Novel Biomarker For Screening Research Articles

Exploring Complexity of Facial Dynamics in Autism Spectrum Disorder.

Atypical facial expression is one of the early symptoms of autism spectrum disorder (ASD) characterized by reduced regularity and lack of coordination of facial movements. Automatic quantification of these behaviors can offer novel biomarkers for screening, diagnosis, and treatment monitoring of ASD. In this work, 40 toddlers with ASD and 396 typically developing toddlers were shown developmentally-appropriate and engaging movies presented on a smart tablet during a well-child pediatric visit. The movies consisted of social and non-social dynamic scenes designed to evoke certain behavioral and affective responses. The front-facing camera of the tablet was used to capture the toddlers' face. Facial landmarks' dynamics were then automatically computed using computer vision algorithms. Subsequently, the complexity of the landmarks' dynamics was estimated for the eyebrows and mouth regions using multiscale entropy. Compared to typically developing toddlers, toddlers with ASD showed higher complexity (i.e., less predictability) in these landmarks' dynamics. This complexity in facial dynamics contained novel information not captured by traditional facial affect analyses. These results suggest that computer vision analysis of facial landmark movements is a promising approach for detecting and quantifying early behavioral symptoms associated with ASD.

Single-cell transcriptome identifies FCGR3B upregulated subtype of alveolar macrophages in patients with critical COVID-19

SummaryUnderstanding host cell heterogeneity is critical for unraveling disease mechanism. Utilizing large-scale single-cell transcriptomics, we analyzed multiple tissue specimens from patients with life-threatening COVID-19 pneumonia, compared with healthy controls. We identified a subtype of monocyte-derived alveolar macrophages (MoAMs) where genes associated with severe COVID-19 comorbidities are significantly upregulated in bronchoalveolar lavage fluid of critical cases. FCGR3B consistently demarcated MoAM subset in different samples from severe COVID-19 cohorts and in CCL3L1-upregulated cells from nasopharyngeal swabs. In silico findings were validated by upregulation of FCGR3B in nasopharyngeal swabs of severe ICU COVID-19 cases, particularly in older patients and those with comorbidities. Additional lines of evidence from transcriptomic data and in vivo of severe COVID-19 cases suggest that FCGR3B may identify a specific subtype of MoAM in patients with severe COVID-19 that may present a novel biomarker for screening and prognosis, as well as a potential therapeutic target.

Combination of RERG and ZNF671 methylation rates in circulating cell-free DNA: A novel biomarker for screening of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia, hence, identifying easily detectable biomarkers for NPC screening is essential for better diagnosis and prognosis. Using genome‐wide and targeted analyses based on next‐generation sequencing approaches, we previously showed that gene promoters are hypermethylated in NPC tissues. To confirm whether DNA methylation rates of genes could be used as biomarkers for NPC screening, 79 histologically diagnosed NPC patients and 29 noncancer patients were recruited. A convenient quantitative analysis of DNA methylation using real‐time PCR (qAMP) was carried out, involving pretreatment of tissue DNA, and circulating cell‐free DNA (ccfDNA) from nonhemolytic plasma, with methylation‐sensitive and/or methylation‐dependent restriction enzymes. The qAMP analyses revealed that methylation rates of RERG, ZNF671, ITGA4, and SHISA3 were significantly higher in NPC primary tumor tissues compared to noncancerous tissues, with sufficient diagnostic accuracy of the area under receiver operating characteristic curves (AUC). Interestingly, higher methylation rates of RERG in ccfDNA were statistically significant and yielded a very good AUC; however, those of ZNF671, ITGA4, and SHISA3 were not significant. Furthermore, the combination of methylation rates of RERG and ZNF671 in ccfDNA showed higher diagnostic accuracy than either of them individually. In conclusion, the methylation rates of specific genes in ccfDNA can serve as novel biomarkers for early detection and screening of NPC.

MiR-141 is up-regulated in biopsies from Vietnamese patients with nasopharyngeal carcinoma.

Novel biomarkers for screening, diagnosis and monitoring the treatment of nasopharyngeal carcinoma (NPC), one of the most common cancers in Vietnam, are urgently required. Increasing evidence suggests that microRNA-141 (miR-141) is associated with NPC, owing to its ability to affect the expression of genes that modulate tumorigenesis. Unfortunately, research on miR-141 expression in Vietnamese patients is limited. Therefore, the objective of the current study was to evaluate miR-141 expression and assess whether miR-141 might be a potential biomarker for diagnosis of NPC in Vietnamese patients. Total RNA isolated from 40 NPC biopsy samples and 37 non-cancerous samples was analyzed by quantitative reverse-transcription PCR. The miR-141 expression levels were compared between NPC biopsy and non-cancerous samples. The frequency of miR-141 detection was 37.50% and 10.80% in the NPC and non-cancerous samples, respectively (p = 0.0143). The miR-141 expression was 5.27 times higher in tumor samples than non-cancerous samples. Additionally, the RR (Relative risk) and OR (Odds ratio) were 1.83 (95%CI = 1.2576-2.6675, p = 0.0016) and 4.95 (95%CI = 1.4625-16.7541, p = 0.01), respectively. In conclusion, miR-141 was up-regulated in the biopsy samples and thus may be a potential biomarker for NPC in the Vietnamese population.

The Fecal M2-PK As A Novel Biomarker for Screening of Cancer Colon

The Fecal M2-PK As A Novel Biomarker for Screening of Cancer Colon

Gestational Obstructive Sleep Apnea: Biomarker Screening Models and Lack of Postpartum Resolution.

To measure prevalence and severity of third trimester obstructive sleep apnea and evaluate postpartum resolution. To assess a novel biomarker for screening for obstructive sleep apnea in pregnancy. This prospective observational study was performed at Wake Forest School of Medicine obstetrics clinics between April 2014 and December 2015. Fractional exhaled nitric oxide measurements and sleep studies were obtained and compared at 32 0/7 to 35 6/7 weeks gestation and postpartum. Exhaled nitric oxide and risk factors for the development of gestational sleep apnea were evaluated for predictive ability independently and in screening models. Of 76 women enrolled, 73 performed valid sleep studies in pregnancy and 65 had an additional valid study 6 to 15 weeks postpartum. Twenty-four women (37%) had gestational sleep apnea compared with 23 (35%) with postpartum sleep apnea (P > .99). Eight of 11 women (73%) retested 6 to 8 months postpartum had persistent sleep apnea. Exhaled nitric oxide had moderate discrimination screening for sleep apnea in pregnancy (area under the receiver operating characteristic curve = 0.64). A model utilizing exhaled nitric oxide, pregnancy-specific screening, and Mallampati score improved ability to identify women at risk for gestational sleep apnea (sensitivity = 46%, specificity = 91% and likelihood ratio = 5.11, area under receiver operating characteristic curve = 0.75). Obstructive sleep apnea is common in the early postpartum period and often persisted at least 6 months. Exhaled nitric oxide as a sole biomarker to screen for sleep apnea in pregnancy has only modest discrimination. Combined with additional parameters sensitivity and specificity improved. Registry: ClinicalTrials.gov, Identifier: NCT02100943, Title: Exhaled Nitric Oxide as a Biomarker of Gestational Obstructive Sleep Apnea and Persistence Postpartum, URL: https://clinicaltrials.gov/ct2/show/NCT02100943.

Alu-based cell-free DNA: a novel biomarker for screening of gastric cancer.

Gastric cancer (GC) is the fourth most common cancer and the second major cause of cancer-related deaths worldwide. In our previous study, a novel and sensitive method for quantifying cell-free DNA (CFD) in human blood was established and tested for its ability to predict patients with tumor. We want to investigate CFD expression in the sera of GC patients in an attempt to explore the clinical significance of CFD in improving the early screening of GC and monitoring GC progression by the branched DNA (bDNA)-based Alu assay. The concentration of CFD was quantitated by bDNA-based Alu assay. CEA, CA19-9, C72-4 and CA50 concentrations were determined by ABBOTT ARCHITECT I2000 SR. We found the CFD concentrations have significant differences between GC patients, benign gastric disease (BGD) patients and healthy controls (P < 0.05). CFD were weakly correlated with CEA (r = −0.197, P < 0.05) or CA50 (r = 0.206, P < 0.05), and no correlation with CA19-9 (r = −0.061, P > 0.05) or CA72-4 (r = 0.011, P > 0.05). In addition, CFD concentrations were significantly higher in stage I GC patients than BGD patients and healthy controls (P < 0.05), but there was no significant difference in CEA, CA19-9 and CA50 among the three traditional tumor markers (P > 0.05). Our analysis showed that CFD was more sensitive than CEA, CA19-9, CA72-4 or CA50 in early screening of GC. Compared with CEA, CA19-9, CA72-4 and CA50, CFD may prove to be a better biomarker for the screening of GC, thus providing a sensitive biomarker for screening and monitoring progression of GC.

Expression and function of peroxiredoxins in gynecological malignancies.

A large family of peroxiredoxin proteins plays essential roles in the regulation of multiple redox-sensitive cellular activities related to cell signaling, cell proliferation and apoptosis. The involvement of these proteins in protecting cells from oxidative damage, induced by reactive oxygen species, points to their potential role in human cancers. According to some studies, the peroxiredoxin proteins in gynecological malignancies, promote tumors development and progression, whereas others indicate that peroxiredoxin proteins function as onco-suppressors in these cancers. Here, we review the utilization of peroxiredoxin proteins as novel biomarkers for screening and early diagnosis of gynecological malignancies, and as the specific therapy targets and prognostic factors as well.

Five microRNAs in plasma as novel biomarkers for screening of early-stage non-small cell lung cancer.

BackgroundIn order to find novel noninvasive biomarkers with high accuracy for the screening of early-stage non-small cell lung cancer (NSCLC), we investigate the predictive power of 5 microRNAs (miR-20a, miR-145, miR-21, miR223 and miR-221) as potential biomarkers in early-stage NSCLC.MethodsIn training set, 25 early-stage NSCLC patients and 25 matched healthy controls are included to assess the miRNA expression profile between early-stage NSCLC patients and healthy controls by real-time RT-PCR. We found that five of these miRNAs (miR-20a, miR-223, miR-21, miR-221 and miR-145) levels in NSCLC patients were significantly dysregulated compared with the healthy groups and thus were selected to validation set. Therefore, a validation experiment was further performed to investigate the potential predictive power of these five miRNAs based on 126 early-stage NSCLC patients, 42 NCPD patients and 60 healthy controls. The receiver operating characteristic (ROC) curves were generated for the five miRNAs.ResultsROC curve analyses suggested that these five plasma miRNAs could be promising biomarkers for NSCLC, with relatively high AUC values as follows: miR-20a, 0.89 with 95% CI of [0.85-0.93]; miR-223, 0.94 with 95% CI of [0.91-0.96]; miR-21, 0.77 with 95% CI of [0.71-0.83]; miR-155, 0.92 with 95% CI of [0.89-0.96]; miR-145, 0.77 with 95% CI of [0.71-0.83]. Stratified analyses indicated that plasma miR-20a, miR-223, miR-21 and miR-145 showed better predictive value in smokers than in non-smokers, while miR-155 might be more suitable for non-smokers. In addition, all of these five miRNAs could differentiate NSCLC from controls with a higher accuracy in advanced stage and squamous carcinoma subgroups.ConclusionsIn conclusion, our study suggested that five plasma miRNAs (miR-20a, miR-145, miR-21, miR-223 and miR-221) can be used as promising biomarkers in early screening of NSCLC. Nevertheless, further validation and optimizing improvement should be performed on larger sample to confirm our results.

Circulating miR-125b is a novel biomarker for screening non-small-cell lung cancer and predicts poor prognosis

MicroRNAs are small, non-coding RNAs that are critical regulators of various diseases including cancer, and may represent a novel class of cancer biomarkers. Recent reports have highlighted the oncogenic aspects of miR-125b. However, the level and clinical relevance of circulating miR-125b transcripts in human serum of non-small-cell lung cancer (NSCLC) patients are unclear. The purpose of this study was to identify circulating miR-125b transcripts in human serum for use as a biomarker for stratification and prediction of prognosis in NSCLC. We analyzed serum levels of miR-125b in 193 patients with different stages of NSCLC. Blood samples were collected before surgery and therapy. Quantitative reverse transcription-polymerase chain reaction of circulating miR-125b transcripts was performed directly in serum to improve the efficiency of miRNA assessment. Receiver operating characteristic analysis was used to evaluate the sensitivity and specificity of serum miR-125b. We found that serum miR-125b was consistently expressed in the non-tumor group and was significantly associated with NSCLC stage. miR-125b expression was capable of separating NSCLC patients from control groups with an area under the curve of 0.786. Furthermore, patients with high miR-125b expression displayed a significantly poorer prognosis compared with patients with low expression (p<0.0001). Multivariate analysis indicated that high miR-125b expression was an independent prognostic factor for survival. We propose that serum miR-125b may represent a novel biomarker in NSCLC patients and that high miR-125b expression is an independent prognostic factor for survival.

Serum gamma glutamyl transferase: a novel biomarker for screening of premature coronary artery disease

We aimed to elucidate the association between gamma glutamyl transferase (GGT) activity with prevalence of premature coronary artery disease (CAD) in young Pakistani patients undergoing diagnostic coronary angiography. A total of 218 young adults (age ≤ 45 years) underwent diagnostic angiography. Serum samples were taken from all the patients and analyzed for serum GGT activity, cholesterol and triglycerides. Coronary artery disease patients had significantly increased GGT activity (P = .001) and exhibited a significant positive correlation with blood pressure, cholesterol, blood glucose, and smoking and negative correlation with total antioxidant status (P < .01). The study revealed good diagnostic accuracy at cutoff of 35 U/L with a sensitivity of 92%, specificity of 81%, and diagnostic odds ratio of 48 in estimation of premature CAD in young Pakistanis.

Brain-Derived Neurotrophic Factor as a Biomarker in Primary Open-Angle Glaucoma

To introduce a novel biomarker for screening of primary open-angle glaucoma (POAG) by detecting and measuring brain-derived neurotrophic factor (BDNF) in the serum of normal subjects and patients with early stage of glaucoma. Twenty-five glaucoma patients as the case group and 25 age- and sex-matched normal persons as the control group were tested. The control group comprised 19 men and 6 women, with the mean age of 59.32 ± 11.8 years and without any apparent ocular or systemic diseases. The case group comprised 20 men and 5 women, with the mean age of 59.64 ± 11.56 years, who were assessed by routinely performed clinical and paraclinical investigations. BDNF levels in serum were determined by enzyme-linked immunosorbent assay using monoclonal antibodies specific for BDNF. The mean of BDNF levels in the serum was 27.16 ± 5.53 ng/mL in the control subjects and 18.42 ± 4.05 ng/mL in the subjects with the early stage glaucoma. A statistically significant difference was evident between the two groups (p < 0.05). We found no significant differences in serum BDNF levels according to the subjects' age, gender, duration of the glaucoma, mean intraocular pressure, and blood pressure (p > 0.05). Glaucoma patients who had lower serum BDNF concentration had disclosed a significant negative correlation with pattern standard deviations. We conclude that BDNF in the serum might be a useful biochemical marker for early detection of POAG. We also propose that this might be a reliable, time efficient, and cost-effective method for diagnosis, screening, and assessing the progression of POAG. However, more studies and trials are needed to investigate these factors in greater detail.

Serum Gamma Glutamyl Transferase: A Novel Biomarker for Screening of Premature Coronary Artery Disease

Serum Gamma Glutamyl Transferase: A Novel Biomarker for Screening of Premature Coronary Artery Disease