Exploring blood-brain barrier passage using atomic weighted vector and machine learning.

CONTEXT: This study investigates the potential of leveraging molecular properties, as determined by MD-LOVIs software and machine learning techniques, to predict the ability of compounds to cross the blood-brain barrier (BBB). Accurate prediction of BBB permeation is critical for the development of central nervous system (CNS) drugs. The study applies various machine learning models, including both classification and regression techniques, to predict BBB passage and molecular activity. Notably, classification models such as GBM-AWV (accuracy = 0.801), GLM-CN (accuracy = 0.808), SVMPoly-means (accuracy = 0.980), SVMPoly-AC (accuracy = 0.980), SVMPoly-MI_TI_SI (accuracy = 0.900), SVMPoly-GI (accuracy = 0.900), RF-means (accuracy = 0.870), and GLM-means (accuracy = 0.818) demonstrate high accuracy in predicting BBB passage. In contrast, regression models like ES-RLM-AG (R2 = 0.902), IB-IBK (R2 = 0.82), IB-Kstar (R2 = 0.834), IB-MLP (R2 = 0.843), and DRF-AWV (R2 = 0.810) exhibit strong performance in predicting molecular activity. The results show that classification models like GBM-AWV, GLM-CN, and SVMPoly variants, as well as regression models like ES-RLM-AG and IB-MLP, achieve high performance, demonstrating the effectiveness of machine learning in predicting BBB permeability. METHODS: The computational methods employed in this study include the MD-LOVIs software for generating molecular descriptors and several machine learning algorithms, including gradient boosting machines (GBM), generalized linear models (GLM), support vector machines (SVM) with polynomial kernels, random forests (RF), ensemble regression models, and instance-based learning algorithms. These models were trained and validated using various datasets to predict BBB passage and molecular activity, with the performance metrics reported for each model. Standard computational techniques were employed throughout, ensuring the reliability of the predictions.

Genomic variation of European beech reveals signals of local adaptation despite high levels of phenotypic plasticity.

Local adaptation is key for ecotypic differentiation and species evolution. Understanding underlying genomic patterns can allow the prediction of future maladaptation and ecosystem stability. Here, we report the whole-genome resequencing of 874 individuals from 100 range-wide populations of European beech (Fagus sylvatica L.), an important forest tree species in Europe. We show that genetic variation closely mirrors geography with a clear pattern of isolation-by-distance. Genome-wide analyses for genotype-environment associations (GEAs) identify relatively few potentially adaptive variants after correcting for an overwhelming signal of statistically significant but non-causal GEAs. We characterize the single high confidence genomic region and pinpoint a candidate gene possibly involved in winter temperature adaptation via modulation of spring phenology. Surprisingly, allelic variation at this locus does not result in any apparent fitness differences in a common garden. More generally, reciprocal transplant experiments across large climate distances suggest extensive phenotypic plasticity. Nevertheless, we find indications of polygenic adaptation which may be essential in natural ecosystems. This polygenic signal exhibits broad- and fine-scale variation across the landscape, highlighting the relevance of spatial resolution. In summary, our results emphasize the importance, but also exemplify the complexity, of employing natural genetic variation for forest conservation under climate change.

Macro- and micro-geographic genetic variation in early fitness traits in populations of maritime pine (Pinus pinaster Ait.).

BACKGROUND AND AIMS: Assessing adaptive genetic variation and its spatial distribution is crucial to conserve forest genetic resources and manage species' adaptive potential. Macro-environmental gradients commonly exert divergent selective pressures that enhance adaptive genetic divergence among populations. Steep micro-environmental variation might also result in adaptive divergence at finer spatial scales, even under high gene flow, but it is unclear how often this is the case. Here, we assess genetic variation in early fitness traits among distant and nearby maritime pine (Pinus pinaster Ait.) populations, to investigate climatic factors associated with trait divergence, and to examine trait integration during seedling establishment. METHODS: Open pollinated seeds were collected from seven population pairs across the European species distribution, with paired populations spatially close (between <1 km up to 21 km) but environmentally divergent. Seeds were sown in semi-natural conditions at three environmentally contrasting sites, where we monitored seedling emergence, growth and survival. KEY RESULTS: At large spatial scales, we found significant genetic divergence among populations in all studied traits, with certain traits exhibiting association with temperature and precipitation gradients. Significant trait divergence was also detected between pairs of nearby populations. Besides, we found consistent trait correlations across experimental sites, notably heavier seeds and earlier seedling emergence were both associated with higher seedling survival and fitness over two years in all experimental conditions. CONCLUSIONS: We identified mean annual temperature and precipitation seasonality as potential drivers of P. pinaster population divergence in the studied early-life traits. Populations genetically diverge also at local spatial scales, potentially suggesting that divergent natural selection can override gene flow along local-scale ecological gradients. These results suggest the species exhibits substantial adaptive potential that has allowed it to survive and evolve under contrasting environmental conditions.

Resilience of genetic diversity in forest trees over the Quaternary.

The effect of past environmental changes on the demography and genetic diversity of natural populations remains a contentious issue and has rarely been investigated across multiple, phylogenetically distant species. Here, we perform comparative population genomic analyses and demographic inferences for seven widely distributed and ecologically contrasting European forest tree species based on concerted sampling of 164 populations across their natural ranges. For all seven species, the effective population size, Ne, increased or remained stable over many glacial cycles and up to 15 million years in the most extreme cases. Surprisingly, the drastic environmental changes associated with the Pleistocene glacial cycles have had little impact on the level of genetic diversity of dominant forest tree species, despite major shifts in their geographic ranges. Based on their trajectories of Ne over time, the seven tree species can be divided into three major groups, highlighting the importance of life history and range size in determining synchronous variation in genetic diversity over time. Altogether, our results indicate that forest trees have been able to retain their evolutionary potential over very long periods of time despite strong environmental changes.

Utilidad de la tomografía de impedancia eléctrica para la programación del ventilador mecánico en paciente crítico pediátrico, una alternativa dinámica y no invasiva: revisión de dos casos clínicos / Utility of electrical impedance tomography for mechanical ventilator programming in pediatric critical patients, a dynamic and non-invasive alternative: a review of two clinical cases

La tomografía por impedancia eléctrica (TIE) es una modalidad de monitorización funcional respiratoria por imagen, no invasiva y libre de radiación, que permite visualizar en tiempo real la ventilación pulmonar regional y global en pacientes adultos y pediátricos conectados a Ventilación Mecánica (VM). OBJETIVO: Se describe la utilidad de la TIE en dos pacientes críticos pediátricos, en quienes no fue factible realizar medición de mecánica pulmonar, como herramienta para el ajuste de parámetros ventilatorios. CASOS CLÍNICOS: Se presentan dos pacientes pediátricos de 27 y 11 meses con condiciones clínicas diferentes, conectados a VM, en quienes se utilizó la TIE como método de monitoreo de la distribución pulmonar y titulación de la presión positiva al final de la espiración (PEEP) óptima, con el objetivo de obtener una ventilación pulmonar más homogénea. Se presentan mediciones funcionales con diferentes niveles de PEEP y valores de distribución en las distintas regiones de interés (ROI), además de un flujograma de situaciones en las que la TIE podría resultar útil para el ajuste ventilatorio. CONCLUSIÓN: La información funcional proporcionada por la TIE, permitió monitorizar de forma dinámica la VM y optimizar los parámetros ventilatorios, facilitando la implementación de estrategias de protección pulmonar en ambos pacientes, imposibilitados de realizar una medición estática de la mecánica respiratoria.

The Electrical Impedance Tomography (EIT) is a non-invasive and radiation-free respiratory functional imaging monitoring modality that allows real-time visualization of regional and global lung ventilation in adult and pediatric patients connected to mechanical ventilation (MV). OBJECTIVE: This paper describes the utility of EIT in two critical pediatric patients for whom measuring pulmonary mechanics was not feasible. EIT is used as a tool for adjusting ventilatory parameters. CLINICAL CASES: Two pediatric patients aged 27 and 11 months, with different clinical conditions, connected to MV are presented. EIT was used to monitor lung distribution and titrate the optimal Positive End-Expiratory Pressure (PEEP), to achieve more homogeneous lung ventilation. Functional measurements are presented with different PEEP levels and distribution values in different regions of interest (ROI), along with a flowchart illustrating situations where EIT could be useful for ventilatory adjustment. CONCLUSION: The functional information provided by EIT, allowed dynamic monitoring of MV, optimizing ventilatory parameters and facilitating the implementation of lung protective strategies in both patients, unable to undergo static respiratory mechanics measurements.

Fluidoterapia reflexiva: desde la fisiología a la práctica clínica / Reflexive fluid therapy: From physiology to clinical practice

Introducción. La fluidoterapia es una intervención ampliamente usada en la práctica clínica. No obstante, su aplicación no está exenta de riesgos y demanda una evaluación cuidadosa de la tolerancia del paciente y su respuesta al volumen. La práctica empírica de la reanimación con líquidos puede ser potencialmente letal. El propósito de esta revisión fue proporcionar una visión general de los principios fisiológicos y terapéuticos para la administración de líquidos intravenosos en pacientes críticamente enfermos, abordando poblaciones especiales, como los pacientes quirúrgicos, sépticos y politraumatizados. Métodos. Se hizo una revisión narrativa a partir de artículos publicados en PUBMED, ScienceDirect y LILACS, entre 2001 y 2023. Para la búsqueda se emplearon los términos MESH fluid therapy, crystalloid solutions y colloids. Resultados. Se encontraron 371 artículos, de los cuales se seleccionaron los estudios clínicos aleatorizados, las revisiones narrativas, las revisiones sistemáticas y los metaanálisis que analizaron el rol de los cristaloides y coloides. Se incluyeron manuscritos publicados en fechas por fuera del rango de búsqueda, que se consideraron relevantes para la descripción de la fisiopatología y los fundamentos del uso de líquidos endovenosos. Conclusión. La reanimación reflexiva se fundamenta en un entendimiento holístico de la fisiología y la individualización de la fluidoterapia. El uso liberal de líquidos endovenosos tiene potenciales efectos nocivos y las estrategias de reanimación deben ser guiadas por medidas dinámicas y estáticas individuales, que proporcionan un panorama seguro para el manejo de los líquidos.

Introduction. Fluid therapy is an intervention widely used in clinical practice. However, its application is not without risks and requires a careful evaluation of patient's tolerance and response to volume. The empirical practice of fluid resuscitation can be potentially lethal. The purpose of this review was to provide an overview of the physiological and therapeutic principles for the administration of intravenous fluids in critically ill patients, addressing special populations, such as surgical, septic, and trauma patients. Methods. A narrative review was carried out based on articles published in PUBMED, ScienceDirect, and LILACS between 2001 and 2023. MESH terms fluid therapy, crystalloid solutions, and colloids were employed. Results. A total of 371 articles were found, of which randomized clinical trials studies, narrative reviews, systematic reviews, and meta-analyses that analyzed the role of crystalloids and colloids were selected. Manuscripts published on dates outside the search range, which were considered relevant for the description of the pathophysiology and the rationale for the use of intravenous fluids, were included. Conclusion. Reflective resuscitation is based on a holistic understanding of physiology and individualization of fluid therapy. The liberal use of intravenous fluids has potential harmful effects and resuscitation strategies should be guided by individual dynamic and static measures, which provide a safe framework for fluid management

Inhibition of Cancer Stem-like Cells by Curcumin and Other Polyphenol Derivatives in MDA-MB-231 TNBC Cells.

Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is highly aggressive. Despite an initial positive response to chemotherapy, most patients experience rapid disease progression leading to relapse and metastasis. This is attributed to the presence of breast cancer stem cells (BCSCs) within the tumor, which are characterized by self-renewal, pluripotency, and resistance mechanisms. Targeting BCSCs has become critical as conventional therapies fail to eradicate them due to a lack of specific targets. Curcumin, a polyphenol derived from turmeric (Curcuma longa), exhibits anticancer effects against breast cancer cells and BCSCs. The use of curcumin derivatives has been suggested as an approach to overcome the bioavailability and solubility problems of curcumin in humans, thereby increasing its anticancer effects. The aim of this study was to evaluate the cellular and molecular effects of six synthetic compounds derived from the natural polyphenol epigallocatechin gallate (EGCG) (TL1, TL2) and curcumin derivatives (TL3, TL4, TL5, and TL6) on a TNBC mesenchymal stem-like cell line. The activity of the compounds against BCSCs was also determined by a mammosphere inhibition assay and studying different BCSC markers by Western blotting. Finally, a drug combination assay was performed with the most promising compounds to evaluate their potential synergistic effects with the chemotherapeutic agents doxorubicin, cisplatin, and paclitaxel. The results showed that compounds exhibited specific cytotoxicity against the TNBC cell line and BCSCs. Interestingly, the combination of the curcumin derivative TL3 with doxorubicin and cisplatin displayed a synergistic effect in TNBC cells.

Hammering nails with a screwdriver: how GPs perceive video consultations.

BACKGROUND: Early in the COVID-19 pandemic, the use of video consultation (VC) expanded considerably, with GPs indicating high satisfaction with it. However, use of VC declined as lockdown measures were eased. AIM: To explore reasons why VC use has declined in Norwegian general practice since the start of the pandemic by investigating GPs' experiences with VC and their attitudes towards it in a post-pandemic setting. DESIGN & SETTING: Qualitative study using semi-structured interviews with 13 GPs in southern Norway between May 2022 and March 2023. METHOD: Data analysis was conducted by applying the six steps of Braun and Clarke's reflexive thematic analysis. RESULTS: Although the implementation of VCs was unplanned, most participants were able to use this modality without much problem. Several GPs initially envisioned long-term VC use. However, despite certain positives, VCs were largely sidelined in favour of face-to-face and telephone consultations, owing to their practicality and VC's limited usefulness when considering the extra effort required. Nonetheless, GPs recognised ways of using VC that might exploit its strengths, but they highlighted how its sustained use would require them to replace other consultation modalities. They also identified extrinsic factors that might lead to the increased use of VC, including improved VC technology and patient demand. CONCLUSION: Although VC is now part of many GPs' consultation toolboxes, its perceived relative lack of usefulness and extra effort compared with other remote consultation modalities mean that most GPs have chosen to abandon it as a routine consultation modality.

[Medical nutrition therapy in amyotrophic lateral sclerosis - Do we act or react? A case report and multidisciplinary review]. / Tratamiento médico nutricional en la esclerosis lateral amiotrófica: ¿Actuamos o reaccionamos? Un caso clínico y revisión multidisciplinar.

Introduction: Background: amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a progressive course. The current prevalence is between 3 and 6 cases/100,000. Malnutrition is closely related to patient prognosis in ALS. The implications of this conditions have been that we should recommend patient care in a multidisciplinary unit. Case report: the case presented shows the evolution of a patient with ALS. The patient was referred to different clinical departments after neurological evaluation and her nutritional, functional and respiratory status were assessed. There was no nutritional deterioration at diagnosis; however, intake was below energy-protein requirements. The clinical evolution of the patient showed a decrease in muscle mass with preservation of weight and fat mass. "Aggressive" measures to control nutritional status such as gastrostomy were rejected in the initial stages of the disease, but had to be carried out after development of dysphagia and associated malnutrition. This situation of progressive morphofunctional deterioration and the development of disease-related complications made essential the participation of different health services and professionals in its control. Dicussion: the management of ALS in a multidisciplinary manner allows to improve the course of the disease and the quality of life of both the patients and their families. Patient follow-up is based on the adjustment and management of complications. The basis of the relationship with these patients includes maintaining an adequate communication with them and their families, and ensuring joint decision-making about their condition.

Introducción: Introducción: la esclerosis lateral amiotrófica (ELA) es una enfermedad neurodegenerativa cuya prevalencia en la actualidad está entre 3 y 6 casos/100.000. La desnutrición está íntimamente relacionada con el pronóstico en el paciente con ELA. Las implicaciones de esta enfermedad hacen que se deba recomendar al paciente la asistencia en una unidad multidisciplinar. Caso clínico: el caso presentado muestra la evolución de una paciente con esclerosis lateral amiotrófica desde el diagnóstico. Tras la valoración por parte de Neurología, se remitió a la paciente a los distintos servicios de seguimiento (Endocrinología, Rehabilitación, Neumología). No se observó deterioro nutricional al diagnóstico; no obstante, la ingesta se encontraba por debajo de los requerimientos. En la progresión de la enfermedad se observó un deterioro de la masa muscular con estabilidad ponderal y de la masa grasa, pero la paciente desarrolló disfagia, síntoma típico de la enfermedad. El planteamiento de medidas "agresivas" para controlar el estado nutricional, como la gastrostomía, fue rechazado al inicio, pero hubo que realizarlas tras la progresión de la disfagia y la desnutrición asociada. Esta situación de deterioro morfofuncional y el desarrollo de complicaciones plantearon la participación de distintos profesionales sanitarios en su control. Discusión: el manejo de la ELA de manera multidisciplinar permite mejorar la evolución de la enfermedad y la calidad de vida del paciente y sus familiares. El seguimiento se basa en el ajuste y el manejo de las complicaciones, en mantener una adecuada comunicación con el paciente y sus familiares, y en tomar de manera conjunta las decisiones sobre su patología.

Effectiveness of Psychobiotics in the Treatment of Psychiatric and Cognitive Disorders: A Systematic Review of Randomized Clinical Trials.

In this study, a systematic review of randomized clinical trials conducted from January 2000 to December 2023 was performed to examine the efficacy of psychobiotics-probiotics beneficial to mental health via the gut-brain axis-in adults with psychiatric and cognitive disorders. Out of the 51 studies involving 3353 patients where half received psychobiotics, there was a notably high measurement of effectiveness specifically in the treatment of depression symptoms. Most participants were older and female, with treatments commonly utilizing strains of Lactobacillus and Bifidobacteria over periods ranging from 4 to 24 weeks. Although there was a general agreement on the effectiveness of psychobiotics, the variability in treatment approaches and clinical presentations limits the comparability and generalization of the findings. This underscores the need for more personalized treatment optimization and a deeper investigation into the mechanisms through which psychobiotics act. The research corroborates the therapeutic potential of psychobiotics and represents progress in the management of psychiatric and cognitive disorders.

Isolation of the Antifungal Compound Alliodorin from the Heartwood of Cordia elaeagnoides A. DC. and the In Silico Analysis of the Laccase.

Cordia elaeagnoides A. DC. is an endemic species of Mexico valued for its timber. Renowned for its durability, resistance, and versatile applications in medicine, this tree holds significant commercial importance. Tetrahydrofuran (THF) extract from the heartwood of C. elaeagnoides was studied. Through chromatographic column purification, the compound 8-(2,5-Dihydroxyphenyl)-2,6-dimethylocta-2,6-dienal, also known as alliodorin, was successfully isolated. Identification of alliodorin was confirmed through comprehensive analysis utilizing NMR, IR, and mass spectrometry techniques. Inhibition tests were conducted using both the THF extract and alliodorin against the rotting fungus Trametes versicolor (L.) Lloyd, employing the agar well diffusion assay. Remarkably, alliodorin exhibited 100% inhibition with a median lethal concentration of 0.079 mg/mL and a total lethal concentration of 0.127 mg/mL, in comparison to the commercial fungicide benomyl, which requires a concentration of 1 mg/mL. In silico analysis through molecular docking on the laccase enzyme was proposed in order to explain the inhibitory activity against the fungus T. versicolor, as this enzyme is one of the main sources of nutrients and development for the fungus. Based on these findings, we deduced that alliodorin holds promise as a potent antifungal agent, potentially applicable in a wide array of technological and environmentally friendly initiatives.

Estimation of contemporary effective population size in plant populations: Limitations of genomic datasets.

Effective population size (N e) is a pivotal evolutionary parameter with crucial implications in conservation practice and policy. Genetic methods to estimate N e have been preferred over demographic methods because they rely on genetic data rather than time-consuming ecological monitoring. Methods based on linkage disequilibrium (LD), in particular, have become popular in conservation as they require a single sampling and provide estimates that refer to recent generations. A software program based on the LD method, GONE, looks particularly promising to estimate contemporary and recent-historical N e (up to 200 generations in the past). Genomic datasets from non-model species, especially plants, may present some constraints to the use of GONE, as linkage maps and reference genomes are seldom available, and SNP genotyping is usually based on reduced-representation methods. In this study, we use empirical datasets from four plant species to explore the limitations of plant genomic datasets when estimating N e using the algorithm implemented in GONE, in addition to exploring some typical biological limitations that may affect N e estimation using the LD method, such as the occurrence of population structure. We show how accuracy and precision of N e estimates potentially change with the following factors: occurrence of missing data, limited number of SNPs/individuals sampled, and lack of information about the location of SNPs on chromosomes, with the latter producing a significant bias, previously unexplored with empirical data. We finally compare the N e estimates obtained with GONE for the last generations with the contemporary N e estimates obtained with the programs currentNe and NeEstimator.

The WHO atlas for female-genital schistosomiasis: Co-design of a practicable diagnostic guide, digital support and training.

Up to 56 million young and adult women of African origin suffer from Female Genital Schistosomiasis (FGS). The transmission of schistosomiasis happens through contact with schistosomiasis infested fresh water in rivers and lakes. The transmission vector is the snail that releases immature worms capable of penetrating the human skin. The worm then matures and mates in the blood vessels and deposits its eggs in tissues, causing urogenital disease. There is currently no gold standard for FGS diagnosis. Reliable diagnostics are challenging due to the lack of appropriate instruments and clinical skills. The World Health Organisation (WHO) recommends "screen-and-treat" cervical cancer management, by means of visual inspection of characteristic lesions on the cervix and point-of-care treatment as per the findings. FGS may be mistaken for cervical cancer or sexually transmitted diseases. Misdiagnosis may lead to the wrong treatment, increased risk of exposure to other infectious diseases (human immunodeficiency virus and human papilloma virus), infertility and stigmatisation. The necessary clinical knowledge is only available to a few experts in the world. For an appropriate diagnosis, this knowledge needs to be transferred to health professionals who have minimal or non-existing laboratory support. Co-design workshops were held with stakeholders (WHO representative, national health authority, FGS experts and researchers, gynaecologists, nurses, medical doctors, public health experts, technical experts, and members of the public) to make prototypes for the WHO Pocket Atlas for FGS, a mobile diagnostic support tool and an e-learning tool for health professionals. The dissemination targeted health facilities, including remote areas across the 51 anglophone, francophone and lusophone African countries. Outcomes were endorsed by the WHO and comprise a practical diagnostic guide for FGS in low-resource environments.

Novel method for chlorine determination in biofuel lipid feedstock by coupling a total sample introduction system (hTISIS) to an inductively coupled plasma tandem mass spectrometry (ICP-MS/MS).

BACKGROUND: Chlorine concentrations above 1 mg kg-1 in lipid feedstocks for biofuel production can generate corrosion issues in the different refining units as well as catalyst deactivation by clogging or fouling. To reach accurate analyses by inductively coupled plasma (ICP) techniques at low concentration levels, dilution in organic solvents rises as a simpler and more straightforward sample preparation methodology than conventional sample decomposition procedures (e.g., microwave-assisted acid digestion). However, matrix effects and the impact of the Cl chemical form on the signal must be overcome to obtain accurate results. RESULTS: In this work, the high temperature torch integrated sample introduction system (hTISIS) operated at 350 °C is coupled to an inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) for the determination of Cl in lipid biofuel feedstock samples diluted in xylene and these results are compared with those reported by a conventional sample introduction system. Under optimal conditions of the hTISIS-ICP-MS/MS configuration, matrix effects are efficiently overcome (recovery values ranged from 101 to 104%) as well as the effect of the Cl chemical form on the signal for 6 organochloride compounds. Thus, an external calibration approach can be set to carry out the quantification of this element in real samples. The method is successfully validated, obtaining a good agreement in the Cl concentration reported in a standard reference material (SRM NIST 1634c) and also by comparing the concentration results obtained by external calibration and standard addition approaches in two biofuel feedstock samples. SIGNIFICANCE AND NOVELTY: The hTISIS coupled to an ICP-MS/MS system is used for the first time to overcome not only matrix effects but also the impact of the Cl chemical form in biofuel feedstock samples. This novel method, with a limit of quantification (LOQ) of 7.1 µg kg-1, give access to an accurate Cl determination in all kind of lipid feedstocks for clean fuel production.

A Prospective, Multicenter, Real-World Registry of Coronary Lithotripsy in Calcified Coronary Arteries: The REPLICA-EPIC18 Study.

BACKGROUND: Intravascular lithotripsy (IVL) has demonstrated effectiveness in the treatment of calcified lesions in selected patients with stable coronary disease. OBJECTIVES: The authors sought to assess the performance of coronary IVL in calcified coronary lesions in a real-life, all comers, setting. METHODS: The REPLICA-EPIC18 study prospectively enrolled consecutive patients treated with IVL in 26 centers in Spain. An independent core laboratory performed the angiographic analysis and event adjudication. The primary effectiveness endpoint assessed procedural success (successful IVL delivery, final diameter stenosis <20%, and absence of in-hospital major adverse cardiovascular events [MACE]). The primary safety endpoint measured freedom from MACE at 30 days. A predefined substudy compared outcomes between acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients. RESULTS: A total of 426 patients (456 lesions) were included, 63% of the patients presenting with ACS. IVL delivery was successful in 99% of cases. Before IVL, 49% of lesions were considered undilatable. The primary effectiveness endpoint was achieved in 66% of patients, with similar rates among CCS patients (68%) and ACS patients (65%). Likewise, there were no significant differences in angiographic success after IVL between CCS and ACS patients. The rate of MACE at 30 days (primary safety endpoint) was 3% (1% in CCS and 5% in ACS patients [P = 0.073]). CONCLUSIONS: Coronary IVL proved to be a feasible and safe procedure in a "real-life" setting, effectively facilitating stent implantation in severely calcified lesions. Patients with ACS on admission showed similar angiographic success rates but showed a trend toward higher 30-day MACE compared with patients with CCS. (REPLICA-EPIC18 study [Registry of Coronary Lithotripsy in Spain]; NCT04298307).

Integrating Egocentric and Robotic Vision for Object Identification Using Siamese Networks and Superquadric Estimations in Partial Occlusion Scenarios.

This paper introduces a novel method that enables robots to identify objects based on user gaze, tracked via eye-tracking glasses. This is achieved without prior knowledge of the objects' categories or their locations and without external markers. The method integrates a two-part system: a category-agnostic object shape and pose estimator using superquadrics and Siamese networks. The superquadrics-based component estimates the shapes and poses of all objects, while the Siamese network matches the object targeted by the user's gaze with the robot's viewpoint. Both components are effectively designed to function in scenarios with partial occlusions. A key feature of the system is the user's ability to move freely around the scenario, allowing dynamic object selection via gaze from any position. The system is capable of handling significant viewpoint differences between the user and the robot and adapts easily to new objects. In tests under partial occlusion conditions, the Siamese networks demonstrated an 85.2% accuracy in aligning the user-selected object with the robot's viewpoint. This gaze-based Human-Robot Interaction approach demonstrates its practicality and adaptability in real-world scenarios.

Semantic representation and comparative analysis of physical activity sensor observations using MOX2-5 sensor in real and synthetic datasets: a proof-of-concept-study.

The widespread use of devices like mobile phones and wearables allows for automatic monitoring of human daily activities, generating vast datasets that offer insights into long-term human behavior. A structured and controlled data collection process is essential to unlock the full potential of this information. While wearable sensors for physical activity monitoring have gained significant traction in healthcare, sports science, and fitness applications, securing diverse and comprehensive datasets for research and algorithm development poses a notable challenge. In this proof-of-concept study, we underscore the significance of semantic representation in enhancing data interoperability and facilitating advanced analytics for physical activity sensor observations. Our approach focuses on enhancing the usability of physical activity datasets by employing a medical-grade (CE certified) sensor to generate synthetic datasets. Additionally, we provide insights into ethical considerations related to synthetic datasets. The study conducts a comparative analysis between real and synthetic activity datasets, assessing their effectiveness in mitigating model bias and promoting fairness in predictive analysis. We have created an ontology for semantically representing observations from physical activity sensors and conducted predictive analysis on data collected using MOX2-5 activity sensors. Until now, there has been a lack of publicly available datasets for physical activity collected with MOX2-5 activity monitoring medical grade (CE certified) device. The MOX2-5 captures and transmits high-resolution data, including activity intensity, weight-bearing, sedentary, standing, low, moderate, and vigorous physical activity, as well as steps per minute. Our dataset consists of physical activity data collected from 16 adults (Male: 12; Female: 4) over a period of 30-45 days (approximately 1.5 months), yielding a relatively small volume of 539 records. To address this limitation, we employ various synthetic data generation methods, such as Gaussian Capula (GC), Conditional Tabular General Adversarial Network (CTGAN), and Tabular General Adversarial Network (TABGAN), to augment the dataset with synthetic data. For both the authentic and synthetic datasets, we have developed a Multilayer Perceptron (MLP) classification model for accurately classifying daily physical activity levels. The findings underscore the effectiveness of semantic ontology in semantic search, knowledge representation, data integration, reasoning, and capturing meaningful relationships between data. The analysis supports the hypothesis that the efficiency of predictive models improves as the volume of additional synthetic training data increases. Ontology and Generative AI hold the potential to expedite advancements in behavioral monitoring research. The data presented, encompassing both real MOX2-5 and its synthetic counterpart, serves as a valuable resource for developing robust methods in activity type classification. Furthermore, it opens avenues for exploration into research directions related to synthetic data, including model efficiency, detection of generated data, and considerations regarding data privacy.

Patients' perceptions of use, needs, and preferences related to a telemedicine solution for HIV care in a Norwegian outpatient clinic: a qualitative study.

BACKGROUND: Telemedicine in outpatient services for people living with human immunodeficiency virus (PLHIV) was scaled up during the COVID-19 pandemic as services transitioned to remote care. Many studies have reported on the challenges and advantages of telemedicine care during the pandemic. However, there is limited research on the provision of telemedicine human immunodeficiency virus (HIV) care beyond the COVID-19 pandemic, which entails different telemedicine components and focuses on ways to improve the telemedicine experience for patients. This study aimed to explore PLHIV's perceptions of use, needs, and preferences related to a telemedicine solution for HIV care in an outpatient clinic in Norway. The telemedicine solution included a pre-consultation questionnaire, asynchronous digital messages, and video consultation. METHODS: Qualitative interviews were conducted with 12 PLHIV. The interviews were analysed using thematic analysis. RESULTS: We identified four main themes that covered the participants' perceptions, needs, and preferences: (1) perceived usability, (2) maintaining confidentiality, (3) accommodating personal preferences, and (4) perceived usefulness. Some participants had difficulty logging into the telemedicine solution. Other participants suggested additional functionalities, such as picture sharing and access to test result. Telemedicine care enabled the avoidance of stigmatising clinic experiences, although a few participants reported concerns about confidentiality and data security. Accommodating personal preferences and needs in terms of the type of consultations (in-person or video) and frequency of visits was essential to the participants. With telemedicine care, participants felt more in control of their own lives, perceiving that it increased their perceived quality of life and saved them both time and money for travelling to the clinic. CONCLUSIONS: Our study identified several specific needs and preferences related to the assessed technical solution and the provision of current and future telemedicine care services. Nevertheless, the telemedicine solution was perceived as a usable, flexible, and person-centred approach to HIV care, contributing to accommodating the participants' personal preferences. However, healthcare professionals need to ensure that individual requirements and preferences are consistent with evidence-based follow-up and supported by person-centred care. Thus, the practice of shared decision making is important in telemedicine care.

Interleukin-6 Induces Stem Cell Propagation through Liaison with the Sortilin-Progranulin Axis in Breast Cancer.

Unraveling the complex network between cancer cells and their tumor microenvironment is of clinical importance, as it might allow for the identification of new targets for cancer treatment. Cytokines and growth factors secreted by various cell types present in the tumor microenvironment have the potential to affect the challenging subpopulation of cancer stem cells showing treatment-resistant properties as well as aggressive features. By using various model systems, we investigated how the breast cancer stem cell-initiating growth factor progranulin influenced the secretion of cancer-associated proteins. In monolayer cultures, progranulin induced secretion of several inflammatory-related cytokines, such as interleukin (IL)-6 and -8, in a sortilin-dependent manner. Further, IL-6 increased the cancer stem fraction similarly to progranulin in the breast cancer cell lines MCF7 and MDA-MB-231 monitored by the surrogate mammosphere-forming assay. In a cohort of 63 patient-derived scaffold cultures cultured with breast cancer cells, we observed significant correlations between IL-6 and progranulin secretion, clearly validating the association between IL-6 and progranulin also in human-based microenvironments. In conclusion, the interplay between progranulin and IL-6 highlights a dual breast cancer stem cell-promoting function via sortilin, further supporting sortilin as a highly relevant therapeutic target for aggressive breast cancer.

Low but significant evolutionary potential for growth, phenology and reproduction traits in European beech.

Local survival of forest tree populations under climate change depends on existing genetic variation and their adaptability to changing environments. Responses to selection were studied in European beech (Fagus sylvatica) under field conditions. A total of 1087 adult trees, seeds, 1-year-old seedlings and established multiyear saplings were genotyped with 16 nuSSRs. Adult trees were assessed for phenotypic traits related to growth, phenology and reproduction. Parentage and paternity analyses were used to estimate effective female and male fecundity as a proxy of fitness and showed that few parents contributed to successful regeneration. Selection gradients were estimated from the relationship between traits and fecundity, while heritability and evolvability were estimated using mixed models and the breeder's equation. Larger trees bearing more fruit and early male flowering had higher total fecundity, while trees with longer growth season had lower total fecundity (directional selection). Stabilizing selection on spring phenology was found for female fecundity, highlighting the role of late frosts as a selection driver. Selection gradients for other traits varied between measurement years and the offspring cohort used to estimate parental fecundity. Compared to other studies in natural populations, we found low to moderate heritability and evolvability for most traits. Response to selection was higher for growth than for budburst, leaf senescence or reproduction traits, reflecting more consistent selection gradients across years and sex functions, and higher phenotypic variability in the population. Our study provides empirical evidence suggesting that populations of long-lived organisms such as forest trees can adapt locally, even at short-time scales.