Measurable Residual FLT3 Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia.

Importance: Persistence of FLT3 internal tandem duplication (ITD) in adults with acute myeloid leukemia (AML) in first complete remission (CR) prior to allogeneic hematopoietic cell transplant (HCT) is associated with increased relapse and death after transplant, but the association between the level of measurable residual disease (MRD) detected and clinical outcome is unknown. Objective: To examine the association between pre-allogeneic HCT MRD level with relapse and death posttransplant in adults with AML in first CR. Design, Setting, and Participants: In this cohort study, DNA sequencing was performed on first CR blood from patients with FLT3-ITD AML transplanted from March 2013 to February 2019. Clinical follow-up was through May 2022. Data were analyzed from October 2022 to December 2023. Exposure: Centralized DNA sequencing for FLT3-ITD in pre-allogeneic HCT first CR blood using a commercially available kit. Main Outcomes and Measures: The primary outcomes were overall survival and cumulative incidence of relapse, with non-relapse-associated mortality as a competing risk post-allogeneic HCT. Kaplan-Meier estimations (log-rank tests), Cox proportional hazards models, and Fine-Gray models were used to estimate the end points. Results: Of 537 included patients with FLT3-ITD AML from the Pre-MEASURE study, 296 (55.1%) were female, and the median (IQR) age was 55.6 (42.9-64.1) years. Using the variant allele fraction (VAF) threshold of 0.01% or greater for MRD positivity, the results closely aligned with those previously reported. With no VAF threshold applied (VAF greater than 0%), 263 FLT3-ITD variants (median [range] VAF, 0.005% [0.0002%-44%]), and 177 patients (33.0%) with positive findings were identified. Multivariable analyses showed that residual FLT3-ITD was the variable most associated with relapse and overall survival, with a dose-dependent correlation. Patients receiving reduced-intensity conditioning without melphalan or nonmyeloablative conditioning had increased risk of relapse and death at any given level of MRD compared with those receiving reduced-intensity conditioning with melphalan or myeloablative conditioning. Conclusions and Relevance: This study provides generalizable and clinically applicable evidence that the detection of residual FLT3-ITD in the blood of adults in first CR from AML prior to allogeneic HCT is associated with an increased risk of relapse and death, particularly for those with a VAF of 0.01% or greater. While transplant conditioning intensification, an intervention not available to all, may help mitigate some of this risk, alternative approaches will be necessary for this high-risk population of patients who are underserved by the current standard of care.

EXPRESS: Development and validation of a pictographic assessment embodiment scale.

Embodiment is a complex concept related with the subjective perception of an object as it belongs to the own body. In general, this construct has been evaluated by means of questionnaires but validation studies in other cultures and limitations related with barriers of language received little attention. The purpose of the present investigation was twofold: to validate the factorial structure of Embodiment Questionnaire (EQ) and to construct a pictographic scale (PAE) to measure embodiment without relapse verbal representations. In a first experiment, one hundred and thirty-six participants underwent a Rubber Hand Illusion (RHI) procedure following both congruent and incongruent (control) visuo-tactile stimulations. Then, they evaluated embodiment illusion in EQ using a Likert scale to rate their agreement or disagreement with 27 statements and with a pictographic scale designed to assess their subjective experience of the illusion. Principal components analysis in EQ scores identified four components that emerged in both conditions: Embodiment, Disembodiment, Affect and Deafference. PAE scale was highly correlated with embodiment factor and can differentiate between conditions. In a second experiment, thirty participants underwent the RHI procedure, and they were assessed using PAE and proprioceptive drift. Results indicates a high positive correlation between PAE and post-illusion drift score. These results provide evidence about the consistency of the factorial structure of EQ across cultures and we also provide a new pictographic tool that allows quick measurement of embodiment overcoming language barriers.

Pollinator-assisted plant phenotyping, selection, and breeding for crop resilience to abiotic stresses.

Food security is threatened by climate change, with heat and drought being the main stresses affecting crop physiology and ecosystem services, such as plant-pollinator interactions. We hypothesize that tracking and ranking pollinators' preferences for flowers under environmental pressure could be used as a marker of plant quality for agricultural breeding to increase crop stress tolerance. Despite increasing relevance of flowers as the most stress sensitive organs, phenotyping platforms aim at identifying traits of resilience by assessing the plant physiological status through remote sensing-assisted vegetative indexes, but find strong bottlenecks in quantifying flower traits and in accurate genotype-to-phenotype prediction. However, as the transport of photoassimilates from leaves (sources) to flowers (sinks) is reduced in low-resilient plants, flowers are better indicators than leaves of plant well-being. Indeed, the chemical composition and amount of pollen and nectar that flowers produce, which ultimately serve as food resources for pollinators, change in response to environmental cues. Therefore, pollinators' preferences could be used as a measure of functional source-to-sink relationships for breeding decisions. To achieve this challenging goal, we propose to develop a pollinator-assisted phenotyping and selection platform for automated quantification of Genotype × Environment × Pollinator interactions through an insect geo-positioning system. Pollinator-assisted selection can be validated by metabolic, transcriptomic, and ionomic traits, and mapping of candidate genes, linking floral and leaf traits, pollinator preferences, plant resilience, and crop productivity. This radical new approach can change the current paradigm of plant phenotyping and find new paths for crop redomestication and breeding assisted by ecological decisions.

Design of a Stem Cell-Based Therapy for Ependymal Repair in Hydrocephalus Associated With Germinal Matrix Hemorrhages.

BACKGROUND: In preterm birth germinal matrix hemorrhages (GMHs) and the consequent posthemorrhagic hydrocephalus (PHH), the neuroepithelium/ependyma development is disrupted. This work is aimed to explore the possibilities of ependymal repair in GMH/PHH using a combination of neural stem cells, ependymal progenitors (EpPs), and mesenchymal stem cells. METHODS: GMH/PHH was induced in 4-day-old mice using collagenase, blood, or blood serum injections. PHH severity was characterized 2 weeks later using magnetic resonance, immunofluorescence, and protein expression quantification with mass spectrometry. Ependymal restoration and wall regeneration after stem cell treatments were tested in vivo and in an ex vivo experimental approach using ventricular walls from mice developing moderate and severe GMH/PHH. The effect of the GMH environment on EpP differentiation was tested in vitro. Two-tailed Student t or Wilcoxon-Mann-Whitney U test was used to find differences between the treated and nontreated groups. ANOVA and Kruskal-Wallis tests were used to compare >2 groups with post hoc Tukey and Dunn multiple comparison tests, respectively. RESULTS: PHH severity was correlated with the extension of GMH and ependymal disruption (means, 88.22% severe versus 19.4% moderate). GMH/PHH hindered the survival rates of the transplanted neural stem cells/EpPs. New multiciliated ependymal cells could be generated from transplanted neural stem cells and more efficiently from EpPs (15% mean increase). Blood and TNFα (tumor necrosis factor alpha) negatively affected ciliogenesis in cells committed to ependyma differentiation (expressing Foxj1 [forkhead box J1] transcription factor). Pretreatment with mesenchymal stem cells improved the survival rates of EpPs and ependymal differentiation while reducing the edematous (means, 18% to 0.5% decrease in severe edema) and inflammatory conditions in the explants. The effectiveness of this therapeutical strategy was corroborated in vivo (means, 29% to 0% in severe edema). CONCLUSIONS: In GMH/PHH, the ependyma can be restored and edema decreased from either neural stem cell or EpP transplantation in vitro and in vivo. Mesenchymal stem cell pretreatment improved the success of the ependymal restoration.

A selective defect in the glial wedge as part of the neuroepithelium disruption in hydrocephalus development in the mouse hyh model is associated with complete corpus callosum dysgenesis.

Introduction: Dysgenesis of the corpus callosum is present in neurodevelopmental disorders and coexists with hydrocephalus in several human congenital syndromes. The mechanisms that underlie the etiology of congenital hydrocephalus and agenesis of the corpus callosum when they coappear during neurodevelopment persist unclear. In this work, the mechanistic relationship between both disorders is investigated in the hyh mouse model for congenital hydrocephalus, which also develops agenesis of the corpus callosum. In this model, hydrocephalus is generated by a defective program in the development of neuroepithelium during its differentiation into radial glial cells. Methods: In this work, the populations implicated in the development of the corpus callosum (callosal neurons, pioneering axons, glial wedge cells, subcallosal sling and indusium griseum glial cells) were studied in wild-type and hyh mutant mice. Immunohistochemistry, mRNA in situ hybridization, axonal tracing experiments, and organotypic cultures from normal and hyh mouse embryos were used. Results: Our results show that the defective program in the neuroepithelium/radial glial cell development in the hyh mutant mouse selectively affects the glial wedge cells. The glial wedge cells are necessary to guide the pioneering axons as they approach the corticoseptal boundary. Our results show that the pioneering callosal axons arising from neurons in the cingulate cortex can extend projections to the interhemispheric midline in normal and hyh mice. However, pioneering axons in the hyh mutant mouse, when approaching the area corresponding to the damaged glial wedge cell population, turned toward the ipsilateral lateral ventricle. This defect occurred before the appearance of ventriculomegaly. Discussion: In conclusion, the abnormal development of the ventricular zone, which appears to be inherent to the etiology of several forms of congenital hydrocephalus, can explain, in some cases, the common association between hydrocephalus and corpus callosum dysgenesis. These results imply that further studies may be needed to understand the corpus callosum dysgenesis etiology when it concurs with hydrocephalus.

Prevalence, Risk Factors, and Relationship between Reproductive Performance and the Presence of Antibodies against Coxiellosis in Dairy Farm Milk Tanks in the Northwest of Spain.

Q fever is a zoonotic disease that has been associated with reproductive problems in animals. As there is little epidemiological data regarding the distribution and risk factors of this disorder in cattle, the objective of this study was to evaluate the prevalence of Coxiella burnetii among dairy herds in the northwest of Spain, and to determine the on-farm risk factors associated with the disease and its effects on reproductive performance. Bulk tank milk (BTM) samples were collected from 262 commercial dairy herds from A Coruña, Lugo, and Pontevedra provinces. Data about location, mean age, and herd management features were obtained. A commercial indirect ELISA kit was used to determine the presence of antibodies against C. burnetii in BTM samples. The relationship between seropositivity to C. burnetii and the risk factors was checked using a Pearson's χ2 test and a classification tree analysis. In addition, a one-way ANOVA test and the Mann-Whitney U test were used to check the impact of seropositivity to C. burnetii on reproductive performance. A total of 60.1% of the farms tested positive for coxiellosis, the herd size, the external purchase of livestock, and the geographical area were identified as the main risk factors. Conception rate and first-service conception rate were significantly lower (p < 0.05) in positive farms (37.1 and 32.9%) compared to negative farms (39.8 and 36.1%). Similarly, positive farms had significant higher incidence of endometritis (13.7% vs. 11.2%, p < 0.05). Consequently, a high seropositivity and slightly negative effects of coxiellosis on reproductive performance were observed, which intensifies the need for further research, including the identification an active infection in positive herds and the characterization of the genotype.

Acoustic Characterization Study of Beef Loins Using Ultrasonic Transducers.

The objective of this study was to non-destructively characterize samples of fresh beef loin by low-intensity ultrasound inspection at various frequencies and to correlate the acoustic parameters of these inspections with quality parameters. In this regard, ultrasonic parameters such as ultrasound pulse velocity (UPV) and variables related to attenuation and frequency components obtained from fast Fourier transform (FFT) were considered. For this, pulsed ultrasonic signal transducers with a frequency of 0.5 and 1.0 MHz were used. Acoustic parameters and those obtained through traditional instrumental analyses (physicochemical and texture) underwent a Pearson correlation analysis. The acoustic determinations revealed numerous significant correlations with the rest of the studied parameters. The results demonstrate that ultrasonic inspection has the ability to characterize samples with a non-destructive nature, and likewise, this methodology can be postulated as a promising predictive tool for determining quality parameters in beef loin samples.

Comparison of automated subcutaneous defibrillator screening between different pacing sites in cardiac pacing device carriers.

AIMS: The compatibility of cardiac pacing with the presence of a subcutaneous implantable cardioverter-defibrillator (S-ICD) has been investigated, but S-ICD screening test results have not been compared among different pacing sites. The objective was to compare S-ICD screening results among different cardiac pacing sites and to assess the electrocardiographic predictors of success. METHODS AND RESULTS: This prospective single-centre study conducted automated S-ICD screening in 102 carriers of cardiac pacing devices in conduction system (CSP), biventricular (BVP), right ventricular outflow tract (RVOT), or right ventricular apex (RVA) pacing sites. The study included 102 patients: 40 with CSP (20 left bundle pacing and 20 His bundle pacing), 21 with BVP, and 20 and 21 with RVOT and RVA pacing, respectively. The percentage of positive screenings was significantly higher for CSP (97.5%) than for the other patient groups (BVP 71.4%, RVOT 70%, and RVA 19%). In multivariate analysis, positive screening was associated with a narrower QRS (OR 0.95 [0.92-0.98] P = 0.001) and higher R/T ratio in precordial leads (1.76 [1.18-2.61]). CONCLUSION: A higher S-ICD eligibility rate of cardiac pacing device carriers was obtained in CSP than in conventional pacing (RVA or RVOT) or BVP. The presence of narrower paced QRS width and paced corrected QT interval and of higher R/T ratio in precordial and limb leads are electrocardiographic predictors of a positive response to screening.

Prevalencia, hábitos de consumo y complicaciones de los suplementos nutricionales proteicos en adolescentes / Protein supplement consumption prevalence, habits and complications in adolescents

Introducción: El consumo de suplementos nutricionales y proteicos por adolescentes puede tener importantes repercusiones para su salud. Material y método: Estudio prospectivo observacional, basado en una encuesta, dirigido a los adolescentes de seis colegios, seleccionados aleatoriamente, de la ciudad de Sevilla. Nuestro objetivo principal es conocer el consumo real de suplementos alimentarios entre la población adolescente, cuantificando su contenido proteico. Resultados: Se obtuvieron 263 respuestas válidas, objetivando una prevalencia de consumo de 19,01% para todos los suplementos nutricionales, de ellos 56,0% tomaban suplementos de proteínas (10,64% del total), con una ingesta media de estas últimas de 0,26±0,18 g/kg/día. El perfil del consumidor de cualquier tipo de suplementos se diferencia del de los que no los utilizan en la edad, el uso de medicación habitual y realizar dieta para perder peso o hiperproteica. Al comparar los adolescentes que ingerían productos proteicos con los no proteicos, la única variación significativa estuvo en el control del consumo. Aunque la mayoría no tiene control externo, en 25,92% de los que tomaban proteínas el seguimiento lo hacía un profesional, vs. 7,38% de los que ingerían suplementos no proteicos. De los consumidores de productos proteicos, 85,18% consiguió el objetivo buscado y 18,51% refirió algún efecto negativo. Conclusiones: La prevalencia de consumo de suplementos proteicos entre los adolescentes de nuestro medio es del 10,64%, en cantidades que suponen un 25% de las proteínas que deben ingerir diariamente. El perfil de consumidor de suplementos proteicos es muy similar al de aquel que toma productos no proteicos. (AU)

Introduction: The consumption of nutritional and protein supplements by adolescents may have important consequences for their health. Material and methods: Prospective observational study based on a survey of adolescents enrolled in six schools selected at random in the city of Seville. Our primary objective was to determine the actual consumption of dietary supplements in the adolescent population and quantifying their protein content. Results: We obtained a total of 263 valid responses that showed a prevalence of consumption of nutritional supplements of any kind of 19.01%, of which 56.0% (10.64% of the total) corresponded to adolescents that consumed protein supplements for a mean protein intake of 0.26 g/kg/day (SD, 0.18). The profile of consumers of any type of supplements differed from that of nonconsumers in age, use of long-term medication and weight loss or high-protein diets. The comparison of adolescents who consumed protein supplements versus nonprotein supplements only evinced a significant difference in the control of supplement consumption. Although most of these adolescents were not subject to external control, 25.92% of those who consumed protein supplements were monitored by a professional, compared to 7.38% of consumers of nonprotein supplements. In the group that consumed protein supplements, 85.18% of adolescents achieved the desired effect and 18.51% reported some form of negative effect. Conclusions: The prevalence of protein supplement consumption among adolescents in our area is 10.64%, with consumption of amounts corresponding to 25% of the recommended daily allowance of protein. The profile of protein supplement consumers is very similar to that of nonprotein supplement consumers. (AU)

Protein supplement consumption prevalence, habits and complications in adolescents.

INTRODUCTION: The consumption of nutritional and protein supplements by adolescents may have important consequences for their health. METHODS: Prospective observational study based on a survey of adolescents enrolled in 6 schools selected at random in the city of Seville. Our primary objective was to determine the actual consumption of dietary supplements in the adolescent population and quantifying their protein content. RESULTS: We obtained a total of 263 valid responses that showed a prevalence of consumption of nutritional supplements of any kind of 19.01%, of which 56.0% (10.64% of the total) corresponded to adolescents that consumed protein supplements for a mean protein intake of 0.26 g/kg/day (SD, 0.18). The profile of consumers of any type of supplements differed from that of nonconsumers in age, use of long-term medication and weight loss or high-protein diets. The comparison of adolescents who consumed protein supplements versus nonprotein supplements only evinced a significant difference in the control of supplement consumption. Although most of these adolescents were not subject to external control, 25.92% of those who consumed protein supplements were monitored by a professional, compared to 7.38% of consumers of nonprotein supplements. In the group that consumed protein supplements, 85.18% of adolescents achieved the desired effect and 18.51% reported some form of negative effect. CONCLUSIONS: The prevalence of protein supplement consumption among adolescents in our area is 10.64%, with consumption of amounts corresponding to 25% of the recommended daily allowance of protein. The profile of protein supplement consumers is very similar to that of nonprotein supplement consumers.

Information manipulation and historical revisionism: Russian disinformation and foreign interference through manipulated history-based narratives.

Background: Disinformation and historical revisionism have been acknowledged as tools for foreign interference that belong to the landscape of hybrid threats. Historical revisionism plays an essential role in Russian foreign policy towards the post-Soviet space and is in strong relation with the concepts of Near Abroad and Russkii Mir ('Russian World') and with certain ideas contained in the neo-Eurasianist Movement. This article examines Russian revisionist narratives disseminated in information and influencing campaigns in Europe and against the West.       Methods: This study uses a mixed methodology combining desk research, including literature review, and analysis of the EUvsDisinfo database of cases identified before the February 2022 invasion of Ukraine. R esults: The manipulation of historical events has been largely employed by the Kremlin as a tool for foreign interference to achieve strategic objectives. First World War treaties, mainly the Trianon Peace Treaty, as well as the Second World War and the communist and fascist historical experiences in countries within the post-Soviet space, are the pivotal topics from which hostile influencing narratives are built. From the analysis of the EUvsDisinfo database, the article identifies seven topic themes.       Conclusions:  Our findings suggest that pre-emptively elaborated counter-narratives based on historical evidence and sound historiography can be an effective tool against hostile revisionist narratives that exploit vulnerabilities and specific target groups within European societies.

A database with frailty, functional and inertial gait metrics for the research of fall causes in older adults.

The GSTRIDE database contains information of the health status assessment of 163 elderly adults. We provide socio-demographic data, functional and frailty variables, and the outcomes from tests commonly performed for the evaluation of elder people. The database contains gait parameters estimated from the measurements of an Inertial Measurement Unit (IMU) placed on the foot of volunteers. These parameters include the total walking distance, the number of strides and multiple spatio-temporal gait parameters, such as stride length, stride time, speed, foot angles and clearance, among others. The main processed database is stored, apart from MS Excel, in CSV format to ensure their usability. The database is complemented with the raw IMU recordings in TXT format, in order to let researchers test other algorithms of gait analysis. We include the Python programming codes as a base to reproduce or modify them. The database stores data to study the frailty-related parameters that distinguish faller and non-faller populations, and analyze the gait-related parameters in the frail subjects, which are essential topics for the elderly.

Measurable Residual IDH1 before Allogeneic Transplant for Acute Myeloid Leukemia.

Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. The persistence of mutated NPM1 or FLT3-ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoetic cell transplant (alloHCT) has been established as associated with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as IDH1, at this treatment landmark however remains incompletely defined. We performed testing for residual IDH1 variants (IDH1m) in pre-transplant CR1 blood of 148 adult patients undergoing alloHCT for IDH1-mutated AML at a CIBMTR site between 2013-2019. No post-transplant differences were observed between those testing IDH1m positive (n=53, 36%) and negative pre-transplant (overall survival: p = 0.4; relapse: p = 0.5). For patients with IDH1 mutated AML co-mutated with NPM1 and/or FLT3-ITD, only detection of persistent mutated NPM1 and/or FLT3-ITD was associated with significantly higher rates of relapse (p = 0.01). These data, from the largest study to date, do not support the detection of IDH1 mutation in CR1 blood prior to alloHCT as evidence of AML MRD or increased post-transplant relapse risk.

Effects of endozoochory and diploendozoochory by captive wild mammals on Juniperus deppeana seeds.

Carnivorous mammals disperse seeds through endozoochory and diploendozoochory. The former consists of ingestion of the fruit, passage through the digestive tract, and expulsion of the seeds, a process that allows scarification and dispersal of the seeds over long or short distances. The latter is typical of predators that expel seeds that were contained in the prey and the effects of which may differ from those of endozoochory with respect to the retention time of the seeds in the tracts, as well as their scarification and viability. The objective of this study was to conduct an experimental evaluation comparing the capacity of each mammal species in terms of the dispersal of Juniperus deppeana seeds and, at the same time, to compare this capacity through the two dispersal systems: endozoochory and diploendozoochory. We measured dispersal capacity using indices of recovery, viability, changes in testas, and retention time of seeds in the digestive tract. Juniperus deppeana fruits were collected in the Sierra Fría Protected Natural Area in Aguascalientes, Mexico, and were administered in the diet of captive mammals: gray fox (Urocyon cinereoargenteus), coati (Nasua narica) and domestic rabbits (Oryctolagus cuniculus). These three mammals represented the endozoochoric dispersers. For the diploendozoochoric treatment, seeds excreted by rabbits were incorporated into the diets of captive mammals: bobcat (Lynx rufus) and cougar (Puma concolor), in a local zoo. Seeds present in the scats were then collected, and recovery rates and retention times were estimated. Viability was estimated by X-ray optical densitometry and testa thicknesses were measured and surfaces checked using scanning electron microscopy. The results showed a recovery of seeds greater than 70% in all the animals. The retention time was <24 h in the endozoochory but longer at 24-96 h in the diploendozoochory (p < .05). Seed viability (x¯ ± SD) was decreased in rabbits (74.0 ± 11.5%), compared to fruits obtained directly from the canopy (89.7 ± 2.0%), while gray fox, coati, bobcat, and cougar did not affect seed viability (p < .05). An increase in the thickness of the testas was also observed in seeds excreted from all mammals (p < .05). Through evaluation, our results suggest that mammalian endozoochory and diploendozoochory contribute to the dispersal of J. deppeana by maintaining viable seeds with adaptive characteristics in the testa to promote forest regeneration and restoration. In particular, feline predators can provide an ecosystem service through scarification and seed dispersal.

Therapeutic strategies to recover ependymal barrier after inflammatory damage: relevance for recovering neurogenesis during development.

The epithelium covering the surfaces of the cerebral ventricular system is known as the ependyma, and is essential for maintaining the physical and functional integrity of the central nervous system. Additionally, the ependyma plays an essential role in neurogenesis, neuroinflammatory modulation and neurodegenerative diseases. Ependyma barrier is severely affected by perinatal hemorrhages and infections that cross the blood brain barrier. The recovery and regeneration of ependyma after damage are key to stabilizing neuroinflammatory and neurodegenerative processes that are critical during early postnatal ages. Unfortunately, there are no effective therapies to regenerate this tissue in human patients. Here, the roles of the ependymal barrier in the context of neurogenesis and homeostasis are reviewed, and future research lines for development of actual therapeutic strategies are discussed.