Early Diagnosis Research Articles

Autoantibodies as putative biomarkers and triggers of cell dysfunctions in systemic sclerosis.

Antinuclear autoantibodies represent a serological hallmark of systemic sclerosis (SSc), with anticentromere, antitopoisomerase-I, and anti-RNA polymerase III antibodies routinely assessed for diagnosis, clinical subset classification, and prognosis. In addition, an increasing number of autoantibodies have been demonstrated to play a pathogenic role by mediating different SSc manifestations. This review aims to give an overview on autoantibodies as putative biomarkers in SSc and discuss their possible pathogenic role as triggers of cell dysfunctions. Over the years, different autoantibodies have been proposed as biomarkers aiding in diagnosis, disease subtype classification, disease progression prediction, organ involvement, as well as in understanding treatment response. Increasing literature also indicates functional autoantibodies as direct contributors to SSc pathogenesis by exerting agonistic or antagonistic activities on their specific cognate targets. In SSc, search and validation of novel autoantibodies with higher diagnostic specificity and more accurate predictive values are increasingly needed for early diagnosis and specific follow-up, and to define the best therapeutic option according to different disease subsets. Moreover, since autoantibodies are also emerging as functional pathogenic players, a better unraveling of their possible pathomechanisms becomes essential to identify new targets and develop promising therapeutic agents able to neutralize their effects.

Clinical Management of Primary Aldosteronism: An Update.

Despite carrying an excess risk of cardiovascular events, primary aldosteronism (PA) is a commonly overlooked secondary form of arterial hypertension. An increased awareness of its high prevalence and broader screening strategies are urgently needed to improve its detection rate and allow early diagnosis and targeted treatment. For patients with unilateral PA, these measures can correct hyperaldosteronism and ensure cure of hypertension, even when resistant to drug treatment, thus preventing adverse cardiovascular events. Among these, atrial fibrillation is the most common, but left ventricular hypertrophy, stroke, chronic kidney disease, and myocardial infarction also occur more often than in patients with hypertension and no PA. Young patients, who have higher chances of being cured long term, and high-risk patients, such as those with stage III or resistant hypertension, are those who will benefit most from an early diagnosis of PA. Therefore, the implementation of strategies to detect PA by a simplified diagnostic algorithm is necessary. In the patients who seek for surgical cure, adrenal vein sampling is key for the identification of unilateral PA and the achievement of optimal outcomes. Unfortunately, being technically demanding and poorly available, adrenal vein sampling represents the bottleneck in the workup of PA. Considering the novel knowledge generated in the past 5 years in many studies, particularly in the AVIS-2 study (Atherothrombosis Intervention in High-Risk Patients Using Serelaxin), based on 4 decades of experience at our center and on the last guidelines, we herein provide an update on the management of PA with recommendations for drug treatment and strategies to avoid adrenal vein sampling wherever it is poorly, or not, available.

Association between perinatal and obstetric factors and early age at diagnosis of type 1 diabetes mellitus: a cohort study.

To evaluate the association between perinatal and obstetric factors as potential triggers for the early onset of T1DM. This was a retrospective cohort study enrolling 409 patients diagnosed with T1DM, in Bauru, São Paulo, Brazil, from 1981 to 2023. Data were retrieved from medical records, regarding sociodemographic parameters as age, sex, ethnicity, and socioeconomic status. Perinatal and obstetric factors as delivery type, gestational age, filiation order, length of exclusive breastfeeding, maternal age, maternal and fetal blood types, and occurrence of maternal gestational diabetes were also analyzed. An adapted survival analysis was employed to gauge the impact of each assessed variable at the age of T1DM diagnosis. The median age of T1DM diagnosis was 10.3 years with an interquartile range between 6.4 and 15.5 years. Delivery type and filiation order were the only factors statistically significantly associated with an early age at T1DM diagnosis. Patients who were born through cesarean section and who were firstborns showed a 28.6 and 18.0 % lower age at T1DM diagnosis, respectively, compared to those born through vaginal delivery and those that were nonfirstborns. Being born by cesarean section and being firstborn showed to be statistically significant factors to determine an early T1DM diagnosis.

Subclinical hypothyroidism and metabolic syndrome in psychiatric patients: A systematic literature review and meta-analysis.

The systematic review evaluated the association of subclinical hypothyroidism (SCH) with metabolic syndrome (MetS) and specific MetS components in people with major psychiatric disorders. A systematic review and meta-analysis was conducted to evaluate the association of SCH with MetS and its components in people with major psychiatric conditions. Five studies incorporating 24,158 participants met the inclusion criteria. All five studies comprised patients with depression and/or anxiety. Three studies incorporating 3365 participants were suitable for the meta-analysis. The pooled Odds Ratio (OR) of MetS was 3.46 (95% Confidence Interval/CI = 1.39-8.62) in major depressive disorder (MDD) and anxiety disorders patients with concurrent SCH compared to those without SCH. Meta-analysis showed a significant positive association between SCH and high body mass index (OR = 2.58, 95%CI = 1.33-5.01), high fasting plasma glucose (OR = 3.05, 95%CI = 1.79-5.18) and low high-density lipoprotein cholesterol (OR = 2.30, 95%CI = 1.82-2.92). These findings suggest a significant positive association between MetS and SCH in people with MDD and anxiety disorders. This review informed the clinical implications of MetS in MDD with comorbid SCH and the importance of early diagnosis and treatment for SCH and MetS in psychiatric patients.

Superior detection of low-allele burden Janus kinase 2 V617F mutation and monitoring clonal evolution in myeloproliferative neoplasms using chip-based digital PCR.

The JAK2 V617F is a prevalent driver mutation in Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPNs), significantly affecting disease progression, immunophenotype, and patient outcomes. The World Health Organization (WHO) guidelines highlight the JAK2 V617F mutation as one of the key diagnostic criterions for Ph-MPNs. In this study, we analyzed 283 MPN samples with the JAK2 V617F mutation to assess the effectiveness of three detection technologies: chip-based digital PCR (cdPCR), real-time quantitative PCR (qPCR), and next-generation sequencing (NGS). Additionally, we investigated the relationship between JAK2 V617F mutant allele burden (% JAK2 V617F) and various laboratory characteristics to elucidate potential implications in MPN diagnosis. Our findings demonstrated high conformance of cdPCR with qPCR/NGS for detecting % JAK2 V617F, but the mutant allele burdens detected by qPCR/NGS were lower than those detected by cdPCR. Moreover, the cdPCR exhibited high sensitivity with a limit of detection (LoD) of 0.08% and a limit of quantification (LoQ) of 0.2% for detecting % JAK2 V617F in MPNs. Clinical implications were explored by correlating % JAK2 V617F with various laboratory characteristics in MPN patients, revealing significant associations with white blood cell counts, lactate dehydrogenase levels, and particularly β2-microglobulin (β2-MG) levels. Finally, a case report illustrated the application of cdPCR in detecting low-allele burdens in a de novo chronic myeloid leukemia (CML) patient with a hidden JAK2 V617F subclone, which expanded during tyrosine kinase inhibitor (TKI) treatment. Our findings underscore the superior sensitivity and accuracy of cdPCR, making it a valuable tool for early diagnosis and monitoring clonal evolution.

Barriers in early detection of colorectal cancer and exploring potential solutions

This editorial discusses the literature review article by Tonini and Zanni, the paper was published in January 2024, and the authors provided very interesting conclusions regarding existing barriers to the early diagnosis of colon cancer. Many cancers do not have identifiable precursors, or there are currently no screening tests to find them. Therefore, these cancers do not have preventive screening options. Early detection is crucial for reducing mortality rates by identifying cancer at an earlier stage through screening, as opposed to no screening. Colorectal cancer develops from precancerous lesions, which can be detected early and potentially prevented and cured. Early detection leads to improved survival rates, decreased complications, and reduced healthcare expenses. This editorial provides a brief description of the biology of colon cancer, emphasizing the contrast in outcomes between early detection and late detection. We also describe screening programs around the globe and examine the barriers in each program. Finally, we explore potential future solutions to enhance inclusion in screening programs and improve patient compliance.

A personalized mRNA signature for predicting hypertrophic cardiomyopathy applying machine learning methods

Hypertrophic cardiomyopathy (HCM) may lead to cardiac dysfunction and sudden death. This study was designed to develop a HCM signature applying bioinformatics and machine learning methods. Data of HCM and normal tissues were obtained from public databases to screen differentially expressed genes (DEGs) using the R software limma package. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed for enrichment analysis of HCM-associated DEGs. Hub genes for HCM were determined using weighted gene co-expression network analysis (WGCNA) together with two machine learning algorithms (SVM-RFE and LASSO). Finally, we introduced a zebrafish model to simulate changes in the hub genes in the HCM and to observe their effects on cardiac disease development. The mRNA expression data from a total of 106 HCM tissues and 39 normal samples were collected and we screened 157 DEGs. Enrichment analysis showed that immune pathways played an important role in the pathogenesis of HCM. Three hub genes (FCN3, MYH6 and RASD1) were identified using WGCNA, SVM-RFE, and LASSO analysis. In a zebrafish model, knockdown of MYH6 and RASD1 resulted in cardiac malformations with reduced ventricular capacity and heart rate, which validated the clinical significance of these genes in the diagnosis of HCM. Based on machine learning algorithms, our study created a signature with potential impact on cardiac function and cardiac quality index for HCM. The current findings had important implications for the early diagnosis and treatment of HCM.

Design, synthesis and application of polarity- and pH-sensitive dual-responsive small molecule fluorescent probe for early cancer diagnosis

Cancer is one of the deadliest and most complex diseases globally. It is well known that cancer cells exhibit a unique intracellular microenvironment characterized by low pH and low polarity compared to normal cells. Thus, dual-responsive fluorescent probe are more suitable for such complex and variable physiological environments than single-response probe. In this study, we designed and synthesized a dual-responsive fluorescent probe, CCT, which responds to both pH and polarity based on intramolecular charge transfer (ICT) and photoelectron transfer (PET) mechanisms.We synthesized probe CCT by combining naphthylimide, a coumarin unit, and morpholine through a six-step process. The PET mechanism between morpholine and naphthylimide renders probe CCT pH-sensitive. Additionally, the direct linkage of the polarity-sensitive units, coumarin and naphthylimide, creates a larger polarity-sensitive system. When both low pH and low polarity conditions are present, the fluorescence intensity of probe CCT is significantly higher than under separate conditions. This increased fluorescence intensity matches the low pH and low polarity microenvironment of cancer cells, facilitating bioimaging.Fluorescence imaging results demonstrate that probe CCT effectively distinguishes between cancer and normal cells, suggesting its potential as a powerful tool for early cancer diagnosis.

Gastric cancer in pregnancy: a review.

Malignant tumors including gastric cancer (GC) are the leading cause of deaths among reproductive women. Physiological morning sickness can mask the clinical manifestations of GC, whereas the clinical presence of metastatic tumors in the abdominal cavity may be easily mistaken for abdominal swelling caused by fetal growth. Pregnancy and delivery processes in young females could accelerate the growth of GC, leading to its rapid development and grave prognosis. Therefore, early diagnosis is critical and gastrointestinal endoscopy is recommended for any suspected pregnant woman with long-term morning sickness. Treatment strategies, including chemotherapy, resection surgery and radiotherapy, will be determined based on a comprehensive consideration of the status of both the fetus and the mother. Rational management, especially clinical multidisciplinary collaboration may significantly benefit such patients.

Typical and Emerging Diagnostic MRI Features in Multiple Sclerosis.

Magnetic resonance imaging (MRI) stands as the most sensitive paraclinical technique for detecting the demyelinating lesions characteristic of multiple sclerosis (MS). Consequently, MRI plays a pivotal role in establishing an accurate and timely diagnosis of the disease, ultimately based on the application of the McDonald criteria. Early diagnosis is particularly important as it facilitates the prompt initiation of disease-modifying treatments, deemed most effective during the initial phases of MS. This review article examines the recommended standardized MRI protocol, as well as the classic imaging features of MS in the brain, optic nerve, and spinal cord, capable of discriminating, in most cases, MS from other disorders that can mimic this disease. Additionally, novel MR imaging findings, such as the central vein sign and paramagnetic rim lesion, which have been proposed as new imaging biomarkers to enhance diagnostic specificity for MS, are also discussed. These emerging features are likely to be incorporated in the future iterations of the McDonald criteria, and therefore, radiologists should be familiar with their appearance and with the optimal MRI protocols required for their detection.

Design of encoded graphene-gold metasurface-based circular ring and square sensors for brain tumor detection and optimization using XGBoost algorithm

This study introduces a circular ring and square metasurfaces-based sensor employing graphene and gold layers for enhanced brain tumor detection. The sensor architecture includes dual graphene circular metasurfaces and a gold square resonator layer on a silicon dioxide substrate. A comprehensive parametric investigation explores the influence of geometric parameters and graphene chemical potential on sensor performance. The sensor achieves a remarkable sensitivity of 769 GHzRIU−1, a high-quality factor of 6.514, a low detection limit of 0.182 RIU, and an FOM of 1.148RIU−1. Electric field intensity analysis identifies optimal transmission frequencies. By employing the XGBoost regressor, the analysis significantly reduces simulation time and resource consumption by at least 80 %. Simulation validation confirms that despite 80 % reduction in simulation time, high prediction accuracy remains achievable, with an impressive R2 score ranging from 0.9 to 1. The proposed sensor presents a promising non-invasive approach for early brain tumor diagnosis, with potential applications in biomedical imaging and other related fields.

Have epilepsy outcomes changed for children with tuberous sclerosis complex in Queensland, Australia?

Historically, epilepsy has been the most frequently presenting feature of tuberous sclerosis complex (TSC). Advances in TSC health care have occurred over the past decade; thus, we studied whether TSC epilepsy outcomes have changed. A retrospective chart review was undertaken for all children with TSC in Queensland, Australia. Epilepsy outcome and TSC diagnosis data were extracted, and data were compared between children born before 2012 with those born in or after 2012. In this retrospective cohort, TSC diagnosis in children born in or after 2012 is now predominantly antenatal (51%, p < .05). Most patients with epilepsy are now known to have TSC before they develop epilepsy. Despite earlier TSC diagnosis, the frequency of epilepsy (85%) has not changed (p = .92), but diagnosis trends toward an earlier age (median = 3 months for patients born in or after 2012 vs. 5.5 months for those born before 2012, p = .23). Most (95%) patients had focal seizures as their initial clinical seizure type; it was rare (5%) for epileptic spasms (ES) to be the initial seizure type. The frequency of ES was lower in patients born in or after 2012 (36% vs. 50%, p = .27). Infantile (<24 months) onset ES was not associated with worse epilepsy outcome. Late onset ES was seen in 14%, and these patients hada lower rate of epilepsy remission. Lennox-Gastaut syndrome was seen in 7%. Febrile/illness-related status epilepticus occurred in 12% of patients, between 1 and 4 years of age. Despite many (78%) patients having multiple daily seizures at maximal seizure frequency, and 74% meeting criteria for treatment-refractory epilepsy, most patients achieved epilepsy remission (66%), either with epilepsy surgery (47%) or with age (53%). At the time of inclusion in this study, only 21% of patients had uncontrolled frequent (daily to 3 monthly) seizures and 14% had uncontrolled infrequent (3 monthly to <2 yearly) seizures. This study provides updated information that informs the counseling of parents of newly diagnosed pediatric TSC patients.

Identification and verification of four candidate biomarkers for early diagnosis of osteoarthritis by machine learning

Identification and verification of four candidate biomarkers for early diagnosis of osteoarthritis by machine learning

Recent Advances in Self‐Powered Electrochemical Biosensors for Early Diagnosis of Diseases

Recent Advances in Self‐Powered Electrochemical Biosensors for Early Diagnosis of Diseases

Preventive medicine in OSA-A systematic review and a call to action.

The purpose of this systematic review is to evaluate the modifiable risk factors associated with OSA and analyze extant publications solely focused on prevention of the disease. Studies focused on prevention strategies for OSA and modifiable risk factors were eligible for inclusion. A detailed individual search strategy for each of the following bibliographic databases was developed: Cochrane, EMBASE, MEDLINE, PubMed and LILACS. The references cited in these articles were also crosschecked and a partial grey literature search was undertaken using Google Scholar. The methodology of selected studies was evaluated using the 14-item Quality Assessment Tool for Diagnostic Accuracy Studies. Search resulted in 720 publications examining risk factors and prevention of OSA, as well as lifestyle modifications. Of these, a thorough assessment of the abstracts and content of each of these manuscripts led to the rejection of all but four papers, the latter being included in this systematic review. In contrast, a search regarding 'Therapeutics' showed that 23,674 articles on OSA were published, clearly illustrating the imbalance between the efforts in prevention and those focused on therapeutics. Notwithstanding the importance and benefits of technological advances in medicine, consideration of the needs of people with OSA and its consequences prompts advocacy for the prevention of the disease. Thus, despite the economic interests that focus only on diagnosis and treatment, strategies preferentially aimed at overall avoidance of OSA emerge as a major priority. Thus, public and healthcare provider education, multidimensional prevention, and early diagnosis of OSA should be encouraged worldwide.

Moderation of thyroid hormones for the relationship between amyloid and tau pathology

BackgroundAltered thyroid hormone levels have been associated with increased risk of Alzheimer's disease (AD) dementia and related cognitive decline. However, the neuropathological substrates underlying the link between thyroid hormones and AD dementia are not yet fully understood. We first investigated the association between serum thyroid hormone levels and in vivo AD pathologies including both beta-amyloid (Aβ) and tau deposition measured by positron emission tomography (PET). Given the well-known relationship between Aβ and tau pathology in AD, we additionally examined the moderating effects of thyroid hormone levels on the association between Aβ and tau deposition.MethodsThis cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. This study included a total of 291 cognitively normal adults aged 55 to 90. All participants received comprehensive clinical assessments, measurements for serum total triiodothyronine (T3), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), and brain imaging evaluations including [11C]-Pittsburgh compound B (PiB)- PET and [18F] AV-1451 PET.ResultsNo associations were found between either thyroid hormones or TSH and Aβ and tau deposition on PET. However, fT4 (p = 0.002) and fT3 (p = 0.001) exhibited significant interactions with Aβ on tau deposition: The sensitivity analyses conducted after the removal of an outlier showed that the interaction effect between fT4 and Aβ deposition was not significant, whereas the interaction between fT3 and Aβ deposition remained significant. However, further subgroup analyses demonstrated a more pronounced positive relationship between Aβ and tau in both the higher fT4 and fT3 groups compared to the lower group, irrespective of outlier removal. Meanwhile, neither T3 nor TSH had any interaction with Aβ on tau deposition.ConclusionOur findings suggest that serum thyroid hormones may moderate the relationship between cerebral Aβ and tau pathology. Higher levels of serum thyroid hormones could potentially accelerate the Aβ-dependent tau deposition in the brain. Further replication studies in independent samples are needed to verify the current results.

Nylon 6 film coated with poly-tetrahydrofuran sol–gel solution in face mask as a non-invasive in vivo sampling device for caffeine in human exhaled breath aerosol

Caffeine is an alkaloid compound that can excite the central nervous system and effectively relieve fatigue in moderation. However, excessive caffeine consumption can block blood vessels, raising blood pressure and increasing the risk of atherosclerosis. The International Agency for Research on Cancer of the World Health Organization has listed caffeine in category 3 carcinogens, so it is crucial that caffeine be detected easily and accurately. Exhaled breath aerosol (EBA), which consists of a large number of volatile substances and complex biological matrices, can not only reflect the physiological state of the human body, ingested substances, and environmental exposures; on the other hand, the characteristics of non-invasive sampling also make EBA analysis has a broad application prospect in the field of human health monitoring and disease diagnosis. This paper used a combination of nylon 6 film coated with poly-tetrahydrofuran (PTHF) and a medical N95 mask to construct a convenient and direct sampling device, which can be used to collect caffeine ingested by humans non-invasively from EBA. Volunteers wore a mask for a defined period of time after consuming a certain amount of caffeine. The samples were next back-extracted with methanol and detected and analyzed using gas chromatography-high resolution mass spectrometry (GC-HRMS). The results showed that under the optimized analytical conditions, the PTHF-coated nylon 6 film was effective in collecting caffeine from human EBA, and the peak time of caffeine was 23.44 min. The mask-loaded coated device in this study has the advantages of being comfortable and efficient, safe and non-invasive as well as easy to operate, and by combining with mass spectrometry molecular techniques it can achieve high sensitivity and specificity analysis of trace components, which is expected to be used for the early diagnosis of respiratory diseases in clinical analysis.

Nano-Photonic Crystal D-Shaped Fiber Devices for Label-Free Biosensing at the Attomolar Limit of Detection.

Maintaining both high sensitivity and large figure of merit (FoM) is crucial in regard to the performance of optical devices, particularly when they are intended for use as biosensors with extremely low limit of detection (LoD). Here, a stack of nano-assembled layers in the form of 1D photonic crystal, deposited on D-shaped single-mode fibers, is created to meet these criteria, resulting in the generation of Bloch surface wave resonances. The increase in the contrast between high and low refractive index (RI) nano-layers, along with the reduction of losses, enables not only to achieve high sensitivity, but also a narrowed resonance bandwidth, leading to a significant enhancement in the FoM. Preliminary testing for bulk RI sensitivity is carried out, and the effect of an additional nano-layer that mimics a biological layer where binding interactions occur is also considered. Finally, the biosensing capability is assessed by detecting immunoglobulin G in serum at very low concentrations, and a record LoD of 70 aM is achieved. An optical fiber biosensor that is capable of attaining extraordinarily low LoD in the attomolar range is not only a remarkable technical outcome, but can also be envisaged as a powerful tool for early diagnosis of diseases.

Evaluation of mtDNA common deletion in esophageal squamous cell carcinoma.

Mitochondrial defects are thought to play a role in cancer initiation and progression for a long time. Because of the absence of protective histones and an inefficiency in the DNA repair process, mitochondrial DNA is known to be prone to mutations. The deletion of 4977bp is one of the most common mutations in human cancers. This study aimed to investigate the relationship between 4977bp common deletion and Esophageal Squamous Cell Carcinoma Disease (SCC) to provide prognostic information. By using a PCR protocol, this study identified the 4977bp deletion of mtDNA. A PCR method was used on tumor samples from 41 squamous cell carcinoma patients and blood samples from 50 healthy individuals to detect DNA. Among the 41 tumor samples (80.5%), 33 were found to have the 4977bp deletion, while none of the blood samples from healthy individuals contained it. It is shown that the deletion of 4977bp of mtDNA correlates significantly with SCC in this study. A 4977bp deletion could be used as an effective cancer screening indicator and biomarker for early diagnosis and prevention of cancer.

The application value of whole exome sequencing technology in diagnosis of hereditary renal cysts

The data of 57 renal cyst patients who visited the First Affiliated Hospital of Zhengzhou University from January 2023 to March 2024 were retrospectively analyzed. The age of patients ranged from three months to 60 years old, with 31 males and 26 females. The whole exome sequencing (WES) detected pathogenic or suspected pathogenic (P/LP) variants in 48 renal cystic probands, with a detection rate of 84.2% (48/57), including PKD1, PKD2, PKHD1, LRP5, COL4A4 and ALG8 gene variants as well as copy number variations (CNV). In addition, four PKD1 gene variants of uncertain significance (VUS) were detected. In five WES negative families, one PKD1 nonsense variation was detected through long-range PCR (LR-PCR)+Oxford nanopore technologies, and one heterozygous deletion in exon 22 of PKD1 gene was detected through multiplex ligation-dependent probe amplification (MLPA). In summary, WES can detect multiple types of variations, which is helpful for early diagnosis and prognosis prediction of renal cyst patients. However, there is still a risk of failing to detect PKD1 gene by WES, therefore, healthcare practitioners should beware of the negative results of WES.