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1.
Int J Mol Sci ; 23(3)2022 Feb 03.
Article in English | MEDLINE | ID: covidwho-1674668

ABSTRACT

CRISPR/Cas is a prokaryotic self-defense system, widely known for its use as a gene-editing tool. Because of their high specificity to detect DNA and RNA sequences, different CRISPR systems have been adapted for nucleic acid detection. CRISPR detection technologies differ highly among them, since they are based on four of the six major subtypes of CRISPR systems. In just 5 years, the CRISPR diagnostic field has rapidly expanded, growing from a set of specific molecular biology discoveries to multiple FDA-authorized COVID-19 tests and the establishment of several companies. CRISPR-based detection methods are coupled with pre-existing preamplification and readout technologies, achieving sensitivity and reproducibility comparable to the current gold standard nucleic acid detection methods. Moreover, they are very versatile, can be easily implemented to detect emerging pathogens and new clinically relevant mutations, and offer multiplexing capability. The advantages of the CRISPR-based diagnostic approaches are a short sample-to-answer time and no requirement of laboratory settings; they are also much more affordable than current nucleic acid detection procedures. In this review, we summarize the applications and development trends of the CRISPR/Cas13 system in the identification of particular pathogens and mutations and discuss the challenges and future prospects of CRISPR-based diagnostic platforms in biomedicine.


Subject(s)
Diagnostic Techniques and Procedures/trends , Disease/genetics , Gene Editing/methods , COVID-19/genetics , CRISPR-Cas Systems/genetics , DNA/genetics , Diagnosis , Humans , Reproducibility of Results , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity
2.
Nat Commun ; 13(1): 269, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1621240

ABSTRACT

A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.


Subject(s)
COVID-19/immunology , SARS-CoV-2/physiology , Aged , Autopsy , COVID-19/diagnosis , COVID-19/genetics , COVID-19/virology , China , Diagnosis , Female , Hepatitis A Virus Cellular Receptor 2/genetics , Hepatitis A Virus Cellular Receptor 2/immunology , Humans , Lymphocyte Activation , Lymphocytes/immunology , Male , Middle Aged , Myeloid Cells/immunology , Programmed Cell Death 1 Receptor/genetics , Programmed Cell Death 1 Receptor/immunology , SARS-CoV-2/immunology , Viral Load
3.
J Med Internet Res ; 23(2): e22841, 2021 02 23.
Article in English | MEDLINE | ID: covidwho-1574897

ABSTRACT

BACKGROUND: Misdiagnosis, arbitrary charges, annoying queues, and clinic waiting times among others are long-standing phenomena in the medical industry across the world. These factors can contribute to patient anxiety about misdiagnosis by clinicians. However, with the increasing growth in use of big data in biomedical and health care communities, the performance of artificial intelligence (Al) techniques of diagnosis is improving and can help avoid medical practice errors, including under the current circumstance of COVID-19. OBJECTIVE: This study aims to visualize and measure patients' heterogeneous preferences from various angles of AI diagnosis versus clinicians in the context of the COVID-19 epidemic in China. We also aim to illustrate the different decision-making factors of the latent class of a discrete choice experiment (DCE) and prospects for the application of AI techniques in judgment and management during the pandemic of SARS-CoV-2 and in the future. METHODS: A DCE approach was the main analysis method applied in this paper. Attributes from different dimensions were hypothesized: diagnostic method, outpatient waiting time, diagnosis time, accuracy, follow-up after diagnosis, and diagnostic expense. After that, a questionnaire is formed. With collected data from the DCE questionnaire, we apply Sawtooth software to construct a generalized multinomial logit (GMNL) model, mixed logit model, and latent class model with the data sets. Moreover, we calculate the variables' coefficients, standard error, P value, and odds ratio (OR) and form a utility report to present the importance and weighted percentage of attributes. RESULTS: A total of 55.8% of the respondents (428 out of 767) opted for AI diagnosis regardless of the description of the clinicians. In the GMNL model, we found that people prefer the 100% accuracy level the most (OR 4.548, 95% CI 4.048-5.110, P<.001). For the latent class model, the most acceptable model consists of 3 latent classes of respondents. The attributes with the most substantial effects and highest percentage weights are the accuracy (39.29% in general) and expense of diagnosis (21.69% in general), especially the preferences for the diagnosis "accuracy" attribute, which is constant across classes. For class 1 and class 3, people prefer the AI + clinicians method (class 1: OR 1.247, 95% CI 1.036-1.463, P<.001; class 3: OR 1.958, 95% CI 1.769-2.167, P<.001). For class 2, people prefer the AI method (OR 1.546, 95% CI 0.883-2.707, P=.37). The OR of levels of attributes increases with the increase of accuracy across all classes. CONCLUSIONS: Latent class analysis was prominent and useful in quantifying preferences for attributes of diagnosis choice. People's preferences for the "accuracy" and "diagnostic expenses" attributes are palpable. AI will have a potential market. However, accuracy and diagnosis expenses need to be taken into consideration.


Subject(s)
Artificial Intelligence , Diagnosis , Patient Preference , Physicians , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19 , China , Choice Behavior , Diagnostic Techniques and Procedures/economics , Female , Health Expenditures , Humans , Latent Class Analysis , Logistic Models , Male , Middle Aged , Pandemics , SARS-CoV-2 , Surveys and Questionnaires , Time Factors , Young Adult
4.
Acta odontol. Colomb. (En linea) ; 11(1): 71-82, 2021. ilus, tab
Article in Spanish | WHO COVID, LILACS (Americas) | ID: covidwho-1498038

ABSTRACT

Objetivo: describir las aplicaciones de la teleodontología para la atención de pacientes durante y posterior a la pandemia de la COVID-19. Método: la búsqueda de artículos sobre teleodontología se realizó en las bases de datos PubMed, EMBASE, EBSCO, SCOPUS, ClinicalKey y LILACS, para identificar estudios publicados en inglés, español y portugués; se incluyeron estudios que contenían las palabras claves teleodontología y COVID-19, publicados desde enero a diciembre de 2020 y que estuvieran completos. La calidad de los artículos se evaluó según las directrices PRISMA-P. Resultados: se identificaron 49 artículos y se incluyeron 14 para la evaluación. De estos estudios, dos eran descriptivos (test de diagnóstico), seis eran estudios descriptivos de corte transversal, cinco eran pruebas pilotos; se identificó, además, un estudio de diseño retrospectivo. Se presenta la teleodontología como alternativa para diagnósticos y tratamientos de enfermedades bucales en tiempos de pandemia, mediante uso de dispositivos móviles, teleorientación y fotografías. La mayoría de los estudios presentaron un riesgo de sesgo de moderado a alto. Conclusión: la teleodontología es una herramienta tecnológica remota para apoyar la orientación, educación y tratamiento, que permite consolidar información de manera sincrónica y asincrónica sin la necesidad del contacto directo entre odontólogo y paciente.


Objective: to describe the applications of teleodontology for patient care during and after the COVID-19 pandemic. Method: the search for articles on teleodontology was carried out in the PubMed, EMBASE, EBSCO, SCOPUS, ClinicalKey and LILACS databases to identify studies published in English, Spanish and Portuguese; Studies that contained the keywords teleodontology and COVID-19, published from January to December 2020 and that were complete, were included. The quality of the articles was evaluated according to the PRISMA-P guidelines. Results: 49 articles were identified and 14 were included for evaluation. Of these studies, two were descriptive (diagnostic tests), six were descriptive cross-sectional studies, five were pilot tests; In addition, a retrospective design study was identified. Teleodontology is presented as an alternative for diagnosing and treating oral diseases in times of pandemic, through the use of mobile devices, remote orientation and photographs. Most of the studies were at moderate to high risk of bias. Conclusion: teleodontology is the remote tool to support remote guidance, education and treatment through technology, allowing the consolidation of information synchronously and asynchronously without the need for direct contact between dentist and patient


Subject(s)
Humans , Coronavirus Infections , Teledentistry , Telemedicine , Remote Consultation , Diagnosis , Health Promotion
5.
Am J Clin Pathol ; 153(6): 725-733, 2020 05 05.
Article in English | MEDLINE | ID: covidwho-1272955

ABSTRACT

OBJECTIVES: To report the methods and findings of two complete autopsies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individuals who died in Oklahoma (United States) in March 2020. METHODS: Complete postmortem examinations were performed according to standard procedures in a negative-pressure autopsy suite/isolation room using personal protective equipment, including N95 masks, eye protection, and gowns. The diagnosis of coronavirus disease 2019 (COVID-19) was confirmed by real-time reverse transcriptase polymerase chain reaction testing on postmortem swabs. RESULTS: A 77-year-old obese man with a history of hypertension, splenectomy, and 6 days of fever and chills died while being transported for medical care. He tested positive for SARS-CoV-2 on postmortem nasopharyngeal and lung parenchymal swabs. Autopsy revealed diffuse alveolar damage and chronic inflammation and edema in the bronchial mucosa. A 42-year-old obese man with a history of myotonic dystrophy developed abdominal pain followed by fever, shortness of breath, and cough. Postmortem nasopharyngeal swab was positive for SARS-CoV-2; lung parenchymal swabs were negative. Autopsy showed acute bronchopneumonia with evidence of aspiration. Neither autopsy revealed viral inclusions, mucus plugging in airways, eosinophils, or myocarditis. CONCLUSIONS: SARS-CoV-2 testing can be performed at autopsy. Autopsy findings such as diffuse alveolar damage and airway inflammation reflect true virus-related pathology; other findings represent superimposed or unrelated processes.


Subject(s)
Autopsy , Coronavirus Infections/pathology , Lung/pathology , Pneumonia, Viral/pathology , Adult , Aged , Autopsy/instrumentation , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Clinical Laboratory Techniques/standards , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Diagnosis , Humans , Hypertension/complications , Male , Myotonic Dystrophy/complications , Obesity/complications , Oklahoma , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , SARS-CoV-2
6.
7.
Intern Emerg Med ; 16(2): 273-279, 2021 03.
Article in English | MEDLINE | ID: covidwho-1137172

ABSTRACT

The practice of clinical medicine needs to be a very flexible discipline which can adapt promptly to continuously changing surrounding events. Despite the huge advances and progress made in recent decades, clinical reasoning to achieve an accurate diagnosis still seems to be the most appropriate and distinctive feature of clinical medicine. This is particularly evident in internal medicine where diagnostic boundaries are often blurred. Making a diagnosis is a multi-stage process which requires proper data collection, the formulation of an illness script and testing of the diagnostic hypothesis. To make sense of a number of variables, physicians may follow an analytical or an intuitive approach to clinical reasoning, depending on their personal experience and level of professionalism. Intuitive thinking is more typical of experienced physicians, but is not devoid of shortcomings. Particularly, the high risk of biases must be counteracted by de-biasing techniques, which require constant critical thinking. In this review, we discuss critically the current knowledge regarding diagnostic reasoning from an internal medicine perspective.


Subject(s)
Diagnosis , Internal Medicine , Thinking , Humans
8.
Infectio ; 24(3,supl.1): 262-292, oct.-dic. 2020. tab
Article in Spanish | WHO COVID, LILACS (Americas) | ID: covidwho-958510

ABSTRACT

RESUMEN ANEXOS. Consenso colombiano de atención, diagnóstico y manejo de la infección por SARS-CoV-2/COVID-19 en establecimientos de atención de la salud: Recomendaciones basadas en consenso de expertos e informadas en la evidencia ACIN-IETS. SEGUNDA EDICIÓN.


Subject(s)
Humans , COVID-19 , Colombia , Delivery of Health Care , Consensus , Diagnosis , SARS-CoV-2
9.
Rev. colomb. cardiol ; 27(5): 446-460, sep.-oct. 2020. tab, graf
Article in Spanish | WHO COVID, LILACS (Americas) | ID: covidwho-917411

ABSTRACT

Introducción estudios recientes han reportado fenómenos trombóticos o coagulopatía en pacientes con COVID-19. Hay posiciones divergentes en cuanto a la prevención, el diagnóstico y el tratamiento de estos fenómenos, y la práctica clínica actual está basada únicamente en deducciones por extensión a partir de estudios retrospectivos, series de casos, estudios observacionales y guías internacionales desarrolladas previas a la pandemia. Objetivo establecer una serie de recomendaciones sobre prevención, diagnóstico y manejo de las complicaciones trombóticas asociadas a COVID-19. Métodos se desarrolló una guía rápida en la que se aplicó el marco de la evidencia a la decisión (EtD) de GRADE y un sistema de participación iterativo, con análisis estadísticos y cualitativos de sus resultados. Resultados se generaron 31 recomendaciones clínicas enfocadas a: a) Pruebas de coagulación en adultos sintomáticos con sospecha de infección o infección confirmada por SARS-CoV-2; b) Tromboprofilaxis en personas adultas con diagnóstico de COVID-19 (escalas de riesgo, tromboprofilaxis de manejo ambulatorio, intrahospitalario y duración de tromboprofilaxis después del egreso de hospitalización), c) Diagnóstico y tratamiento de las complicaciones trombóticas y d) Manejo de personas con indicación previa a usar agentes anticoagulantes. Conclusiones las recomendaciones clínicas de este consenso orientan la toma de decisiones clínicas respecto a prevención, diagnóstico y tratamiento de fenómenos trombóticos en pacientes con COVID-19, y representan un acuerdo que ayudará a disminuir la dispersión en las prácticas clínicas acorde con el desafío que impone la pandemia.


Abstract Introduction: recent studies have reported the occurrence of thrombotic phenomena or coagulopathy in patients with COVID-19. There are divergent positions regarding the prevention, diagnosis, and treatment of these phenomena, and current clinical practice is based solely on deductions by extension from retrospective studies, case series, observational studies, and international guidelines developed prior to the pandemic. Objective: to generate a group of recommendations on the prevention, diagnosis and management of thrombotic complications associated with COVID-19. Methods: a rapid guidance was carried out applying the GRADE Evidence to Decision (EtD) frameworks and an iterative participation system, with statistical and qualitative analysis. Results: 31 clinical recommendations were generated focused on: a) Coagulation tests in symptomatic adults with suspected infection or confirmed SARS CoV-2 infection; b) Thromboprophylaxis in adults diagnosed with COVID-19 (Risk scales, thromboprophylaxis for outpatient, in-hospital management, and duration of thromboprophylaxis after discharge from hospitalization), c) Diagnosis and treatment of thrombotic complications, and d) Management of people with previous indication of anticoagulant agents. Conclusions: recommendations of this consensus guide clinical decision-making regarding the prevention, diagnosis, and treatment of thrombotic phenomena in patients with COVID-19, and represent an agreement that will help decrease the dispersion in clinical practices according to the challenge imposed by the pandemic.


Subject(s)
Humans , Adult , Consensus , Diagnosis , COVID-19 , Blood Coagulation Disorders , Embolism and Thrombosis , SARS-CoV-2 , COVID-19 , Anticoagulants
10.
Lancet Public Health ; 5(10): e543-e550, 2020 10.
Article in English | MEDLINE | ID: covidwho-803320

ABSTRACT

BACKGROUND: To date, research on the indirect impact of the COVID-19 pandemic on the health of the population and the health-care system is scarce. We aimed to investigate the indirect effect of the COVID-19 pandemic on general practice health-care usage, and the subsequent diagnoses of common physical and mental health conditions in a deprived UK population. METHODS: We did a retrospective cohort study using routinely collected primary care data that was recorded in the Salford Integrated Record between Jan 1, 2010, and May 31, 2020. We extracted the weekly number of clinical codes entered into patient records overall, and for six high-level categories: symptoms and observations, diagnoses, prescriptions, operations and procedures, laboratory tests, and other diagnostic procedures. Negative binomial regression models were applied to monthly counts of first diagnoses of common conditions (common mental health problems, cardiovascular and cerebrovascular disease, type 2 diabetes, and cancer), and corresponding first prescriptions of medications indicative of these conditions. We used these models to predict the expected numbers of first diagnoses and first prescriptions between March 1 and May 31, 2020, which were then compared with the observed numbers for the same time period. FINDINGS: Between March 1 and May 31, 2020, 1073 first diagnoses of common mental health problems were reported compared with 2147 expected cases (95% CI 1821 to 2489) based on preceding years, representing a 50·0% reduction (95% CI 41·1 to 56·9). Compared with expected numbers, 456 fewer diagnoses of circulatory system diseases (43·3% reduction, 95% CI 29·6 to 53·5), and 135 fewer type 2 diabetes diagnoses (49·0% reduction, 23·8 to 63·1) were observed. The number of first prescriptions of associated medications was also lower than expected for the same time period. However, the gap between observed and expected cancer diagnoses (31 fewer; 16·0% reduction, -18·1 to 36·6) during this time period was not statistically significant. INTERPRETATION: In this deprived urban population, diagnoses of common conditions decreased substantially between March and May 2020, suggesting a large number of patients have undiagnosed conditions. A rebound in future workload could be imminent as COVID-19 restrictions ease and patients with undiagnosed conditions or delayed diagnosis present to primary and secondary health-care services. Such services should prioritise the diagnosis and treatment of these patients to mitigate potential indirect harms to protect public health. FUNDING: National Institute of Health Research.


Subject(s)
Coronavirus Infections/epidemiology , Diagnosis , Pandemics , Pneumonia, Viral/epidemiology , Primary Health Care/statistics & numerical data , Adult , COVID-19 , Cardiovascular Diseases/diagnosis , Cerebrovascular Disorders/diagnosis , Diabetes Mellitus, Type 2/diagnosis , Female , General Practice/statistics & numerical data , Humans , Male , Mental Disorders/diagnosis , Middle Aged , Models, Statistical , Neoplasms/diagnosis , Retrospective Studies , United Kingdom/epidemiology , Young Adult
12.
Pesqui. bras. odontopediatria clín. integr ; 20(supl.1): e0112, 2020.
Article in English | WHO COVID, LILACS (Americas) | ID: covidwho-699462

ABSTRACT

Abstract Covid-19 is a respiratory disease caused by the SARS-CoV-2 virus. The high rate of contagion and the spread of the virus in the population make the early detection of the pathogen the means for the adequate targeting of infection control measures. WHO directs sample collection on upper respiratory specimens, including nasopharyngeal and oropharyngeal swab or wash in ambulatory patients, as well as lower respiratory specimens: sputum and/or endotracheal aspirate or bronchoalveolar lavage, in addition to citing blood and feces. Among the various sample collection methods, saliva has been investigated and reported as a potential source for diagnosis. Thus, we propose to evaluate the current scenario, based on recent publications on the perspective of detecting SARS-CoV-2 in saliva as a diagnostic method for Covid-19. The detection of SARS-CoV-2 through saliva seems to be very promising, although obstacles such as the technique and the location of the collection and the sample size of the research carried out so far may present a limitation for its use. The current scenario presents saliva as a reliable method for the detection of SARS-CoV-2, due to the ease of obtaining the samples, the possibility of self-collection, low cost because there is no need to use specific equipment, in addition to reducing the risk of transmission for health professionals.


Subject(s)
Respiratory Tract Diseases/pathology , Saliva/microbiology , Coronavirus Infections/pathology , SARS Virus , Diagnosis , Brazil/epidemiology , Infection Control , Low Cost Technology , Betacoronavirus
13.
J Neural Transm (Vienna) ; 127(9): 1217-1228, 2020 09.
Article in English | MEDLINE | ID: covidwho-680347

ABSTRACT

While there is abounding literature on virus-induced pathology in general and coronavirus in particular, recent evidence accumulates showing distinct and deleterious brain affection. As the respiratory tract connects to the brain without protection of the blood-brain barrier, SARS-CoV-2 might in the early invasive phase attack the cardiorespiratory centres located in the medulla/pons areas, giving rise to disturbances of respiration and cardiac problems. Furthermore, brainstem regions are at risk to lose their functional integrity. Therefore, long-term neurological as well as psychiatric symptomatology and eventual respective disorders cannot be excluded as evidenced from influenza-A triggered post-encephalitic Parkinsonism and HIV-1 triggered AIDS-dementia complex. From the available evidences for coronavirus-induced brain pathology, this review concludes a number of unmet needs for further research strategies like human postmortem brain analyses. SARS-CoV-2 mirroring experimental animal brain studies, characterization of time-dependent and region-dependent spreading behaviours of coronaviruses, enlightening of pathological mechanisms after coronavirus infection using long-term animal models and clinical observations of patients having had COVID-19 infection are calling to develop both protective strategies and drug discoveries to avoid early and late coronavirus-induced functional brain disturbances, symptoms and eventually disorders. To fight SARS-CoV-2, it is an urgent need to enforce clinical, molecular biological, neurochemical and genetic research including brain-related studies on a worldwide harmonized basis.


Subject(s)
Betacoronavirus , Brain/pathology , Coronavirus Infections/pathology , Diagnosis , Pneumonia, Viral/pathology , Blood-Brain Barrier/pathology , Blood-Brain Barrier/virology , Brain/virology , COVID-19 , Diagnostic Techniques and Procedures/trends , Humans , Pandemics , SARS-CoV-2 , Time Factors
14.
J Thromb Thrombolysis ; 51(1): 25-28, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-548286

ABSTRACT

Acute viral pneumonia, hypoxemic respiratory failure and severe inflammatory response are hallmarks of severe coronavirus disease 2019 (COVID-19). The COVID-19-associated inflammatory state may further lead to symptomatic thromboembolic complications despite prophylaxis. We report a 66-year-old female patient with post-mortem diagnosis of COVID-19 who presented progressive livedo racemosa, acute renal failure and myocardial injury, as well as an absence of respiratory symptoms. Transthoracic echocardiography showed severe spontaneous echo contrast in the right cardiac chambers and right-sided cardiac overload presumed to result from pulmonary microvascular thrombosis or embolism. D-dimer levels were increased. The patient developed an acute ischemic stroke and died 2 days following presentation despite therapeutic anticoagulation. Her predominantly thromboembolic presentation supports the concept of coronavirus infection of endothelial cells and hypercoagulability, or COVID-19 endotheliitis. The case we report highlights that COVID-19-associated hyperacute multi-organ thromboembolic storm may precede or present disproportionately to respiratory involvement.


Subject(s)
Anticoagulants/administration & dosage , COVID-19 , Cardiomyopathies , Echocardiography/methods , Ischemic Stroke , SARS-CoV-2/isolation & purification , Thromboembolism , Thrombophilia , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Aged , Anticoagulants/classification , COVID-19/blood , COVID-19/diagnosis , COVID-19/physiopathology , COVID-19/therapy , Cardiomyopathies/diagnosis , Cardiomyopathies/etiology , Cardiomyopathies/physiopathology , Clinical Deterioration , Diagnosis , Fatal Outcome , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Ischemic Stroke/diagnosis , Ischemic Stroke/etiology , Livedo Reticularis/diagnosis , Livedo Reticularis/etiology , Lung/diagnostic imaging , Pneumonia, Viral/diagnosis , Pneumonia, Viral/etiology , Thromboembolism/diagnosis , Thromboembolism/drug therapy , Thromboembolism/etiology , Thrombophilia/blood , Thrombophilia/diagnosis , Thrombophilia/drug therapy , Thrombophilia/etiology , Tomography, X-Ray Computed/methods
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