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Objective To evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE).Design Observational cohort analysis based on a multicentre international registry.Setting Data were extracted from the Registro Informatizado de Enfermedad TromboEmbolica Registry, which involves 205 centres across 27 countries.Participants A total of 73 659 patients diagnosed with VTE were classified based on their anticoagulant therapy (DOACs) versus low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKAs) and concurrent use of statins.Methods Multivariable Cox proportional hazards models adjusted for confounding variables to assess the risk of major bleeding events stratified by the type of anticoagulant use and statin use.Results From October 2013 to February 2023, 73 659 patients were recruited: 2573 were statin users on DOACs, 14 090 were statin users on LMWH or VKA therapy, 10 088 were non-statin users on DOACs and 46 908 were non-statin users on LMWH or VKA therapy. Statin users were 10 years older and more likely to have hypertension, diabetes, renal failure or prior artery disease. During anticoagulation (median, 187 days), 1917 patients (2.6%) suffered major bleeding. Rates of major bleeding per 100 patient-years were 2.33 (95% CI 1.72 to 3.09), 3.75 (95% CI 3.43 to 4.10), 1.39 (95% CI 1.13 to 1.69) and 3.10 (95% CI 2.93 to 3.27), respectively. On multivariable analysis, patients treated with DOACs had a significantly lower risk of major bleeding compared with those on LMWH or VKA therapy (adjusted HR 0.59; 95% CI 0.48 to 0.74). The adjusted HR in statin users versus non-users was 1.03 (95% CI 0.92 to 1.14), while in statin users on DOACs versus the rest of patients, it was 1.18 (95% CI 0.79 to 1.76).Conclusions In patients with VTE receiving statins, long-term anticoagulation with DOACs was associated with a reduced risk of major bleeding, regardless of the statin use. These findings support the safety profile of DOACs over VKAs or LMWH in the management of VTE in patients requiring statins.

Introduction and objectives: B-cell precursor acute lymphoblastic leukemia (B-ALL) is characterized by a variety of genomic alterations relevant for risk stratification and prognosis of patients. Notably, Philadelphia-like (Ph-like) ALL is defined by a gene expression profile similar to Philadelphia-positive patients but without the historically known BCR::ABL1 rearrangement. The Ph-like subgroup is associated with an unfavorable prognosis and is observed in 15% of children and 40% of adolescents and young adults (AYA) with B-ALL. The characterization of this subgroup involves the evaluation of gene expression of 8 genes, and it is a complex challenge for centers of leukemia diagnosis. Given this scenario, the aim of this study is to establish a predictive genetic panel for defining the Ph-like subgroup in the Brazilian Unified Health System (SUS), thereby improving and expediting its diagnosis. Materials and methods: 108 samples from children and adult patients diagnosed with B-ALL according to World Health Organization criteria, and collected from different cancer treatment centers in Brazil were included. The patients were classified as B-other based on the absence of recurrent primary alterations: high-hyperdiploidy, ETV6::RUNX1, BCR::ABL1, TCF3::PBX1 and KMT2Ar. The Ph-like subgroup was characterized using cDNA samples to analyze the expression profile of SPATS2L, MUC4, CRLF2, CA6, NRXN3, BMPR1B, JCHAIN, and ADGFR1 genes by quantitative PCR (qPCR) using commercial TaqMan assays (Life Technologies). Gene expression profiles were correlated with the presence of rearrangements in genes frequently altered in this subgroup, including PDGFRB, CRLF2, JAK2, ABL1, ABL2, IGH and CSF1R, evaluated by Fluorescent in situ Hybridization (FISH) using break-apart probes (Zytovision and Cytocell). Patients positive for primary alterations were used as a reference control group. This study was approved by the Research Ethics Committee of INCA (CAEE #87793418.0.0000.5274). Results and conclusion: A total of 53 samples were included so far. Among them, 32 patients were classified as B-other and the remaining 21 patients had recurrent abnormalities: ETV6::RUNX1 (n = 6), BCR::ABL1 (n = 5), KMT2A-r (n = 3), TCF3::PBX1 (n = 3), and high-hyperdiploidy (n = 4). The Ph-like profile was identified in 37.5% of patients, based on the occurrence of CRLF2, ABL1 or JAK2 rearrangements and the expression profile, simultaneously. Most Ph-like patients were AYA (66.7%) and had low white blood cell count at diagnosis. It was observed that 11 of the 12 Ph-like patients had at least one overexpressed gene. Our preliminary results confirm the existence of distinct molecular profiles previously described among the subtypes of Ph+ and Ph-like B-ALL. While FISH has demonstrated effectiveness to identifying Ph-like cases when a differential gene expression was not observed, the current sample size is not enough to confirm the most appropriate diagnostic strategy for characterize this complex B-ALL subtype. Support: CNPq, FAPERJ, Ministério da Saúde, Swiss Bridge Foundation.

B-cell precursor acute lymphoblastic leukemia (B-ALL) is the most prevalent form of ALL and its development varies with age. It is characterized by chromosomal and genetic alterations such as aneuploidy, gene fusions, copy number alterations (CNA) and point mutations, which are crucial for diagnosis and therapy risk stratification. However, ̃25% of pediatric and ̃8% of adult cases with B-ALL lacking recurrent alterations are classified as “B-other”. New clinically relevant genetic alterations involving PAX5 gene are being demonstrated in this subtype, including rearrangements (PAX5 -r), deletions (PAX5 del), amplifications (PAX5 amp), and a point mutation (PAX5 P80R). Around 30% of B-ALL cases show PAX5 alterations (PAX5 alt), which are associated with relapses and poor outcomes. This study aims to characterize PAX5 alterations and evaluate their prognostic impact in children, adolescents and young adults (AYA) with B-other ALL. Pediatric (< 15 years) and AYA (15-39 years) cases diagnosed with B-ALL between 2018 and 2023 in different Brazilian cancer treatment centers were included. Recurrent and primary alterations were previously characterized by reverse transcription PCR (RT-PCR) or quantitative PCR (qPCR). Only patients categorized as B-other, defined by the lack of ETV6::RUNX1, BCR::ABL1, TCF3::PBX1, KMT2A::AFF1 and high-hyperdiploidy (DNA index), were included. CNA were identified by multiplex ligation-dependent probe amplification (MLPA), using the P335-C1 probemix (MRC-Holland). PAX5 -r were detected by fluorescence in situ hybridization (FISH - ZytoLight SPEC PAX5 Dual Color Break Apart Probe - Zyto Vision), and the PAX5 P80R mutation was assessed by TaqMan customized allelic discrimination assay (Life Technologies). This study was approved by the institutional ethical committee (CAEE #87793418.0.0000.5274). A total of 62 B-other ALL cases were evaluated (44 pediatric and 18 AYAs). Approximately 27% of these cases were characterized as PAX5 alt, due to the presence of PAX5 amp (̃23%), PAX5 del (̃52%) or PAX5 -r (̃41%), occurring alone or simultaneously. In this subtype, most cases were pediatric (71%), with a median age of 8 years-old, and low white blood cell count at diagnosis (̃64%). CDKN2A/B del (̃47%) and JAK2 del (̃17%) were concomitantly observed with PAX5alt. On the other hand, in PAX5 wild-type patients, CDKN2A/Bdel (̃26%) and IKZF1 del (20%) were the most prevalent. Curiously, the IGH -rearrangements were commonly found among PAX5 alt cases (̃23%). PAX5 P80R were not found in any cases. Considering that the genetic alterations knowledge is essential for the treatment decisions, a better understanding of PAX5 alterations in B-other ALL is crucial for precision medicine. Besides, our findings suggest that the IGH gene may be a frequent partner of PAX5 fusions, though it requires further investigation.

Introdução: A Leucemia Linfoblástica Aguda de precursores B (LLA-pB) é uma das neoplasias mais comuns na infância, representando cerca de 25% dos casos em crianças abaixo de 15 anos, com pico de incidência entre 2 e 3 anos. Mecanismos de reparo de DNA, como a Reparação por Excisão de Base (BER), a Reparação por Excisão de Nucleotídeo (NER) e a Recombinação Homóloga (HRR), são cruciais para manter a estabilidade do genoma. Alterações nesses mecanismos podem afetar negativamente a resposta ao tratamento e a sobrevivência. Objetivo: Relatar um caso de resistência à quimioterapia em um paciente pediátrico com LLA-pB, com foco nas alterações genéticas e moleculares, especialmente nos mecanismos de reparo de DNA. Relato de caso: Menino de 11 anos com astenia, palidez e dor abdominal, apresentando HB 4,5 g/dL, leucometria 4.500/mm3 e plaquetas 258.000/mm3. A imunofenotipagem da medula óssea revelou LLA-pB com 40% de células precursoras B leucêmicas, e a citogenética mostrou 46XY. Foi tratado com o protocolo BFM AEIOP 2013. A medula óssea permaneceu infiltrada no D15 (18% de blastos) e D33/TP1 (21% de blastos), e entrou em remissão morfológica no D78/TP2 (4% de blastos), detectados por citometria de fluxo (CF). Alcançou a primeira Doença Residual Mensurável (MRD) negativa (< 0,001%) após o bloco HR-II. Na avaliação pré-protocolo III, foi observada progressão com 3,2% de DRM, evoluindo rapidamente para 55% de blastos. O protocolo de recaída Flag-Ida foi realizado sem resposta. O tratamento com anti-CD19 (Blinatumomab) por 28 dias também foi ineficaz, impossibilitando o transplante haploidêntico, previamente agendado. O paciente faleceu em maio de 2020, 11 meses após o diagnóstico. Em análise genética retrospectiva, realizada a partir de material genético criopreservado, a técnica de MLPA revelou deleções nos genes IKZF1, CDKN2A, CDKN2B e PAX5, classificando o paciente como IKZF1plus devido à ausência de deleção no gene ERG1. O sequenciamento dos genes de reparo de DNA APEX1, XRCC1, XPD, XPA, RAD51 e XRCC3 revelou 54 variantes, das quais 19 eram mutações raras com frequência populacional menor que 0,01. Polimorfismos de único nucleotídeo (SNPs) de reconhecida relevância clínica foram identificados nos genes APEX1 (Asp148Glu) e XRCC1 (Arg399Gln e Arg194Trp). Discussão: A presença de múltiplas variantes raras é considerado um indicativo de mutagênese elevada. Os genes APEX1 e XRCC1 estão envolvidos na via BER, e os SNPs são encontrados associados como fatores de pior prognóstico em diversas neoplasias. A via BER é fundamental na proteção do tecido hematopoiético, e defeitos nesta via podem afetar negativamente a resposta ao tratamento e a evolução da doença. A mutagênese aumentada pode ter contribuído para o surgimento de alterações secundárias, como o perfil IKZF1plus. Estudos sobre o papel do reparo de DNA em neoplasias hematológicas são escassos, sem dados suficientes para uma correlação estatística conclusiva. Conclusão: Integrar análises genéticas com achados clínicos é essencial para otimizar o tratamento em pacientes com perfis genéticos complexos. Identificamos defeitos na via BER como potenciais moduladores da resposta terapêutica. Avaliar individualmente o reparo de DNA pode ajudar a entender como variações genéticas individuais influenciam a resposta clínica e assim melhorar a precisão do prognóstico.

The purpose of this document is to identify which actions in the Equal Opportunities Plan 2023–2026 of the Ourense Provincial Council have the potential to increase equality of opportunity between women and men in positions of similar status, with respect to an analysis of the objectives of the First Equality Plan of (2017–2021). The methodology for measuring the achievements of these strategic objectives consisted of a descriptive comparative study, where the changes in the stated objectives were analyzed, and a quantitative functional study was undertaken to determine the relationship between the typology and functionality of each position. A clear distinction was made between the goals achieved and those requiring more decisive intervention in future. In addition, it recognizes that women are very underrepresented in the most desirable positions at Ourense Provincial Council.

The techniques of differential thermal analysis are frequently employed to study the kinetics of the transformation reactions and, in particular, the crystallization of the glassy alloys. The corresponding thermal data can be analyzed by the Kissinger method, which was originally derived for the study of homogeneous reactions. The consensus in the literature, in several decades, was that such applications (i.e. to heterogeneous solid state transformations) of the Kissinger method are not valid. In the present work the principal objections to the mentioned applications are addressed and alternative derivations of theoretical results are provided. These results demonstrate that the Kissinger method is valid for heterogeneous reactions of the type described by Johnson-Mehl-Avrami equation in the isothermal case. Also the isothermal and non-isothermal data on crystallization of the Cu0.10As0.40Se0.50 glassy alloy are given. The experimental results and the discussion carried out here, help to clarify the effects of incubation time in non-isothermal transformation kinetics and provide a further demonstration of validity of the generalized Johnson-Mehl-Avrami theory for the description of heterogeneous solid state transformations.Las técnicas de análisis térmico diferencial se emplean con frecuencia para estudiar la cinética de las reacciones de transformación y, en particular la de la cristalización de aleaciones vítreas. Los datos térmicos correspondientes pueden analizarse por el método de Kissinger, que se desarrolló originalmente para el estudio de reacciones homogéneas. Durante varias décadas, el consenso en la literatura fue que tales aplicaciones (es decir, a transformaciones heterogéneas de estado sólido) del método de Kissinger no eran válidas. En el presente trabajo se señalan las principales objeciones a las aplicaciones mencionadas y se da una deducción alternativa de los resultados teóricos. Estos resultados demuestran que el método de Kissinger es válido para reacciones heterogéneas del tipo descrito por la ecuación de Johnson-Mehl-Avrami en el caso isotermo. También se dan los datos de cristalización isoterma y no isoterma de la aleación vítrea Cu0.10As0.40Se0.50. Los resultados experimentales y la discusión realizada aquí, ayudan a aclarar los efectos del tiempo de incubación en la cinética de transformaciones no isotermas y proporcionan una demostración adicional de la validez de la teoría generalizada de Johnson-Mehl-Avrami para la descripción de transformaciones heterogéneas de estado sólido.

A procedure has been developed for analyzing the evolution with time of the crystallized fraction and for calculating the kinetic parameters at non-isothermal reactions involving formation and growth of nuclei. Considering the assumptions of extended volume and random nucleation, a general expression of the transformed fraction as a function of time has been obtained in isothermal crystallization processes. The crystallization rate deduced has been applied to the non-isothermal processes under the restriction of a nucleation which takes place early in the transformation and the nucleation frequency is zero thereafter. In these conditions, the kinetic parameters have been deduced by using the technique of single-scan. The theoretical method developed has been applied to the crystallization kinetics of the semiconducting Sb0.12As0.40Se0.48 alloy. The kinetic parameters obtained differ by only about 6% of those calculated by multiple-scan techniques, which confirms the reliability and accuracy of the single-scan technique when calculating the mentioned parameters in non-isothermal processes.Se ha desarrollado un procedimiento para analizar la evolución temporal de la fracción cristalizada y calcular los parámetros cinéticos de reacciones no isotermas que implican la formación y crecimiento de núcleos. Considerando las hipótesis de volumen extendido y nucleación al azar, se ha obtenido una expresión general de la fracción transformada como función del tiempo en procesos de cristalización isotermos. La velocidad de cristalización deducida se ha aplicado a procesos no isotermos bajo la restricción de nucleación al principio de la transformación y que se anula posteriormente. En estas condiciones, se han deducido los parámetros cinéticos usando la técnica de barrido único. El método teórico desarrollado se ha aplicado a la cristalización de la aleación semiconductora Sb0.12As0.40Se0.48. Los parámetros cinéticos obtenidos difieren alrededor del 6% de los calculados por técnicas de barrido múltiple, lo que confirma la fiabilidad y exactitud de la técnica de barrido único cuando se calculan los mencionados parámetros en procesos no isotermos.

Las políticas públicas dirigidas al bienestar de la población han influido en la composición de la dieta humana, particularmente en el aumento del consumo de carne de origen animal. Para abordar esta creciente demanda alimenticia, los gobiernos locales destinan más espacio para el faenamiento de animales, lo que podría generar externalidades ambientales negativas debido a una inadecuada gestión de los desechos. Esta investigación exploratoria y trasnversal con enfoque mixto tiene por objetivo analizar la cadena de valor del centro de faenamiento de bovinos y porcinos del cantón Montúfar, provincia del Carchi, y las posibles externalidades ambientales derivadas de su localización en el área urbana. Para analizar la cadena de valor se aplicó el método Value Links, la observación directa y la revisión documental; así como, las técnicas de entrevista y encuesta para identificar las externalidades y conocer la percepción de la población sobre problemas de contaminación. Los hallazgos revelan que, la cadena de valor no integra todos los componentes necesarios, restando competitividad al servicio final ofrecido al consumidor. Se destaca el interés de la población en participar en el cuidado ambiental y se reconoce el potencial de la organización colectiva para aportar a la internalización de externalidades ambientales.

Summary: Background: The clinical relevance of recurrent venous thromboembolism (VTE) after discontinuing anticoagulation in patients with COVID-19-associated VTE remains uncertain. We estimated the incidence rates and mortality of VTE recurrences developing after discontinuing anticoagulation in patients with COVID-19-associated VTE. Methods: A prospective, multicenter, non-interventional study was conducted between March 25, 2020, and July 26, 2023, including patients who had discontinued anticoagulation after at least 3 months of therapy. All patients from the registry were analyzed during the study period to verify inclusion criteria. Patients with superficial vein thrombosis, those who did not receive at least 3 months of anticoagulant therapy, and those who were followed for less than 15 days after discontinuing anticoagulation were excluded. Outcomes were: 1) Incidence rates of symptomatic VTE recurrences, and 2) fatal PE. The rate of VTE recurrences was defined as the number of patients with recurrent VTE divided by the patient-years at risk of recurrent VTE during the period when anticoagulation was discontinued. Findings: Among 1106 patients with COVID-19-associated VTE (age 62.3 ± 14.4 years; 62.9% male) followed-up for 12.5 months (p25-75, 6.3–20.1) after discontinuing anticoagulation, there were 38 VTE recurrences (3.5%, 95% confidence interval [CI]: 2.5–4.7%), with a rate of 3.1 per 100 patient-years (95% CI: 2.2–4.2). No patient died of recurrent PE (0%, 95% CI: 0–7.6%). Subgroup analyses showed that patients with diagnosis in 2021–2022 (vs. 2020) (Hazard ratio [HR] 2.86; 95% CI 1.45–5.68) or those with isolated deep vein thrombosis (vs. pulmonary embolism) (HR 2.31; 95% CI 1.19–4.49) had significantly higher rates of VTE recurrences. Interpretation: In patients with COVID-19-associated VTE who discontinued anticoagulation after at least 3 months of treatment, the incidence rate of recurrent VTE and the case-fatality rate was low. Therefore, it conceivable that long-term anticoagulation may not be required for many patients with COVID-19-associated VTE, although further research is needed to confirm these findings. Funding: Sanofi and Rovi, Sanofi Spain.

Abstract Intracellular pathogens develop elaborate mechanisms to survive within the hostile environments of host cells. Theileria parasites infect bovine leukocytes and cause devastating diseases in cattle in developing countries. Theileria spp. have evolved sophisticated strategies to hijack host leukocytes, inducing proliferative and invasive phenotypes characteristic of cell transformation. Intracellular Theileria parasites secrete proteins into the host cell and recruit host proteins to induce oncogenic signaling for parasite survival. It is unknown how Theileria parasites evade host cell defense mechanisms, such as autophagy, to survive within host cells. Here, we show that Theileria annulata parasites sequester the host eIF5A protein to their surface to escape elimination by autophagic processes. We identified a small-molecule compound that reduces parasite load by inducing autophagic flux in host leukocytes, thereby uncoupling Theileria parasite survival from host cell survival. We took a chemical genetics approach to show that this compound induced host autophagy mechanisms and the formation of autophagic structures via AMPK activation and the release of the host protein eIF5A which is sequestered at the parasite surface. The sequestration of host eIF5A to the parasite surface offers a strategy to escape elimination by autophagic mechanisms. These results show how intracellular pathogens can avoid host defense mechanisms and identify a new anti-Theileria drug that induces autophagy to target parasite removal.

Abstract Background Neural tube defects (NTDs) are caused by genetic and environmental factors. ARMC5 is part of a novel ubiquitin ligase specific for POLR2A, the largest subunit of RNA polymerase II (Pol II). Results We find that ARMC5 knockout mice have increased incidence of NTDs, such as spina bifida and exencephaly. Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised. The enlarged Pol II pool does not lead to generalized Pol II stalling or a generalized decrease in mRNA transcription. In neural progenitor cells, ARMC5 knockout only dysregulates 106 genes, some of which are known to be involved in neural tube development. FOLH1, critical in folate uptake and hence neural tube development, is downregulated in the knockout intestine. We also identify nine deleterious mutations in the ARMC5 gene in 511 patients with myelomeningocele, a severe form of spina bifida. These mutations impair the interaction between ARMC5 and Pol II and reduce Pol II ubiquitination. Conclusions Mutations in ARMC5 increase the risk of NTDs in mice and humans. ARMC5 is part of an E3 controlling the degradation of all 12 subunits of Pol II under physiological conditions. The Pol II pool size might have effects on NTD pathogenesis, and some of the effects might be via the downregulation of FOLH1. Additional mechanistic work is needed to establish the causal effect of the findings on NTD pathogenesis.

This quasi-experimental, pre-post design study aimed to determine the effects of the Ready for Success classroom program (Brigman & Webb, 2012) on the social/emotional skills and competence of third-grade students. A multivariate analysis of covariance revealed a statistically significant difference at post-tests for third-grade students' self-awareness, self-management, social awareness, relationship skills, responsible decision-making skills, and overall social/emotional competence as measured by the Devereux Student Strengths Assessment. This study supports school counselor-led social/emotional learning classroom programs to promote students' social/emotional development in the school setting.

This meta-analysis investigates the impact of the "Leader in Me" process on teachers' perceptions of their school climates and student behaviour. Twelve studies involving 198,176 students resulted in an overall effect size of d = 0.20. The effect sizes for student climate (d = 0.34) and student behaviour (d = 0.16) were determined separately. The results of this meta-analysis connect the "Leader in Me" intervention with the whole-school implementation model for maintaining a supportive learning environment.

We have used a Ligand Knowledge Base for bidentate P,P-donor ligands of potential interest to homogeneous catalysis to compare three dimensionality reduction techniques, namely Principal Component Analysis (PCA), Uniform Manifold Approximation and Projection (UMAP) and t-distributed Stochastic Neighbor Embedding (t-SNE). While our previous work on Ligand Knowledge Bases has focused on PCA, here we compare this approach with more recently-published approaches and assess the information retention, visualization, clustering and interpretability which can be achieved for each approach. We find that potential advantages of t-SNE are not realized with a database of the current size (275 entries), and that there is a degree of complementarity between PCA and UMAP. The statistics underlying PCA rely on linear relationships, making interpretation of the resulting plots comparatively straightforward. Since much of chemistry relies on linear structure-property relationships and low-dimensional visualization, the explainability and information retention achieved is attractive. UMAP proved more challenging to interpret, but achieved clear clustering which was often chemically meaningful, and it would be a useful approach for ensuring that distinct subsets of compounds are sampled in a machine-learning context. This analysis also highlighted that the tunability of catalysis achieved through ligand exchange maps well onto some areas of chemical space where closely related ligands cluster, while others represent outliers; these arise from different combinations of steric and electronic effects which chemists will find intuitive.

Background A quality assurance programme for the tissue donation process was launched in Andalusia in 2020 to facilitate the integration of tissue donation into end-of-life care, and to respond to the growing need for human tissue for therapeutic purposes. The results of this programme are presented here.Methods After identifying the hospital departments in which to intensify the detection of tissue donors, expanding training activities and designing a specific data collection system for possible tissue donors who do not donate their tissues, the results of the donation activity were quantified and the causes of non-donation were analysed by applying the critical pathway for deceased tissue donation methodology.Results After an initial drop in activity, which coincided with the coronavirus pandemic, the number of tissue donors increased by 48.4% in 2022 compared to 2019. From the eligible donors, 83% were actual tissue donors and 71% were utilised donors. The modifiable causes of tissue donation loss, in order of frequency, were family refusal, followed by organisational or logistical issues, failure to notify or failure to identify possible donors, and failure to complete donor evaluation.Conclusion As a result of the collaboration of the various professionals involved in the programme, tissue donation activity has increased remarkably, the potential and effectiveness of the donation process have been evaluated, and areas for improvement have been identified, which we hope will lead to continuous improvement of the process.

Objectives: To evaluate the compassionate use of plitidepsin as an antiviral treatment in hospitalized immunocompromised adult patients with moderate-to-severe COVID-19. Design: Retrospective observational study of data —collected from January 01, 2021 to April 30, 2022— from 35 immunocompromised adult patients with COVID-19 non-eligible for other available antiviral treatments. Main outcome measures were time to respiratory recovery (SpFi ≥ 315); COVID-19-related 30-day-cumulative mortality after first plitidepsin infusion; and time to undetectable levels of viral RNA. Results: Thirty-three patients receiving a full course of plitidepsin (2.5 mg [n = 29] or 1.5 mg [n = 4]) were included. Most (69.7%) had a malignant hematologic disease and 27.3% had solid tumors. A total of 111 infusions were administered with lack of relevant safety events. Median time from plitidepsin initiation to SpFi ≥315 was 8 days (95% confidence interval [CI], 7-19). Median time to first negative reverse transcription-polymerase chain reaction for SARS-CoV-2 (cycle threshold >36) was 17 days (95% CI 13-25). Mortality rate was 16.3% (95% CI 3-37.3). Conclusion: These data support plitidepsin as a well-tolerated treatment that might have potential clinical and antiviral efficacy in COVID-19 immunocompromised patients.

The aim of this study is to analyse the variables related to knowledge (Talent Management and Training) as a source of human capital in the companies listed in the ranking of the most attractive organisations within the Spanish labour market, published annually by the journal Actualidad Económica (period 2016–2022). We seek to determine the socio-economic variables impacting this assessment, while also exploring the sustainability of the companies in the ranking. Ten hypotheses are thus examined by descriptive statistics, ANOVA, and multiple linear regression models. The results show a significant relationship between permanence, nationality, professional–scientific–technical sector, size, stock market listing, and both variables representative of knowledge in the ranked companies. Focusing on Talent Management, it is noted that permanence in the ranking (>4 years), Anglo-Saxon nationality, being active in the professional, scientific, and technical sector, and being listed on the stock market all play a part. However, Training differs in that size is a factor that positively influences valuation, whereas the international area is irrelevant. Our findings are a key contribution, as there are no previous applied studies that correlate knowledge in the business environment, the valuation of organisations from the employee’s perspective, and several socio-economic variables.

La presente investigación pretende analizar la diversificación de las exportaciones ecuatorianas y su aporte al crecimiento económico del país en el periodo 2000-2021. El estudio descriptivo con enfoque cuantitativo tiene como objetivo analizar la importancia de la diversificación de exportaciones con énfasis en la identificación de los productos más relevantes que inciden en el crecimiento ecónomico en los años comprendidos entre 2000 y 2021; para lo cual se emplearon los métodos analítico-sintético y estadístico. La data se tomó de la información estadística e indicadores emitidos por el Banco Central de Ecuador. Entre los principales resultados se observa que en estas dos décadas de análisis se produjo una ligera variación en el país destino de las exportaciones ecuatorianas y del volumen de las agroexportaciones tradicionales. Sin embargo, no hubo una variación significativa del conjunto de bienes exportables, posiblemente debido a factores como una deficiente política pública para impulsar las exportaciones y a la escasa inversión en investigación, innovación y tecnología por parte del Estado y del sector empresarial exportador. A corto plazo y mediano plazo, los volúmenes de exportación muestran un cambio poco dinámico en relación con los precios, evidenciando una pérdida de la capacidad productiva.

Abstract Objective: To assess whether the Mediterranean Diet (MedDiet) is associated with lower micronutrients inadequacy in a sample of Spanish preschoolers. Design: We conducted a cross-sectional study with 4–5-year-old children participating in the SENDO project. Information was gathered through an online questionnaire completed by parents. Dietary information was collected with a previously validated semi-quantitative FFQ. The estimated average requirements or adequate intake levels as proposed by the Institute of Medicine were used as cut-off point to define inadequate intake. Statistical analyses: Crude and multivariable adjusted estimates were calculated with generalised estimated equations to account for intra-cluster correlation between siblings. Participants: We used baseline information of 1153 participants enrolled in the SENDO project between January 2015 and June 2022. Main outcomes measures: OR and 95 % CI of presenting an inadequate intake of ≥ 3 micronutrients associated with the MedDiet. Results: The adjusted proportion of children with inadequate intake of ≥ 3 micronutrients was 27·2 %, 13·5 % and 8·1 % in the categories of low, medium and high adherence to the MedDiet, respectively. After adjusting for all potential confounders, children who had a low adherence to the MedDiet showed a significant lower odds of inadequate intake of ≥ 3 micronutrients compared to those with a high adherence (OR 9·85; 95 % CI 3·33, 29·09). Conclusion: Lower adherence to the MedDiet is associated with higher odds of nutritional inadequacy.

We utilized a mixed-methods design to understand how a national sample of 589 school counselors adapted their approach to address K-12 students' academic, social/emotional, and career development during the COVID-19 pandemic. More specifically, we examined how COVID-19--induced disparities influenced school counselors' delivery of services. We identified six themes using thematic analysis and conducted a "t" test to further understand what services and strategies counselors were actively using 6 months after the onset of COVID-19. Our findings suggest that school counselors continued to adjust their comprehensive school counseling programs to address pandemic-induced disparities.

The development of fully biobased hydrogels obtained by simple routes and in the absence of toxic or environmentally harmful reagents is a major challenge in meeting new societal demands. In this work, we discuss the development of hydrogels made from cellulose nanocrystals (CNCs) and xyloglucan (XG), two non-toxic, renewable, and biobased components. We present three strategies to fine-tune the functional properties. The first one consists in varying the XG/CNC ratio that leads to the modulation of the mechanical properties of hydrogels as well as a better comprehension of the gel mechanism formation. The second relies on tuning the XG chains’ interaction by enzymatic modification to achieve thermoresponsive systems. Finally, the third one is based on the increase in the hydrogel solid content by osmotic concentration. The high-solid-content gels were found to have very high mechanical properties and self-healing properties that can be used for molding materials. Overall, these approaches are a case study of potential modifications and properties offered by biobased nanocolloidal hydrogels.

Liquid biopsy (LB) is a minimally invasive procedure that detects biomarkers in body fluids for real-time monitoring of patients. This study developed a new LB approach to analyze Circulating Epithelial Cells (CECs) in Intensive Care Unit (ICU) patients with severe COVID-19 and High-Exposure Negative Population to COVID-19 (HENPC) as the control group. The CECs were characterized by multispectral imaging flow cytometry, and an anti-SARS-CoV-2 Spike S1 protein (ProtS) antibody was used to detect infection. The results showed that CECs were present in most ICU patients (p = 0.0412), and their median number was significantly higher (p = 0.0004) than in controls. CEC clusters were only identified in patients, and high positive ProtS expression was observed in CECs from ICU patients compared to negative controls. In conclusion, LB could be a minimally invasive tool for detecting tissue damage caused by infectious agents and could provide real-time biological information about disease status and evolution. However, further validation in a larger population of patients is needed.