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Biomedicines
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Novel Biomarkers and Technologies in the Research and Diagnosis of...
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Novel Biomarkers and Technologies in the Research and Diagnosis of Human Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 August 2024) | Viewed by 11879

Special Issue Editor

Dr. Benjamin M. Liu

E-Mail Website
Guest Editor
Departments of Pathology, Pediatrics, and Microbiology, Immunology & Tropical Medicine, Children's National Hospital, Washington, DC, USA
Interests: pathology; biomarkers; diagnosis; novel technologies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Coincident with progress in basic and translational sciences, novel technologies, such as nucleic acid amplification tests, proteomics and next-generation sequencing, have been widely employed in the research, diagnosis and management of human diseases. These novel diagnostic and therapeutic techniques not only provide more sensitive and specific approaches to providing enhanced patient care, but also offer advanced tools with which to discover and study novel biomarkers (e.g., novel molecular targets, protein biomarkers and clinical indexes) in order to characterize the underlying mechanisms of pathogenesis, disease severity and prognosis. Notably, the emergence of novel technologies and biomarkers has led to more challenges and opportunities in the validation and verification of their clinical application, the thorough evaluation of their clinical utility, as well as the correlation between new and traditional biomarkers/techniques. This calls for a careful investigation of these topics and an improved R&D process in order to suitably utilize these novel biomarkers and technologies. In this Special Issue, we will focus on the application of novel technologies in the research, diagnosis and management of human diseases. In addition, we will also address the characterization and utilization of novel biomarkers for these diseases.

Dr. Benjamin M. Liu
Guest Editor

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Keywords

  • pathology
  • diseases
  • biomarkers
  • diagnosis
  • novel technologies

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Published Papers (6 papers)

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Research

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12 pages, 246 KiB  
Article
Adult-Onset Still’s Disease (AOSD)—On the Basis of Own Cases
by Małgorzata Wisłowska
Biomedicines 2024, 12(9), 2067; https://doi.org/10.3390/biomedicines12092067 - 10 Sep 2024
Cited by 1 | Viewed by 1647
Abstract
Introduction: Adult-onset Still’s disease (AOSD) is a rare chronic autoinflammatory condition characterized by a spiking fever, arthritis, a rash, hepatosplenomegaly, lymphadenopathy, leucocytosis, and hyperferritinemia. It is sometimes accompanied by life-threatening complications like macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH). Treatment options for AOSD include glucocorticoids [...] Read more.
Introduction: Adult-onset Still’s disease (AOSD) is a rare chronic autoinflammatory condition characterized by a spiking fever, arthritis, a rash, hepatosplenomegaly, lymphadenopathy, leucocytosis, and hyperferritinemia. It is sometimes accompanied by life-threatening complications like macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH). Treatment options for AOSD include glucocorticoids (GCs), immunosuppressive drugs, biological medications, and Janus kinase (JAK) inhibitors. The features that differentiate MAS/HLH from AOSD are: in MAS/HLH, a different type of fever, which is persistent, a sharp decrease in the number of leukocytes and thrombocytes, a further increase in the level of transaminases and ferritin, significant hepatosplenomegaly, lymphadenopathy, symptoms of the central nervous system (CNS), disseminated intravascular coagulation (DIC) and hemophagocytosis in the bone marrow. This study aimed to evaluate the course of AOSD, which results in MAS/HLD. Patients and methods: Nine AOSD patients, four of whom developed MAS/HLH, were treated at the Rheumatology Clinic in the Central Clinical Hospital of the Ministry of Interior Affairs from 1 January 2015 to 15 March 2020 and at the Rheumatology Clinic in the National Institute of Geriatric, Rheumatology and Rehabilitation from 1 September 2021 to 1 March 2024. Medical history, clinical data, demographic data, laboratory data, imaging data, Hscore, and treatment data were collected. Results: All the patients with MAS and an Hscore above 150 recovered. Discussion: MAS/HLH requires rapid diagnosis as well as treatment with methylprednisolone pulses, cyclosporine A, and etoposide. When comparing patients who developed MAS/HLH with those who did not, possible risk factors were identified: the presence of pregnancy (two cases) and an aggressive course of AOSD. The Hscore is a useful tool for identifying patients with MAS/HLH. Full article
(This article belongs to the Special Issue Novel Biomarkers and Technologies in the Research and Diagnosis of Human Diseases)
14 pages, 4117 KiB  
Article
Leveraging Hypotension Prediction Index to Forecast LPS-Induced Acute Lung Injury and Inflammation in a Porcine Model: Exploring the Role of Hypoxia-Inducible Factor in Circulatory Shock
by Yuan-Ming Tsai, Yu-Chieh Lin, Chih-Yuan Chen, Hung-Che Chien, Hung Chang and Ming-Hsien Chiang
Biomedicines 2024, 12(8), 1665; https://doi.org/10.3390/biomedicines12081665 - 25 Jul 2024
Cited by 1 | Viewed by 1359
Abstract
Acute respiratory distress syndrome (ARDS) is a critical illness in critically unwell patients, characterized by refractory hypoxemia and shock. This study evaluates an early detection tool and investigates the relationship between hypoxia and circulatory shock in ARDS, to improve diagnostic precision and therapy [...] Read more.
Acute respiratory distress syndrome (ARDS) is a critical illness in critically unwell patients, characterized by refractory hypoxemia and shock. This study evaluates an early detection tool and investigates the relationship between hypoxia and circulatory shock in ARDS, to improve diagnostic precision and therapy customization. We used a porcine model, inducing ARDS with mechanical ventilation and intratracheal plus intravenous lipopolysaccharide (LPS) injection. Hemodynamic changes were monitored using an Acumen IQ sensor and a ForeSight Elite sensor connected to the HemoSphere platform. We evaluated tissue damage, inflammatory response, and hypoxia-inducible factor (HIF) alterations using enzyme-linked immunosorbent assay and immunohistochemistry. The results showed severe hypotension and increased heart rates post-LPS exposure, with a notable rise in the hypotension prediction index (HPI) during acute lung injury (p = 0.024). Tissue oxygen saturation dropped considerably in the right brain region. Interestingly, post-injury HIF-2α levels were lower at the end of the experiment. Our findings imply that the HPI can effectively predict ARDS-related hypotension. HIF expression levels may serve as possible markers of rapid ARDS progression. Further research should be conducted on the clinical value of this novel approach in critical care, as well as the relationship between the HIF pathway and ARDS-associated hypotension. Full article
(This article belongs to the Special Issue Novel Biomarkers and Technologies in the Research and Diagnosis of Human Diseases)
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12 pages, 1347 KiB  
Article
Dual-Time-Point 18F-FDG PET/CT in Infective Endocarditis: Impact of Delayed Imaging in the Definitive Diagnosis of Endocarditis
by Amanda Padilla Bermejo, Francisco José Pena Pardo, Edel Noriega-Álvarez, Mariano Amo-Salas, María de las Nieves Sicilia Pozo, Ana María García Vicente and Víctor Manuel Poblete-García
Biomedicines 2024, 12(4), 861; https://doi.org/10.3390/biomedicines12040861 - 13 Apr 2024
Cited by 1 | Viewed by 1715
Abstract
Infective endocarditis (IE) is a major public health condition due to the associated high morbidity and mortality. Our objective was to evaluate the utility of dual-time 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) Positron Emission Tomography/Computed Tomography (PET/CT) imaging in the diagnosis of active IE in patients [...] Read more.
Infective endocarditis (IE) is a major public health condition due to the associated high morbidity and mortality. Our objective was to evaluate the utility of dual-time 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) Positron Emission Tomography/Computed Tomography (PET/CT) imaging in the diagnosis of active IE in patients with suspected native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE). For this purpose, a retrospective study was carried out, including patients suspicious of NVE or PVE who underwent a dual-time-point 18F-FDG PET/CT. A final diagnosis was established by the Endocarditis Team after patient follow-up using all the available findings. Sixty-nine patients were assessed. A final diagnosis of NVE was established in 3 patients of the 34 by 18F-FDG PET/CT and in the case of PVE was established in 20 patients of the 35. A statistically significant association was found when evaluating the association between PET diagnosis at early acquisition and final diagnosis of IE (χ2 = 30.198, p < 0.001) and PET diagnosis at delayed acquisition for final diagnosis of IE (χ2 = 9.412, p = 0.002). Delayed PET/CT imaging determined the IE diagnosis in 16/58 of the studies. In conclusion, delayed 18F-FDG PET/CT imaging seems to be useful in improving the definitive diagnosis of IE. Full article
(This article belongs to the Special Issue Novel Biomarkers and Technologies in the Research and Diagnosis of Human Diseases)
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Review

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16 pages, 5163 KiB  
Review
Mechanisms and Assessment of Genotoxicity of Metallic Engineered Nanomaterials in the Human Environment
by Benjamin M. Liu and A. Wallace Hayes
Biomedicines 2024, 12(10), 2401; https://doi.org/10.3390/biomedicines12102401 - 20 Oct 2024
Cited by 5 | Viewed by 1782
Abstract
Engineered nanomaterials (ENMs) have a broad array of applications in agriculture, engineering, manufacturing, and medicine. Decades of toxicology research have demonstrated that ENMs can cause genotoxic effects on bacteria, mammalian cells, and animals. Some metallic ENMs (MENMs), e.g., metal or metal oxide nanoparticles [...] Read more.
Engineered nanomaterials (ENMs) have a broad array of applications in agriculture, engineering, manufacturing, and medicine. Decades of toxicology research have demonstrated that ENMs can cause genotoxic effects on bacteria, mammalian cells, and animals. Some metallic ENMs (MENMs), e.g., metal or metal oxide nanoparticles TiO2 and CuO, induce genotoxicity via direct DNA damage and/or reactive oxygen species-mediated indirect DNA damage. There are various physical features of MENMs that may play an important role in promoting their genotoxicity, for example, size and chemical composition. For a valid genotoxicity assessment of MENMs, general considerations should be given to various factors, including, but not limited to, NM characterization, sample preparation, dosing selection, NM cellular uptake, and metabolic activation. The recommended in vitro genotoxicity assays of MENMs include hprt gene mutation assay, chromosomal aberration assay, and micronucleus assay. However, there are still knowledge gaps in understanding the mechanisms underlying the genotoxicity of MENMs. There are also a variety of challenges in the utilization and interpretation of the genotoxicity assessment assays of MENMs. In this review article, we provide mechanistic insights into the genotoxicity of MENMs in the human environment. We review advances in applying new endpoints, biomarkers, and methods to the genotoxicity assessments of MENMs. The guidance of the United States, the United Kingdom, and the European Union on the genotoxicity assessments of MENMs is also discussed. Full article
(This article belongs to the Special Issue Novel Biomarkers and Technologies in the Research and Diagnosis of Human Diseases)
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14 pages, 1358 KiB  
Review
Changes in Whole Blood Polyamine Levels and Their Background in Age-Related Diseases and Healthy Longevity
by Kuniyasu Soda
Biomedicines 2023, 11(10), 2827; https://doi.org/10.3390/biomedicines11102827 - 18 Oct 2023
Cited by 4 | Viewed by 2514
Abstract
The relationship between polyamines and healthy longevity has received much attention in recent years. However, conducting research without understanding the properties of polyamines can lead to unexpected pitfalls. The most fundamental consideration in conducting polyamine studies is that bovine serum used for cell [...] Read more.
The relationship between polyamines and healthy longevity has received much attention in recent years. However, conducting research without understanding the properties of polyamines can lead to unexpected pitfalls. The most fundamental consideration in conducting polyamine studies is that bovine serum used for cell culture contains bovine serum amine oxidase. Bovine serum amine oxidase, which is not inactivated by heat treatment, breaks down spermine and spermidine to produce the highly toxic aldehyde acrolein, which causes cell damage and activates autophagy. However, no such enzyme activity has been found in humans. Polyamine catabolism does not produce toxic aldehydes under normal conditions, but inflammation and some pathogens provoke an inducible enzyme, spermine oxidase, which only breaks down spermine to produce acrolein, resulting in cytotoxicity and the activation of autophagy. Therefore, spermine oxidase activation reduces spermine concentration and the ratio of spermine to spermidine, a feature recently reported in patients with age-related diseases. Spermine, which is increased by a long-term, continuous high polyamine diet, suppresses aberrant gene methylation and the pro-inflammatory status that progress with age and are strongly associated with the development of several age-related diseases and senescence. Changes in spermine concentration and the spermine/spermidine ratio should be considered as indicators of human health status. Full article
(This article belongs to the Special Issue Novel Biomarkers and Technologies in the Research and Diagnosis of Human Diseases)
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Other

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16 pages, 2851 KiB  
Brief Report
Revisiting Fold-Change Calculation: Preference for Median or Geometric Mean over Arithmetic Mean-Based Methods
by Jörn Lötsch, Dario Kringel and Alfred Ultsch
Biomedicines 2024, 12(8), 1639; https://doi.org/10.3390/biomedicines12081639 - 23 Jul 2024
Viewed by 2181
Abstract
Background: Fold change is a common metric in biomedical research for quantifying group differences in omics variables. However, inconsistent calculation methods and inadequate reporting lead to discrepancies in results. This study evaluated various fold-change calculation methods aiming at a recommendation of a preferred [...] Read more.
Background: Fold change is a common metric in biomedical research for quantifying group differences in omics variables. However, inconsistent calculation methods and inadequate reporting lead to discrepancies in results. This study evaluated various fold-change calculation methods aiming at a recommendation of a preferred approach. Methods: The primary distinction in fold-change calculations lies in defining group expected values for log ratio computation. To challenge method interchangeability in a “stress test” scenario, we generated diverse artificial data sets with varying distributions (identity, uniform, normal, log-normal, and a mixture of these) and compared calculated fold-changes to known values. Additionally, we analyzed a multi-omics biomedical data set to estimate to what extent the findings apply to real-world data. Results: Using arithmetic means as expected values for treatment and reference groups yielded inaccurate fold-change values more frequently than other methods, particularly when subgroup distributions and/or standard deviations differed significantly. Conclusions: The arithmetic mean method, often perceived as standard or picked without considering alternatives, is inferior to other definitions of the group expected value. Methods using median, geometric mean, or paired fold-change combinations are more robust against violations of equal variances or dissimilar group distributions. Adhering to methods less sensitive to data distribution without trade-offs and accurately reporting calculation methods in scientific reports is a reasonable practice to ensure correct interpretation and reproducibility. Full article
(This article belongs to the Special Issue Novel Biomarkers and Technologies in the Research and Diagnosis of Human Diseases)
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