Podophyllic Aldehyde, a Podophyllotoxin Derivate, Elicits Different Cell Cycle Profiles Depending on the Tumor Cell Line: A Systematic Proteomic Analysis.

When new antitumor therapy drugs are discovered, it is essential to address new target molecules from the point of view of chemical structure and to carry out efficient and systematic evaluation. In the case of natural products and derived compounds, it is of special importance to investigate chemomodulation to further explore antitumoral pharmacological activities. In this work, the compound podophyllic aldehyde, a cyclolignan derived from the chemomodulation of the natural product podophyllotoxin, has been evaluated for its viability, influence on the cell cycle, and effects on intracellular signaling. We used functional proteomics characterization for the evaluation. Compared with the FDA-approved drug etoposide (another podophyllotoxin derivative), we found interesting results regarding the cytotoxicity of podophyllic aldehyde. In addition, we were able to observe the effect of mitotic arrest in the treated cells. The use of podophyllic aldehyde resulted in increased cytotoxicity in solid tumor cell lines, compared to etoposide, and blocked the cycle more successfully than etoposide. High-throughput analysis of the deregulated proteins revealed a selective antimitotic mechanism of action of podophyllic aldehyde in the HT-29 cell line, in contrast with other solid and hematological tumor lines. Also, the apoptotic profile of podophyllic aldehyde was deciphered. The cell death mechanism is activated independently of the cell cycle profile. The results of these targeted analyses have also shown a significant response to the signaling of kinases, key proteins involved in signaling cascades for cell proliferation or metastasis. Thanks to this comprehensive analysis of podophyllic aldehyde, remarkable cytotoxic, antimitotic, and other antitumoral features have been discovered that will repurpose this compound for further chemical transformations and antitumoral analysis.

The relationship between object-based spatial ability and virtual navigation performance.

Spatial navigation is a multi-faceted behaviour drawing on many different aspects of cognition. Visuospatial abilities, such as mental rotation and visuospatial working memory, in particular, may be key factors. A range of tests have been developed to assess visuospatial processing and memory, but how such tests relate to navigation ability remains unclear. This understanding is important to advance tests of navigation for disease monitoring in various disorders (e.g., Alzheimer's disease) where spatial impairment is an early symptom. Here, we report the use of an established mobile gaming app, Sea Hero Quest (SHQ), as a measure of navigation ability in a sample of young, predominantly female university students (N = 78; 20; female = 74.3%; mean age = 20.33 years). We used three separate tests of navigation embedded in SHQ: wayfinding, path integration and spatial memory in a radial arm maze. In the same participants, we also collected measures of mental rotation (Mental Rotation Test), visuospatial processing (Design Organization Test) and visuospatial working memory (Digital Corsi). We found few strong correlations across our measures. Being good at wayfinding in a virtual navigation test does not mean an individual will also be good at path integration, have a superior memory in a radial arm maze, or rate themself as having a strong sense of direction. However, we observed that participants who were good in the wayfinding task of SHQ tended to perform well on the three visuospatial tasks examined here, and to also use a landmark strategy in the radial maze task. These findings help clarify the associations between different abilities involved in spatial navigation.

Social and temporal disorientation during the Covid-19 pandemic: An analysis of 3306 responses to a quantitative questionnaire.

The societal hallmark of the Covid-19 pandemic was a set of mitigation measures such as lockdowns and curfews. The cognitive impact on the public of the resulting spatial, social and temporal constraints is still being investigated. While pandemic time has been extensively studied and mostly described as slowed down and elongated, opposite experimental patterns across national and social contexts leave open an important explanatory gap in order to understand which factor has been causally fundamental in determining the phenomenology of the crisis. In this paper, we use a quantitative questionnaire developed for measuring temporal and social disorientation on a sample of 3306 respondents during an acute phase of restrictions in France. We show that social disorientation greatly contributed to the temporal disruptions experienced during the pandemic. This result reinforces the importance for public authorities to address the compounding effect of feeling isolated during crises.

Spanish registry of hemoglobinopathies and rare anemias (REHem-AR): demographics, complications, and management of patients with ß-thalassemia.

INTRODUCTION: The increase in the number of patients with hemoglobinopathies in Europe in recent decades highlights the need for more detailed epidemiological information in Spain. To fulfil this need, the Spanish Society of Pediatric Hematology and Oncology (SEHOP) sponsored the creation of a national registry of hemoglobinopathies known as REHem-AR (Spanish Registry of Hemoglobinopathies and Rare Anemias). Data from the transfusion-dependent (TDT) and non-transfusion-dependent (NTDT) ß-thalassemia cohorts are described and analyzed. METHODS: We performed an observational, multicenter, and ambispective study, which included patients of any age with TDT and NTDT, registered up to December 31, 2021. RESULTS: Among the 1741 patients included, 168 cases of thalassemia were identified (103 TDT and 65 NTDT-patients). Survival at 18 years was 93% for TDT and 100% for NTDT. Regarding management, 80 patients with TDT (77.7%) and 23 patients with NTDT (35.4%) started chelation treatment during follow-up, with deferasirox being the most widely used. A total of 76 patients within the TDT cohort presented at least 1 complication (73.8%), the most frequent being hemosiderosis and osteopenia-osteoporosis. Comparison of both cohorts revealed significant differences in the diagnosis of hepatic hemosiderosis (p = 0.00024), although these were not observed in the case of cardiac iron overload (p = 0.27). DISCUSSION: Our registry enabled us to describe the management of ß thalassemia in Spain and to analyze the morbidity and mortality of the cohorts of patients with TDT and NTDT. Complications related to iron overload in TDT and NTDT account for most of the morbidity and mortality of the disease, which is associated with a considerable social, psychological, and economic impact, although cardiac, osteopathy and endocrinological complications requiring more attention. The convenience and simplicity of online registries make it possible to homogenize variables and periodically update data, thus providing valuable information on these diseases.

Clinical Evaluation of an Artificial Intelligence-Based Decision Support System for the Diagnosis and American College of Radiology Thyroid Imaging Reporting and Data System Classification of Thyroid Nodules.

Background: This study aimed to evaluate the clinical impact of an artificial intelligence (AI)-based decision support system (DSS), Koios DS, on the analysis of ultrasound imaging and suspicious characteristics for thyroid nodule risk stratification. Methods: A retrospective ultrasound study was conducted on all thyroid nodules with histological findings from June 2021 to December 2022 in a thyroid nodule clinic. The diagnostic performance of ultrasound imaging was evaluated by six readers on the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) before and after the use of the AI-based DSS and by AI itself. Results: A total of 172 patients (83.1% women) with a mean age of 52.3 ± 15.3 years were evaluated. The mean maximum nodular diameter was 2.9 ± 1.2 cm, with 11.0% being differentiated thyroid carcinomas. Among the nodules initially classified as ACR TI-RADS 3 and 4, AI reclassified 81.4% and 24.5% into lower risk categories, respectively. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the readers and the AI-based DSS versus histological diagnosis. There was an increase in the area under the ROC curve (AUROC) after the use of AI (0.776 vs. 0.817, p < 0.001). The AI-based DSS improved the mean sensitivity (Sens) (82.3% vs. 86.5%) and specificity (Spe) (38.3% vs. 54.8%), produced a high negative predictive value (94.5% vs. 96.4%), and increased the positive predictive value (PPV) (14.0% vs. 16.1%) and diagnostic precision (43.0% vs. 49.3%). Based on the ACR TI-RADS score, there was significant improvement in interobserver agreement after the use of AI (r = 0.741 for ultrasound imaging alone vs. 0.981 for ultrasound imaging and the AI-based DSS, p < 0.001). Conclusions: The use of an AI-based DSS was associated with overall improvement in the diagnostic efficacy of ultrasound imaging, based on the AUROC, as well as an increase in Sens, Spe, negative and PPVs, and diagnostic accuracy. There was also a reduction in interobserver variability and an increase in the degree of concordance with the use of AI. AI reclassified more than half of the nodules with intermediate ACR TI-RADS scores into lower risk categories.

Chromosomal instability in aneuploid acute lymphoblastic leukemia associates with disease progression.

Chromosomal instability (CIN) lies at the core of cancer development leading to aneuploidy, chromosomal copy-number heterogeneity (chr-CNH) and ultimately, unfavorable clinical outcomes. Despite its ubiquity in cancer, the presence of CIN in childhood B-cell acute lymphoblastic leukemia (cB-ALL), the most frequent pediatric cancer showing high frequencies of aneuploidy, remains unknown. Here, we elucidate the presence of CIN in aneuploid cB-ALL subtypes using single-cell whole-genome sequencing of primary cB-ALL samples and by generating and functionally characterizing patient-derived xenograft models (cB-ALL-PDX). We report higher rates of CIN across aneuploid than in euploid cB-ALL that strongly correlate with intraclonal chr-CNH and overall survival in mice. This association was further supported by in silico mathematical modeling. Moreover, mass-spectrometry analyses of cB-ALL-PDX revealed a "CIN signature" enriched in mitotic-spindle regulatory pathways, which was confirmed by RNA-sequencing of a large cohort of cB-ALL samples. The link between the presence of CIN in aneuploid cB-ALL and disease progression opens new possibilities for patient stratification and offers a promising new avenue as a therapeutic target in cB-ALL treatment.

Functional proteomics based on protein microarray technology for biomedical research.

This chapter traces a route through Proteomics from its origins to the present day. The different proteomics applications are discussed with a focus on microarray technology. Analytical microarrays, functional microarrays and reverse phase microarrays and their different applications are discussed. Several studies are mentioned where the great versatility of this approach is shown. Finally, the advantages and future challenges of microarray technology are outlined.

Metacognitive Feelings: A Predictive-Processing Perspective.

Metacognitive feelings are affective experiences that concern the subject's mental processes and capacities. Paradigmatic examples include the feeling of familiarity, the feeling of confidence, or the tip-of-the-tongue experience. In this article, we advance an account of metacognitive feelings based on the predictive-processing framework. The core tenet of predictive processing is that the brain is a hierarchical hypothesis-testing mechanism, predicting sensory input on the basis of prior experience and updating predictions on the basis of the incoming prediction error. According to the proposed account, metacognitive feelings arise out of a process in which visceral changes serve as cues to predict the error dynamics relating to a particular mental process. The expected rate of prediction-error reduction corresponds to the valence at the core of the emerging metacognitive feeling. Metacognitive feelings use prediction dynamics to model the agent's situation in a way that is both descriptive and directive. Thus, metacognitive feelings are not only an appraisal of ongoing cognitive performance but also a set of action policies. These action policies span predictive trajectories across bodily action, mental action, and interoceptive changes, which together transform the epistemic landscape within which metacognitive feelings unfold.

Wayfinding across ocean and tundra: what traditional cultures teach us about navigation.

Research on human navigation by psychologists and neuroscientists has come mainly from a limited range of environments and participants inhabiting western countries. By contrast, numerous anthropological accounts illustrate the diverse ways in which cultures adapt to their surrounding environment to navigate. Here, we provide an overview of these studies and relate them to cognitive science research. The diversity of cues in traditional navigation is much higher and multimodal compared with navigation experiments in the laboratory. It typically involves an integrated system of methods, drawing on a detailed understanding of the environmental cues, specific tools, and forms part of a broader cultural system. We highlight recent methodological developments for measuring navigation skill and modelling behaviour that will aid future research into how culture and environment shape human navigation.

Do electric bicycles cause an increased injury risk compared to conventional bicycles? The potential impact of data visualisations and corresponding conclusions.

The increasing number of bicycle crashes leading to injuries in the Netherlands is frequently related (e.g., in the media) to increased use of the electric bicycle. For this reason, policy makers face the challenge of selecting and implementing the most promising countermeasures including those focused on electric bicycles. It may be questioned, however, to what extent the electric bicycle itself is a (direct) cause of crashes leading to injuries or whether other factors are important for explaining the increased number of bicycle injury crashes. On the basis of an abbreviated list of criteria by Elvik (2011), this paper illustrates the potential influence of factor inclusions, analysis selections, and data presentations on the general impression about crash causation with the electric bicycle as an example. The aim is to provide a 'best practice guide' by taking into account (1) a theoretical explanation of causal mechanisms, (2) control for confounders, and (3) a statistical association of sufficient strength and consistency in the expected direction. We conclude that an apparent increased risk of electric bicycles may be explained by factors such as age, exposure, health factors, and gender of the cyclist. A relatively simple analysis, by comparing fatality numbers of conventional and electric bicycles, showed that including or excluding these factors may lead to vastly different interpretations of fatality causes and the relative risk of electric bicycles compared to conventional bicycles.

The relationship between cycle track width and the lateral position of cyclists, and implications for the required cycle track width.

INTRODUCTION: Sufficient cycle track width is important to prevent single-bicycle crashes and collisions between cyclists. The assumptions on which the minimum width is based in guidelines is founded on only a few studies. The aim of the present study is to investigate the relationship between cycle track width and lateral position of cyclists. METHOD: We conducted an experiment to evaluate the lateral position of cyclists along cycle tracks with different widths (Study 1). Participants cycled on an instrumented bicycle with a LIDAR to measure their lateral position. Five conditions were defined: cycle track width of 100 cm, 150 cm and 200 cm without interaction, and cycle track width of 150 cm and 200 cm with an oncoming cyclist simulated by a parked bicycle. The cross-sectional Study 2 is based on the collected lateral position measurements at cycle tracks with varying width reported in Dutch studies since 2010. RESULTS: The experimental Study 1 with 24 participants shows that an increase in cycle track width causes cyclists to ride further away from the verge and keep more distance from an oncoming cyclist. The cross-sectional Study 2 was based on lateral position measured at 33 real-life Dutch cycle tracks. Study 2 yielded similar results, indicating that doubling pavement width increases lateral position by some 50%. Study 2 shows that, compared with a solo cyclist without interaction, a right-hand cyclist of a duo and a cyclist meeting an oncoming cyclist ride around 30% closer to the verge. CONCLUSIONS: The wider the cycle track, the more distance cyclists maintain from the verge. Cyclists ride closer to the verge due to oncoming cyclists. PRACTICAL APPLICATIONS: Given a cyclists' lateral position while meeting, common variations between cyclists' steering behavior, and vehicle width and circumstances, a cycle track width of 250 cm is needed for safe meeting maneuvers.

Unveiling plant defense arsenal: metabolic strategies in Brassica oleracea during black rot disease.

Alterations in plant metabolism play a key role in the complex plant-pathogen interactions. However, there is still a lack of knowledge about the connection between changes in primary and specialized metabolism and the plant defense against diseases that impact crops. Thus, we aim to study the metabolic reprograming in Brassica oleracea plants upon infection by Xanthomonas campestris pv. campestris (Xcc). To accomplish this, we utilized a combination of untargeted and targeted metabolomics, through UPLC-Q-TOF-MS/MS and 1H-NMR, in two crop lines differing in resistance that were evaluated at two- and four-week intervals following inoculation (T1 and T2, respectively). Besides, to depict the physiological status of the plant during infection, enzymatic activities related to the carbohydrate pathway and oxidative stress were studied. Our results revealed different temporal dynamics in the responses of the susceptible vs. resistant crops lines. Resistant B. oleracea line suppresses carbohydrate metabolism contributing to limit nutrient supplies to the bacterium and prioritizes the induction of defensive compounds such as indolic glucosinolates, salicylic acid, phenylpropanoids and phytoalexins precursors at early infection stages. In contrast, the susceptible line invests in carbohydrate metabolism, including enzymatic activities related to the hexoses turnover, and activates defense signaling related to reactive oxygen species. Thus, each line triggers a different metabolic strategy that will affect how the plant overcomes the disease in terms of resistance and growth. This work provides first insights of a fine-tuned metabolic regulation during Xcc infection in B. oleracea that will contribute to develop new strategies for plant disease management.

Systemic biochemical changes in pepper (Capsicum annuum L.) against Rhizoctonia solani by kale (Brassica oleracea var. acephala L.) green manure application.

BACKGROUND: In the search for new alternatives to avoid the problems associated with the use of synthetic chemical fungicides in agriculture, the use of green manure (GrM) could help combat fungal diseases of crops, such as those produced by the necrotrophic pathogen Rhizoctonia solani. In the case of the use of Brassica tissues as GrM, it could have an elicitor capacity for systemic plant resistance. RESULTS: We used kale leaves as a GrM and applied it to pepper plants infected with R. solani. The application of freeze-dried kale tissues to the roots of pepper plants produced a systemic activation of foliar defences via the salicylic acid (SA) and ethylene (ET) pathways, significantly reducing pathogen damage. In addition, this systemic response led to the accumulation of secondary defence metabolites, such as pipecolic acid, hydroxycoumarin and gluconic acid, in leaves. Remarkably, pepper plants treated with lyophilised kale GrM accumulated glucosinolates when infected with R. solani. We also confirmed that autoclaving removed part of the glucobrassicin (85%) and sinigrin (19%) content of the kale tissues. CONCLUSIONS: GrM kale tissues can activate systemic defences in bell pepper against foliar pathogens through SA/ET hormonal pathways, accumulating secondary defence metabolites.

The relapsed acute lymphoblastic leukemia network (ReALLNet): a multidisciplinary project from the spanish society of pediatric hematology and oncology (SEHOP).

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, with survival rates exceeding 85%. However, 15% of patients will relapse; consequently, their survival rates decrease to below 50%. Therefore, several research and innovation studies are focusing on pediatric relapsed or refractory ALL (R/R ALL). Driven by this context and following the European strategic plan to implement precision medicine equitably, the Relapsed ALL Network (ReALLNet) was launched under the umbrella of SEHOP in 2021, aiming to connect bedside patient care with expert groups in R/R ALL in an interdisciplinary and multicentric network. To achieve this objective, a board consisting of experts in diagnosis, management, preclinical research, and clinical trials has been established. The requirements of treatment centers have been evaluated, and the available oncogenomic and functional study resources have been assessed and organized. A shipping platform has been developed to process samples requiring study derivation, and an integrated diagnostic committee has been established to report results. These biological data, as well as patient outcomes, are collected in a national registry. Additionally, samples from all patients are stored in a biobank. This comprehensive repository of data and samples is expected to foster an environment where preclinical researchers and data scientists can seek to meet the complex needs of this challenging population. This proof of concept aims to demonstrate that a network-based organization, such as that embodied by ReALLNet, provides the ideal niche for the equitable and efficient implementation of "what's next" in the management of children with R/R ALL.

Impact of glucose variability on the assessment of the glycemia risk index (GRI) and classic glycemic metrics.

OBJECTIVE: To evaluate the impact of glucose variability on the relationship between the GRI and other glycemic metrics in a cohort of pediatric and adult patients with type 1 diabetes (T1D) using intermittent scanning continuous glucose monitoring (isCGM). METHODS: We performed a cross-sectional study of 202 patients with T1D under intensive insulin treatment (25.2% CSII) using isCGM. Clinical, metabolic, and glycemic metrics were collected, and the GRI was calculated with its hypoglycemia (CHypo) and hyperglycemia (CHyper) components. The correlation between the GRI and other classical glycometrics in relation to the coefficient of variation (CV) was evaluated. RESULTS: A total of 202 patients were included (53% male; 67.8% adults) with a mean age of 28.6 ± 15.7 years and 12.5 ± 10.9 years of T1D evolution (TIR 59.0 ± 17.0%; CV 39.8 ± 8.0%; GMI 7.3 ± 1.1%). The mean GRI was 54.0 ± 23.3 with a CHypo and CHyper component of 5.7 ± 4.8 and 23.4 ± 14.3, respectively. A strong negative correlation was observed between the GRI and TIR (R = -0.917; R2 = 0.840; p < 0.001), showing differences when dividing patients with low glycemic variability (CV < 36%) (R = -0.974; R2 = 0.948; p < 0.001) compared to those with greater CV instability (≥36%) (R = -0.885; R2 = 0.784; p < 0.001). The relationship of GRI with its two components was strongly positive with CHyper (R = 0.801; R2 = 0.641; p < 0.001) and moderately positive with CHypo (R = 0.398; R2 = 0.158; p < 0.001). When the GRI was evaluated with the rest of the classic glycemic metrics, a strong positive correlation was observed with HbA1c (R = 0.617; R2 = 0.380; p < 0.001), mean glucose (R = 0.677; R2 = 0.458; p < 0.001), glucose standard deviation (R = 0.778; R2 = 0.605; p < 0.001), TAR > 250 (R = 0.801; R2 = 0.641; p < 0.001), and TBR < 54 (R = 0.481; R2 = 0.231; p < 0.001). CONCLUSIONS: The GRI correlated significantly with all the glycemic metrics analyzed, especially with the TIR. Glycemic variability (GV) significantly affected the correlation of the GRI with other parameters and should be taken into consideration.

Enhancement of Tumor Cell Immunogenicity and Antitumor Properties Derived from Platinum-Conjugated Iron Nanoparticles.

From chemistry design to clinical application, several approaches have been developed to overcome platinum drawbacks in antitumoral therapies. An in-depth understanding of intracellular signaling may hold the key to the relationship of both conventional drugs and nanoparticles. Within these strategies, first, nanotechnology has become an essential tool in oncotherapy, improving biopharmaceutical properties and providing new immunomodulatory profiles to conventional drugs mediated by activation of endoplasmic reticulum (ER) stress. Secondly, functional proteomics techniques based on microarrays have proven to be a successful method for high throughput screening of proteins and profiling of biomolecule mechanisms of action. Here, we conducted a systematic characterization of the antitumor profile of a platinum compound conjugated with iron oxide nanoparticles (IONPs). As a result of the nano-conjugation, cytotoxic and proteomics profiles revealed a significant improvement in the antitumor properties of the starting material, providing selectivity in certain tumor cell lines tested. Moreover, cell death patterns associated with immunogenic cell death (ICD) response have also been identified when ER signaling pathways have been triggered. The evaluation in several tumor cell lines and the analysis by functional proteomics techniques have shown novel perspectives on the design of new cisplatin-derived conjugates, the high value of IONPs as drug delivery systems and ICD as a rewarding approach for targeted oncotherapy and onco-immunotherapies.

Communication transforms the impact of the COVID-19 pandemic on children with cancer and their families.

BACKGROUND: The COVID-19 pandemic altered healthcare systems globally, causing delays in care delivery and increased anxiety among patients and families. This study examined how hospital stakeholders and clinicians perceived the global impact of the COVID-19 pandemic on children with cancer and their families. METHODS: This secondary analysis examined data from a qualitative study consisting of 19 focus groups conducted in 8 languages throughout 16 countries. A codebook was developed with novel codes derived inductively from transcript review. In-depth analysis focused on the impact of the COVID-19 pandemic on children with cancer and their families. RESULTS: Eight themes describing the impact of the pandemic on patients and their families were identified and classified into three domains: contributing factors (COVID-19 Policies, Cancer Treatment Modifications, COVID-19 Symptoms, Beliefs), patient-related impacts (Quality of Care, Psychosocial impacts, Treatment Reluctance), and the central transformer (Communication). Participants described the ability of communication to transform the effect of contributing factors on patient-related impacts. The valence of impacts depended on the quality and quantity of communication among clinicians and between clinicians and patients and families. CONCLUSIONS: Communication served as the central factor impacting whether the COVID-19 pandemic positively or negatively affected children with cancer and families. These findings emphasize the key role communication plays in delivering patient-centered care and can guide future development of communication-centered interventions globally.

Haploidentical vs. HLA-matched donor hematopoietic stem-cell transplantation for pediatric patients with acute lymphoblastic leukemia in second remission: A collaborative retrospective study of the Spanish Group for Bone Marrow Transplantation in Children (GETMON/GETH) and the Spanish Childhood Relapsed ALL Board (ReALLNet).

Introduction: Studies addressing the role of haploidentical as alternative to HLA-matched donors for stem cell transplantation (SCT) often include patients with diverse hematological malignancies in different remission statuses. Methods: We compared outcomes of children with acute lymphoblastic leukemia (ALL) undergoing SCT in second complete remission (CR2) from haploidentical (n = 25) versus HLA-matched donor (n = 51). Results: Patients were equally distributed across both groups according to age, immunophenotype, time to and site of relapse, relapse risk-group allocation, and minimal residual disease (MRD) before SCT. Incidence of graft failure, acute graft versus host disease (GVHD), and other early complications did not differ between both groups. We found no differences in overall survival (58.7% versus 59.5%; p = .8), leukemia free survival (LFS) (48% versus 36.4%; p = .5), event free survival (40% versus 34.4%; p = .69), cumulative incidence (CI) of subsequent relapse (28% versus 40.9%; p = .69), treatment related mortality (24% versus 23.6%; p = .83), CI of cGVHD (4.5% versus 18.7%; p = .2), and chronic GVHD-free and leukemia-free survival (44% versus 26.3%; p = .3) after haploidentical donor SCT. Chronic GVHD (HR = 0.09; p=.02) had protective impact, and MRD ≥ 0.01% before SCT (HR = 2.59; p=.01) had unfavorable impact on LFS. Discussion: These results support the role of haploidentical donor SCT in children with ALL in CR2.

Trichoderma hamatum can act as an inter-plant communicator of foliar pathogen infections by colonizing the roots of nearby plants: A new inter-plant "wired communication".

Trichoderma is a genus of filamentous fungi widely studied and used as a biological control agent in agriculture. However, its ability to form fungal networks for inter-plant communication by means of the so-called inter-plant "wired communication" has not yet been addressed. In our study we used the model plant Arabidopsis thaliana, the fungus Trichoderma hamatum (isolated from Brassicaceae plants) and the pathogens Sclerotinia sclerotiorum and Xanthomonas campestris (necrotrophic fungus and hemibiotrophic bacteria, respectively). We performed different combinations of isolated/neighboring plants and root colonization/non-colonization by T. hamatum, as well as foliar infections with the pathogens. In this way, we were able to determine how, in the absence of T. hamatum, there is an inter-plant communication that induces systemic resistance in neighboring plants of plants infected by the pathogens. On the other hand, the plants colonized by T. hamatum roots show a greater systemic resistance against the pathogens. Regarding the role of T. hamatum as an inter-plant communicator, it is the result of an increase in foliar signaling by jasmonic acid (increased expression of LOX1 and VSP2 genes and decreased expression of ICS1 and PR-1 genes), antagonistically increasing root signaling by salicylic acid (increased expression of ICS1 and PR-1 genes and decreased expression of LOX1 and VSP2). This situation prevents root colonization by T. hamatum of the foliarly infected plant and leads to massive colonization of the neighboring plant, where jasmonic acid-mediated systemic defenses are induced.