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Purpose To describe the design, conduct, and results of the Breast Multiparametric MRI for prediction of neoadjuvant chemotherapy Response (BMMR2) challenge. Materials and Methods The BMMR2 computational challenge opened on May 28, 2021, and closed on December 21, 2021. The goal of the challenge was to identify image-based markers derived from multiparametric breast MRI, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI, along with clinical data for predicting pathologic complete response (pCR) following neoadjuvant treatment. Data included 573 breast MRI studies from 191 women (mean age [±SD], 48.9 years ± 10.56) in the I-SPY 2/American College of Radiology Imaging Network (ACRIN) 6698 trial (ClinicalTrials.gov: NCT01042379). The challenge cohort was split into training (60%) and test (40%) sets, with teams blinded to test set pCR outcomes. Prediction performance was evaluated by area under the receiver operating characteristic curve (AUC) and compared with the benchmark established from the ACRIN 6698 primary analysis. Results Eight teams submitted final predictions. Entries from three teams had point estimators of AUC that were higher than the benchmark performance (AUC, 0.782 [95% CI: 0.670, 0.893], with AUCs of 0.803 [95% CI: 0.702, 0.904], 0.838 [95% CI: 0.748, 0.928], and 0.840 [95% CI: 0.748, 0.932]). A variety of approaches were used, ranging from extraction of individual features to deep learning and artificial intelligence methods, incorporating DCE and DWI alone or in combination. Conclusion The BMMR2 challenge identified several models with high predictive performance, which may further expand the value of multiparametric breast MRI as an early marker of treatment response. Clinical trial registration no. NCT01042379 Keywords: MRI, Breast, Tumor Response Supplemental material is available for this article. © RSNA, 2024.

Abstract Background Cardiovascular disease (CVD), particularly ischemic heart disease, remains the leading cause of death and morbidity in patients with type 1 diabetes. Detecting subclinical atherosclerosis could enhance cardiovascular risk stratification and enable individualised therapies. The aim of this study is to investigate the prevalence and predictors of subclinical atherosclerosis in patients with type 1 diabetes without overt cardiovascular disease (CVD) and to assess its impact on patient survival over a follow-up period of at least 5 years. Methods This observational study included 507 patients treated at the Diabetes Unit of the Hospital of Girona Doctor Josep Trueta between 2015 and 2023. The inclusion criteria for patients were as follows: those aged 18 and older with diabetes for a minimum of 10 years or those aged 40 and older with a diabetes for at least 5 years. Subclinical atherosclerosis was identified via ultrasound imaging of the carotid and femoral arteries. Clinical and biochemical evaluations were also conducted. Major cardiovascular events (MACE) and deaths from other causes were monitored, and survival analysis was performed using Kaplan‒Meier methods. Results Subclinical atherosclerosis was detected in 218 patients (43%). Multivariate analysis revealed that the male sex, diabetic nephropathy, tobacco exposure, higher HbA1c levels, older age, and longer diabetes duration were significant predictors. During a mean follow-up of 70.64 ± 27.08 months, 19 patients experienced MACE, and 13 died from any cause. The probability of MACE or death was greater in patients with subclinical atherosclerosis, with a hazard ratio (HR) of 25.1 (95% CI 5.81–108, p

In pancreatic ductal adenocarcinoma (PDAC), metabolic rewiring and resistance to standard therapy are closely associated. PDAC cells show enormous requirements for glucose‐derived citrate, the first rate‐limiting metabolite in the synthesis of new lipids. Both the expression and activity of citrate synthase (CS) are extraordinarily upregulated in PDAC. However, no previous relationship between gemcitabine response and citrate metabolism has been documented in pancreatic cancer. Here, we report for the first time that pharmacological doses of vitamin C are capable of exerting an inhibitory action on the activity of CS, reducing glucose‐derived citrate levels. Moreover, ascorbate targets citrate metabolism towards the de novo lipogenesis pathway, impairing fatty acid synthase (FASN) and ATP citrate lyase (ACLY) expression. Lowered citrate availability was found to be directly associated with diminished proliferation and, remarkably, enhanced gemcitabine response. Moreover, the deregulated citrate‐derived lipogenic pathway correlated with a remarkable decrease in extracellular pH through inhibition of lactate dehydrogenase (LDH) and overall reduced glycolytic metabolism. Modulation of citric acid metabolism in highly chemoresistant pancreatic adenocarcinoma, through molecules such as vitamin C, could be considered as a future clinical option to improve patient response to standard chemotherapy regimens.

Abstract This article introduces a novel approach to perform the simulation of a single qubit quantum-inspired algorithm using laser beams. Leveraging the polarization states of photonic qubits, and inspired by variational quantum eigensolvers, we develop a variational quantum-inspired algorithm implementing a clustering procedure following the approach proposed by some of us in SciRep 13, 13284 (2023). A key aspect of our research involves the utilization of non-orthogonal states within the photonic domain, harnessing the potential of polarization schemes to reproduce unitary circuits. By mapping these non-orthogonal states into polarization states, we achieve an efficient and versatile quantum information processing unit which serves as a clustering device for a diverse set of datasets.

Abstract A genomic database of all Earth’s eukaryotic species could contribute to many scientific discoveries; however, only a tiny fraction of species have genomic information available. In 2018, scientists across the world united under the Earth BioGenome Project (EBP), aiming to produce a database of high-quality reference genomes containing all ~1.5 million recognized eukaryotic species. As the European node of the EBP, the European Reference Genome Atlas (ERGA) sought to implement a new decentralised, equitable and inclusive model for producing reference genomes. For this, ERGA launched a Pilot Project establishing the first distributed reference genome production infrastructure and testing it on 98 eukaryotic species from 33 European countries. Here we outline the infrastructure and explore its effectiveness for scaling high-quality reference genome production, whilst considering equity and inclusion. The outcomes and lessons learned provide a solid foundation for ERGA while offering key learnings to other transnational, national genomic resource projects and the EBP.

Abstract Digital twins of the Earth are digital representations of the Earth system, spanning scales and domains. Their purpose is to monitor, forecast and assess the Earth system and the consequences of human interventions on the Earth system. Providing users with the capability to interact with and interrogate the system, digital twins of the Earth are decision support systems for addressing environmental challenges. By informing humans of their impact on the Earth system, digital twins aspire to promote new pathways moving forward. By answering causal queries through intervention analysis, they can enhance evidence-based policy making. Existing digital twins of the Earth are primarily technological information systems that represent the physical world. However, as the social and physical worlds are intrinsically interconnected, we argue that humans must be accounted for both within and outside digital twins of the Earth: Within twins to represent human impacts and responses that are integral to the Earth system; and outside twins to govern access and development and to guide responsible use of information acquired from twins. Incorporating human interactions in digital twins of the Earth represents a transformative frontier, promising unparalleled insights into Earth system dynamics and empower humans for action.

El abandono de la práctica de actividad física durante la adolescencia es un problema de salud pública, especialmente para las chicas. Este estudio tuvo como objetivo analizar la literatura científica para identificar los factores que favorecen el mantenimiento de los hábitos de actividad física y los que llevan a las chicas a abandonar la práctica deportiva. Se realizó una búsqueda de artículos publicados en la base de datos Web of Science desde 2010 hasta diciembre de 2022, utilizando las palabras clave: (Physical activity OR Physical exercise OR Sport) AND (Adolesc* OR Children) AND (Female OR Gender OR Girl OR Wom*) AND (Barrier* OR Facilitator*). Para el desarrollo del estudio se tuvo en cuenta la declaración PRISMA. Como criterios de inclusión se establecieron: i) la edad de las personas participantes en los estudios (hasta 21 años); ii) el idioma (español, catalán o inglés) y iii) el tipo de documento (artículo). Se obtuvieron un total de 597 trabajos, de los que se seleccionaron 29 artículos para esta revisión. Los resultados revelaron distintos factores internos y externos que influyen en el abandono o mantenimiento de la actividad deportiva de las chicas durante la adolescencia: motivación, autopercepción, autopresentación, identidad deportiva, cambios durante la adolescencia, entorno deportivo, entorno educativo, apoyo social, modelos de conducta y estereotipos. Al final del trabajo se proponen estrategias para revertir la tendencia al abandono de la práctica de actividad física y deporte por parte de las adolescentes.

The aim of this study was to expand knowledge about endocrine disorders in individuals with Cornelia de Lange syndrome (CdLS), a rare developmental genetic disorder with anomalies in multiple organs and systems. Hormone levels, clinical scores, anthropometric measurements, and molecular analysis were assessed in 24 individuals with CdLS. Hyperprolactinemia was the most common endocrine disorder. Three patients showed subclinical hypothyroidism. Concerning the gonadotropic axis, mildly delayed puberty was observed, as well as genital anomalies, such as cryptorchidism. Despite short stature, levels of insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 tended to be normal. Three prepubertal individuals without risk factors had higher than normal values for the homeostatic model assessment of insulin resistance (HOMA-IR) and for insulinemia, suggesting insulin resistance. Furthermore, two adults had elevated body mass indexes associated with HOMA-IR values over the cut-off values. CdLS may lead to dysregulation of the endocrine system, particularly in patients with high HOMA-IR values and insulinemia who are at risk of insulin resistance. Therefore, clinical follow-up with comprehensive hormonal assessment appears warranted in individuals with CdLS.

Let $ X $ be an infinite Tychonoff space, and $ Y $ be a topological subspace of $ X $. In this paper, we study some covering properties of the subspace $ C_{p}\left(Y|X\right) $ of $ C_{p}\left(Y\right) $ consisting of those functions $ f\in C\left(Y\right) $ which admit a continuous extension to $ X $ equipped with the relative topology of $ C_{p}\left(Y\right) $. Among other results, we show that $ \left(i\right) $ $ C_{p}(Y|X) $ has a fundamental bounded resolution if and only if $ Y $ is countable; when $ X $ is realcompact and $ Y $ is closed in $ X $, we have $ \left(ii\right) $ if $ C_{p}(Y|X) $ admits a resolution of convex compact sets that swallows the local null sequences in $ C_{p}(Y|X) $, then $ Y $ is countable and discrete; $ \left(iii\right) $ if $ C_{p}(Y|X) $ admits a compact resolution that swallows the compact sets, then $ Y $ is also countable and discrete, and, as a corollary, we deduce that $ C_{p}(Y|X) $ admits a compact resolution that swallows the compact sets if and only if $ C_{p}(Y|X) $ is a Polish space. We also prove that $ \left(iv\right) $ for a metrizable space $ X $, $ C_{p}\left(X\right) $ is a quasi-$ \left(LB\right) $-space if and only if $ X $ is $ \sigma $-compact, and hence for a subspace $ Y $ of $ X $, the space $ C_{p}\left(Y|X\right) $ is a quasi-$ \left(LB\right) $-space. We include some examples and observations that answer natural questions raised in this paper.

Abstract Background The purpose of this study was to test how musical flow using baroque (BM) and classical era music (CM) as a non-pharmacological therapy can control anxiety and pain levels among patients undergoing IPI (Immediate post-extraction implants). Methods 78 patients who required an IPI were enrolled in this randomized clinical trial. Each patient was assigned to one of the three experimental groups with a simple randomization: Group I (n = 26) listened to BM; Group II (n = 27) listened to CM; and Group III (n = 25) did not listen to music and was the control group (C). The physiological dependent variables analyzed were systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and oxygen saturation (SpO2). The psychological dependent variable analyzed was modified dental anxiety scale (MDAS) and visual analogue scale (VAS), measured before and after surgery. In all cases, the level of statistical significance was set at p

Cornelia de Lange syndrome (CdLS) is a rare congenital developmental disorder with multisystemic involvement. The clinical presentation is highly variable, but the classic phenotype, characterized by distinctive craniofacial features, pre- and postnatal growth retardation, extremity reduction defects, hirsutism and intellectual disability can be distinguished from the nonclassic phenotype, which is generally milder and more difficult to diagnose. In addition, the clinical features overlap with those of other neurodevelopmental disorders, so the use of consensus clinical criteria and artificial intelligence tools may be helpful in confirming the diagnosis.Pathogenic variants in NIPBL, which encodes a protein related to the cohesin complex, have been identified in more than 60% of patients, and pathogenic variants in other genes related to this complex in another 15%: SMC1A, SMC3, RAD21, and HDAC8. Technical advances in large-scale sequencing have allowed the description of additional genes (BRD4, ANKRD11, MAU2), but the lack of molecular diagnosis in 15% of individuals and the substantial clinical heterogeneity of the syndrome suggest that other genes and mechanisms may be involved.Although there is no curative treatment, there are symptomatic/palliative treatments that paediatricians should be aware of. The main medical complication in classic SCdL is gastro-esophageal reflux (GER), which should be treated early. Resumen: El síndrome de Cornelia de Lange (SCdL) es un raro trastorno congénito del desarrollo de afectación multisistémica. Las manifestaciones clínicas son muy variables, pero se distingue entre un fenotipo clásico, caracterizado por unos rasgos craneofaciales distintivos, retraso del crecimiento pre y postnatal, defectos por reducción de las extremidades, hirsutismo y discapacidad intelectual y un fenotipo no clásico, generalmente más leve y más difícil de diagnosticar. Además, las características clínicas se superponen con las de otros desordenes del neurodesarrollo, por lo que la utilización de criterios clínicos consensuados y herramientas de inteligencia artificial pueden ser útiles para confirmar el diagnóstico.En más del 60% de los pacientes se han identificado variantes patogénicas en el gen NIPBL, que codifica una proteína relacionada con el complejo de la cohesina, y en otro 15% en 4 genes también asociados a este complejo: SMC1A, SMC3, RAD21 y HDAC8. Los progresos técnicos en las técnicas de secuenciación masiva han permitido describir otros genes relacionados (BRD4, ANKRD11 y MAU2), pero la ausencia de diagnóstico molecular en el 15% de los casos y la gran heterogeneidad clínica del síndrome, sugiere la existencia de otros genes y mecanismos relacionados.Aunque no haya un tratamiento curativo, sí hay tratamientos sintomáticos/paliativos que deben ser conocidos por el pediatra. La principal complicación médica en el SCdL clásico es el reflujo gastroesofágico (RGE), que debe ser tratado de forma precoz y contundente, ya que es una de las causas más frecuentes de fallecimiento en estos pacientes.

The present study examined the relative effectiveness of bilingual subtitles for L2 viewing comprehension, compared to other subtitling types. Learners' allocation of attention to the image and subtitles/captions in different viewing conditions, as well as the relationship between attention and comprehension, were also investigated. A total of 112 Chinese learners of English watched an English documentary clip in one of four conditions (bilingual subtitles, captions, L1 subtitles, no subtitles) while their eye movements were recorded. The results revealed that bilingual subtitles were as beneficial as L1 subtitles for comprehension, which both outscored captions and no subtitles. Participants using bilingual subtitles spent significantly more time processing L1 than L2 lines. L1 lines in bilingual subtitles were processed significantly longer than in L1 subtitles, but L2 lines were processed significantly shorter than in captions. No significant relationship was found between the processing time and comprehension for either the L1 or L2 lines of bilingual subtitles.

With the advent of Big Data, traditional digital computing is struggling to cope with intricate tasks related to data classification or pattern recognition. To mitigate this limitation, software‐based neural networks are implemented, but they are run in conventional computers whose operation principle (with separate memory and data‐processing units) is highly inefficient compared to the human brain. Brain‐inspired in‐memory computing is achieved through a wide variety of methods, for example, artificial synapses, spiking neural networks, or reservoir computing. However, most of these methods use materials (e.g., memristor arrays, spintronics, phase change memories) operated with electric currents, resulting in significant Joule heating effect. Tuning magnetic properties by voltage‐driven ion motion (i.e., magnetoionics) has recently emerged as an alternative energy‐efficient approach to emulate functionalities of biological synapses: potentiation/depression, multilevel storage, or transitions from short‐term to long‐term plasticity. In this perspective, the use of magnetoionics in neuromorphic applications is critically reviewed, with emphasis on modulating synaptic weight through: 1) control of magnetization by voltage‐induced ion retrieval/insertion; and 2) control of magnetic stripe domains and skyrmions in gated magnetic thin films adjacent to solid‐state ionic supercapacitors. The potential prospects in this emerging research area together with a forward‐looking discussion on future opportunities are provided.

Le cahier des charges en agriculture biologique (AB) interdit les traitements à base d’hormones ou substances analogues en vue de maîtriser la reproduction. En AB, la reproduction des petits ruminants est possible à contre-saison grâce à l’effet mâle. Les traitements lumineux sans mélatonine pour désaisonner la reproduction peuvent aussi être appliqués en bâtiments ouverts et sont compatibles avec le pâturage mais peu utilisés sur le terrain. L’insémination animale (IA) est peu répandue pour les ovins et caprins en AB, elle peut être réalisée sur chaleurs naturelles (saison sexuelle) ou induites et synchronisées par effet mâle (contre-saison). Dans les deux cas, les IA s’étalent sur plusieurs jours et nécessitent une détection des chaleurs préalable. En élevages caprins, la conduite en lactation longue est également une alternative pour désaisonner la production laitière. Dans les élevages porcins en AB, l’effet mâle peut faciliter l’induction de la puberté des cochettes, la stimulation d’œstrus de lactation, et la diminution de l’intervalle sevrage-œstrus ; toutefois il est utilisé principalement pour améliorer l’expression des chaleurs. La stimulation par le transport et le changement social et/ou d’environnement est largement utilisée pour induire et synchroniser les œstrus des cochettes de renouvellement. Chez les bovins, l’interdiction des traitements hormonaux n’est pas pénalisante en AB, car la reproduction est possible toute l’année par monte naturelle (majoritaire en élevage allaitant) ou par IA (majoritaire en élevage laitier) sur chaleurs naturelles. Dans toutes les espèces, le « flushing » alimentaire avant la mise à la reproduction est pratiqué dans le but d’améliorer la fertilité. La mise en œuvre de ces pratiques en AB est le résultat d’un équilibre entre enjeux financier, réglementaire et éthique.

Se presentan resultados de una experiencia formativa con futuros profesores de matemáticas, centrada en el análisis didáctico de materiales curriculares sobre probabilidad. Aunque hubo progreso en la identificación de objetos matemáticos, se encontraron dificultades para reconocer situaciones-problema, procedimientos, proposiciones y argumentos, así como los significados de probabilidad. En la valoración experta de la idoneidad didáctica de la normativa, se observaron deficiencias, pero los participantes no evaluaron adecuadamente dichas carencias, especialmente en las facetas epistémica y cognitiva. Estas limitaciones podrían deberse a la falta de formación específica y al poco tiempo para familiarizarse con los indicadores de idoneidad.

Naegleria fowleri, known as the brain-eating amoeba, is the pathogen that causes the primary amoebic meningoencephalitis (PAM), a severe neurodegenerative disease with a fatality rate exceeding 95%. Moreover, PAM cases commonly involved previous activities in warm freshwater bodies that allow amoebae-containing water through the nasal passages. Hence, awareness among healthcare professionals and the general public are the key to contribute to a higher and faster number of diagnoses worldwide. Current treatment options for PAM, such as amphotericin B and miltefosine, are limited by potential cytotoxic effects. In this context, the repurposing of existing compounds has emerged as a promising strategy. In this study, the evaluation of the COVID Box which contains 160 compounds demonstrated significant in vitro amoebicidal activity against two type strains of N. fowleri. From these compounds, terconazole, clemastine, ABT-239 and PD-144418 showed a higher selectivity against the parasite compared to the remaining products. In addition, programmed cell death assays were conducted with these four compounds, unveiling compatible metabolic events in treated amoebae. These compounds exhibited chromatin condensation and alterations in cell membrane permeability, indicating their potential to induce programmed cell death. Assessment of mitochondrial membrane potential disruption and a significant reduction in ATP production emphasized the impact of these compounds on the mitochondria, with the identification of increased ROS production underscoring their potential as effective treatment options. This study emphasizes the potential of the mentioned COVID Box compounds against N. fowleri, providing a path for enhanced PAM therapies.