Diagnostic Approach Research Articles

Comprehensive Diagnostic Approach to Head and Neck Masses

Head and neck masses are a significant diagnostic challenge and differential diagnoses range from inflammatory, infectious, and neoplastic conditions. Timely, accurate evaluation is essential for optimal patient outcomes. This review highlights a systematic approach to diagnosing head and neck masses through comprehensive history, physical examination, and a variety of diagnostic tools. Imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound are integral in diagnosis. Fine-needle aspiration (FNA) biopsy is a minimally invasive option for a preliminary diagnosis. However, in cases where it may be inconclusive or when extensive tissue sampling is needed to confirm a diagnosis, open tissue biopsy is considered. Collaboration among a multidisciplinary team (surgeons, radiologists, and pathologists) is vital in developing an effective individualized treatment plan. Early detection and accurate diagnosis of head and neck masses are critical for achieving favorable clinical outcomes.

Integrated analysis of single-cell RNA sequencing and bulk transcriptome data identifies a pyroptosis-associated diagnostic model for Parkinson’s disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by an insidious onset. Despite the emphasis on motor symptom-based diagnosis, there remains an unmet clinical need for effective diagnostic approaches during the prodromal phase of PD. Recent advances in single-cell RNA sequencing (scRNA-seq) and bulk transcriptomic analyses of PD patients open avenues for identifying potential diagnostic biomarkers. A comprehensive cell trajectory analysis was conducted using scRNA-seq datasets to identify gene expressions associated with the cellular transition from healthy to PD-associated states. Integration of scRNA-seq datasets with weighted gene co-expression network analysis (WGCNA) allowed extraction of pyroptosis-associated differentially expressed genes (PDEGs). Using LASSO logistic regression, support vector machine recursive feature elimination (SVM-RFE) and random forest methods, we developed a diagnostic model centred on PDEGs. In addition, immunoinfiltration, inflammatory signalling pathways and intercellular communication were detected by scRNA-seq analyses. In PD patients, the number of cells including metencephalic-like cells, excitatory neurons, inhibitory neurons and MHB-like cells was significantly reduced, whereas the proportion of astrocytes and microglia, immunoinfiltration and inflammatory signalling pathways were upregulated compared to healthy individuals. Using scRNA-seq and WGCNA analyses, two pyroptosis-related diagnostic genes, POLR2K and TIMM8B, were identified and a diagnostic model based on them was constructed, which showed promising performance upon validation. This study established a pyroptosis-related diagnostic model for PD through the analyses of scRNA-seq combined with bulk transcriptome data, which improved the understanding of the role of PDEGs in PD and provided new insights into the diagnostic strategies for this neurodegenerative disease.

Cervical Anatomical Characteristics in Women with Endometriosis: A Diagnostic Approach

Background: Endometriosis is a gynecologic disorder which causes dysmenorrhea and infertility. Early diagnosis of endometriosis can help prevent the necessity for invasive diagnostic procedures. Medical imaging has been widely utilized to diagnose various diseases without the need for invasive procedures. The purpose of this study was to investigate the cervical length in women with endometriosis. Methods: In this case-control study, the case group consisted of nulliparous women with endometriosis, while the control group comprised nulliparous women without endometriosis. A total of 42 individuals were included in each group. Cervical length was measured using transvaginal ultrasound from the external os to the internal os. The patients in the case group underwent laparoscopy to confirm the diagnosis. Pearson chi-square test and Fisher’s exact test were employed to compare categorical variables with a p<0.05 considered statistically significant. Results: In both groups, there were no notable variations in any of the demographic characteristics. However, the severity of dysmenorrhea was significantly different between the two groups (p=0.01). The average diameter of the mediolateral cervix (29.48±6.2 and 27.14±3.8) was statistically significant between the patient group and control group, respectively (p=0.04). The mediolateral width may have a positive predictive effect on the presence of endometriosis, while cervical length appears to have a protective effect against endometriosis. Conclusion: Demographic data do not predict endometriosis. This study suggests that mediolateral width in transvaginal sonography can serve as a minimally invasive diagnostic tool for endometriosis, showing correlation with endometriosis symptoms like dysmenorrhea and dyspareunia.

Epidemiology and clinical management of canine Leishmaniasis in northeastern Algeria: A preliminary study

Canine leishmaniasis (CanL) caused by Leishmania infantum is a prevalent vector-borne disease in the Mediterranean region, notably Algeria. This research aims to assess the epidemiology and the clinical management practices of CanL employed by veterinarians in the Skikda and Constantine regions in the northeastern part of Algeria. A retrospective survey comprising 37 open and closed questions was distributed to 139 veterinary clinics between 2022 and 2023. The objective was to collect comparable epidemiological information on clinical presentations, diagnostic approaches, treatment protocols, preventive strategies, and awareness of the disease's public health implications. The findings from this study have revealed a notable prevalence of CanL in both regions, accompanied by similar clinical manifestations. Serological techniques, particularly rapid detection kits, are predominantly utilized alongside direct methods, while euthanasia remains the primary approach to combat the disease. The results show that only a few veterinarians educate pet owners about zoonotic diseases and prevention measures (32,79 %), while most do not provide this information. This investigation sheds more light on the current status of CanL in the selected studied area and suggests the need for standardizing diagnosis and treatment of CanL using evidence-based medicine criteria to enhance disease management. This will provide a proper way of conducting a more comprehensive epidemiological assessment of the condition for improving the handling and management of CanL in Algeria.

The Management of Osteoporosis in Chronic Kidney Disease: A Review of Diagnostic and Therapeutic Approaches

The Management of Osteoporosis in Chronic Kidney Disease: A Review of Diagnostic and Therapeutic Approaches

Machine learning model based on SERPING1, C1QB, and C1QC: A novel diagnostic approach for latent tuberculosis infection

AbstractBackgroundLatent tuberculosis infection (LTBI) is a significant source of active tuberculosis (ATB), yet distinguishing between them is challenging because specific biomarkers are lacking.MethodsWe analyzed four microarray datasets (GSE19491, GSE37250, GSE54992, GSE28623) from the gene expression omnibus to identify differentially expressed genes (DEGs). Using protein–protein interaction (PPI) networks and LASSO‐SVM algorithms, we selected three candidate biomarkers and evaluated their diagnostic efficacy. The expression levels of core genes were validated by RNA sequencing of healthy, ATB, and LTBI groups in a real‐world cohort. We conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, predicted shared upstream miRNAs, constructed miRNA–hub and transcription factor (TF)–hub gene networks, and performed immune infiltration analysis.ResultsThree hub genes (SERPING1, C1QC, C1QB) were identified from 45 DEGs by PPI networks and machine learning screening. The diagnostic model based on the three hub genes had an area under the curve (AUC) value of 0.843 in the training set GSE19491 and 0.865 in the validation set GSE28623. Real‐world transcriptome sequencing confirmed the expression trends of the hub genes across healthy, LTBI, and ATB groups. GO analysis showed that the 45 hub genes were primarily associated with immune inflammatory responses and pattern recognition receptors, whereas KEGG analysis indicated enrichment in complement and coagulation cascades. The miRNA–hub and TF–hub gene network analysis identified nine miRNAs and the zinc finger TF GATA2 as potential co‐regulators of SERPING1, C1QC, and C1QB. Immune cell infiltration analysis identified significant differences in the immune microenvironment between LTBI and ATB, with macrophages and natural killer cells showing significant correlations with tuberculosis infection.ConclusionThe diagnostic model with SERPING1, C1QC, and C1QB shows promise in distinguishing LTBI from ATB, indicating its potential as a diagnostic tool.

Application of artificial intelligence in VSD prenatal diagnosis from fetal heart ultrasound images

BackgroundDeveloping a combined artificial intelligence (AI) and ultrasound imaging to provide an accurate, objective, and efficient adjunctive diagnostic approach for fetal heart ventricular septal defects (VSD).Methods1,451 fetal heart ultrasound images from 500 pregnant women were comprehensively analyzed between January 2016 and June 2022. The fetal heart region was manually labeled and the presence of VSD was discriminated by experts. The principle of five-fold cross-validation was followed in the training set to develop the AI model to assist in the diagnosis of VSD. The model was evaluated in the test set using metrics such as mAP@0.5, precision, recall, and F1 score. The diagnostic accuracy and inference time were also compared with junior doctors, intermediate doctors, and senior doctors.ResultsThe mAP@0.5, precision, recall, and F1 scores for the AI model diagnosis of VSD were 0.926, 0.879, 0.873, and 0.88, respectively. The accuracy of junior doctors and intermediate doctors improved by 6.7% and 2.8%, respectively, with the assistance of this system.ConclusionsThis study reports an AI-assisted diagnostic method for VSD that has a high agreement with manual recognition. It also has a low number of parameters and computational complexity, which can also improve the diagnostic accuracy and speed of some physicians for VSD.

The Utilization of a Pregnancy-Associated Glycoprotein Profile and PAG/P4 Ratio Biomarker for the Diagnosis of Pseudopregnancy in Dairy Goats.

Pseudopregnancy (PPG) is a common reproductive disorder in dairy goats, characterized by the accumulation of sterile fluid in the uterus and persistence of a corpus luteum, leading to temporary infertility and reduced farm efficiency. This study aimed to determine the pregnancy-associated glycoprotein (PAG) profile in dairy goats and to evaluate the PAG/P4 ratio as a potential novel biomarker for PPG diagnosis. A total of 605 Saanen and crossbreed mated goats were evaluated via transabdominal ultrasonography between 31 and 52 days after the removal of bucks in four intensive dairy farms, presenting an overall PPG incidence of 7.8%. Blood samples from PPG (n = 47), nonpregnant (NPG; negative control; n = 11), and pregnant (PG; positive control; n = 10) does were collected for PAG and P4 analysis. The PAG plasma levels were 0.08 ± 0.02, 0.13 ± 0.04, and 1.45 ± 0.04 OD (optical density) in the PPG, NPG, and PG groups, respectively (p < 0.001). The PAG/P4 ratio was lower in the PPG group (0.01 ± 0.11; p < 0.001) than in the NPG (0.24 ± 0.23) and PG (0.18 ± 0.23) groups. This difference allows for the establishment of a new methodological diagnostic approach to PPG. The area under the curve (AUC) was 0.996 for a cut-off of 0.04 and 97.9% and 100% sensitivity and specificity, respectively. This study suggests that the PAG/P4 ratio can serve as a reliable biomarker for PPG diagnosis, helping to distinguish it from pregnancy and nonpregnancy and improving reproductive management in dairy goats.

Comparison of RT.PCR and ELISA Methods in the Diagnosis of Human Cytomegalovirus in Kidney Transplant Patients

Background: In kidney transplant recipients prone to infections like cytomegalovirus (CMV), a vital need for an accurate diagnostic method is evident. This study at Khorshid Laboratory in Tehran rigorously compares real-time PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) for CMV detection in transplant patients. Methods: In January to March 1400, 70 kidney transplant recipients were assessed for CMV DNA using RT-PCR and concurrent ELISA tests, with statistical analysis aided by SPSS. Results: In kidney transplant patients (average age: 49.40 ± 13.64 years), 4.3% tested positive for CMV via PCR. Strong correlation between serological and molecular methods. IgG and IgM antibody detection both showed high sensitivity and specificity, advocating for efficient CMV diagnosis at Khorshid Laboratory, Tehran. Conclusion: This study emphasizes the need for a quick and efficient CMV diagnostic approach in kidney transplant patients. The strong correlation between molecular and serological methods favors using the faster RT-PCR method, crucial for timely management, especially with the increasing age- related CMV incidence. The findings strongly recommend RT-PCR integration for enhanced sensitivity in kidney transplant patients at Khorshid Laboratory, Tehran.

Possibilities of Peroral Transpapillary Cholangioscopy in Treatment of Complex Choledocholithiasis

Background: Сomplex choledocholithiasis remains an urgent socio-medical problem in modern medicine. This pathology is more common in patients with cholelithiasis and causes such complications as obstructive jaundice, acute and chronic pancreatitis, cholangitis, etc. Effective treatment depends on proper preoperative examination, which is quite challenging. In such cases, minimally invasive diagnostic methods play a fundamental role. Endoscopic cholangioscopy is an effective and highly informative method for diagnosis and treatment of biliary diseases including сomplex choledocholithiasis; in many cases it is the only examination technique that allows for a reliable diagnosis. The effectiveness of this technique and possibilities of its implementation by leading specialists in the Russian Federation and around the world remain important issues.Objective: To summarize available literature data on possibilities of using cholangioscopy in diagnosis and treatment of сomplex choledocholithiasis.Materials and methods: We conducted a literature review using PubMed and eLIBRARY. Our goal was to cover the most up-to-date medical articles published on the subject in the past 10 years. Studies included in our review are based on experimental and clinical data. Thus, we obtained the most reliable results that can be used in further research and practice.Results: We found that cholangioscopy has significant clinical value, which confirms its role as an important diagnostic and therapeutic approach in addition to endoscopic retrograde cholangiopancreatography in treatment of complex choledocholithiasis. This technique should be further thoroughly studied.

Illuminating Malaria: Spectroscopy’s Vital Role in Diagnosis and Research

Spectroscopic techniques have emerged as crucial tools in the field of malaria research, offering immense potential for improved diagnosis and enhanced understanding of the disease. This review article pays tribute to the pioneering contributions of Professor Henry Mantsch in the realm of clinical biospectroscopy, by comprehensively exploring the diverse applications of spectroscopic methods in malaria research. From the identification of reliable biomarkers to the development of innovative diagnostic approaches, spectroscopic techniques spanning the ultraviolet to far-infrared regions have played a pivotal role in advancing our knowledge of malaria. This review will highlight the multifaceted ways in which spectroscopy has contributed to the field, with a particular emphasis on its impact on diagnostic advancements and drug research. By leveraging the minimally invasive and highly accurate nature of spectroscopic techniques, researchers have made significant strides in improving the detection and monitoring of malaria parasites. These advancements hold the promise of enhancing patient outcomes and aiding in the global efforts towards the eradication of this devastating disease.

Minimally Invasive and Emerging Diagnostic Approaches in Endometrial Cancer: Epigenetic Insights and the Promise of DNA Methylation.

Endometrial cancer (EC) is the most common gynecological malignancy, with rising incidence and mortality rates. Key risk factors, including obesity, prolonged estrogen exposure, and metabolic disorders, underscore the urgent need for non-invasive, early diagnostic tools. This review focuses on the role of DNA methylation as a potential biomarker for early EC detection. Aberrant DNA methylation in the promoter regions of tumor suppressor genes can lead to gene silencing and cancer progression. We examine recent studies utilizing minimally invasive samples, such as urine, cervicovaginal, and cervical scrapes, to detect early-stage EC through DNA methylation patterns. Markers such as RASSF1A, HIST1H4F, GHSR, SST, and ZIC1 have demonstrated high diagnostic accuracy, with AUC values up to 0.95, effectively distinguishing EC from non-cancerous conditions. This review highlights the potential of DNA methylation-based testing as a non-invasive alternative to traditional diagnostic methods, offering earlier detection, better risk stratification, and more personalized treatment plans. These innovations hold the promise of transforming clinical practice by enabling more timely and effective management of endometrial cancer.

Endoscopic Findings of 'Salmon Roe-like Nodular Lesions' in a Case of Severe Disseminated Strongyloidiasis in a Foreign Resident in Japan.

A Southeast Asian man in his 30s residing in Japan developed severe disseminated strongyloidiasis during long-term steroid therapy. Initially misdiagnosed as gastroenteritis, his condition was later identified as strongyloidiasis by fecal smears and endoscopy. An endoscopic examination revealed salmon roe-like nodular lesions, indicating an advanced stage. Despite treatment, the patient died of the illness. This case underscores the importance of considering the patient's geographical background and immunosuppressive history in medical assessments. It further highlights the need for early and proactive diagnostic approaches, such as stool testing and gastrointestinal endoscopy, to effectively detect and treat imported infectious diseases.

Differentiating Essential and Dystonic Head Tremor: Exploring Arm Position Effects.

Head tremor poses diagnostic problems, especially when present as an isolated or predominant symptom. To assess how maneuvers activating upper limb postural tremor can help differentiate head tremor in essential tremor (ET) from dystonic tremor (DT) in cervical dystonia. 48 patients with head tremor (25 ET, 23 DT), underwent clinical examination and accelerometric evaluation of head and upper limb tremor during routine tremor-inducing tasks. While accelerometric power and clinical scores of head tremor did not significantly differ between patient groups, task-induced variations revealed distinctions. ET patients exhibited increased head tremor power and clinical scores during forward outstretched and lateral wing-beating arm positions, unlike DT patients. Coherence between head and upper limb tremor remained consistent. Tremor stability index showed no significant differences. Task-induced changes in head tremor could aid in distinguishing between ET and DT. Further research is needed to refine diagnostic approaches for head tremor.

Diagnostics and classification of fractures of the thoracic and lumbar spine in adults : Approach depending on the bone structure

The epidemiology, treatment and prognosis of thoracolumbar vertebral fractures are fundamentally influenced by the bone quality of the patient. In individuals with healthy bone structure, ahigh-energy trauma is typically required to cause afracture. In contrast, osteoporosis can cause fractures and also be present as acomorbid pathology in traumatic fractures. Comprehensive diagnostics and a precise classification are essential for appropriate treatment. This narrative review outlines the diagnostic approach and classification of thoracolumbar vertebral fractures depending on the bone quality as the basis of treatment. In addition to aphysical examination, conventional radiographs with the patient in a standing position and computed tomography (CT) scans of the affected region serve as the foundation for fracture classification. Supplementary magnetic resonance imaging (MRI) primarily assesses discoligamentous and neurological structures of the spine as well as the age of the fracture. In suspected cases of osteoporotic fractures, ashort-tau inversion recovery (STIR) sequence of the entire thoracic and lumbar spine is recommended for reliable detection of bone marrow edema. For patients with healthy bone structure, the AOSpine classification is used, whereas the osteoporotic fracture (OF) classification and the OF score are applied in cases of osteoporosis.

Recent Therapeutic Advancements for Gaucher Disease

AbstractGaucher Disease (GD) is a well‐known lysosomal storage disease resulting from mutations in the GBA1 gene. GD exhibits a range of clinical manifestations, each with unique symptoms and severity levels. This review explores the genetic foundations of GD, highlighting the significance of Glucocerebrosidase (GCase) deficiency, resulting in the skeletal complications associated with GD, such as osteonecrosis, fractures, and bone pain, all of which significantly negatively influence the quality of life for patients. Over 700 mutations in the GBA1 gene are found to cause variations in gene expression in GD, indicating the disease's complexity and the need for continued research. Early diagnosis and prognosis evaluation depend heavily on diagnostic approaches integrating laboratory assessments, genetic testing, and clinical symptoms. Treatment strategies like enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) have advanced, but issues like high costs and invasiveness still exist. This review focuses on novel therapeutic approaches that show promise in treating GD, including gene and cell‐based therapies, pharmacological chaperone therapy (PCT), and drug delivery via nanoparticles. Finally, discussions on current clinical trials, limitations of the advanced therapies, and future scope are summarized.

A review of multiple diagnostic approaches in the undiagnosed diseases network to identify inherited metabolic diseases

BackgroundThe number of known inherited metabolic diseases (IMDs) has been expanding, and the rate of diagnosis is improving with the development of innovative approaches including next generation sequencing (NGS). However, a substantial proportion of IMDs remain undetected by traditional diagnostic approaches. We aim to highlight the spectrum of IMDs diagnosed by the Undiagnosed Diseases Network (UDN) and to learn from the UDN diagnostic processes that were able to detect IMDs.MethodsWe conducted a retrospective analysis of 757 UDN participants diagnosed from 2015 until 2023 using the cohort database, which were divided into a cohort with IMDs (n = 194; 27%) and a cohort whose phenotypes were not explained by an IMD (n = 563; 73%), based on the International Classification of Inherited Metabolic Disorders (ICIMD). Then, we divided the causes of the metabolic 194 diagnoses into seven groups that included all the ICIMD categories. We inspected which clinical and laboratory approaches contributed to a final UDN diagnosis. We also present a UDN case example from each group to highlight the diagnostic yields that resulted from combining newer diagnostic approaches in the UDN and illustrate potential pitfalls of current NGS methods.ResultsThese 194 cases of IMDs included examples from 21/25 (84%) of the ICIMD categories. Of the UDN subjects 164/194 (85%) were diagnosed with IMDs through NGS.ConclusionThe spectrum of IMDs detected in the UDN cohort is large and growing and appropriate use of newer multiple diagnostic approaches should further increase diagnosis of IMDs that are presently missed by the traditional laboratory screening methods.

A label-free optical biosensor-based point-of-care test for the rapid detection of Monkeypox virus

Diagnostic approaches that combine the high sensitivity and specificity of laboratory-based digital detection with the ease of use and affordability of point-of-care (POC) technologies could revolutionize disease diagnostics. This is especially true in infectious disease diagnostics, where rapid and accurate pathogen detection is critical to curbing the spread of disease. We have pioneered an innovative label-free digital detection platform that utilizes Interferometric Reflectance Imaging Sensor (IRIS) technology. IRIS leverages light interference from an optically transparent thin film, eliminating the need for complex optical resonances to enhance the signal by harnessing light interference and the power of signal averaging in shot-noise-limited operation In our latest work, we have further improved our previous 'Single-Particle' IRIS (SP-IRIS) technology by allowing the construction of the optical signature of target nanoparticles (whole virus) from a single image. This new platform, 'Pixel-Diversity' IRIS (PD-IRIS), eliminated the need for z-scan acquisition, required in SP-IRIS, a time-consuming and expensive process, and made our technology more applicable to POC settings. Using PD-IRIS, we quantitatively detected the Monkeypox virus (MPXV), the etiological agent for Monkeypox (Mpox) infection. MPXV was captured by anti-A29 monoclonal antibody (mAb 69-126-3) on Protein G spots on the sensor chips and were detected at a limit-of-detection (LOD) - of 200 PFU/mL (∼3.3 aM). PD-IRIS was superior to the laboratory-based ELISA (LOD - 1800 PFU/mL) used as a comparator. The specificity of PD-IRIS in MPXV detection was demonstrated using Herpes simplex virus, type 1 (HSV-1), and Cowpox virus (CPXV). This work establishes the effectiveness of PD-IRIS and opens possibilities for its advancement in clinical diagnostics of Mpox at POC. Moreover, PD-IRIS is a modular technology that can be adapted for the multiplex detection of pathogens for which high-affinity ligands are available that can bind their surface antigens to capture them on the sensor surface.

Non-Coding RNAs as Potential Diagnostic/Prognostic Markers for Hepatocellular Carcinoma.

The increasing incidence of hepatocellular carcinoma (HCC), together with the poor effectiveness of the available treatments, make early diagnosis and effective screening of utmost relevance. Liquid biopsy represents a potential novel approach to early HCC detection and monitoring. The identification of blood markers has many desirable features, including the absence of any significant risk for the patients, the possibility of being used as a screening tool, and the ability to perform multiple tests, thus allowing for the real-time monitoring of HCC evolution. Unfortunately, the available blood markers for HCC have several limitations, mostly related to specificity and sensitivity. In this context, employing non-coding RNAs (ncRNAs) may represent an interesting and novel diagnostic approach. ncRNAs, which include, among others, micro interfering RNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), regulate human gene expression via interactions with their target mRNA. Notably, their expression can be altered in HCC, thus reflecting disease status. In this review, we discuss some notable works that describe the use of miRNAs, lncRNAs, and circRNAs as HCC biomarkers. Despite some open aspects related to ncRNA use, the presented works strongly support the potential effectiveness of these molecules as diagnostic/prognostic markers for HCC.

Individuals with SATB2-associated syndrome have impaired vitamin and energy metabolism pathways.

Special AT-rich sequence-binding protein 2 (SATB2) is a master regulator of gene expression. Mutations of the SATB2 gene results in the SATB2-associated syndrome (SAS), a genetic disorder characterized by neurodevelopmental disabilities and autism-related phenotype. The importance of plasma as an indicator of SAS phenotypes is unknown. We aim to investigate if pathogenic variants in SATB2 are associated with alteration to relevant pathways in the plasma of SAS patients and identify key differentially regulated proteins which may serve as biomarkers to improve diagnostic and future pharmacological approaches. We used well-validated proteomic technologies to determine the proteomic profile of plasma from SAS patients compared to healthy control subjects. Bioinformatical analysis was performed to identify significant proteins and functionally enriched pathways. We identified differentially expressed proteins in the plasma of SAS patients that are significantly involved in metabolism-related pathways. Energy metabolism, glucose metabolism and vitamin metabolism pathways are significantly enriched in SAS patients as compared to healthy controls. Our study linked SATB2 mutations to the impairment of plasma proteins involved in different metabolic pathways in SAS patients.