A novel CDA liquid biopsy technology for effective non-small cell lung cancer diagnosis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23131-e23131
Author(s):  
Junjie Wu ◽  
Gengxi Jiang ◽  
Yutao Li ◽  
Xuedong Du ◽  
Hongmei Tao ◽  
...  

e23131 Background: Cancer Differentiation Analysis liquid biopsy (CDA) has been investigated as a viable clinical utility in NSCLC diagnosis, as well as a new candidate for part of an overall post-CT scan clinical diagnostic and treatment decision tool kit. It has been also evaluated in NSCLC diagnosis, combined with imaging technologies. Methods: This was a retrospective investigation in which 160 individuals were recruited at Changhai Hospital of Shanghai from July to Dec. in 2014. CDA and CT scan tests were performed on all samples before final confirmation by biopsy. For CDA tests, peripheral blood was drawn in EDTA tubes before operation. A performance predication model of CDA and CT scan test results was built using pROC package in R Language for the data of Area Under the Curve (AUC) and CDA threshold values. Further analysis was carried out based on the CDA threshold values. Results: Out of the 160 individuals, 40 were diagnosed as benign lung diseases selected as control group, 120 were confirmed as NSCLC by pathology. CDA and CT test data along with epidemiological information were collected and complied. Details of other statistical results were given in the Table below. Conclusions: CDA liquid biopsy is a novel, multi-level, multi-parameter based disease diagnosis technology with improvements in multiple areas including but not limited to higher sensitivity and specificity, ability to diagnose cancer early, no side effects, and covering a wide range of cancer sites. Results showed that AUC values of CDA were higher than those of CT scan for all NSCLC stage groups. CDA plus CT scan combination has the highest average AUC value for all stages. CDA test can provide more accurate and reliable diagnostic information and data for oncologists in making crucial clinical decisions. It is expected that CDA liquid biopsy technology will play an important and critical role in NSCLC diagnosis. [Table: see text]

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 42-42
Author(s):  
Gengxi Jiang ◽  
Hongmei Tao ◽  
Xing Tang ◽  
Da Lou ◽  
Yue Lin ◽  
...  

42 Background: For esophageal cancer, no viable non-invasive detection technologies are available today. In earlier investigations, Cancer Differentiation Analysis (CDA) Technology which measures information relating to both protein fragments and cellular signals in blood samples in a single test has showed a significant advantage in esophageal cancer diagnosis. Methods: Blood samples from 105 individuals in EDTA tubes were collected from Shanghai Changhai Hospital, China, between July and December 2014, CDA and endoscopy tests were carried out on all samples before clinically diagnosed. A performance predication model of CDA and endoscopy test results was built using pROC package in R Language for the data of Area Under the Curve (AUC) and CDA threshold values. Further analysis was carried out based on the CDA threshold values. Results: Out of the 105 individuals, samples from 6 individuals diagnosed as esophageal benign diseases were selected as control group. 99 samples from individuals diagnosed as esophageal cancer, of which 3 and 82 cases were adenocarcinoma and squamous carcinoma, 2, 26, 33, 31 and 7 cases were classified as stage 0,I,II, III, IV, respectively. Details of AUC results of endoscopy, and CDA plus endoscopy for each group were given in Table 1 below. Conclusions: Even though the sensitivity of the endoscopy is usually high due to its pathological examination, this investigation showed that CDA technology could further enhance the diagnosis sensitivity of endoscope, especially for early stage of esophageal cancer, and it (CDA) can be an effective complementary tool to clinical diagnosis and operation determination while obtaining the pathological information via endoscopy. In conclusion, CDA technology is of great value in esophageal diagnosis and therapeutic decision-making. [Table: see text]


2021 ◽  
Vol 8 ◽  
Author(s):  
Jinwen Xian ◽  
Pengpeng Zhao ◽  
Ning Wang ◽  
Weiye Wang ◽  
Yanyan Zhang ◽  
...  

Cystic echinococcosis (CE) is a cosmopolitan zoonosis caused by the larval stage of Echinococcus granulosus, which affects humans and a wide range of mammalian intermediate hosts. Parasite tetraspanin proteins are crucial for host-parasite interactions, and therefore they may be useful for vaccine development or disease diagnosis. In the present study, the major antigen coding sequence of tetraspanin 11 (Eg-TSP11) from E. granulosus was determined. The results of immunolocalization showed that Eg-TSP11 was mainly located in the tegument of adult worms and protoscoleces. Western blotting analysis showed that the serum from dogs injected with recombinant Eg-TSP11 (rEg-TSP11) could recognize Eg-TSP11 among natural protoscolex proteins. Moreover, the serum from dogs with E. granulosus infection also recognized rEg-TSP11. Serum indirect enzyme-linked immunosorbent assays demonstrated that IgG levels gradually increased after the first immunization with rEg-TSP11 compared with those in the control group. Furthermore, the serum levels of interleukin 4, interleukin 5, and interferon gamma were significantly altered in the rEg-TSP11 group. Importantly, we found that vaccination with rEg-TSP11 significantly decreased worm burden and inhibited segment development in a dog model of E. granulosus infection. Based on these findings, we speculated that rEg-TSP11 might be a potential candidate vaccine antigen against E. granulosus infection in dogs.


Author(s):  
Jacob A Kurowski ◽  
Jean-Paul Achkar ◽  
Rishi Gupta ◽  
Iulia Barbur ◽  
Tracey L Bonfield ◽  
...  

Abstract Background Hypertrophy of visceral adipose tissue (VAT) is a hallmark of Crohn disease (CD). The VAT produces a wide range of adipokines, biologically active factors that contribute to metabolic disorders in addition to CD pathogenesis. The study aim was to concomitantly evaluate serum adipokine profiles and VAT volumes as predictors of disease outcomes and treatment course in newly diagnosed pediatric patients with CD. Methods Pediatric patients ages 6 to 20 years were enrolled, and their clinical data and anthropometric measurements were obtained. Adipokine levels were measured at 0, 6, and 12 months after CD diagnosis and baseline in control patients (CP). The VAT volumes were measured by magnetic resonance imaging or computed tomography imaging within 3 months of diagnosis. Results One hundred four patients undergoing colonoscopy were prospectively enrolled: 36 diagnosed with CD and 68 CP. The serum adipokine resistin and plasminogen activator inhibitor (PAI)-1 levels were significantly higher in patients with CD at diagnosis than in CP. The VAT volume was similar between CD and CP. Baseline resistin levels at the time of diagnosis in patients with CD who were escalated to biologics was significantly higher than in those not treated using biologic therapy by 12 months (29.8 ng/mL vs 13.8 ng/mL; P = 0.004). A resistin level of ≥29.8 ng/mL at the time of diagnosis predicted escalation to biologic therapy in the first year after diagnosis with a specificity of 95% (sensitivity = 53%; area under the curve = 0.82; P = 0.015 for model with log-scale). There was a significantly greater reduction in resistin (P = 0.002) and PAI-1 (P = 0.010) at the 12-month follow-up in patients on biologics compared with patients who were not treated using biologics. Conclusions Serum resistin levels at diagnosis of pediatric CD predict the escalation to biologic therapy at 12 months, independent of VAT volumes. Resistin and PAI-1 levels significantly improved in patients with CD after treatment using biologics compared with those not on biologics. These results suggest the utility of resistin as a predictive biomarker in pediatric CD.


Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1443
Author(s):  
Norberto A. Guzman ◽  
Daniel E. Guzman

Over the years, multiple biomarkers have been used to aid in disease screening, diagnosis, prognosis, and response to therapy. As of late, protein biomarkers are gaining strength in their role for early disease diagnosis and prognosis in part due to the advancements in identification and characterization of a distinct functional pool of proteins known as proteoforms. Proteoforms are defined as all of the different molecular forms of a protein derived from a single gene caused by genetic variations, alternative spliced RNA transcripts and post-translational modifications. Monitoring the structural changes of each proteoform of a particular protein is essential to elucidate the complex molecular mechanisms that guide the course of disease. Clinical proteomics therefore holds the potential to offer further insight into disease pathology, progression, and prevention. Nevertheless, more technologically advanced diagnostic methods are needed to improve the reliability and clinical applicability of proteomics in preventive medicine. In this manuscript, we review the use of immunoaffinity capillary electrophoresis (IACE) as an emerging powerful diagnostic tool to isolate, separate, detect and characterize proteoform biomarkers obtained from liquid biopsy. IACE is an affinity capture-separation technology capable of isolating, concentrating and analyzing a wide range of biomarkers present in biological fluids. Isolation and concentration of target analytes is accomplished through binding to one or more biorecognition affinity ligands immobilized to a solid support, while separation and analysis are achieved by high-resolution capillary electrophoresis (CE) coupled to one or more detectors. IACE has the potential to generate rapid results with significant accuracy, leading to reliability and reproducibility in diagnosing and monitoring disease. Additionally, IACE has the capability of monitoring the efficacy of therapeutic agents by quantifying companion and complementary protein biomarkers. With advancements in telemedicine and artificial intelligence, the implementation of proteoform biomarker detection and analysis may significantly improve our capacity to identify medical conditions early and intervene in ways that improve health outcomes for individuals and populations.


2019 ◽  
Vol 1 (1) ◽  
pp. 11-15 ◽  
Author(s):  
Sarah Yaziz ◽  
Ahmad Sobri Muda ◽  
Wan Asyraf Wan Zaidi ◽  
Nik Azuan Nik Ismail

Background : The clot burden score (CBS) is a scoring system used in acute ischemic stroke (AIS) to predict patient outcome and guide treatment decision. However, CBS is not routinely practiced in many institutions. This study aimed to investigate the feasibility of CBS as a relevant predictor of good clinical outcome in AIS cases. Methods:  A retrospective data collection and review of AIS patients in a teaching hospital was done from June 2010 until June 2015. Patients were selected following the inclusion and exclusion criteria. These patients were followed up after 90 days of discharge. The Modified Rankin scale (mRS) was used to assess their outcome (functional status). Linear regression Spearman Rank correlation was performed between the CBS and mRS. The quality performance of the correlations was evaluated using Receiver operating characteristic (ROC) curves. Results: A total of 89 patients with AIS were analysed, 67.4% (n=60) male and 32.6% (n=29) female. Twenty-nine (29) patients (33.7%) had a CBS ?6, 6 patients (6.7%) had CBS <6, while 53 patients (59.6%) were deemed clot free. Ninety (90) days post insult, clinical assessment showed that 57 (67.6%) patients were functionally independent, 27 (30.3%) patients functionally dependent, and 5 (5.6%) patients were deceased. Data analysis reported a significant negative correlation (r= -0.611, p<0.001). ROC curves analysis showed an area under the curve of 0.81 at the cut-off point of 6.5. This showed that a CBS of more than 6 predicted a good mRS clinical outcome in AIS patients; with sensitivity of 98.2%, specificity of 53.1%, positive predictive value (PPV) of 76%, and negative predictive value (NPV) of 21%. Conclusion: CBS is a useful additional variable for the management of AIS cases, and should be incorporated into the routine radiological reporting for acute ischemic stroke (AIS) cases.


2020 ◽  
Vol 19 (31) ◽  
pp. 2816-2823 ◽  
Author(s):  
Dario Di Stasio ◽  
Laura Mosca ◽  
Alberta Lucchese ◽  
Donatella Delle Cave ◽  
Hiromichi Kawasaki ◽  
...  

Background: microRNAs play a critical role in auto-immunity, cell proliferation, differentiation and cell death. miRNAs are present in all biological fluids, and their expression is essential in maintaining regular immune functions and preventing autoimmunity, whereas miRNA dysregulation may be associated with the pathogenesis of autoimmune and inflammatory diseases. Oral lichen planus (OLP) is an inflammatory disease mediated by cytotoxic T cells attack against epithelial cells. The present study aims to perform a specific microRNA expression profile through the analysis of saliva in this disease. Methods: The study group was formed by five patients (mean age 62.8±1.98 years; 3 females/2 males) affected by oral lichen planus and control group by five healthy subjects (mean age 59.8 years±2.3; 3 females/ 2 males); using a low-density microarray analysis, we recorded a total of 98 differentially expressed miRNAs in the saliva of patients with oral lichen planus compared to the control group. The validation was performed for miR-27b with qRT-PCR in all saliva samples of oral lichen planus group. Results: 89 miRNAs were up-regulated and nine down-regulated. In details, levels of miR-21, miR- 125b, miR-203 and miR15b were increased (p<0.001) in study group while levels of miR-27b were about 3.0-fold decreased compared to controls (p<0.001) of miR-27b expression in OLP saliva. QRTPCR validation confirmed the down regulation of miR-27b in all saliva samples. Conclusions: Collecting saliva samples is a non-invasive procedure and is well accepted by all patients. microRNAs can be readily isolated and identified and can represent useful biomarkers of OLP.


Author(s):  
Vijaya Ramadas Mandala

The main contention of Shooting a Tiger is that hunting during the colonial period was not merely a recreational activity, but a practice intimately connected with imperial governance. The book positions shikar or hunting at the heart of colonial rule by demonstrating that, for the British in India, it served as a political, practical, and symbolic apparatus in the consolidation of power and rule during the nineteenth and early twentieth centuries. The book analyses early colonial hunting during the Company period, and then surveys different aspects of hunting during the high imperial decades in the later nineteenth and early twentieth centuries. The book draws upon an impressive array of archival material and uses a wide range of evidence to support its contentions. It examines hunting at a variety of social and ethnic levels—military, administrative, elite, princely India, Indian professional hunters, and in terms of Indian auxiliaries and (sometimes) resisters. It also deals with different geographical contexts—the plains, the mountains, north and south India. The exclusive privilege of hunting exercised by the ruling classes, following colonial forest legislation, continued to be extended to the Indian princes who played a critical role in sustaining the lavish hunts that became the hallmark of the late nineteenth-century British Raj. Hunting was also a way of life in colonial India, undertaken by officials and soldiers alike alongside their everyday duties, necessary for their mental sustenance and vital for the smooth operation of the colonial administration. There are also two final chapters on conservation, particularly the last chapter focusing on two British hunter-turned-conservationists, Jim Corbett and Colonel Richard Burton.


Micromachines ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 72 ◽  
Author(s):  
Da-Quan Yang ◽  
Bing Duan ◽  
Xiao Liu ◽  
Ai-Qiang Wang ◽  
Xiao-Gang Li ◽  
...  

The ability to detect nanoscale objects is particular crucial for a wide range of applications, such as environmental protection, early-stage disease diagnosis and drug discovery. Photonic crystal nanobeam cavity (PCNC) sensors have attracted great attention due to high-quality factors and small-mode volumes (Q/V) and good on-chip integrability with optical waveguides/circuits. In this review, we focus on nanoscale optical sensing based on PCNC sensors, including ultrahigh figure of merit (FOM) sensing, single nanoparticle trapping, label-free molecule detection and an integrated sensor array for multiplexed sensing. We believe that the PCNC sensors featuring ultracompact footprint, high monolithic integration capability, fast response and ultrahigh sensitivity sensing ability, etc., will provide a promising platform for further developing lab-on-a-chip devices for biosensing and other functionalities.


2021 ◽  
Vol 10 (2) ◽  
pp. 319
Author(s):  
Hee Cheol Yang ◽  
Won Jong Rhee

Because cancers are heterogeneous, it is evident that multiplexed detection is required to achieve disease diagnosis with high accuracy and specificity. Extracellular vesicles (EVs) have been a subject of great interest as sources of novel biomarkers for cancer liquid biopsy. However, EVs are nano-sized particles that are difficult to handle; thus, it is necessary to develop a method that enables efficient and straightforward EV biomarker detection. In the present study, we developed a method for single step in situ detection of EV surface proteins and inner miRNAs simultaneously using a flow cytometer. CD63 antibody and molecular beacon-21 were investigated for multiplexed biomarker detection in normal and cancer EVs. A phospholipid-polymer-phospholipid conjugate was introduced to induce clustering of the EVs analyzed using nanoparticle tracking analysis, which enhanced the detection signals. As a result, the method could detect and distinguish cancer cell-derived EVs using a flow cytometer. Thus, single step in situ detection of multiple EV biomarkers using a flow cytometer can be applied as a simple, labor- and time-saving, non-invasive liquid biopsy for the diagnosis of various diseases, including cancer.


BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e044500
Author(s):  
Yauhen Statsenko ◽  
Fatmah Al Zahmi ◽  
Tetiana Habuza ◽  
Klaus Neidl-Van Gorkom ◽  
Nazar Zaki

BackgroundDespite the necessity, there is no reliable biomarker to predict disease severity and prognosis of patients with COVID-19. The currently published prediction models are not fully applicable to clinical use.ObjectivesTo identify predictive biomarkers of COVID-19 severity and to justify their threshold values for the stratification of the risk of deterioration that would require transferring to the intensive care unit (ICU).MethodsThe study cohort (560 subjects) included all consecutive patients admitted to Dubai Mediclinic Parkview Hospital from February to May 2020 with COVID-19 confirmed by the PCR. The challenge of finding the cut-off thresholds was the unbalanced dataset (eg, the disproportion in the number of 72 patients admitted to ICU vs 488 non-severe cases). Therefore, we customised supervised machine learning (ML) algorithm in terms of threshold value used to predict worsening.ResultsWith the default thresholds returned by the ML estimator, the performance of the models was low. It was improved by setting the cut-off level to the 25th percentile for lymphocyte count and the 75th percentile for other features. The study justified the following threshold values of the laboratory tests done on admission: lymphocyte count <2.59×109/L, and the upper levels for total bilirubin 11.9 μmol/L, alanine aminotransferase 43 U/L, aspartate aminotransferase 32 U/L, D-dimer 0.7 mg/L, activated partial thromboplastin time (aPTT) 39.9 s, creatine kinase 247 U/L, C reactive protein (CRP) 14.3 mg/L, lactate dehydrogenase 246 U/L, troponin 0.037 ng/mL, ferritin 498 ng/mL and fibrinogen 446 mg/dL.ConclusionThe performance of the neural network trained with top valuable tests (aPTT, CRP and fibrinogen) is admissible (area under the curve (AUC) 0.86; 95% CI 0.486 to 0.884; p<0.001) and comparable with the model trained with all the tests (AUC 0.90; 95% CI 0.812 to 0.902; p<0.001). Free online tool at https://med-predict.com illustrates the study results.


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