y por la necesidad de validación de la misma. Debe tenerse en cuenta que el inmunofenotipo de los blastos mieloides suele ser más heterogéneo que el de los blastos en LLA, presentando, en muchos casos, subpoblaciones diferentes entre sí, lo cual dificulta su detección certera y no hay consenso definido en cuanto a la metodología más eficaz. En este trabajo describimos una nueva estrategia de marcación y análisis estandarizada en un estudio multicéntrico internacional para LMA y la utilidad de la EMR como parámetro de respuesta y de estratificación. Asimismo, detallamos los resultados preliminares de nuestra cohorte de pacientes (AU)

Despite the improvement in treatment and supportive care of patients with Acute Myeloid Leukemia (AML), 27% of them relapse. This is due to the persistence of small amounts of malignant cells (blasts) resistant to therapy, among other causes. These small amounts of blasts are called Minimal Residual Disease (MRD). The determination of MRD requires not only techniques with high sensitivity but also with high specificity, and allows to evaluate the individual response to treatment. The introduction of MRD as a response parameter is well established in Acute Lymphoblastic Leukemia (ALL), and it is used in current stratification protocols. On the other hand, even though there are some reports regarding the prognostic impact of MRD in AML, it is still not included in the current national protocols due to the lack of validation of the determination, among other causes. This is due to the fact that the immunophenotype of myeloid blasts is more heterogeneous than in ALL, presenting different subpopulations, which difficults their accurate detection. Thus, there is still no consensus regarding the most effective approach. In this article, we describe a new staining and analysis strategy standardized by an international multicentric study, and the utility of EMR as a response and stratification parameter. Additionally, we show the preliminary results of our patient cohort. (AU)

Comparison of skin and shoe marker placement on metatarsophalangeal joint kinematics and kinetics during running.

This study investigated the effects of marker placement (skin- vs shoe-mounted) on metatarsophalangeal joint (MTP) kinematics and kinetics during running. Fifteen trained men ran on a 15-m track at 10 and 13 km/h with three (low, standard and high stiffness) shoe longitudinal bending stiffnesses (LBS). Reflective markers were fixed on the shoe upper, and on the skin using holes cut in the shoe. Three-dimensional marker positions and ground reaction forces were recorded at 200 and 2000 Hz, respectively. Kinematic and kinetic parameters were analyzed using one-dimensional metrics (statistical parametric mapping). MTP joint was less dorsiflexed at midstance ([57% to 100%] of braking phase and [0% to 48%] of pushing phase), and the MTP joint plantarflexion moment was higher ([22% to 55%] of pushing phase) with the shoe markerset in comparison with the skin markerset. The effect of LBS on MTP angle was found to be significant for a larger percentage of each stride using the shoe markerset compared to the skin markerset. However, the effect of LBS on plantarflexion moment was significant with the shoe markerset only. The effect of running speed on MTP angle was significant for a larger percentage of each stride with the skin markerset. This study demonstrates that the placement of markers influences the measurement of MTP kinematics and kinetics and that these effects are mediated by other variables such as LBS or running speed. It is concluded that the shoe markerset does not fully reflect the movement of the MTP joint.

RF generation using a compact bench gyromagnetic line.

The search for new technologies aiming to reach radiofrequency (RF) generation in different manners for diverse ends is a constant demand for several applications. The goal is to develop cost-effective and simpler systems compared to those that already exist. Our motivation is to reach an alternative way of generating RF in pulsed transmission systems employing a gyromagnetic nonlinear transmission line (GNLTL). The GNLTL consists of a ferrite-loaded-coaxial transmission line and can produce a large frequency spectrum with RF conversion efficiency above 10% from about 200 MHz up to the frequency of 2-4 GHz (S-band) for potential space-based applications. In a GNLTL, the signal amplitude is related to its propagation velocity since the peak voltage travels faster than its portion of lower amplitudes since the ferrite permeability decreases with the current amplitude. As the pulse crest travels faster than its valley, a time reduction happens in the output rise time, called pulse sharpening. Besides, the magnetic moments of ferrite dipoles initially aligned with the axial magnetic bias are displaced from their original position by the azimuthal field generated around the inner conductor by the current pulse, resulting in a damped precession movement. This movement happens along the line length as the current pulse propagates, inducing high-frequency oscillations. In short, the paper's goal is to present the experimental results using a 60-cm gyromagnetic line to provide RF in the GHz range using a solenoid for magnetic bias on a testing bench. Finally, the paper discusses the influence of the azimuthal and the axial magnetic fields on the output signal with the ferrite rings operating in a saturation state during the current pulse propagation.

Climate change impact on the potential geographical distribution of two invading Xylosandrus ambrosia beetles.

Xylosandrus compactus and X. crassiusculus are two polyphagous ambrosia beetles originating from Asia and invasive in circumtropical regions worldwide. Both species were recently reported in Italy and further invaded several other European countries in the following years. We used the MaxEnt algorithm to estimate the suitable areas worldwide for both species under the current climate. We also made future projections for years 2050 and 2070 using 11 different General Circulation Models, for 4 Representative Concentration Pathways (2.6, 4.5, 6.0 and 8.5). Our analyses showed that X. compactus has not been reported in all potentially suitable areas yet. Its current distribution in Europe is localised, whereas our results predicted that most of the periphery of the Mediterranean Sea and most of the Atlantic coast of France could be suitable. Outside Europe, our results also predicted Central America, all islands in Southeast Asia and some Oceanian coasts as suitable. Even though our results when modelling its potential distribution under future climates were more variable, the models predicted an increase in suitability poleward and more uncertainty in the circumtropical regions. For X. crassiusculus, the same method only yielded poor results, and the models thus could not be used for predictions. We discuss here these results and propose advice about risk prevention and invasion management of both species.

Cost-effectiveness of Artificial Intelligence for Proximal Caries Detection.

Artificial intelligence (AI) can assist dentists in image assessment, for example, caries detection. The wider health and cost impact of employing AI for dental diagnostics has not yet been evaluated. We compared the cost-effectiveness of proximal caries detection on bitewing radiographs with versus without AI. U-Net, a fully convolutional neural network, had been trained, validated, and tested on 3,293, 252, and 141 bitewing radiographs, respectively, on which 4 experienced dentists had marked carious lesions (reference test). Lesions were stratified for initial lesions (E1/E2/D1, presumed noncavitated, receiving caries infiltration if detected) and advanced lesions (D2/D3, presumed cavitated, receiving restorative care if detected). A Markov model was used to simulate the consequences of true- and false-positive and true- and false-negative detections, as well as the subsequent decisions over the lifetime of patients. A German mixed-payers perspective was adopted. Our health outcome was tooth retention years. Costs were measured in 2020 euro. Monte-Carlo microsimulations and univariate and probabilistic sensitivity analyses were conducted. The incremental cost-effectiveness ratio (ICER) and the cost-effectiveness acceptability at different willingness-to-pay thresholds were quantified. AI showed an accuracy of 0.80; dentists' mean accuracy was significantly lower at 0.71 (minimum-maximum: 0.61-0.78, P < 0.05). AI was significantly more sensitive than dentists (0.75 vs. 0.36 [0.19-0.65]; P = 0.006), while its specificity was not significantly lower (0.83 vs. 0.91 [0.69-0.98]; P > 0.05). In the base-case scenario, AI was more effective (tooth retention for a mean 64 [2.5%-97.5%: 61-65] y) and less costly (298 [244-367] euro) than assessment without AI (62 [59-64] y; 322 [257-394] euro). The ICER was -13.9 euro/y (i.e., AI saved money at higher effectiveness). In the majority (>77%) of all cases, AI was less costly and more effective. Applying AI for caries detection is likely to be cost-effective, mainly as fewer lesions remain undetected. Notably, this cost-effectiveness requires dentists to manage detected early lesions nonrestoratively.

[Cystatin C: Biomarker of cardiovascular risk in HIV]. / Cistatina C: Biomarcador de riesgo cardiovascular en VIH.

INTRODUCTION: Patients infected with the human immunodeficiency virus (HIV) have a higher cardiovascular risk (CVR). The development of cardiovascular disease (CVD) in this population involves traditional CVR factors and factors related to the infection itself, such as chronic inflammatory status, immune dysfunction, as well as the antiretroviral therapy received. Cystatin C (CC) has shown to be useful in assessing the presence of CVR factors and CVD established in the general population, the elderly population, and patients with chronic kidney disease. An analysis was performed on this association in an HIV positive population (HIV+). MATERIAL AND METHODS: Analytical, observational, cross-sectional study was conducted, and included collecting information about CVR factors and CVD in HIV+, as well as measuring CC. The patients were divided into 2 groups: Group1=high CC (≥0.95mg/L) and Group2=normal CC (<0.95mg/L). RESULTS: A total of 95 patients were included. Group1=27 (28.4%) and Group2=68 (71.5%). A value of CC≥0.95mg/L was related to the presence of CVD (P=.01). It was also related with and an increase in waist circumference (P=.05), neck circumference (P=.04), systolic blood pressure (P=.04), diastolic blood pressure (P=.01), Framingham score (P=.03), and Framingham score adapted for HIV (P=.01). After performing multivariate analysis with incorporation of variables associated with CVD in the bivariate analysis, only CC≥0.95mg/L continued to be related to CVD. CONCLUSION: CC≥0.95mg/L was independently associated with CVD. This cut-off point was also linked to higher levels of blood pressure, and higher CVR at 10 years using the Framingham Score and Framingham Score adapted for HIV population.

Application of the Johnson-Cook plasticity model in the finite element simulations of the nanoindentation of the cortical bone.

The mechanical behavior of the cortical bone in nanoindentation is a complicated mechanical problem. The finite element analysis has commonly been assumed to be the most appropriate approach to this issue. One significant problem in nanoindentation modeling of the elastic-plastic materials is pile-up deformation, which is not observed in cortical bone nanoindentation testing. This phenomenon depends on the work-hardening of materials; it doesn't occur for work-hardening materials, which suggests that the cortical bone could be considered as a work-hardening material. Furthermore, in a recent study [59], a plastic hardening until failure was observed on the micro-scale of a dry ovine osteonal bone samples subjected to micropillar compression. The purpose of the current study was to apply an isotropic hardening model in the finite element simulations of the nanoindentation of the cortical bone to predict its mechanical behavior. The Johnson-Cook (JC) model was chosen as the constitutive model. The finite element modeling in combination with numerical optimization was used to identify the unknown material constants and then the finite element solutions were compared to the experimental results. A good agreement of the numerical curves with the target loading curves was found and no pile-up was predicted. A Design Of Experiments (DOE) approach was performed to evaluate the linear effects of the material constants on the mechanical response of the material. The strain hardening modulus and the strain hardening exponent were the most influential parameters. While a positive effect was noticed with the Young's modulus, the initial yield stress and the strain hardening modulus, an opposite effect was found with the Poisson's ratio and the strain hardening exponent. Finally, the JC model showed a good capability to describe the elastoplastic behavior of the cortical bone.

Natural flavonoids inhibit the plasma membrane Ca2+-ATPase.

Research on flavonoids from plant sources has recently sparked increasing interest because of their beneficial health properties. Different studies have shown that flavonoids change the intracellular Ca2+ homeostasis linked to alterations in the function of mitochondria, Ca2+ channels and Ca2+ pumps. These findings hint at plasma membrane Ca2+-ATPase (PMCA) involvement, as it transports Ca2+ actively to the extracellular medium coupled to ATP hydrolysis, thus maintaining ion cellular homeostasis. The present study aims to investigate the effect of several natural flavonoids on PMCA both in isolated protein systems and in living cells, and to establish the relationship between flavonoid structure and inhibitory activity on PMCA. Our results show that natural flavonoids inhibited purified and membranous PMCA with different effectiveness: quercetin and gossypin were the most potent and their inhibition mechanisms seem to be different, as quercetin does not prevent ATP binding whereas gossypin does. Moreover, PMCA activity was inhibited in human embryonic kidney cells which transiently overexpress PMCA, suggesting that the effects observed on isolated systems could occur in a complex structure like a living cell. In conclusion, this work reveals a novel molecular mechanism through which flavonoids inhibit PMCA, which leads to Ca2+ homeostasis and signaling alterations in the cell.

Effects of the foot strike pattern on muscle activity and neuromuscular fatigue in downhill trail running.

Minimizing musculo-skeletal damage and fatigue is considered paramount for performance in trail running. Our purposes were to investigate the effects of the foot strike pattern and its variability on (a) muscle activity during a downhill trail run and (b) immediate and delayed neuromuscular fatigue. Twenty-three runners performed a 6.5-km run (1264 m of negative elevation change). Electromyographic activity of lower-limb muscles was recorded continuously. Heel and metatarsal accelerations were recorded to identify the running technique. Peripheral and central fatigue was assessed in knee extensors (KE) and plantar flexors (PF) at Pre-, Post-, and 2 days post downhill run (Post2d). Anterior patterns were associated with (a) higher gastrocnemius lateralis activity and lower tibialis anterior and vastus lateralis activity during the run and (b) larger decreases in KE high-frequency stimulus-evoked torque Post and larger decrements in KE MVC Post2d. High patterns variability during the run was associated with (a) smaller decreases in KE Db100 Post and MVC Post2d and (b) smaller decreases in PF MVC Post and Post2d. Anterior patterns increase the severity of KE peripheral fatigue. However, high foot strike pattern variability during the run reduced acute and delayed neuromuscular fatigue in KE and PF.

A dataset on the inventory of coniferous urban trees in the city of Orléans (France).

The dataset supplied in this article provides the spatial location and the species composition of urban trees belonging to three coniferous genera (Pinus, Cedrus and Pseudotsuga) inventoried in 5 districts of the city of Orléans (France). A total of 9321 trees were georeferenced. The most abundant species was the black pine Pinus nigra for which a total of 2420 trees were observed. Other common species were the scots pine P. sylvestris, the Douglas-fir Pseudotsuga menziesii and different species of the genus Cedrus. The data supplied in this article are related to "A citywide survey of the pine processionary moth Thaumetopoea pityocampa spatial distribution in Orléans (France)" by J.-P. Rossi, V. Imbault, T. Lamant, J. Rousselet,) [3].

NPM1, FLT3 and CEBPA mutations in pediatric patients with AML from Argentina: incidence and prognostic value.

Mutations in NPM1, FLT3 and CEBPA genes are found in 25-35 % of adult acute myeloblastic leukemia (AML) cases and correlate with prognosis. To date, there have been no reports about these mutations in pediatric AML from Argentina. The aims of the present study were to describe the incidence of NPM1, FLT3 and CEBPA mutations and to analyze their prognostic impact in this population. The incidences of these mutations within a population of 216 pediatric AML cases were: NPM1-mutated 4.2 %, CEBPA-mutated 1.9 %, FLT3-ITD 10.2 % and FLT3-TKD 7.9 %. Among 33 patients with normal karyotype, we found significantly higher frequencies for NPM1-mutated 24.2 % and CEBPA-mutated 12.1 %. Overall survival (pOS) for the 163 eligible non-acute promyelocytic leukemia cases was 46.2 ± 4.3 %, while leukemia-free survival probability was 51.0 ± 4.4 % (n = 135). The NPM1-mutated/FLT3-ITD-negative genotype showed better outcome than any other combined NPM1/FLT3 genotype; this difference was statistically significant within the group of high-risk patients (pOS ± SE 83.3 ± 15.2 % versus 33.1 ± 4.7 %; p = 0.0251). This is the first report of the frequencies of these mutations in Argentina. Despite the limited number of patients, a favorable prognosis of AML with genotype NPM1-mutated/FLT3-ITD-negative was confirmed. This is especially relevant within the high-risk group of patients, as it may contribute to the detection of patients with better prognosis, and thus avoid unnecessary treatment intensification.

Shiga toxigenic and enteropathogenic Escherichia coli in water and fish from pay-to-fish ponds.

UNLABELLED: Escherichia coli is part of the normal microflora of the intestines of mammals. However, among the enteric pathogens, it is one of the leading causes of intestinal diseases, especially Shiga toxigenic E. coli, which can cause diarrhoea, haemorrhagic colitis and complications like haemolytic uraemic syndrome and thrombotic thrombocytopaenic purpura. Escherichia coli is considered a serious public health problem. Water and fish samples were subjected to biochemical tests to confirm the presence of E. coli and by PCR to verify the presence of pathogenic strains (O157, enteropathogenic and shiga toxigenic) in water and fish (skin, gastrointestinal tract and muscles) from pay-to-fish ponds located in the Córrego Rico watershed in the northeastern region of the state of São Paulo, Brazil. Of the 115 E. coli isolates from fish or water, five (4·34%) contained eae and stx2 genes, one had only the eae gene and two had the stx1 gene. An isolate containing the stx2 gene was also found in the water sample. In addition, eight isolates (6·95%) from the fish gastrointestinal tract contained rfbEO157:H7 (O157 gene), and three (2·61%) contained stx2 and eae genes, demonstrating the potential risk to the environment and public health. The results provide useful basic information for the proper management of these environments and animals in order to prevent faecal pollution, reducing health risks to the Brazilian population. SIGNIFICANCE AND IMPACT OF THE STUDY: Pay-to-fish ponds are a common commercial activity in Brazil. Samples of water and Oreochromis niloticus were examined by PCR to detect the presence of pathogenic strains of Escherichia coli (O157, enteropathogenic and shiga toxigenic). Several pathogenic strains were detected in this study, providing useful epidemiological information for the proper management of these environments and animals in order to prevent faecal pollution, reducing health risks to the Brazilian population.

Acute and delayed peripheral and central neuromuscular alterations induced by a short and intense downhill trail run.

Downhill sections are highly strenuous likely contributing to the development of neuromuscular fatigue in trail running. Our purpose was to investigate the consequences of an intense downhill trail run (DTR) on peripheral and central neuromuscular fatigue at knee extensors (KE) and plantar flexors (PF). Twenty-three runners performed a 6.5-km DTR (1264-m altitude drop) as fast as possible. The electromyographic activity of vastus lateralis (VL) and gastrocnemius lateralis (GL) was continuously recorded. Neuromuscular functions were assessed Pre-, Post-, and 2-day Post-DTR (Post2d). Maximal voluntary torques decreased Post (∼ -19% for KE, ∼ -25% for PF) and Post2d (∼ -9% for KE, ∼ -10% for PF). Both central and peripheral dysfunctions were observed. Decreased KE and PF voluntary activation (VA), evoked forces, VL M-wave amplitude, and KE low-frequency fatigue were observed at Post. Changes in VL M-wave amplitude were negatively correlated to VL activity during DTR. Changes in PF twitch force and VA were negatively correlated to GL activity during DTR. The acute KE VA deficit was about a third of that reported after ultramarathons, although peripheral alterations were similar. The prolonged force loss seems to be mainly associated to VA deficit likely induced by the delayed inflammatory response to DTR-induced ultrastructural muscle damage.

RANK/OPG ratio of expression in primary clear-cell renal cell carcinoma is associated with bone metastasis and prognosis in patients treated with anti-VEGFR-TKIs.

BACKGROUND: Bone metastases (BMs) are associated with poor outcome in metastatic clear-cell renal carcinoma (m-ccRCC) treated with anti-vascular endothelial growth factor tyrosine kinase inhibitors (anti-VEGFR-TKIs). We aimed to investigate whether expression in the primary tumour of genes involved in the development of BM is associated with outcome in m-ccRCC patients treated with anti-VEGFR-TKIs. METHODS: Metastatic clear-cell renal cell carcinoma patients with available fresh-frozen tumour and treated with anti-VEGFR-TKIs. Quantitative real-time PCR (qRT-PCR) for receptor activator of NF-kB (RANK), RANK-ligand (RANKL), osteoprotegerin (OPG), the proto-oncogene SRC and DKK1 (Dickkopf WNT signalling pathway inhibitor-1). Time-to-event analysis by Kaplan-Meier estimates and Cox regression. RESULTS: We included 129 m-ccRCC patients treated between 2005 and 2013. An elevated RANK/OPG ratio was associated with shorter median time to metastasis (HR 0.50 (95% CI 0.29-0.87); P=0.014), shorter time to BM (HR 0.54 (95% CI 0.31-0.97); P=0.037), shorter median overall survival (mOS) since initial diagnosis (HR 2.27 (95% CI 1.44-3.60); P=0.0001), shorter median progression-free survival (HR 0.44 (95% CI 0.28-0.71); P=0.001) and mOS (HR 0.31 (95% CI 0.19-0.52); P<0.0001) on first-line anti-VEGFR-TKIs in the metastatic setting. Higher RANK expression was associated with shorter mOS on first-line anti-VEGFR-TKIs (HR 0.46 (95% CI 0.29-0.73); P=0.001). CONCLUSIONS: RANK/OPG ratio of expression in primary ccRCC is associated with BM and prognosis in patients treated with anti-VEGFR-TKIs. Prospective validation is warranted.