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Previous studies have shown that the left hemisphere dominates motor function, often observed through homotopic activation measurements. Using a functional connectivity approach, this study investigated the lateralization of the sensorimotor cortex during handwriting and drawing, two complex visuomotor tasks with varying contextual demands. We found that both left- and right-lateralized connectivity in the primary motor cortex (M1), dorsal premotor cortex (PMd), somatosensory cortex, and visual regions were evident in adults (males and females), primarily in an interhemispheric integrative fashion. Critically, these lateralization tendencies remained highly invariant across task contexts, representing a task-invariant neural architecture for encoding fundamental motor programs consistently implemented in different task contexts. Additionally, the PMd exhibited a slight variation in lateralization degree between task contexts, reflecting the ability of the high-order motor system to adapt to varying task demands. However, connectivity-based lateralization of the sensorimotor cortex was not detected in 10-year-old children (males and females), suggesting that the maturation of connectivity-based lateralization requires prolonged development. In summary, this study demonstrates both task-invariant and task-sensitive connectivity lateralization in sensorimotor cortices that support the resilience and adaptability of skilled visuomotor performance. These findings align with the hierarchical organization of the motor system and underscore the significance of the functional connectivity-based approach in studying functional lateralization.
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Corteza Motora , Corteza Sensoriomotora , Adulto , Masculino , Femenino , Niño , Humanos , Imagen por Resonancia Magnética , Corteza Motora/fisiología , Corteza Somatosensorial , Mapeo EncefálicoRESUMEN
In recent years, artificial intelligence (AI) has demonstrated exceptional performance in mitosis identification and quantification. However, the implementation of AI in clinical practice needs to be evaluated against the existing methods. This study is aimed at assessing the optimal method of using AI-based mitotic figure scoring in breast cancer (BC). We utilized whole slide images from a large cohort of BC with extended follow-up comprising a discovery (n = 1715) and a validation (n = 859) set (Nottingham cohort). The Cancer Genome Atlas of breast invasive carcinoma (TCGA-BRCA) cohort (n = 757) was used as an external test set. Employing automated mitosis detection, the mitotic count was assessed using 3 different methods, the mitotic count per tumor area (MCT; calculated by dividing the number of mitotic figures by the total tumor area), the mitotic index (MI; defined as the average number of mitotic figures per 1000 malignant cells), and the mitotic activity index (MAI; defined as the number of mitotic figures in 3 mm2 area within the mitotic hotspot). These automated metrics were evaluated and compared based on their correlation with the well-established visual scoring method of the Nottingham grading system and Ki67 score, clinicopathologic parameters, and patient outcomes. AI-based mitotic scores derived from the 3 methods (MCT, MI, and MAI) were significantly correlated with the clinicopathologic characteristics and patient survival (P < .001). However, the mitotic counts and the derived cutoffs varied significantly between the 3 methods. Only MAI and MCT were positively correlated with the gold standard visual scoring method used in Nottingham grading system (r = 0.8 and r = 0.7, respectively) and Ki67 scores (r = 0.69 and r = 0.55, respectively), and MAI was the only independent predictor of survival (P < .05) in multivariate Cox regression analysis. For clinical applications, the optimum method of scoring mitosis using AI needs to be considered. MAI can provide reliable and reproducible results and can accurately quantify mitotic figures in BC.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Antígeno Ki-67 , Inteligencia Artificial , Mitosis , Índice MitóticoRESUMEN
INTRODUCTION: Traumatic brain injury (TBI) is associated with an accelerated course of dementia, although biological relationships are incompletely understood. METHODS: The study examined 1124 participants, including 343 with Alzheimer disease (AD), 127 with AD with TBI, 266 cognitively normal adults with TBI, and 388 cognitively normal adults without TBI. Cortical thickness was quantified from T1-weighted magnetic resonance imaging data. Multiple linear regression was used to determine the interaction between AD and TBI on cortical thickness. RESULTS: Among those with AD, TBI was associated with an earlier age of AD onset but, counterintuitively, less cortical thinning in frontotemporal regions relative to non-AD controls. DISCUSSION: AD with TBI represents a distinct group from AD, likely with distinct pathologic contributions beyond gray matter loss. This finding has important implications for the diagnosis and treatment of AD in the presence of TBI and indicates that models of AD, aging, and neural loss should account for TBI history.
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Enfermedad de Alzheimer , Lesiones Traumáticas del Encéfalo , Humanos , Enfermedad de Alzheimer/diagnóstico , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/patología , Envejecimiento/patología , Imagen por Resonancia Magnética/métodosRESUMEN
Computational pathology is currently witnessing a surge in the development of AI techniques, offering promise for achieving breakthroughs and significantly impacting the practices of pathology and oncology. These AI methods bring with them the potential to revolutionize diagnostic pipelines as well as treatment planning and overall patient care. Numerous peer-reviewed studies reporting remarkable performance across diverse tasks serve as a testimony to the potential of AI in the field. However, widespread adoption of these methods in clinical and pre-clinical settings still remains a challenge. In this review article, we present a detailed analysis of the major obstacles encountered during the development of effective models and their deployment in practice. We aim to provide readers with an overview of the latest developments, assist them with insights into identifying some specific challenges that may require resolution, and suggest recommendations and potential future research directions. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Inteligencia Artificial , Humanos , Reino UnidoRESUMEN
Optical tracking of head pose via fiducial markers has been proven to enable effective correction of motion artifacts in the brain during magnetic resonance imaging but remains difficult to implement in the clinic due to lengthy calibration and set up times. Advances in deep learning for markerless head pose estimation have yet to be applied to this problem because of the sub-millimetre spatial resolution required for motion correction. In the present work, two optical tracking systems are described for the development and training of a neural network: one marker-based system (a testing platform for measuring ground truth head pose) with high tracking fidelity to act as the training labels, and one markerless deep-learning-based system using images of the markerless head as input to the network. The markerless system has the potential to overcome issues of marker occlusion, insufficient rigid attachment of the marker, lengthy calibration times, and unequal performance across degrees of freedom (DOF), all of which hamper the adoption of marker-based solutions in the clinic. Detail is provided on the development of a custom moiré-enhanced fiducial marker for use as ground truth and on the calibration procedure for both optical tracking systems. Additionally, the development of a synthetic head pose dataset is described for the proof of concept and initial pre-training of a simple convolutional neural network. Results indicate that the ground truth system has been sufficiently calibrated and can track head pose with an error of <1 mm and <1°. Tracking data of a healthy, adult participant are shown. Pre-training results show that the average root-mean-squared error across the 6 DOF is 0.13 and 0.36 (mm or degrees) on a head model included and excluded from the training dataset, respectively. Overall, this work indicates excellent feasibility of the deep-learning-based approach and will enable future work in training and testing on a real dataset in the MRI environment.
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Cabeza , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Cabeza/diagnóstico por imagen , Movimientos de la Cabeza , Redes Neurales de la Computación , Marcadores Fiduciales , Calibración , Procesamiento de Imagen Asistido por Computador/métodos , Aprendizaje Profundo , Encéfalo/diagnóstico por imagen , ArtefactosRESUMEN
PURPOSE: Numerous classification systems have been developed for neck of femur fractures, but none have been tested for reliability in gunshot injuries. Our primary objective was to assess the inter-observer and intra-observer reliability of the AO/OTA classification system when applied to intracapsular neck of femur fractures secondary to low-velocity civilian gunshots wounds (GSWs). Our secondary objective was to test the reliability of the AO/OTA classification system in guiding surgeon treatment choices for these fractures. PATIENTS AND METHODS: Eighteen reviewers (six orthopaedic traumatologists, six general orthopaedic surgeons and six junior orthopaedic fellows) were given a set of 25 plain radiographs and CT scans of femur neck fractures secondary to GSW. For each clinical case, all reviewers selected a classification as well as treatment option from a list of given options. Inter-observer reliability was measured at the initial classification. The exercise was repeated 10-12 weeks later by the same 18 reviewers to test intra-observer reliability. RESULTS: The Fleiss kappa values indicate only slight agreement amongst raters, across all experience levels, for both injury classification and treatment. Intra-observer agreement was fair across all experience levels for both injury classification and treatment. CONCLUSION: The AO/OTA classification showed only slight reliability in classification of gunshot fractures of the femur neck. With only fair reliability, it also failed to guide surgical treatment thus rendering its routine use in daily clinical practice of questionable value.
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Fracturas del Cuello Femoral , Variaciones Dependientes del Observador , Heridas por Arma de Fuego , Humanos , Heridas por Arma de Fuego/diagnóstico por imagen , Heridas por Arma de Fuego/complicaciones , Fracturas del Cuello Femoral/clasificación , Fracturas del Cuello Femoral/cirugía , Fracturas del Cuello Femoral/diagnóstico por imagen , Reproducibilidad de los Resultados , Tomografía Computarizada por Rayos X , RadiografíaRESUMEN
OBJECTIVES: Uniformly classifying long bone open fractures is challenging. The purpose of this study was to propose a modified Orthopaedic Trauma Society (OTS) Open Fracture Classification System, developed in a setting with a high incidence of civilian gunshot fractures. METHODS: From our prospectively collected database, we identified all patients with open tibia and femur fractures treated with intramedullary nailing over a 4 year period. All open fractures were retrospectively reclassified from the Gustilo-Anderson Classification system to the OTS Open Fracture Classification System. RESULTS: One hundred and thirty-seven cases were identified. Ninety per cent of subjects were males. Their mean age was 34 years. The most common mechanism of injury was low-velocity civilian gunshot wounds (GSW) in 54.7% of cases. Soft tissue management was primary closure in 23.4% and soft tissue reconstruction in 24.1%. In 52.6% of cases (these all being secondary to civilian GSW), soft tissue management was healing via secondary intention. This is not included as a soft tissue management option in the OTS classification system. Fracture reclassification using the OTS Open Fracture Classification System was only possible in 47.5% of cases (Simple in 23.4%, Complex B in 24.1%). CONCLUSION: We conclude that the OTS Open Fracture Classification System is not inclusive of all open tibia and femur fractures as it does not cater for gunshot fractures. We propose a modification as follows: alter 'wound debridement' to 'appropriate wound care' and to subcategorise 'Simple' into type A and B: healing via secondary intention and primary closure, respectively.
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Fracturas del Fémur , Fracturas Abiertas , Ortopedia , Fracturas de la Tibia , Heridas por Arma de Fuego , Masculino , Humanos , Adulto , Femenino , Fracturas Abiertas/cirugía , Heridas por Arma de Fuego/cirugía , Estudios Retrospectivos , Fracturas de la Tibia/cirugía , Fracturas del Fémur/etiología , Fracturas del Fémur/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVE: To develop an interpretable artificial intelligence algorithm to rule out normal large bowel endoscopic biopsies, saving pathologist resources and helping with early diagnosis. DESIGN: A graph neural network was developed incorporating pathologist domain knowledge to classify 6591 whole-slides images (WSIs) of endoscopic large bowel biopsies from 3291 patients (approximately 54% female, 46% male) as normal or abnormal (non-neoplastic and neoplastic) using clinically driven interpretable features. One UK National Health Service (NHS) site was used for model training and internal validation. External validation was conducted on data from two other NHS sites and one Portuguese site. RESULTS: Model training and internal validation were performed on 5054 WSIs of 2080 patients resulting in an area under the curve-receiver operating characteristic (AUC-ROC) of 0.98 (SD=0.004) and AUC-precision-recall (PR) of 0.98 (SD=0.003). The performance of the model, named Interpretable Gland-Graphs using a Neural Aggregator (IGUANA), was consistent in testing over 1537 WSIs of 1211 patients from three independent external datasets with mean AUC-ROC=0.97 (SD=0.007) and AUC-PR=0.97 (SD=0.005). At a high sensitivity threshold of 99%, the proposed model can reduce the number of normal slides to be reviewed by a pathologist by approximately 55%. IGUANA also provides an explainable output highlighting potential abnormalities in a WSI in the form of a heatmap as well as numerical values associating the model prediction with various histological features. CONCLUSION: The model achieved consistently high accuracy showing its potential in optimising increasingly scarce pathologist resources. Explainable predictions can guide pathologists in their diagnostic decision-making and help boost their confidence in the algorithm, paving the way for its future clinical adoption.
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Inteligencia Artificial , Medicina Estatal , Humanos , Masculino , Femenino , Estudios Retrospectivos , Algoritmos , BiopsiaRESUMEN
BACKGROUND: Tumour infiltrating lymphocytes (TILs) are a prognostic parameter in triple-negative and human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). However, their role in luminal (oestrogen receptor positive and HER2 negative (ER + /HER2-)) BC remains unclear. In this study, we used artificial intelligence (AI) to assess the prognostic significance of TILs in a large well-characterised cohort of luminal BC. METHODS: Supervised deep learning model analysis of Haematoxylin and Eosin (H&E)-stained whole slide images (WSI) was applied to a cohort of 2231 luminal early-stage BC patients with long-term follow-up. Stromal TILs (sTILs) and intratumoural TILs (tTILs) were quantified and their spatial distribution within tumour tissue, as well as the proportion of stroma involved by sTILs were assessed. The association of TILs with clinicopathological parameters and patient outcome was determined. RESULTS: A strong positive linear correlation was observed between sTILs and tTILs. High sTILs and tTILs counts, as well as their proximity to stromal and tumour cells (co-occurrence) were associated with poor clinical outcomes and unfavourable clinicopathological parameters including high tumour grade, lymph node metastasis, large tumour size, and young age. AI-based assessment of the proportion of stroma composed of sTILs (as assessed visually in routine practice) was not predictive of patient outcome. tTILs was an independent predictor of worse patient outcome in multivariate Cox Regression analysis. CONCLUSION: AI-based detection of TILs counts, and their spatial distribution provides prognostic value in luminal early-stage BC patients. The utilisation of AI algorithms could provide a comprehensive assessment of TILs as a morphological variable in WSIs beyond eyeballing assessment.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama/patología , Linfocitos Infiltrantes de Tumor/patología , Inteligencia Artificial , Pronóstico , Neoplasias de la Mama Triple Negativas/patología , Biomarcadores de Tumor/metabolismoRESUMEN
There has been growing attention on the effect of COVID-19 on white-matter microstructure, especially among those that self-isolated after being infected. There is also immense scientific interest and potential clinical utility to evaluate the sensitivity of single-shell diffusion magnetic resonance imaging (MRI) methods for detecting such effects. In this work, the performances of three single-shell-compatible diffusion MRI modeling methods are compared for detecting the effect of COVID-19, including diffusion-tensor imaging, diffusion-tensor decomposition of orthogonal moments and correlated diffusion imaging. Imaging was performed on self-isolated patients at the study initiation and 3-month follow-up, along with age- and sex-matched controls. We demonstrate through simulations and experimental data that correlated diffusion imaging is associated with far greater sensitivity, being the only one of the three single-shell methods to demonstrate COVID-19-related brain effects. Results suggest less restricted diffusion in the frontal lobe in COVID-19 patients, but also more restricted diffusion in the cerebellar white matter, in agreement with several existing studies highlighting the vulnerability of the cerebellum to COVID-19 infection. These results, taken together with the simulation results, suggest that a significant proportion of COVID-19 related white-matter microstructural pathology manifests as a change in tissue diffusivity. Interestingly, different b-values also confer different sensitivities to the effects. No significant difference was observed in patients at the 3-month follow-up, likely due to the limited size of the follow-up cohort. To summarize, correlated diffusion imaging is shown to be a viable single-shell diffusion analysis approach that allows us to uncover opposing patterns of diffusion changes in the frontal and cerebellar regions of COVID-19 patients, suggesting the two regions react differently to viral infection.
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COVID-19 , Sustancia Blanca , COVID-19/diagnóstico por imagen , COVID-19/patología , Imagen de Difusión Tensora , Estudios de Factibilidad , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/ultraestructura , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/ultraestructura , Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , AncianoRESUMEN
Tumor-associated stroma in breast cancer (BC) is complex and exhibits a high degree of heterogeneity. To date, no standardized assessment method has been established. Artificial intelligence (AI) could provide an objective morphologic assessment of tumors and stroma, with the potential to identify new features not discernible by visual microscopy. In this study, we used AI to assess the clinical significance of (1) stroma-to-tumor ratio (S:TR) and (2) the spatial arrangement of stromal cells, tumor cell density, and tumor burden in BC. Whole-slide images of a large cohort (n = 1968) of well-characterized luminal BC cases were examined. Region and cell-level annotation was performed, and supervised deep learning models were applied for automated quantification of tumor and stromal features. S:TR was calculated in terms of surface area and cell count ratio, and the S:TR heterogeneity and spatial distribution were also assessed. Tumor cell density and tumor size were used to estimate tumor burden. Cases were divided into discovery (n = 1027) and test (n = 941) sets for validation of the findings. In the whole cohort, the stroma-to-tumor mean surface area ratio was 0.74, and stromal cell density heterogeneity score was high (0.7/1). BC with high S:TR showed features characteristic of good prognosis and longer patient survival in both the discovery and test sets. Heterogeneous spatial distribution of S:TR areas was predictive of worse outcome. Higher tumor burden was associated with aggressive tumor behavior and shorter survival and was an independent predictor of worse outcome (BC-specific survival; hazard ratio: 1.7, P = .03, 95% CI, 1.04-2.83 and distant metastasis-free survival; hazard ratio: 1.64, P = .04, 95% CI, 1.01-2.62) superior to absolute tumor size. The study concludes that AI provides a tool to assess major and subtle morphologic stromal features in BC with prognostic implications. Tumor burden is more prognostically informative than tumor size.
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Pigs are natural hosts for the same subtypes of influenza A viruses as humans and integrally involved in virus evolution with frequent interspecies transmissions in both directions. The emergence of the 2009 pandemic H1N1 virus illustrates the importance of pigs in evolution of zoonotic strains. Here we generated pig influenza-specific monoclonal antibodies (mAbs) from H1N1pdm09 infected pigs. The mAbs recognized the same two major immunodominant haemagglutinin (HA) epitopes targeted by humans, one of which is not recognized by post-infection ferret antisera that are commonly used to monitor virus evolution. Neutralizing activity of the pig mAbs was comparable to that of potent human anti-HA mAbs. Further, prophylactic administration of a selected porcine mAb to pigs abolished lung viral load and greatly reduced lung pathology but did not eliminate nasal shedding of virus after H1N1pdm09 challenge. Hence mAbs from pigs, which target HA can significantly reduce disease severity. These results, together with the comparable sizes of pigs and humans, indicate that the pig is a valuable model for understanding how best to apply mAbs as therapy in humans and for monitoring antigenic drift of influenza viruses in humans, thereby providing information highly relevant to making influenza vaccine recommendations.
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Anticuerpos Antivirales/farmacología , Epítopos/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Gripe Humana/tratamiento farmacológico , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Hemaglutininas/inmunología , Hemaglutininas/farmacología , Humanos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/virología , PorcinosRESUMEN
[This corrects the article DOI: 10.1371/journal.ppat.1009330.].
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OBJECTIVE: To identify structural and neurochemical properties that underlie functional connectivity impairments of the primary motor cortex (PMC) and how these relate to clinical findings in amyotrophic lateral sclerosis (ALS). METHODS: 52 patients with ALS and 52 healthy controls, matched for age and sex, were enrolled from 5 centres across Canada for the Canadian ALS Neuroimaging Consortium study. Resting-state functional MRI, diffusion tensor imaging and magnetic resonance spectroscopy data were acquired. Functional connectivity maps, diffusion metrics and neurometabolite ratios were obtained from the analyses of the acquired multimodal data. A clinical assessment of foot tapping (frequency) was performed to examine upper motor neuron function in all participants. RESULTS: Compared with healthy controls, the primary motor cortex in ALS showed reduced functional connectivity with sensory (T=5.21), frontal (T=3.70), temporal (T=3.80), putaminal (T=4.03) and adjacent motor (T=4.60) regions. In the primary motor cortex, N-acetyl aspartate (NAA, a neuronal marker) ratios and diffusion metrics (mean, axial and radial diffusivity, fractional anisotropy (FA)) were altered. Within the ALS cohort, foot tapping frequency correlated with NAA (r=0.347) and white matter FA (r=0.537). NAA levels showed associations with disturbed functional connectivity of the motor cortex. CONCLUSION: In vivo neurochemistry may represent an effective imaging marker of impaired motor cortex functional connectivity in ALS.
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Esclerosis Amiotrófica Lateral , Corteza Motora , Neuroquímica , Humanos , Imagen de Difusión Tensora/métodos , Canadá , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: Neurological symptoms associated with coronavirus disease 2019 (COVID-19), such as fatigue and smell/taste changes, persist beyond infection. However, little is known of brain physiology in the post-COVID-19 timeframe. PURPOSE: To determine whether adults who experienced flu-like symptoms due to COVID-19 would exhibit cerebral blood flow (CBF) alterations in the weeks/months beyond infection, relative to controls who experienced flu-like symptoms but tested negative for COVID-19. STUDY TYPE: Prospective observational. POPULATION: A total of 39 adults who previously self-isolated at home due to COVID-19 (41.9 ± 12.6 years of age, 59% female, 116.5 ± 62.2 days since positive diagnosis) and 11 controls who experienced flu-like symptoms but had a negative COVID-19 diagnosis (41.5 ± 13.4 years of age, 55% female, 112.1 ± 59.5 since negative diagnosis). FIELD STRENGTH AND SEQUENCES: A 3.0 T; T1-weighted magnetization-prepared rapid gradient and echo-planar turbo gradient-spin echo arterial spin labeling sequences. ASSESSMENT: Arterial spin labeling was used to estimate CBF. A self-reported questionnaire assessed symptoms, including ongoing fatigue. CBF was compared between COVID-19 and control groups and between those with (n = 11) and without self-reported ongoing fatigue (n = 28) within the COVID-19 group. STATISTICAL TESTS: Between-group and within-group comparisons of CBF were performed in a voxel-wise manner, controlling for age and sex, at a family-wise error rate of 0.05. RESULTS: Relative to controls, the COVID-19 group exhibited significantly decreased CBF in subcortical regions including the thalamus, orbitofrontal cortex, and basal ganglia (maximum cluster size = 6012 voxels and maximum t-statistic = 5.21). Within the COVID-19 group, significant CBF differences in occipital and parietal regions were observed between those with and without self-reported on-going fatigue. DATA CONCLUSION: These cross-sectional data revealed regional CBF decreases in the COVID-19 group, suggesting the relevance of brain physiology in the post-COVID-19 timeframe. This research may help elucidate the heterogeneous symptoms of the post-COVID-19 condition. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.
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COVID-19 , Adulto , Femenino , Humanos , Masculino , Circulación Cerebrovascular/fisiología , COVID-19/diagnóstico por imagen , Prueba de COVID-19 , Estudios Transversales , Fatiga/diagnóstico por imagen , Imagen por Resonancia Magnética , Marcadores de Spin , Persona de Mediana EdadRESUMEN
Alcohol use disorder (AUD) is a highly prevalent, often refractory, medical illness. The symptoms of AUD are driven by dysfunction in several neurocircuits centered on the nucleus accumbens (NAc). Case reports and animal studies suggest NAc-DBS may be an effective harm-reduction treatment in severe AUD. Six patients with severe, refractory AUD underwent NAc-DBS. Safety metrics and clinical outcomes were recorded. Positron emission tomography (FDG-PET) was used to measure glucose metabolism in the NAc at baseline and 6 months. Functional magnetic resonance imaging (fMRI) was used to characterize postoperative changes in NAc functional connectivity to the rest of the brain, as well as NAc and dorsal striatal reactivity to alcoholic visual cues. This study was registered with ClinicalTrials.gov, NCT03660124. All patients experienced a reduction in craving. There was a significant reduction in alcohol consumption, alcohol-related compulsivity, and anxiety at 12 months. There was no significant change in depression. FDG-PET analysis demonstrated reduced NAc metabolism by 6 months, which correlated with improvements in compulsive drinking behaviors. Clinical improvement correlated with reduced functional connectivity between the NAc and the visual association cortex. Active DBS was associated with reduced activation of the dorsal striatum during passive viewing of alcohol-containing pictures. NAc-DBS is feasible and safe in patients with severe, otherwise refractory AUD. It is associated with a reduction in cravings and addictive behavior. A potential mechanism underlying this process is a down-regulation of the NAc, a disruption of its functional connectivity to the visual association cortex, and interference of cue-elicited dorsal striatum reactivity. Trial Registration NCT03660124 ( www.clinicaltrials.gov ).
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Alcoholismo , Estimulación Encefálica Profunda , Animales , Alcoholismo/terapia , Estimulación Encefálica Profunda/métodos , Fluorodesoxiglucosa F18 , Núcleo Accumbens/diagnóstico por imagen , Proyectos PilotoRESUMEN
BACKGROUND: Clinical neuroimaging studies often investigate group differences between patients and controls, yet multivariate imaging features may enable individual-level classification. This study aims to classify youth with bipolar disorder (BD) versus healthy youth using grey matter cerebral blood flow (CBF) data analyzed with logistic regressions. METHODS: Using a 3 Tesla magnetic resonance imaging (MRI) system, we collected pseudo-continuous, arterial spin-labelling, resting-state functional MRI (rfMRI) and T 1-weighted images from youth with BD and healthy controls. We used 3 logistic regression models to classify youth with BD versus controls, controlling for age and sex, using mean grey matter CBF as a single explanatory variable, quantitative CBF features based on principal component analysis (PCA) or relative (intensity-normalized) CBF features based on PCA. We also carried out a comparison analysis using rfMRI data. RESULTS: The study included 46 patients with BD (mean age 17 yr, standard deviation [SD] 1 yr; 25 females) and 49 healthy controls (mean age 16 yr, SD 2 yr; 24 females). Global mean CBF and multivariate quantitative CBF offered similar classification performance that was above chance. The association between CBF images and the feature map was not significantly different between groups (p = 0.13); however, the multivariate classifier identified regions with lower CBF among patients with BD (ΔCBF = -2.94 mL/100 g/min; permutation test p = 0047). Classification performance decreased when considering rfMRI data. LIMITATIONS: We cannot comment on which CBF principal component is most relevant to the classification. Participants may have had various mood states, comorbidities, demographics and medication records. CONCLUSION: Brain CBF features can classify youth with BD versus healthy controls with above-chance accuracy using logistic regression. A global CBF feature may offer similar classification performance to distinct multivariate CBF features.
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Trastorno Bipolar , Femenino , Humanos , Adolescente , Trastorno Bipolar/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Circulación Cerebrovascular , Corteza Cerebral , Sustancia Gris/diagnóstico por imagenRESUMEN
BACKGROUND: Intraoperative adverse events lead to patient injury and death, and are increasing. Early warning systems (EWSs) have been used to detect patient deterioration and save lives. However, few studies have used EWSs to monitor surgical performance and caution about imminent technical errors. Previous (non-surgical) research has investigated neural activity to predict future motor errors using electroencephalography (EEG). The present proof-of-concept cohort study investigates whether EEG could predict technical errors in surgery. METHODS: In a large academic hospital, three surgical fellows performed 12 elective laparoscopic general surgeries. Audiovisual data of the operating room and the surgeon's neural activity were recorded. Technical errors and epochs of good surgical performance were coded into events. Neural activity was observed 40 s prior and 10 s after errors and good events to determine how far in advance errors were detected. A hierarchical regression model was used to account for possible clustering within surgeons. This prospective, proof-of-concept, cohort study was conducted from July to November 2021, with a pilot period from February to March 2020 used to optimize the technique of data capture and included participants who were blinded from study hypotheses. RESULTS: Forty-five technical errors, mainly due to too little force or distance (n = 39), and 27 good surgical events were coded during grasping and dissection. Neural activity representing error monitoring (p = .008) and motor uncertainty (p = .034) was detected 17 s prior to errors, but not prior to good surgical performance. CONCLUSIONS: These results show that distinct neural signatures are predictive of technical error in laparoscopic surgery. If replicated with low false-alarm rates, an EEG-based EWS of technical errors could be used to improve individualized surgical training by flagging imminent unsafe actions-before errors occur and cause patient harm.
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Competencia Clínica , Laparoscopía , Humanos , Estudios de Cohortes , Estudios Prospectivos , Laparoscopía/efectos adversos , ElectroencefalografíaRESUMEN
OBJECTIVE: To examine the roles of the default mode network (DMN) and executive control network (ECN) in prolonged recovery after mild traumatic brain injury (mTBI), and relationships with indices of white matter microstructural injury. METHODS: Seventeen mTBI patients with persistent symptoms were imaged an average of 21.5 months post-injury, along with 23 healthy controls. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to evaluate functional connectivity (FC) of the DMN and ECN. Diffusion tensor imaging (DTI) quantified fractional anisotropy, along with mean, axial and radial diffusivity of white matter tracts. RESULTS: Compared to controls, patients with mTBI had increased functional connectivity of the DMN and ECN to brain regions implicated in salience and frontoparietal networks, and increased white matter diffusivity within the cerebrum and brainstem. Among the patients, FC was correlated with better neurocognitive test scores, while diffusivity was correlated with more severe self-reported symptoms. The FC and diffusivity values within abnormal brain regions were not significantly correlated. CONCLUSION: For female mTBI patients with prolonged symptoms, hyper-connectivity may represent a compensatory response that helps to mitigate the effects of mTBI on cognition. These effects are unrelated to indices of microstructural injury, which are correlated with symptom severity, suggesting that rs-fMRI and DTI may capture distinct aspects of pathophysiology.
Asunto(s)
Conmoción Encefálica , Síndrome Posconmocional , Humanos , Femenino , Síndrome Posconmocional/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Función Ejecutiva , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodosRESUMEN
Studies of Aboriginal young people have often followed a deficit approach depicting them as 'risky' and in need of help. In contrast, this study took a strengths-based approach and focussed on what Aboriginal young people value, how they stay safe and how their culture impacts their lives. 16 Aboriginal men aged 16 to 24 years were interviewed in Sydney, Australia. We examined Aboriginal young men's perspectives about relationships, sex and gender. Interviews were conducted by young Aboriginal men in 2019 and 2020. Overall, four features of positive sexual and romantic relationships were discussed: (1) love, connection and support; (2) enjoyment and fun; (3) responsibility, safety and consent; and 4) honesty, respect and trust. Additionally, three topics related to gender roles: (1) becoming a man; (2) sex as a masculine achievement; and (3) inequality and gender stereotypes. Our study suggests that Aboriginal young men are exploring sexual and romantic relationships, and although they value enjoyment and fun, they are aware of broader issues such as consent and respect. The young men acknowledged gender stereotypes faced by young women. Our results could be used by future school safe sex education programmes to better meet the needs of Aboriginal young men.