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1.
BMC Med Inform Decis Mak ; 24(1): 137, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802809

RESUMEN

BACKGROUND: Modeling causality through graphs, referred to as causal graph learning, offers an appropriate description of the dynamics of causality. The majority of current machine learning models in clinical decision support systems only predict associations between variables, whereas causal graph learning models causality dynamics through graphs. However, building personalized causal graphs for each individual is challenging due to the limited amount of data available for each patient. METHOD: In this study, we present a new algorithmic framework using meta-learning for learning personalized causal graphs in biomedicine. Our framework extracts common patterns from multiple patient graphs and applies this information to develop individualized graphs. In multi-task causal graph learning, the proposed optimized initial guess of shared commonality enables the rapid adoption of knowledge to new tasks for efficient causal graph learning. RESULTS: Experiments on one real-world biomedical causal graph learning benchmark data and four synthetic benchmarks show that our algorithm outperformed the baseline methods. Our algorithm can better understand the underlying patterns in the data, leading to more accurate predictions of the causal graph. Specifically, we reduce the structural hamming distance by 50-75%, indicating an improvement in graph prediction accuracy. Additionally, the false discovery rate is decreased by 20-30%, demonstrating that our algorithm made fewer incorrect predictions compared to the baseline algorithms. CONCLUSION: To the best of our knowledge, this is the first study to demonstrate the effectiveness of meta-learning in personalized causal graph learning and cause inference modeling for biomedicine. In addition, the proposed algorithm can also be generalized to transnational research areas where integrated analysis is necessary for various distributions of datasets, including different clinical institutions.


Asunto(s)
Algoritmos , Aprendizaje Automático , Humanos , Causalidad
2.
J Exp Med ; 221(4)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38417019

RESUMEN

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a clear genetic component. While most SLE patients carry rare gene variants in lupus risk genes, little is known about their contribution to disease pathogenesis. Amongst them, SH2B3-a negative regulator of cytokine and growth factor receptor signaling-harbors rare coding variants in over 5% of SLE patients. Here, we show that unlike the variant found exclusively in healthy controls, SH2B3 rare variants found in lupus patients are predominantly hypomorphic alleles, failing to suppress IFNGR signaling via JAK2-STAT1. The generation of two mouse lines carrying patients' variants revealed that SH2B3 is important in limiting the number of immature and transitional B cells. Furthermore, hypomorphic SH2B3 was shown to impair the negative selection of immature/transitional self-reactive B cells and accelerate autoimmunity in sensitized mice, at least in part due to increased IL-4R signaling and BAFF-R expression. This work identifies a previously unappreciated role for SH2B3 in human B cell tolerance and lupus risk.


Asunto(s)
Autoinmunidad , Lupus Eritematoso Sistémico , Animales , Humanos , Ratones , Autoinmunidad/genética , Factor Activador de Células B/metabolismo , Linfocitos B , Lupus Eritematoso Sistémico/genética , Células Precursoras de Linfocitos B
3.
IEEE Rev Biomed Eng ; 17: 80-97, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37824325

RESUMEN

With the recent advancement of novel biomedical technologies such as high-throughput sequencing and wearable devices, multi-modal biomedical data ranging from multi-omics molecular data to real-time continuous bio-signals are generated at an unprecedented speed and scale every day. For the first time, these multi-modal biomedical data are able to make precision medicine close to a reality. However, due to data volume and the complexity, making good use of these multi-modal biomedical data requires major effort. Researchers and clinicians are actively developing artificial intelligence (AI) approaches for data-driven knowledge discovery and causal inference using a variety of biomedical data modalities. These AI-based approaches have demonstrated promising results in various biomedical and healthcare applications. In this review paper, we summarize the state-of-the-art AI models for integrating multi-omics data and electronic health records (EHRs) for precision medicine. We discuss the challenges and opportunities in integrating multi-omics data with EHRs and future directions. We hope this review can inspire future research and developing in integrating multi-omics data with EHRs for precision medicine.


Asunto(s)
Inteligencia Artificial , Multiómica , Humanos , Medicina de Precisión , Registros Electrónicos de Salud , Atención a la Salud
4.
Sci Adv ; 9(49): eadi9566, 2023 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-38055819

RESUMEN

Autosomal dominant loss-of-function (LoF) variants in cytotoxic T-lymphocyte associated protein 4 (CTLA4) cause immune dysregulation with autoimmunity, immunodeficiency and lymphoproliferation (IDAIL). Incomplete penetrance and variable expressivity are characteristic of IDAIL caused by CTLA-4 haploinsufficiency (CTLA-4h), pointing to a role for genetic modifiers. Here, we describe an IDAIL proband carrying a maternally inherited pathogenic CTLA4 variant and a paternally inherited rare LoF missense variant in CLEC7A, which encodes for the ß-glucan pattern recognition receptor DECTIN-1. The CLEC7A variant led to a loss of DECTIN-1 dimerization and surface expression. Notably, DECTIN-1 stimulation promoted human and mouse regulatory T cell (Treg) differentiation from naïve αß and γδ T cells, even in the absence of transforming growth factor-ß. Consistent with DECTIN-1's Treg-boosting ability, partial DECTIN-1 deficiency exacerbated the Treg defect conferred by CTL4-4h. DECTIN-1/CLEC7A emerges as a modifier gene in CTLA-4h, increasing expressivity of CTLA4 variants and acting in functional epistasis with CTLA-4 to maintain immune homeostasis and tolerance.


Asunto(s)
Haploinsuficiencia , Lectinas Tipo C , Animales , Humanos , Ratones , Autoinmunidad , Antígeno CTLA-4/genética , Lectinas Tipo C/genética
5.
Sci Rep ; 13(1): 19488, 2023 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-37945586

RESUMEN

Recent advances in artificial intelligence (AI) have sparked interest in developing explainable AI (XAI) methods for clinical decision support systems, especially in translational research. Although using XAI methods may enhance trust in black-box models, evaluating their effectiveness has been challenging, primarily due to the absence of human (expert) intervention, additional annotations, and automated strategies. In order to conduct a thorough assessment, we propose a patch perturbation-based approach to automatically evaluate the quality of explanations in medical imaging analysis. To eliminate the need for human efforts in conventional evaluation methods, our approach executes poisoning attacks during model retraining by generating both static and dynamic triggers. We then propose a comprehensive set of evaluation metrics during the model inference stage to facilitate the evaluation from multiple perspectives, covering a wide range of correctness, completeness, consistency, and complexity. In addition, we include an extensive case study to showcase the proposed evaluation strategy by applying widely-used XAI methods on COVID-19 X-ray imaging classification tasks, as well as a thorough review of existing XAI methods in medical imaging analysis with evaluation availability. The proposed patch perturbation-based workflow offers model developers an automated and generalizable evaluation strategy to identify potential pitfalls and optimize their proposed explainable solutions, while also aiding end-users in comparing and selecting appropriate XAI methods that meet specific clinical needs in real-world clinical research and practice.


Asunto(s)
COVID-19 , Sistemas de Apoyo a Decisiones Clínicas , Humanos , Inteligencia Artificial , COVID-19/diagnóstico por imagen , Rayos X , Benchmarking
6.
Sci Rep ; 13(1): 18981, 2023 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-37923795

RESUMEN

Personalized medicine plays an important role in treatment optimization for COVID-19 patient management. Early treatment in patients at high risk of severe complications is vital to prevent death and ventilator use. Predicting COVID-19 clinical outcomes using machine learning may provide a fast and data-driven solution for optimizing patient care by estimating the need for early treatment. In addition, it is essential to accurately predict risk across demographic groups, particularly those underrepresented in existing models. Unfortunately, there is a lack of studies demonstrating the equitable performance of machine learning models across patient demographics. To overcome this existing limitation, we generate a robust machine learning model to predict patient-specific risk of death or ventilator use in COVID-19 positive patients using features available at the time of diagnosis. We establish the value of our solution across patient demographics, including gender and race. In addition, we improve clinical trust in our automated predictions by generating interpretable patient clustering, patient-level clinical feature importance, and global clinical feature importance within our large real-world COVID-19 positive patient dataset. We achieved 89.38% area under receiver operating curve (AUROC) performance for severe outcomes prediction and our robust feature ranking approach identified the presence of dementia as a key indicator for worse patient outcomes. We also demonstrated that our deep-learning clustering approach outperforms traditional clustering in separating patients by severity of outcome based on mutual information performance. Finally, we developed an application for automated and fair patient risk assessment with minimal manual data entry using existing data exchange standards.


Asunto(s)
COVID-19 , Humanos , Medición de Riesgo , Evaluación de Resultado en la Atención de Salud , Pronóstico , Aprendizaje Automático , Estudios Retrospectivos
7.
Phage (New Rochelle) ; 4(2): 55-67, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37350995

RESUMEN

Phage-antibiotic synergy (PAS) has been extensively explored over the past decade, with the aim of developing more effective treatments against multidrug-resistant organisms. However, it remains unclear how to effectively combine these two approaches. To address this uncertainty, we assessed four main aspects of PAS interactions in this review, seeking to identify commonalities of combining treatments within and between bacterial species. We examined all literature on PAS efficacy toward ESKAPE pathogens and present an analysis of the data in papers focusing on: (1) order of treatment, (2) dose of both phage and antibiotics, (3) mechanism of action, and (4) viability of transfer from in vivo or animal model trials to clinical applications. Our analysis indicates that there is little consistency within phage-antibiotic therapy regimens, suggesting that highly individualized treatment regimens should be used. We propose a set of experimental studies to address these research gaps. We end our review with suggestions on how to improve studies on phage-antibiotic combination therapy to advance this field.

8.
PLoS One ; 18(5): e0285534, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37167225

RESUMEN

Contact investigation and TB preventive treatment of children under five years of age who are close contacts of a TB case is a key component of TB prevention. However, the uptake of TB preventive treatment is low in many high-TB burden settings. This study explores factors affecting the implementation of TB contact investigation and preventive treatment among children in Malaysia's city of Kota Kinabalu, Sabah State. This study was conducted in three primary health clinics between 2019 and 2020. We purposively sampled 34 parents and guardians of child contacts eligible for TB preventive treatment, and 25 healthcare providers involved in the management of child contacts. We conducted thematic analysis of semi-structured interviews and focus group discussions to illicit factors affecting implementation and uptake of TB contact investigation and TB preventive therapy. Six main themes emerged from the analyses-four of these relating to contact investigation and two relating to TB preventive therapy. Factors affecting TB contact investigation were addressed under system related factors (external factors, stakeholder collaboration, healthcare workers' and clients' concerns), clinic related factors (perceived performance, clinic schedule, and space), healthcare worker related factors (cooperation, commitment, knowledge, misconception, counselling and communication) and patient and contact related factors (cooperation and commitment). Factors affecting TB preventive treatment delivery were addressed under guardian related factors (cooperation, commitment, knowledge and misconception) and treatment related factors (child-friendly form and adverse effects). To address gaps and barriers identified in our study, we recommend developing system capacity to maintain routine contact investigation and preventive treatment in the context of external program risks, providing training to healthcare workers to address misconceptions, safeguarding vulnerable clients against the risk of detention and deportation while accessing care, ensuring public and private services are provided regardless of migration status, and improving processes and resources for contact investigation and preventive treatment.


Asunto(s)
Trazado de Contacto , Tuberculosis , Humanos , Preescolar , Malasia , Tuberculosis/prevención & control , Tuberculosis/epidemiología , Investigación Cualitativa , Grupos Focales
9.
Front Neuroinform ; 17: 1123376, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37006636

RESUMEN

Introduction: Multimodal classification is increasingly common in electrophysiology studies. Many studies use deep learning classifiers with raw time-series data, which makes explainability difficult, and has resulted in relatively few studies applying explainability methods. This is concerning because explainability is vital to the development and implementation of clinical classifiers. As such, new multimodal explainability methods are needed. Methods: In this study, we train a convolutional neural network for automated sleep stage classification with electroencephalogram (EEG), electrooculogram, and electromyogram data. We then present a global explainability approach that is uniquely adapted for electrophysiology analysis and compare it to an existing approach. We present the first two local multimodal explainability approaches. We look for subject-level differences in the local explanations that are obscured by global methods and look for relationships between the explanations and clinical and demographic variables in a novel analysis. Results: We find a high level of agreement between methods. We find that EEG is globally the most important modality for most sleep stages and that subject-level differences in importance arise in local explanations that are not captured in global explanations. We further show that sex, followed by medication and age, had significant effects upon the patterns learned by the classifier. Discussion: Our novel methods enhance explainability for the growing field of multimodal electrophysiology classification, provide avenues for the advancement of personalized medicine, yield unique insights into the effects of demographic and clinical variables upon classifiers, and help pave the way for the implementation of multimodal electrophysiology clinical classifiers.

10.
J Biomed Inform ; 139: 104303, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36736449

RESUMEN

Expert microscopic analysis of cells obtained from frequent heart biopsies is vital for early detection of pediatric heart transplant rejection to prevent heart failure. Detection of this rare condition is prone to low levels of expert agreement due to the difficulty of identifying subtle rejection signs within biopsy samples. The rarity of pediatric heart transplant rejection also means that very few gold-standard images are available for developing machine learning models. To solve this urgent clinical challenge, we developed a deep learning model to automatically quantify rejection risk within digital images of biopsied tissue using an explainable synthetic data augmentation approach. We developed this explainable AI framework to illustrate how our progressive and inspirational generative adversarial network models distinguish between normal tissue images and those containing cellular rejection signs. To quantify biopsy-level rejection risk, we first detect local rejection features using a binary image classifier trained with expert-annotated and synthetic examples. We converted these local predictions into a biopsy-wide rejection score via an interpretable histogram-based approach. Our model significantly improves upon prior works with the same dataset with an area under the receiver operating curve (AUROC) of 98.84% for the local rejection detection task and 95.56% for the biopsy-rejection prediction task. A biopsy-level sensitivity of 83.33% makes our approach suitable for early screening of biopsies to prioritize expert analysis. Our framework provides a solution to rare medical imaging challenges currently limited by small datasets.


Asunto(s)
Insuficiencia Cardíaca , Trasplante de Corazón , Humanos , Niño , Diagnóstico por Imagen , Aprendizaje Automático , Medición de Riesgo , Complicaciones Posoperatorias
11.
IEEE Rev Biomed Eng ; 16: 5-21, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35737637

RESUMEN

Despite the myriad peer-reviewed papers demonstrating novel Artificial Intelligence (AI)-based solutions to COVID-19 challenges during the pandemic, few have made a significant clinical impact, especially in diagnosis and disease precision staging. One major cause for such low impact is the lack of model transparency, significantly limiting the AI adoption in real clinical practice. To solve this problem, AI models need to be explained to users. Thus, we have conducted a comprehensive study of Explainable Artificial Intelligence (XAI) using PRISMA technology. Our findings suggest that XAI can improve model performance, instill trust in the users, and assist users in decision-making. In this systematic review, we introduce common XAI techniques and their utility with specific examples of their application. We discuss the evaluation of XAI results because it is an important step for maximizing the value of AI-based clinical decision support systems. Additionally, we present the traditional, modern, and advanced XAI models to demonstrate the evolution of novel techniques. Finally, we provide a best practice guideline that developers can refer to during the model experimentation. We also offer potential solutions with specific examples for common challenges in AI model experimentation. This comprehensive review, hopefully, can promote AI adoption in biomedicine and healthcare.


Asunto(s)
Inteligencia Artificial , COVID-19 , Humanos , Pandemias , Atención a la Salud
12.
IEEE Rev Biomed Eng ; 16: 53-69, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36269930

RESUMEN

At the beginning of the COVID-19 pandemic, there was significant hype about the potential impact of artificial intelligence (AI) tools in combatting COVID-19 on diagnosis, prognosis, or surveillance. However, AI tools have not yet been widely successful. One of the key reason is the COVID-19 pandemic has demanded faster real-time development of AI-driven clinical and health support tools, including rapid data collection, algorithm development, validation, and deployment. However, there was not enough time for proper data quality control. Learning from the hard lessons in COVID-19, we summarize the important health data quality challenges during COVID-19 pandemic such as lack of data standardization, missing data, tabulation errors, and noise and artifact. Then we conduct a systematic investigation of computational methods that address these issues, including emerging novel advanced AI data quality control methods that achieve better data quality outcomes and, in some cases, simplify or automate the data cleaning process. We hope this article can assist healthcare community to improve health data quality going forward with novel AI development.


Asunto(s)
Inteligencia Artificial , COVID-19 , Humanos , Exactitud de los Datos , Pandemias , Algoritmos
13.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 4687-4690, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-36085809

RESUMEN

Shriners Children's (SHC) is a hospital system whose mission is to advance the treatment and research of pediatric diseases. SHC success has generated a wealth of clinical data. Unfortunately, barriers to healthcare data access often limit data-driven clinical research. We decreased this burden by allowing access to clinical data via the standardized data access standard called FHIR (Fast Healthcare Interoperability Resources). Specifically, we converted existing data in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) standard into FHIR data elements using a technology called OMOP-on-FHIR. In addition, we developed two applications leveraging the FHIR data elements to facilitate patient cohort curation to advance research into pediatric musculoskeletal diseases. Our work enables clinicians and clinical researchers to use hundreds of currently available open-sourced FHIR applications. Our successful implementation of OMOP-on-FHIR within a large hospital system will accelerate advancements in pediatric disease treatment and research.


Asunto(s)
Informática Médica , Enfermedades Musculoesqueléticas , Niño , Instituciones de Salud , Hospitales , Humanos , Tecnología
14.
Prog Mol Biol Transl Sci ; 190(1): 1-37, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36007995

RESUMEN

Achieving predictive, precise, participatory, preventive, and personalized health (abbreviated as p-Health) requires comprehensive evaluations of an individual's conditions captured by various measurement technologies. Since the 1950s, analysis of care providers' and physicians' notes and measurement data by computers to improve healthcare delivery has been termed clinical informatics. Since the 2010s, wide adoptions of Electronic Health Records (EHRs) have greatly improved clinical informatics development with fast growing pervasive wearable technologies that continuously capture the human physiological profile in-clinic (EHRs) and out-of-clinic (PHRs or Personal Health Records) to bolster mobile health (mHealth). In addition, after the Human Genome Project in the 1990s, medical genomics has emerged to capture the high-throughput molecular profile of a person. As a result, integrated data analytics is becoming one of the fast-growing areas under Biomedical Big Data to improve human healthcare outcomes. In this chapter, we first introduce the scope of data integration and review applications, data sources, and tools for clinical informatics and medical genomics. We then describe the data integration analytics at the raw data level, feature level, and decision level with case studies, and the opportunity for research and translation using advanced artificial intelligence (AI), such as deep learning. Lastly, we summarize the opportunities in biomedical big data integration that can reshape healthcare toward p-health.


Asunto(s)
Informática Médica , Medicina de Precisión , Inteligencia Artificial , Atención a la Salud , Genómica , Humanos
15.
Geophys Res Lett ; 49(11): e2021GL097390, 2022 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-35865009

RESUMEN

We present 14 simultaneous Chandra X-ray Observatory (CXO)-Hubble Space Telescope (HST) observations of Jupiter's Northern X-ray and ultraviolet (UV) aurorae from 2016 to 2019. Despite the variety of dynamic UV and X-ray auroral structures, one region is conspicuous by its persistent absence of emission: the dark polar region (DPR). Previous HST observations have shown that very little UV emission is produced by the DPR. We find that the DPR also produces very few X-ray photons. For all 14 observations, the low level of X-ray emission from the DPR is consistent (within 2-standard deviations) with scattered solar emission and/or photons spread by Chandra's Point Spread Function from known X-ray-bright regions. We therefore conclude that for these 14 observations the DPR produced no statistically significant detectable X-ray signature.

16.
Front Artif Intell ; 5: 640926, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35481281

RESUMEN

More than 5 million patients have admitted annually to intensive care units (ICUs) in the United States. The leading causes of mortality are cardiovascular failures, multi-organ failures, and sepsis. Data-driven techniques have been used in the analysis of patient data to predict adverse events, such as ICU mortality and ICU readmission. These models often make use of temporal or static features from a single ICU database to make predictions on subsequent adverse events. To explore the potential of domain adaptation, we propose a method of data analysis using gradient boosting and convolutional autoencoder (CAE) to predict significant adverse events in the ICU, such as ICU mortality and ICU readmission. We demonstrate our results from a retrospective data analysis using patient records from a publicly available database called Multi-parameter Intelligent Monitoring in Intensive Care-II (MIMIC-II) and a local database from Children's Healthcare of Atlanta (CHOA). We demonstrate that after adopting novel data imputation on patient ICU data, gradient boosting is effective in both the mortality prediction task and the ICU readmission prediction task. In addition, we use gradient boosting to identify top-ranking temporal and non-temporal features in both prediction tasks. We discuss the relationship between these features and the specific prediction task. Lastly, we indicate that CAE might not be effective in feature extraction on one dataset, but domain adaptation with CAE feature extraction across two datasets shows promising results.

17.
IEEE J Biomed Health Inform ; 26(4): 1422-1431, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35349461

RESUMEN

Each year there are nearly 57 million deaths worldwide, with over 2.7 million in the United States. Timely, accurate and complete death reporting is critical for public health, especially during the COVID-19 pandemic, as institutions and government agencies rely on death reports to formulate responses to communicable diseases. Unfortunately, determining the causes of death is challenging even for experienced physicians. The novel coronavirus and its variants may further complicate the task, as physicians and experts are still investigating COVID-related complications. To assist physicians in accurately reporting causes of death, an advanced Artificial Intelligence (AI) approach is presented to determine a chronically ordered sequence of conditions that lead to death (named as the causal sequence of death), based on decedent's last hospital discharge record. The key design is to learn the causal relationship among clinical codes and to identify death-related conditions. There exist three challenges: different clinical coding systems, medical domain knowledge constraint, and data interoperability. First, we apply neural machine translation models with various attention mechanisms to generate sequences of causes of death. We use the BLEU (BiLingual Evaluation Understudy) score with three accuracy metrics to evaluate the quality of generated sequences. Second, we incorporate expert-verified medical domain knowledge as constraints when generating the causal sequences of death. Lastly, we develop a Fast Healthcare Interoperability Resources (FHIR) interface that demonstrates the usability of this work in clinical practice. Our results match the state-of-art reporting and can assist physicians and experts in public health crisis such as the COVID-19 pandemic.


Asunto(s)
Inteligencia Artificial , COVID-19 , Humanos , Pandemias , Salud Pública , Informática en Salud Pública , Estados Unidos
18.
Crit Care Med ; 50(2): 212-223, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-35100194

RESUMEN

OBJECTIVES: Body temperature trajectories of infected patients are associated with specific immune profiles and survival. We determined the association between temperature trajectories and distinct manifestations of coronavirus disease 2019. DESIGN: Retrospective observational study. SETTING: Four hospitals within an academic healthcare system from March 2020 to February 2021. PATIENTS: All adult patients hospitalized with coronavirus disease 2019. INTERVENTIONS: Using a validated group-based trajectory model, we classified patients into four previously defined temperature trajectory subphenotypes using oral temperature measurements from the first 72 hours of hospitalization. Clinical characteristics, biomarkers, and outcomes were compared between subphenotypes. MEASUREMENTS AND MAIN RESULTS: The 5,903 hospitalized coronavirus disease 2019 patients were classified into four subphenotypes: hyperthermic slow resolvers (n = 1,452, 25%), hyperthermic fast resolvers (1,469, 25%), normothermics (2,126, 36%), and hypothermics (856, 15%). Hypothermics had abnormal coagulation markers, with the highest d-dimer and fibrin monomers (p < 0.001) and the highest prevalence of cerebrovascular accidents (10%, p = 0.001). The prevalence of venous thromboembolism was significantly different between subphenotypes (p = 0.005), with the highest rate in hypothermics (8.5%) and lowest in hyperthermic slow resolvers (5.1%). Hyperthermic slow resolvers had abnormal inflammatory markers, with the highest C-reactive protein, ferritin, and interleukin-6 (p < 0.001). Hyperthermic slow resolvers had increased odds of mechanical ventilation, vasopressors, and 30-day inpatient mortality (odds ratio, 1.58; 95% CI, 1.13-2.19) compared with hyperthermic fast resolvers. Over the course of the pandemic, we observed a drastic decrease in the prevalence of hyperthermic slow resolvers, from representing 53% of admissions in March 2020 to less than 15% by 2021. We found that dexamethasone use was associated with significant reduction in probability of hyperthermic slow resolvers membership (27% reduction; 95% CI, 23-31%; p < 0.001). CONCLUSIONS: Hypothermics had abnormal coagulation markers, suggesting a hypercoagulable subphenotype. Hyperthermic slow resolvers had elevated inflammatory markers and the highest odds of mortality, suggesting a hyperinflammatory subphenotype. Future work should investigate whether temperature subphenotypes benefit from targeted antithrombotic and anti-inflammatory strategies.


Asunto(s)
Temperatura Corporal , COVID-19/patología , Hipertermia/patología , Hipotermia/patología , Fenotipo , Centros Médicos Académicos , Anciano , Antiinflamatorios/uso terapéutico , Biomarcadores/sangre , Coagulación Sanguínea , Estudios de Cohortes , Dexametasona/uso terapéutico , Femenino , Humanos , Inflamación , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Estudios Retrospectivos , SARS-CoV-2
19.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 2363-2366, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34891757

RESUMEN

Many automated sleep staging studies have used deep learning approaches, and a growing number of them have used multimodal data to improve their classification performance. However, few studies using multimodal data have provided model explainability. Some have used traditional ablation approaches that "zero out" a modality. However, the samples that result from this ablation are unlikely to be found in real electroencephalography (EEG) data, which could adversely affect the importance estimates that result. Here, we train a convolutional neural network for sleep stage classification with EEG, electrooculograms (EOG), and electromyograms (EMG) and propose an ablation approach that replaces each modality with values that approximate the line-related noise commonly found in electrophysiology data. The relative importance that we identify for each modality is consistent with sleep staging guidelines, with EEG being important for most sleep stages and EOG being important for Rapid Eye Movement (REM) and non-REM stages. EMG showed low relative importance across classes. A comparison of our approach with a "zero out" ablation approach indicates that while the importance results are consistent for the most part, our method accentuates the importance of modalities to the model for the classification of some stages like REM (p < 0.05). These results suggest that a careful, domain-specific selection of an ablation approach may provide a clearer indicator of modality importance. Further, this study provides guidance for future research on using explainability methods with multimodal electrophysiology data.Clinical Relevance- While explainability is helpful for clinical machine learning classifiers, it is important to consider how explainability methods interact with clinical data, a domain for which they were not originally designed.


Asunto(s)
Fases del Sueño , Sueño , Electrooculografía , Electrofisiología , Polisomnografía
20.
Front Big Data ; 4: 568352, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34337396

RESUMEN

As a highly sophisticated disease that humanity faces, cancer is known to be associated with dysregulation of cellular mechanisms in different levels, which demands novel paradigms to capture informative features from different omics modalities in an integrated way. Successful stratification of patients with respect to their molecular profiles is a key step in precision medicine and in tailoring personalized treatment for critically ill patients. In this article, we use an integrated deep belief network to differentiate high-risk cancer patients from the low-risk ones in terms of the overall survival. Our study analyzes RNA, miRNA, and methylation molecular data modalities from both labeled and unlabeled samples to predict cancer survival and subsequently to provide risk stratification. To assess the robustness of our novel integrative analytics, we utilize datasets of three cancer types with 836 patients and show that our approach outperforms the most successful supervised and semi-supervised classification techniques applied to the same cancer prediction problems. In addition, despite the preconception that deep learning techniques require large size datasets for proper training, we have illustrated that our model can achieve better results for moderately sized cancer datasets.

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