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BACKGROUND: Activities of daily living (ADL) are essential for independence and personal well-being, reflecting an individual's functional status. Impairment in executing these tasks can limit autonomy and negatively affect quality of life. The assessment of physical function during ADL is crucial for the prevention and rehabilitation of movement limitations. Still, its traditional evaluation based on subjective observation has limitations in precision and objectivity. OBJECTIVE: The primary objective of this study is to use innovative technology, specifically wearable inertial sensors combined with artificial intelligence techniques, to objectively and accurately evaluate human performance in ADL. It is proposed to overcome the limitations of traditional methods by implementing systems that allow dynamic and noninvasive monitoring of movements during daily activities. The approach seeks to provide an effective tool for the early detection of dysfunctions and the personalization of treatment and rehabilitation plans, thus promoting an improvement in the quality of life of individuals. METHODS: To monitor movements, wearable inertial sensors were developed, which include accelerometers and triaxial gyroscopes. The developed sensors were used to create a proprietary database with 6 movements related to the shoulder and 3 related to the back. We registered 53,165 activity records in the database (consisting of accelerometer and gyroscope measurements), which were reduced to 52,600 after processing to remove null or abnormal values. Finally, 4 deep learning (DL) models were created by combining various processing layers to explore different approaches in ADL recognition. RESULTS: The results revealed high performance of the 4 proposed models, with levels of accuracy, precision, recall, and F1-score ranging between 95% and 97% for all classes and an average loss of 0.10. These results indicate the great capacity of the models to accurately identify a variety of activities, with a good balance between precision and recall. Both the convolutional and bidirectional approaches achieved slightly superior results, although the bidirectional model reached convergence in a smaller number of epochs. CONCLUSIONS: The DL models implemented have demonstrated solid performance, indicating an effective ability to identify and classify various daily activities related to the shoulder and lumbar region. These results were achieved with minimal sensorization-being noninvasive and practically imperceptible to the user-which does not affect their daily routine and promotes acceptance and adherence to continuous monitoring, thus improving the reliability of the data collected. This research has the potential to have a significant impact on the clinical evaluation and rehabilitation of patients with movement limitations, by providing an objective and advanced tool to detect key movement patterns and joint dysfunctions.
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This study aimed to assess acute and residual changes in sprint-related hamstring injury (HSI) risk factors after a football (soccer) match, focusing on recovery within the commonly observed 72-h timeframe between elite football matches. We used a multifactorial approach within a football context, incorporating optical and ultrastructural microscopic analysis of BFlh (biceps femoris long head) muscle fibres, along with an examination of BFlh fibre composition. Changes in sprint performance-related factors and HSI modifiable risk factors were examined until 3 days after the match (MD +3) in 20 football players. BFlh biopsy specimens were obtained before and at MD +3 in 10 players. The findings indicated that at MD +3, sprint-related performance and HSI risk factors had not fully recovered, with notable increases in localized BFlh fibre disruptions. Interestingly, match load (both external and internal) did not correlate with changes in sprint performance or HSI risk factors nor with BFlh fibre disruption. Furthermore, our study revealed a balanced distribution of ATPase-based fibre types in BFlh, with type-II fibres associated with sprint performance. Overall, the results suggest that a 72-h recovery period may not be adequate for hamstring muscles in terms of both HSI risk factors and BFlh fibre structure following a football match.
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Traumatismos en Atletas , Músculos Isquiosurales , Fútbol , Humanos , Fútbol/lesiones , Fútbol/fisiología , Músculos Isquiosurales/lesiones , Factores de Riesgo , Masculino , Adulto Joven , Factores de Tiempo , Fibras Musculares Esqueléticas/fisiología , Adulto , Rendimiento Atlético/fisiología , Recuperación de la Función , Carrera/fisiología , Carrera/lesionesRESUMEN
Through extensive Monte Carlo simulations, we systematically study the effect of chain stiffness on the packing ability of linear polymers composed of hard spheres in extremely confined monolayers, corresponding effectively to 2D films. First, we explore the limit of random close packing as a function of the equilibrium bending angle and then quantify the local and global order by the degree of crystallinity and the nematic or tetratic orientational order parameter, respectively. A multi-scale wealth of structural behavior is observed, which is inherently absent in the case of athermal individual monomers and is surprisingly richer than its 3D counterpart under bulk conditions. As a general trend, an isotropic to nematic transition is observed at sufficiently high surface coverages, which is followed by the establishment of the tetratic state, which in turn marks the onset of the random close packing. For chains with right-angle bonds, the incompatibility of the imposed bending angle with the neighbor geometry of the triangular crystal leads to a singular intra- and inter-polymer tiling pattern made of squares and triangles with optimal local filling at high surface concentrations. The present study could serve as a first step toward the design of hard colloidal polymers with a tunable structural behavior for 2D applications.
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Reports on neoplasms in bears are scarce, especially concerning ovarian tumors. A large primary ovarian neoplasm with multiple metastasis was found during the necropsy of a 14-year-old free-ranging Eurasian brown bear (Ursus arctos) from Northwestern Spain. Histopathology and immunohistochemistry allowed for the diagnosis of a sex cord stromal tumor. This is a complex group of neoplasms which differ in the predominant cell morphology and immunohistochemical features. The microscopic examination revealed two types of cells, one with eosinophilic cytoplasm, intermingled with larger vacuolated cells rich in lipids. The evaluation of the immunoreactivity to different markers, frequently used in the characterization of gonadal tumors (INHA, inhibin-alpha; PLAP, placental alkaline phosphatase; Ki-67; α-SMA, actin alpha-smooth muscle) and inflammation patterns (IBA1, ionized calcium-binding adapter molecule for macrophages; CD3 for T lymphocytes; CD20 for B lymphocytes), displayed significant INHA positive immunostaining of neoplastic cells, as well as inflammatory cell infiltration, mainly composed of macrophages and B lymphocytes. These findings were consistent with a malignant ovarian steroid cell tumor, not otherwise specified. The present study characterizes an unusual type of neoplasm, and also represents the first report of an ovarian sex cord stromal tumor in Ursidae.
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This study addresses the pressing issue of plastic pollution in coastal and marine ecosystems, challenging the misconception that the entrapment of plastics can be considered as an ecosystem service. We differentiate between essential natural processes that sustain ecological balance and biodiversity and the detrimental accumulation of synthetic polymers. The pathways through which plastics enter these environments-from terrestrial to maritime sources-are examined, alongside their pervasive impacts on crucial ecosystem services such as habitat quality, the vitality of marine species, and nutrient cycling. Our findings highlight the paradox of resilience and vulnerability in these ecosystems: while capable of accumulating substantial amounts of plastic debris, they suffer long-lasting ecological, socio-economic, and health repercussions. We argue for a paradigm shift in management strategies aimed at reducing plastic production at the source, improving waste management practices, conducting targeted cleanup operations, and rehabilitating impacted ecosystems. Emphasizing a comprehensive understanding of plastic pollution is vital for framing effective solutions and necessitates a reevaluation of societal, industrial, and regulatory frameworks. This shift is imperative not only to address current pollution levels but also to safeguard and sustain the functionality of coastal ecosystems, ensuring their ability to continue providing essential services and supporting biodiversity.
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Plásticos , Administración de Residuos , Ecosistema , Océanos y Mares , Contaminación Química del Agua/prevención & control , Contaminación Química del Agua/estadística & datos numéricos , Contaminantes Químicos del Agua/análisis , Administración de Residuos/métodos , Monitoreo del Ambiente , Política AmbientalRESUMEN
Natural products (NPs) or their derivatives represent a large proportion of drugs that successfully progress through clinical trials to approval. This study explores the presence of NPs in both early- and late-stage drug discovery to determine their success rate, and the factors or features of natural products that contribute to such success. As a proxy for early drug development stages, we analyzed patent applications over several decades, finding a consistent proportion of NP, NP-derived, and synthetic-compound-based patent documents, with the latter group outnumbering NP and NP-derived ones (approximately 77% vs 23%). We next assessed clinical trial data, where we observed a steady increase in NP and NP-derived compounds from clinical trial phases I to III (from approximately 35% in phase I to 45% in phase III), with an inverse trend observed in synthetics (from approximately 65% in phase I to 55% in phase III). Finally, in vitro and in silico toxicity studies revealed that NPs and their derivatives were less toxic alternatives to their synthetic counterparts. These discoveries offer valuable insights for successful NP-based drug development, highlighting the potential benefits of prioritizing NPs and their derivatives as starting points.
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Productos Biológicos , Desarrollo de Medicamentos , Productos Biológicos/química , Productos Biológicos/farmacología , Humanos , Ensayos Clínicos como Asunto , Descubrimiento de Drogas , Estructura MolecularRESUMEN
Worldwide, governments are implementing strategies to combat marine litter. However, their effectiveness is largely unknown because we lack tools to systematically monitor marine litter over broad spatio-temporal scales. Metre-sized aggregations of floating debris generated by sea-surface convergence lines have been reported as a reliable target for detection from satellites. Yet, the usefulness of such ephemeral, scattered aggregations as proxy for sustained, large-scale monitoring of marine litter remains an open question for a dedicated Earth-Observation mission. Here, we track this proxy over a series of 300,000 satellite images of the entire Mediterranean Sea. The proxy is mainly related to recent inputs from land-based litter sources. Despite the limitations of in-orbit technology, satellite detections are sufficient to map hot-spots and capture trends, providing an unprecedented source-to-sink view of the marine litter phenomenon. Torrential rains largely control marine litter inputs, while coastal boundary currents and wind-driven surface sweep arise as key drivers for its distribution over the ocean. Satellite-based monitoring proves to be a real game changer for marine litter research and management. Furthermore, the development of an ad-hoc sensor can lower the minimum detectable concentration by one order of magnitude, ensuring operational monitoring, at least for seasonal-to-interannual variability in the mesoscale.
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In this work, we present an electrochemical sensor for fast, low-cost, and easy detection of the SARS-CoV-2 spike protein in infected patients. The sensor is based on a selected combination of nanomaterials with a specific purpose. A bioconjugate formed by Few-layer bismuthene nanosheets (FLB) and tetrahedral DNA nanostructures (TDNs) is immobilized on Carbon Screen-Printed Electrodes (CSPE). The TDNs contain on the top vertex an aptamer that specifically binds to the SARS-CoV-2 spike protein, and a thiol group at the three basal vertices to anchor to the FLB. The TDNs are also marked with a redox indicator, Azure A (AA), which allows the direct detection of SARS-CoV-2 spike protein through changes in the current intensity of its electrolysis before and after the biorecognition reaction. The developed sensor can detect SARS-CoV-2 spike protein with a detection limit of 1.74 fg mL-1 directly in nasopharyngeal swab human samples. Therefore, this study offers a new strategy for rapid virus detection since it is versatile enough for different viruses and pathogens.
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Técnicas Biosensibles , COVID-19 , Límite de Detección , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , SARS-CoV-2/aislamiento & purificación , Técnicas Biosensibles/métodos , Humanos , Glicoproteína de la Espiga del Coronavirus/análisis , Glicoproteína de la Espiga del Coronavirus/química , COVID-19/virología , COVID-19/diagnóstico , Técnicas Electroquímicas/métodos , Nanoestructuras/química , ADN/química , Aptámeros de Nucleótidos/químicaRESUMEN
Climate change influences forest ecosystems in several ways, such as modifying forest growth or ecosystem functionality. To fully understand the impact of changing climatic conditions on forest growth it is necessary to undertake long-term spatiotemporal analyses. The main purpose of this work is to describe the major trends in tree growth of Pinus pinaster in Spain over the last 70 years, differentiating homogeneous ecological units using an unsupervised classification algorithm and additive modelling techniques. We also aim to relate these growth trends with temporal series for precipitation and temperature, as well as forest variables. We leverage information from a large data set of tree cores (around 2200) extracted during the field campaign of the Fourth Spanish National Forest Inventory. An unsupervised algorithm classified the plots into five classes, which were consistent in ecological terms. We also found a general decline in growth in three of the five ecoregions since the 1970s, concomitant with an increase in temperature and a reduction in precipitation. However, this tree growth decline has not been observed in the Atlantic influenced ecoregion, where the cooler, more humid climatic conditions are more stable. Certain stand features, such as low basal area through forest management practices, may have alleviated the impact of harsh climatic conditions on some areas of inner Spain, while denser stands display a more pronounced decline in tree growth. We concluded that Southern populations show some degrees of growth decline and low growth trends while Northern populations did not exhibit growth decline and have the largest growth rates. Under a forecasted increment of temperatures, the growth decline can be expanded.
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Cambio Climático , Bosques , Pinus , Pinus/crecimiento & desarrollo , España , Árboles/crecimiento & desarrollo , Análisis Espacio-Temporal , Ecosistema , Monitoreo del Ambiente/métodosRESUMEN
OBJECTIVES: Identifying profiles of hospitalized COVID-19 patients and explore their association with different degrees of severity of COVID-19 outcomes (i.e. in-hospital mortality, ICU assistance, and invasive mechanical ventilation). The findings of this study could inform the development of multiple care intervention strategies to improve patient outcomes. METHODS: Prospective multicentre cohort study during four different waves of COVID-19 from March 1st, 2020 to August 31st, 2021 in four health consortiums within the southern Barcelona metropolitan region. From a starting point of over 292 demographic characteristics, comorbidities, vital signs, severity scores, and clinical analytics at hospital admission, we used both clinical judgment and supervised statistical methods to reduce to the 36 most informative completed covariates according to the disease outcomes for each wave. Patients were then grouped using an unsupervised semiparametric method (KAMILA). Results were interpreted by clinical and statistician team consensus to identify clinically-meaningful patient profiles. RESULTS: The analysis included nw1 = 1657, nw2 = 697, nw3 = 677, and nw4 = 787 hospitalized-COVID-19 patients for each of the four waves. Clustering analysis identified 2 patient profiles for waves 1 and 3, while 3 profiles were determined for waves 2 and 4. Patients allocated in those groups showed a different percentage of disease outcomes (e.g., wave 1: 15.9% (Cluster 1) vs. 31.8% (Cluster 2) for in-hospital mortality rate). The main factors to determine groups were the patient's age and number of obese patients, number of comorbidities, oxygen support requirement, and various severity scores. The last wave is also influenced by the massive incorporation of COVID-19 vaccines. CONCLUSION: Our study suggests that a single care model at hospital admission may not meet the needs of hospitalized-COVID-19 adults. A clustering approach appears to be appropriate for helping physicians to differentiate patients and, thus, apply multiple care intervention strategies, as another way of responding to new outbreaks of this or future diseases.
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COVID-19 , Mortalidad Hospitalaria , Hospitalización , Humanos , COVID-19/epidemiología , COVID-19/mortalidad , COVID-19/terapia , España/epidemiología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Análisis por Conglomerados , Estudios Prospectivos , Hospitalización/estadística & datos numéricos , SARS-CoV-2/aislamiento & purificación , Unidades de Cuidados Intensivos , Respiración Artificial , Índice de Severidad de la Enfermedad , Anciano de 80 o más Años , Adulto , ComorbilidadRESUMEN
INTRODUCTION: In addition to clinical factors, blood-based biomarkers can provide useful information on the risk of developing post-stroke epilepsy (PSE). Our aim was to identify serum biomarkers at stroke onset that could contribute to predicting patients at higher risk of PSE. PATIENTS AND METHODS: From a previous study in which 895 acute stroke patients were followed-up, 51 patients developed PSE. We selected 15 patients with PSE and 15 controls without epilepsy. In a biomarker discovery setting, 5 Olink panels of 96 proteins each, were used to determine protein levels. Biomarkers that were down-regulated and overexpressed in PSE patients, and those that showed the strongest interactions with other proteins were validated using an enzyme-linked immunosorbent assay in samples from 50 PSE patients and 50 controls. A ROC curve analysis was used to evaluate the predictive ability of significant biomarkers to develop PSE. RESULTS: Mean age of the PSE discovery cohort was 68.56 ± 15.1, 40% women and baseline NIHSS 12 [IQR 1-25]. Nine proteins were down-expressed: CASP-8, TNFSF-14, STAMBP, ENRAGE, EDA2R, SIRT2, TGF-alpha, OSM and CLEC1B. VEGFa, CD40 and CCL4 showed greatest interactions with the remaining proteins. In the validation analysis, TNFSF-14 was the single biomarker showing statistically significant downregulated levels in PSE patients (p = 0.006) and it showed a good predictive capability to develop PSE (AUC 0.733, 95% CI 0.601-0.865). DISCUSSION AND CONCLUSION: Protein expression in PSE patients differs from that of non-epileptic stroke patients, suggesting the involvement of several different proteins in post-stroke epileptogenesis. TNFSF-14 emerges as a potential biomarker for predicting PSE.
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Conflicting results remain on the impacts of climate change on marine organisms, hindering our capacity to predict the future state of marine ecosystems. To account for species-specific responses and for the ambiguous relation of most metrics to fitness, we develop a meta-analytical approach based on the deviation of responses from reference values (absolute change) to complement meta-analyses of directional (relative) changes in responses. Using this approach, we evaluate responses of fish and invertebrates to warming and acidification. We find that climate drivers induce directional changes in calcification, survival, and metabolism, and significant deviations in twice as many biological responses, including physiology, reproduction, behavior, and development. Widespread deviations of responses are detected even under moderate intensity levels of warming and acidification, while directional changes are mostly limited to more severe intensity levels. Because such deviations may result in ecological shifts impacting ecosystem structures and processes, our results suggest that climate change will likely have stronger impacts than those previously predicted based on directional changes alone.
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Ecosistema , Agua de Mar , Animales , Agua de Mar/química , Invertebrados/fisiología , Cambio Climático , Organismos Acuáticos , Concentración de Iones de Hidrógeno , Océanos y Mares , Calentamiento GlobalRESUMEN
Lymphocyte activation gene-3 (LAG-3) is an inhibitory receptor expressed on activated T cells and an emerging immunotherapy target. Domain 1 (D1) of LAG-3, which has been purported to directly interact with major histocompatibility complex class II (MHCII) and fibrinogen-like protein 1 (FGL1), has been the major focus for the development of therapeutic antibodies that inhibit LAG-3 receptor-ligand interactions and restore T cell function. Here, we present a high-resolution structure of glycosylated mouse LAG-3 ectodomain, identifying that cis-homodimerization, mediated through a network of hydrophobic residues within domain 2 (D2), is critically required for LAG-3 function. Additionally, we found a previously unidentified key protein-glycan interaction in the dimer interface that affects the spatial orientation of the neighboring D1 domain. Mutation of LAG-3 D2 residues reduced dimer formation, dramatically abolished LAG-3 binding to both MHCII and FGL1 ligands, and consequentially inhibited the role of LAG-3 in suppressing T cell responses. Intriguingly, we showed that antibodies directed against D1, D2, and D3 domains are all capable of blocking LAG-3 dimer formation and MHCII and FGL-1 ligand binding, suggesting a potential allosteric model of LAG-3 function tightly regulated by dimerization. Furthermore, our work reveals unique epitopes, in addition to D1, that can be targeted for immunotherapy of cancer and other human diseases.
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Antígenos de Histocompatibilidad Clase II , Linfocitos T , Animales , Humanos , Ratones , Dimerización , Fibrinógeno/metabolismo , Ligandos , MutaciónRESUMEN
Inhibitors of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) such as nirmatrelvir (NTV) and ensitrelvir (ETV) have proven effective in reducing the severity of COVID-19, but the presence of resistance-conferring mutations in sequenced viral genomes raises concerns about future drug resistance. Second-generation oral drugs that retain function against these mutants are thus urgently needed. We hypothesized that the covalent hepatitis C virus protease inhibitor boceprevir (BPV) could serve as the basis for orally bioavailable drugs that inhibit SARS-CoV-2 Mpro more efficiently than existing drugs. Performing structure-guided modifications of BPV, we developed a picomolar-affinity inhibitor, ML2006a4, with antiviral activity, oral pharmacokinetics, and therapeutic efficacy similar or superior to those of NTV. A crucial feature of ML2006a4 is a derivatization of the ketoamide reactive group that improves cell permeability and oral bioavailability. Last, ML2006a4 was found to be less sensitive to several mutations that cause resistance to NTV or ETV and occur in the natural SARS-CoV-2 population. Thus, anticipatory design can preemptively address potential resistance mechanisms to expand future treatment options against coronavirus variants.
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COVID-19 , Proteasas 3C de Coronavirus , Humanos , SARS-CoV-2 , Mutación/genética , Antivirales/farmacología , Antivirales/uso terapéutico , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/uso terapéuticoRESUMEN
Importance: It is unclear whether breast cancer (BC) with low ERBB2 expression (ERBB2-low) is a distinct clinical, pathological, and epidemiological entity from BC classified as no ERBB2 expression (ERBB2-negative). Objective: To evaluate the clinical, pathological, and epidemiologic features of BC with ERBB2-low expression compared with ERBB2-negative BC in a large population study. Design, Setting, and Participants: This cohort study was conducted as part of the Pathways Study, a prospective, racially and ethnically diverse cohort study of women with BC enrolled between 2006 and 2013 in Kaiser Permanente Northern California (KPNC). The hematoxylin and eosin slides underwent centralized pathology review, including the percentage of tumor infiltrating lymphocytes (TILs). Breast biomarker results were extracted from pathology reports, and women were included if they had a documented ERBB2 value that was not classified ERBB2-positive. Data were analyzed from February 2023 through January 2024. Exposure: Clinical and tumor characteristics associated with BC and ERBB2-low or ERBB2-negative status. Main Outcome and Measures: ERBB2-low was defined as immunohistochemistry score of 1+ or 2+ (negative by in situ hybridization); ERBB2-negative was defined as immunohistochemistry score of 0+. Other data were collected by self-report or extraction from electronic health records, including BC risk factors, tumor characteristics, treatment modality, and survival outcomes, with recurrence-free survival (RFS) as the primary outcome and overall survival (OS) and BC-specific mortality (BCSM) as secondary outcomes. The clinical, pathological, and epidemiological variables were compared between ERBB2-low and ERBB2-negative BC. Results: Of 2200 eligible patients (all female; with mean [SD] age, 60.4 [11.9] years), 1295 (57.2%) had tumors that were ERBB2-low. Hormone receptors were positive in 1956 patients (88.9%). The sample included 291 Asian patients (13.2%), 166 Black patients (7.5%), 253 Hispanic patients (11.5%), 1439 White patients (65.4%), and 51 patients (2.3%) who identified as other race or ethnicity (eg, American Indian or Alaska Native and Pacific Islander). Within the hormone receptor-negative group, patients whose tumors had ERBB2-low staining, compared with those with ERBB2-negative tumors, had better OS (hazard ratio [HR], 0.54; 95% CI, 0.33-0.91; P = .02), RFS (HR, 0.53; 95% CI, 0.30-0.95; P = .03), and BCSM (HR, 0.43; 95% CI, 0.22-0.84; P = .01). In multivariable survival analysis stratified by hormone receptor status and adjusted for key covariates, patients with ERBB2-low and hormone receptor-negative tumors had lower overall mortality (HR, 0.48; 95% CI, 0.27-0.83; P = .009), RFS (HR, 0.45; 95% CI, 0.24-0.86; P = .02), and BCSM (subdistribution HR, 0.21; 95% CI, 0.10-0.46; P < .001) compared with patients with ERBB2-negative and hormone receptor-negative tumors. Within the hormone receptor-negative subtype, patients with ERBB2-low and high TILs tumors had better survival across all 3 outcomes compared with patients with ERBB2-negative and low TILs tumors. Additionally, patients with ERBB2-low and low TILs tumors had better BCSM (subdistribution HR, 0.36; 95% CI, 0.14-0.92; P = .03). Conclusions and Relevance: These findings suggest that there were clinical, pathological, and epidemiological differences between ERBB2-low and ERBB2-negative BC, raising the possibility that ERBB2-low might be a unique biologic entity.
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Neoplasias de la Mama , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Mama/tratamiento farmacológico , Estudios de Cohortes , Hormonas/uso terapéutico , Linfocitos Infiltrantes de Tumor , Estudios Prospectivos , Receptor ErbB-2 , AncianoRESUMEN
BACKGROUND AND OBJECTIVES: The occurrence of seizures after aneurysmal subarachnoid hemorrhage (aSAH) is associated with a poorer functional and cognitive prognosis and less favorable quality of life. It would be of value to promptly identify patients at risk of epilepsy to optimize follow-up protocols and design preventive strategies. Our aim was to develop a predictive score to help stratify epilepsy risk in patients with aSAH. METHODS: This is a retrospective, longitudinal study of all adults with aSAH admitted to our center (2012-2021). We collected demographic data, clinical and radiologic variables, data on early-onset seizures (EOSs), and data on development of epilepsy. Exclusion criteria were previous structural brain lesion, epilepsy, and ≤7 days' follow-up. Multiple Cox regression was used to evaluate factors independently associated with unprovoked remote seizures (i.e., epilepsy). The best fitting regression model was used to develop a predictive score. Performance was evaluated in an external validation cohort of 308 patients using receiver-operating characteristic curve analysis. RESULTS: From an initial database of 743 patients, 419 met the inclusion criteria and were included in the analysis. The mean age was 60 ± 14 years, 269 patients (64%) were women, and 50 (11.9%) developed epilepsy within a median follow-up of 4.2 years. Premorbid modified Rankin Score (mRS) (hazard ratio [HR] 4.74 [1.8-12.4], p = 0.001), VASOGRADE score (HR 2.45 [1.4-4.2], p = 0.001), surgical treatment (HR 2.77 [1.6-4.9], p = 0.001), and presence of EOSs (HR 1.84 [1.0-3.4], p = 0.05) were independently associated with epilepsy. The proposed scale, designated RISE, scores 1 point for premorbid mRS ≥ 2 (R), VASOGRADE-Yellow (I, Ischemia), surgical intervention (S), and history of EOSs (E) and 2 points for VASOGRADE-Red. RISE stratifies patients into 3 groups: low (0-1), moderate (2-3), and high (4-5) risk (2.9%, 20.8%, and 75.7% developed epilepsy, respectively). On validation in a cohort from a different tertiary care center (N = 308), the new scale yielded a similar risk distribution and good predictive power for epilepsy within 5 years after aSAH (area under the curve [AUC] 0.82; 95% CI 0.74-0.90). DISCUSSION: The RISE scale is a robust predictor of post-SAH epilepsy with immediate clinical applicability. In addition to facilitating personalized diagnosis and treatment, RISE may be of value for exploring future antiepileptogenesis strategies.
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Epilepsia , Hemorragia Subaracnoidea , Adulto , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/epidemiología , Estudios Longitudinales , Estudios Retrospectivos , Calidad de Vida , Pronóstico , Epilepsia/etiología , Epilepsia/complicaciones , Convulsiones/complicacionesRESUMEN
PURPOSE: Currently, there is a limited availability of tools to predict seizure recurrence after discontinuation of antiseizure medications (ASMs). This study aimed to establish the seizure recurrence rate following ASM cessation in adult patients with idiopathic generalized epilepsy (IGE) and to assess the predictive performance of the Lamberink and the Stevelink prediction models using real-world data. METHODS: Retrospective longitudinal study in IGE patients who underwent ASM withdrawal in a tertiary epilepsy clinic since June 2011, with the latest follow up in January 2024. The minimum follow-up period was 12 months. Clinical and demographic variables were collected, and the seizure recurrence prediction models proposed by Lamberink and Stevelink were applied and evaluated. RESULTS: Forty-seven patients (mean age 33.15 ± 8 [20-55] years; 72.35 % women) were included. During the follow-up period, seizures recurred in 25 patients (53.2 %). Median time to recurrence was 8 months [IQR 3-13.5 months], and 17 patients (68 %) relapsed within the first year. None of the relapsing patients developed drug-resistant epilepsy. The only significant risk factor associated with recurrence was a seizure-free period of less than 2 years before discontinuing medication (91.7 % vs 40 %, p =.005). The Stevelink prediction model at both 2 (p =.015) and 5 years (p =.020) achieved statistical significance, with an AUC of 0.72 (95 % CI 0.56-0.88), while the Lamberink model showed inadequate prognostic capability. CONCLUSION: In our real-world cohort, a seizure-free period of at least 2 years was the only factor significantly associated with epilepsy remission after ASM withdrawal. Larger studies are needed to accurately predict seizure recurrence in IGE patients.
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Epilepsia Generalizada , Epilepsia , Adulto , Humanos , Femenino , Masculino , Anticonvulsivantes/uso terapéutico , Estudios Retrospectivos , Estudios Longitudinales , Convulsiones/tratamiento farmacológico , Epilepsia Generalizada/tratamiento farmacológico , Epilepsia/tratamiento farmacológico , Recurrencia , Inmunoglobulina E/uso terapéuticoRESUMEN
PURPOSE: There is insufficient evidence on the management of refractory status epilepticus (RSE) and super-RSE (SRSE). Ketamine is a N-methyl-d-aspartate receptor antagonist in the treatment of these entities. Our objectives were to study the effectiveness and safety of ketamine in the treatment of adult patients with RSE and SRSE, to determine the factors that can influence the response to ketamine, and to explore its use in patients without mechanical ventilation. METHODS: Adult patients who had received intravenous ketamine for the treatment of RSE or SRSE at Hospital Universitario Clínico San Carlos (Madrid, Spain) or Hospital Universitari Vall d'Hebron (Barcelona, Spain) from 2017 to 2023 were retrospectively analysed. RESULTS: This study included 58 adult patients, mean (standard deviation) age 60.2 (15.7) years, of whom 41 (70.7 %) were male; 33 (56.9 %) patients responded to ketamine without recurrence, with a low rate of adverse effects (8.6 %). The presence of SRSE at the time of ketamine initiation (OR 0.287, p = 0.028) and the time elapsed between status epilepticus onset and ketamine administration (OR 0.991, p = 0.034) were associated with worse response to ketamine. Patients treated without mechanical ventilation had similar rates of response without recurrence (62.5% vs 56.9 %) and lower mortality (37.5% vs 53.5 %) compared to the overall group. CONCLUSION: Ketamine is an effective drug with few adverse effects. Prompt administration should be considered in patients with RSE requiring anaesthesia, in patients with SRSE, and in patients with RSE who do not respond to standard antiseizure drugs and in whom mechanical ventilation is not advised.
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Ketamina , Estado Epiléptico , Humanos , Ketamina/administración & dosificación , Ketamina/uso terapéutico , Estado Epiléptico/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Adulto , Epilepsia Refractaria/tratamiento farmacológico , Resultado del Tratamiento , Antagonistas de Aminoácidos Excitadores/administración & dosificación , Antagonistas de Aminoácidos Excitadores/uso terapéutico , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/uso terapéuticoRESUMEN
BACKGROUND: The increase in breast cancer cases and breast cancer survival makes it advisable to quantify the impact of the health-related stigma of this disease. PURPOSE/OBJECTIVES: To develop and validate a breast cancer stigma scale in Spanish. METHODS: Women diagnosed with, or survivors of, breast cancer were included. The development of the Breast Cancer Stigma Assessment Scale (BCSAS) involved both a literature review and personal interviews. Content validity was assessed using a Delphi study and a pilot test; construct validity was evaluated using an exploratory factor analysis; and convergent validity was assessed using six scales. Cronbach's α internal consistency and test-retest reliability were used to determine the reliability of the scales. RESULTS: 231 women responded to the 28-item scale. The BCSAS showed good reliability, with α = 0.897. Seven factors emerged: concealment (α = 0.765), disturbance (α = 0.772), internalized stigma (α = 0.750), aesthetics (α = 0.779), course (α = 0.599), danger (α = 0.502), and origin (α = 0.350). The test-retest reliability was 0.830 (p < 0.001). Significant correlation was observed with event centrality (r = 0.701), anxiety-depression (r = 0.668), shame (r = 0.645), guilt (r = 0.524), and quality of life (r = -0.545). CONCLUSIONS: The BCSAS is a reliable and valid measure of stigma in women with breast cancer and its survivors. It could be useful for detecting stigma risk and establishing psychotherapeutic and care priorities.
RESUMEN
BACKGROUND: a lack of adequate training in palliative care leads to a greater emotional burden on nurses. PURPOSE: to assess the effect of a simulation using standardized patients on self-efficacy in palliative care, ability to cope with death, and emotional intelligence among nursing students. METHODS: a randomized clinical trial and qualitative study. A total of 264 nursing students in a palliative care module completed the Bugen, trait meta-mood, and self-efficacy in palliative care scales after active participation in the simulation (n = 51), watching the simulation (n = 113), and the control group (n = 100). An ANOVA with a multi-comparative analysis and McNemar's tests for paired samples were calculated. Active participants were interviewed, and a thematic analysis was conducted. RESULTS: there was an improvement after the assessment in all three groups assessed for coping with death (p < 0.01), emotional intelligence (p < 0.01), and self-efficacy (p < 0.01). In addition, the active group improved more than the observer group and the control group in coping with death, attention, and repair. The students in the interviews identified sadness and an emotional lack of control. CONCLUSIONS: the simulation improved nursing students' self-efficacy in palliative care. This effect was partially stronger in the active group.