scholarly journals Human disease biomarkers: challenges, advances, and trends in their validation

2021 ◽  
Vol 11 (2) ◽  
pp. 16-28
Author(s):  
J. R. De Jesus ◽  
Marco Arruda

Biomarkers are important tools in the medical field, once they allow better prediction, characterization, and treatment of diseases. In this scenario, it is essential that biomarkers are highly accurate. Thus, biomarker validation is an essential part of ensuring the effectiveness of a biomarker. Validation of biomarkers is the process by which biomarkers are evaluated for accuracy and consistency, as well as their ability to inform the condition of health or disease. Although, there is no unique measure that can be used to determine the validity for all biomarkers, there are general criteria that all biomarkers must meet to be useful. In this work, we review the definition of biomarkers and discuss the validity components. We then critically discuss the main methods used to validate biomarkers and consider some examples of biomarkers of the diseases which most killer in the world (cardiovascular diseases, cancer, and viral infections), highlighting the potential biochemical pathways of these biomarkers in the biological system. In addition, we also comment on the omic strategies used in the biomarker discovery process and conclude with information about perspectives in biomarker validation through imaging techniques.

2020 ◽  
Author(s):  
Weihua Yang ◽  
Bo Zheng ◽  
Maonian Wu ◽  
Shaojun Zhu ◽  
Hongxia Zhou ◽  
...  

BACKGROUND Artificial intelligence (AI) is widely applied in the medical field, especially in ophthalmology. In the development of ophthalmic artificial intelligence, some problems worthy of attention have gradually emerged, among which the ophthalmic AI-related recognition issues are particularly prominent. That is to say, currently, there is a lack of research into people's familiarity with and their attitudes toward ophthalmic AI. OBJECTIVE This survey aims to assess medical workers’ and other professional technicians’ familiarity with AI, as well as their attitudes toward and concerns of ophthalmic AI. METHODS An electronic questionnaire was designed through the Questionnaire Star APP, an online survey software and questionnaire tool, and was sent to relevant professional workers through Wechat, China’s version of Facebook or WhatsApp. The participation was based on a voluntary and anonymous principle. The questionnaire mainly consisted of four parts, namely the participant’s background, the participant's basic understanding of AI, the participant's attitude toward AI, and the participant's concerns about AI. A total of 562 participants were counted, with 562 valid questionnaires returned. The results of the questionnaires are displayed in an Excel 2003 form. RESULTS A total of 562 professional workers completed the questionnaire, of whom 291 were medical workers and 271 were other professional technicians. About 37.9% of the participants understood AI, and 31.67% understood ophthalmic AI. The percentages of people who understood ophthalmic AI among medical workers and other professional technicians were about 42.61% and 15.6%, respectively. About 66.01% of the participants thought that ophthalmic AI would partly replace doctors, with about 59.07% still having a relatively high acceptance level of ophthalmic AI. Meanwhile, among those with ophthalmic AI application experiences (30.6%), respectively about 84.25% of medical professionals and 73.33% of other professional technicians held a full acceptance attitude toward ophthalmic AI. The participants expressed concerns that ophthalmic AI might bring about issues such as the unclear definition of medical responsibilities, the difficulty of ensuring service quality, and the medical ethics risks. And among the medical workers and other professional technicians who understood ophthalmic AI, 98.39%, and 95.24%, respectively, said that there was a need to increase the study of medical ethics issues in the ophthalmic AI field. CONCLUSIONS Analysis of the questionnaire results shows that the medical workers have a higher understanding level of ophthalmic AI than other professional technicians, making it necessary to popularize ophthalmic AI education among other professional technicians. Most of the participants did not have any experience in ophthalmic AI, but generally had a relatively high acceptance level of ophthalmic AI, believing that doctors would partly be replaced by it and that there was a need to strengthen research into medical ethics issues of the field.


2021 ◽  
Vol 59 (1) ◽  
pp. 51-57
Author(s):  
Daniela Maria Cardinale ◽  
Martina Zaninotto ◽  
Carlo Maria Cipolla ◽  
Claudio Passino ◽  
Mario Plebani ◽  
...  

AbstractDrug-induced cardiotoxicity is a major clinical problem; cardiotoxic drugs may induce both cardiac dysfunction and myocardial injury. Several recent studies reported that cardiac troponins measured with high-sensitivity methods (hs-cTn) can enable the early detection of myocardial injury related to chemotherapy or abuse of drugs that are potentially cardiotoxic. Several authors have some concerns about the standard definition of cardiotoxicity, in particular, regarding the early evaluation of chemotherapy cardiotoxicity in cancer patients. Several recent studies using the hs-cTn assay indicate that myocardial injury may precede by some months or years the diagnosis of heart failure (HF) based on the evaluation of left ventricular ejection fraction (LVEF). Accordingly, hs-cTn assay should considered to be a reliable laboratory test for the early detection of asymptomatic or subclinical cardiotoxic damage in patients undergoing cancer chemotherapy. In accordance with the Fourth Universal Definition of Myocardial Infarction and also taking into account the recent experimental and clinical evidences, the definition of drug-cardiotoxicity should be updated considering the early evaluation of myocardial injury by means of hs-cTn assay. It is conceivable that the combined use of hs-cTn assay and cardiac imaging techniques for the evaluation of cardiotoxicity will significantly increase both diagnostic sensitivity and specificity, and also better prevent chemotherapy-related left ventricular (LV) dysfunction and other adverse cardiac events. However, large randomized clinical trials are needed to evaluate the cost/benefit ratio of standardized protocols for the early detection of cardiotoxicity using hs-cTn assay in patients receiving chemotherapy for malignant diseases.


2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i1-i1
Author(s):  
Gilbert Hangel ◽  
Cornelius Cadrien ◽  
Philipp Lazen ◽  
Sukrit Sharma ◽  
Julia Furtner ◽  
...  

Abstract OBJECTIVES Neurosurgical resection in gliomas depends on the precise preoperative definition of the tumor and its margins to realize a safe maximum resection that translates into a better patient outcome. New metabolic imaging techniques could improve this delineation as well as designate targets for biopsies. We validated the performance of our fast high-resolution whole-brain 3D-magnetic resonance spectroscopic imaging (MRSI) method at 7T in high-grade gliomas (HGGs) as first step to this regard. METHODS We measured 23 patients with HGGs at 7T with MRSI covering the whole cerebrum with 3.4mm isotropic resolution in 15 min. Quantification used a basis-set of 17 neurochemical components. They were evaluated for their reliability/quality and compared to neuroradiologically segmented tumor regions-of-interest (necrosis, contrast-enhanced, non-contrast-enhanced+edema, peritumoral) and histopathology (e.g., grade, IDH-status). RESULTS We found 18/23 measurements to be usable and ten neurochemicals quantified with acceptable quality. The most common denominators were increases of glutamine, glycine, and total choline as well as decreases of N-acetyl-aspartate and total creatine over most tumor regions. Other metabolites like taurine and serine showed mixed behavior. We further found that heterogeneity in the metabolic images often continued into the peritumoral region. While 2-hydroxy-glutarate could not be satisfyingly quantified, we found a tendency for a decrease of glutamate in IDH1-mutant HGGs. DISCUSSION Our findings corresponded well to clinical tumor segmentation but were more heterogeneous and often extended into the peritumoral region. Our results corresponded to previous knowledge, but with previously not feasible resolution. Apart from glycine/glutamine and their role in glioma progression, more research on the connection of glutamate and others to specific mutations is necessary. The addition of low-grade gliomas and statistical ROI analysis in a larger cohort will be the next important steps to define the benefits of our 7T MRSI approach for the definition of spatial metabolic tumor profiles.


PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2058 ◽  
Author(s):  
Xundou Li ◽  
Youhe Gao

Urine is a very good source for biomarker discovery because it accumulates changes in the body. However, a major challenge in urinary biomarker discovery is the fact that the urinary proteome is influenced by various elements. To circumvent these problems, simpler systems, such as animal models, can be used to establish associations between physiological or pathological conditions and alterations in the urinary proteome. In this study, the urinary proteomes of young (two months old) and old rats (20 months old; nine in each group) were analyzed using LC-MS/MS and quantified using the Progenesis LC-MS software. A total of 371 proteins were identified, 194 of which were shared between the young and old rats. Based on criteria of a fold change ≥2,P< 0.05 and identification in each rat of the high-abundance group, 33 proteins were found to be changed (15 increased and 18 decreased in old rats). By adding a more stringent standard (protein spectral counts from every rat in the higher group greater than those in the lower group), eight proteins showed consistent changes in all rats of the groups; two of these proteins are also altered in the urinary proteome of aging humans. However, no shared proteins between our results and the previous aging plasma proteome were identified. Twenty of the 33 (60%) altered proteins have been reported to be disease biomarkers, suggesting that aging may share similar urinary changes with some diseases. The 33 proteins corresponded to 28 human orthologs which, according to the Human Protein Atlas, are strongly expressed in the kidney, intestine, cerebellum and lung. Therefore, the urinary proteome may reflect aging conditions in these organs.


2019 ◽  
Vol 21 (4) ◽  
pp. 405 ◽  
Author(s):  
Oana Șerban ◽  
Daniela Fodor ◽  
Iulia Papp ◽  
Mihaela Cosmina Micu ◽  
Dan Gabriel Duma ◽  
...  

Aim: To compare the ultrasonography (US) performance with magnetic resonance imaging (MRI) in identifying pathology in ankles, hindfeet and heels of rheumatoid arthritis (RA) patients and to evaluate the reasons for discordances between the two imaging methods.Material and methods: RA patients were enrolled and evaluated using the Clinical Disease Activity Index (CDAI) and the Disease Activity Score 28 with C-reactive Protein (DAS28-CRP). The ankle (tibiotalar joint, tendons), hindfoot (talonavicular, subtalar joints) and heel of the most symptomatic or dominant foot (for the asymptomatic patient)were evaluated by two pairs of examiners using US and contrast-enhanced MRI.Results: Totally, 105 joints, 245 tendons and 35 heels in 35 patients [mean age 59.2±11.25 years old, median disease duration 36 (16.5-114), mean CDAI 19.87±12.7] were evaluated. The interobserver agreements between the two sonographers, and the two radiologists were good and very good (k=0.624-0.940). The overall agreement between US and MRI was very good for subcalcaneal panniculitis (k=0.928, p<0.001), moderate for synovitis (k=0.463, p<0.001) and tenosynovitis (k=0.514, p<0.001), fair for osteophytes (k=0.260, p=0.004), and poor for erosions (k=0.063, p=0.308) and heel’s structures. MRI found more erosions, synovitis, osteophytes,tenosynovitis and retrocalcaneal bursitis, but US found more enthesophytes and plantar fasciitis. Many of the discordancesbetween the two imaging techniques have explanations related to the technique itself or definition of the pathologic findings.Conclusions: US is comparable to MRI for the evaluation of ankle, hindfoot and heel in RA patients and discordances in theinterpretation of the pathological findings/normal structures must be carefully analyzed.


2018 ◽  
Vol 3 (4) ◽  
pp. 19-32
Author(s):  
Hebert Jair Barrales-Cureño ◽  
César Reyes-Reyes ◽  
Maximino Diaz-Bautista ◽  
Adrián Gómez-de Jesús ◽  
Salvador Chávez-Salinas ◽  
...  

The interferon (IFN) is a cytokine produced by immunocompetent cells in response to various stimuli. Five types of IFNs are identified: alpha, beta, gamma, tau and omega 1. In particular, interferons inhibit viral replication directly by antiviral mechanisms, as they do so indirectly by amplifying immune responses to viral proteins. Likewise, they are also essential elements in clinical oncology. They are used in the treatment of chronic myelocytic and hairy cell leukemia, multiple myeloma, non-Hodgkin's lymphoma, melanoma, renal carcinoma, and Kaposi's sarcoma, as well as in the papilloma. They are also used in diseases of viral origin such as hepatitis B and C, acute respiratory syndrome, and HIV (experimentally in the latter), as well as in neurodegenerative diseases, including multiple sclerosis or amyotrophic lateral sclerosis. The combination of interferons with other therapies is contributing to enhance its antiviral and antitumor activity. This work aims to present an updated reference on the use of interferons in the medical field.


2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Antonio Maconi ◽  
Mariateresa Dacquino ◽  
Federica Viazzi ◽  
Emanuela Bovo ◽  
Federica Grosso ◽  
...  

Objectives: The aim of this paper is to demonstrate how, while remaining within a specific field such as medicine, it is possible to use different languages depending on the target audience (doctors, professionals from other fields or patients) in order to improve its degree of health literacy. In particular, the aim is to show how even the definition of a disease, which should in principle be unambiguous, can in fact be linguistically adapted to the reader's basic knowledge. Methodology: Five definitions of mesothelioma are examined, analysed lexically, syntactically and graphically. Specifically, this comparison is made on three main levels, which in turn have different nuances: popular, including definitions from Wikipedia and the UK Mesothelioma patient portal; intermediate, corresponding to the Collins English language dictionary; and specialist, with definitions from the MeSH thesaurus and the Orphanet database. Results: At the end of the comparative analysis, it is possible to state that in linguistic and Health Literacy terms there is no single definition for this rare disease but as many definitions as there are targets. In particular, they vary in syntactic structure, graphic form and vocabulary, as they have to use technicalities typical of the medical field but have different nuances of complexity. Conclusion: A comparison of the definitions shows that the degree of readability does not always correspond to that of comprehensibility. The analysis demonstrates that it is difficult to explain complex medical concepts to practitioners and patients in a simple, clear and usable way and that this requires specific techniques of Health Literacy, related to both the linguistic and graphic aspects. The comparison of definitions is therefore a methodological premise for the creation of brochures dedicated to mesothelioma and the revision of the "Mai soli" site for mesothelioma patients.


Author(s):  
Ali Yilmaz ◽  
Heiko Mahrholdt ◽  
Udo Sechtem

The symptoms and signs of myocarditis are non-specific. Thus, myocarditis is a differential diagnosis in many patients with heart complaints. As myocarditis may accompany common viral infections of the upper respiratory and gastrointestinal tracts, and mild ECG changes are not uncommon in such patients, the diagnosis needs to be considered in large patient cohorts. Establishing the correct diagnosis is of importance as the disease may lead to sudden cardiac death or dilated cardiomyopathy. As clinical tools such as history taking, physical examination, blood tests, the ECG, and the chest X-ray are not sufficient to ascertain the diagnosis of myocarditis, additional information from cardiac imaging techniques, or endomyocardial biopsy are necessary to confirm or exclude the disease. In daily clinical routine, however, the use of biopsy is limited to severely ill patients with reduced left ventricular function due to its invasiveness and potential complications. Thus, this chapter reviews how non-invasive cardiac imaging techniques can be used in clinical practice to diagnose myocarditis.


2008 ◽  
Vol 3 (1) ◽  
pp. 95-105 ◽  
Author(s):  
Diane Mataija-Botelho ◽  
Patrick Murphy ◽  
Devanand M. Pinto ◽  
Dawn L. MacLellan ◽  
Chantale Langlois ◽  
...  

2018 ◽  
Vol 10 (3) ◽  
pp. 136-150 ◽  
Author(s):  
Mercedes Espada ◽  
Elena Alvarez-Moreno ◽  
Mar Jimenez de la Pena ◽  
Veronica Munoz Capio ◽  
Shannon Reid ◽  
...  

Endometriosis is a common gynecological condition affecting up to 15% of the general female population. Here, we present a systematic review of imaging techniques of endometriosis. The aim of this review is to determine the most accurate site-specific preoperative diagnostic tools in order to map, locate, evaluate the extension, and stage the disease. There are important reasons to stage endometriosis: to create a common language, to enable specificity of diagnosis, standardize comparisons, and to facilitate research applications. The requirements of an ideal endometriosis classification system are that it be empirically and scientifically based, be of general consensus, have unambiguous definition of terms, be comprehensive in all cases, have a simple translation from anatomic features to verbal description, reflect disease, predict fertility, predict pain relief, be useful to guide treatment, indicate risk of recurrence, identify clinical situations in which it does not apply, be simple to calculate, and be easy to communicate to women. An extensive search of papers regarding imaging techniques in endometriosis was performed in Pubmed from January 1992 to February 2018, including original peer-reviewed papers, reviews, and international guidelines.


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