The Report on China-Spain Joint Clinical Testing for Rapid COVID-19 Risk Screening by Eye-region Manifestations

BackgroundThe worldwide surge in coronavirus cases has led to the COVID-19 testing demand surge. Rapid, accurate, and cost-effective COVID-19 screening tests working at a population level are in imperative demand globally. MethodsBased on the eye symptoms of COVID-19, we developed and tested a COVID-19 rapid prescreening model using the eye-region images captured in China and Spain with cellphone cameras. The convolutional neural networks (CNNs)-based model was trained on these eye images to complete binary classification task of identifying the COVID-19 cases. The performance was measured using area under receiver-operating-characteristic curve (AUC), sensitivity, specificity, accuracy, and F1. The application programming interface was open access. FindingsThe multicenter study included 2436 pictures corresponding to 657 subjects (155 COVID-19 infection, 23{middle dot}6%) in development dataset (train and validation) and 2138 pictures corresponding to 478 subjects (64 COVID-19 infections, 13{middle dot}4%) in test dataset. The image-level performance of COVID-19 prescreening model in the China-Spain multicenter study achieved an AUC of 0{middle dot}913 (95% CI, 0{middle dot}898-0{middle dot}927), with a sensitivity of 0{middle dot}695 (95% CI, 0{middle dot}643-0{middle dot}748), a specificity of 0{middle dot}904 (95% CI, 0{middle dot}891-0{middle dot}919), an accuracy of 0{middle dot}875(0{middle dot}861-0{middle dot}889), and a F1 of 0{middle dot}611(0{middle dot}568-0{middle dot}655). InterpretationThe CNN-based model for COVID-19 rapid prescreening has reliable specificity and sensitivity. This system provides a low-cost, fully self-performed, non-invasive, real-time feedback solution for continuous surveillance and large-scale rapid prescreening for COVID-19. FundingThis project is supported by Aimomics (Shanghai) Intelligent

Report on Three Round COVID-19 Risk Blind Tests by Screening Eye-region Manifestations

The Coronavirus disease 2019 (COVID-19) has affected several million people since 2019. Despite various vaccines of COVID-19 protect million people in many countries, the worldwide situations of more the asymptomatic and mutated strain discovered are urging the more sensitive COVID-19 testing in this turnaround time. Unfortunately, it is still nontrivial to develop a new fast COVID-19 screening method with the easier access and lower cost, due to the technical and cost limitations of the current testing methods in the medical resource-poor districts. On the other hand, there are more and more ocular manifestations that have been reported in the COVID-19 patients as growing clinical evidence[1]. This inspired this project. We have conducted the joint clinical research since January 2021 at the ShiJiaZhuang City, Hebei province, China, which approved by the ethics committee of The fifth hospital of ShiJiaZhuang of Hebei Medical University. We undertake several blind tests of COVID-19 patients by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Meantime as an important part of the ongoing globally COVID-19 eye test program by AIMOMICS since February 2020, we propose a new fast screening method of analyzing the eye-region images, captured by common CCD and CMOS cameras. This could reliably make a rapid risk screening of COVID-19 with the sustainable stable high performance in different countries and races. For this clinical trial in ShiJiaZhuang, we compare and analyze 1194 eye-region images of 115 patients, including 66 COVID-19 positive patients, 44 rehabilitation patients (nucleic acid changed from positive to negative), 5 liver patients, as well as 117 healthy people. Remarkably, we consistently achieved very high testing results (> 0.94) in terms of both sensitivity and specificity in our blind test of COVID-19 patients. This confirms the viability of the COVID-19 fast screening by the eye-region manifestations. Particularly and impressively, the results have the similar conclusion as the other clinical trials of the globally COVID-19 eye test program[1]. Hopefully, this series of ongoing globally COVID-19 eye test study, and potential rapid solution of fully self-performed COVID risk screening method, can be inspiring and helpful to more researchers in the world soon. Our model for COVID-19 rapid prescreening have the merits of the lower cost, fully self-performed, non-invasive, importantly real-time, and thus enables the continuous health surveillance. We further implement it as the open accessible APIs, and provide public service to the world. Our pilot experiments show that our model is ready to be usable to all kinds of surveillance scenarios, such as infrared temperature measurement device at airports and stations, or directly pushing to the target people groups smartphones as a packaged application.

Establishment and application of a MassARRAY platform-based method to detect multiplex genetic mutations in lung cancer / 中国肿瘤临床

Objective:To establish a method based on the iPLEX analysis of MassARRAY mass spectrometry platform to detect multiplex genetic mutations among Chinese lung cancer patients. Methods:We reviewed the related literature and data of lung cancer treatments. We also determined 99 mutation hot spots in 13 target genes, namely, EGFR, KRAS, ALK, FGFR1, FGFR2, FGFR3, PIK3CA, BRAF, PTEN, MET, ERBB2, AKT1, and STK11, which are closely related to the pathogenesis, drug resistance, and metastasis of lung cancer and are associated with relevant transduction pathways. A total of 297 primers comprising 99 paired forward and reverse amplification primers and 99 matched extension primers were designed by using Assay Design in accordance with the mutation label and format requirements of the MassARRAY platform. The detection method was established by analyzing eight cell lines and six lung cancer specimens;the proposed method was then validated through comparisons with a LungCarta kit. The sensitivity and specificity of the proposed method were evaluated by directly sequencing EGFR and KRAS genes in 100 lung cancer cases. Results:The proposed method could detect multiplex genetic mutations in the lung cancer cell lines, and this finding is consistent with that observed using previously reported methods. The proposed method could also detect such mutations in clinical lung cancer specimens;this result is also consistent with that observed by using the LungCarta kit. However, an FGFR2 mutation was detected only by using the proposed method. The measured sensitivity and specificity were 100%and 96.3%, respectively. Conclusion:The proposed MassARRAY technology-based method could detect multiplex genetic mutations among Chinese lung cancer patients. Indeed, the proposed method can be potentially applied to detect mutations in cancer cells.

Diversity of EML4-ALK fusion variants in non-small cell lung cancer / 中华检验医学杂志

ObjectiveTo investigate the fusion sequence complexity of EML4-ALK in non-small cell lung cancer (NSCLC) patients,and the potential mutation in tyrosine kinase ( TK ) domain of ALK gene.MethodsIn routine practice,a novel echinoderm microtubule-associated protein-like4 and anaplastic lymphoma kinase (EML4-ALK) V3c variant was detected by rapid amplification of cDNA ends-polymerase chain reaction ( RACE-PCR )-sequencing technology in a patient with NSCLC.The further consecutive 39 cases( total of 40 cases)were screened by use of reverse transcription (RT)-PCR for EML4-ALK fusion.Positive PCR products were purified and cloned into T vectors,transformed into DH5a germ cells and colony picked up and sequenced for sequence complexity analysis.Tyrosine kinase domain of ALK was amplified by RT-PCR and sequenced.ResultsThree out of 40 cases had EML4-ALK fusion.One case had six novel variants of EML4-ALK co-existing,termed as V3c ( 64.6％ ),V3d ( 25.0％ ),V3e ( 2.1％ ),V3f (4.2％ ),V3g(2.1％ )and V3h(2.1％ ) variants,whereas without common V3a and V3b variants.In other two positive cases,one was V1 variant,another was concurrent V2,V3a and V3b variants.No mutations were detected in the TK domain of EML4-ALK in any case.ConclusionsSeveral EML-ALK variants could co-exist in a given lung cancer tissue,which suggest that the diversity and sequence complexity of EML4-ALK fusion are exist.Attentions should be paid to screen all the variants in clinic to improve the pick-up rate.

Expression of reconstructed BCR-ABL-pIRES-SEA plasmids in the skeletal muscles of BALB/c mice / 生物医学工程学杂志

This paper is aimed to investigate the transcription and expression of BCR-ABL-pIRES-SEA fusion gene vaccines in vivo in mice. The reconstructed plasmids (BCR-ABL-pIRES-SEA) which were developed previously in our laboratory were injected into the skeletal muscles of BALB/c mice at 14d intervals for three cycles. The transcription and expression of BCR-ABL and staphylococcal enterotoxin A (SEA) in injection site were detected using RT-PCR and immunohistological methods. The BCR-ABL/SEA mRNA and protein could be identified in the injection site of BCR-ABL-pIRES-SEA vaccinated mice. The reconstructed BCR-ABL-pIRES-SEA plasmids can effectively express gene production in the skeletal muscles of mice and have the common features of DNA vaccine.

Effect of cimetidine on clonal expansion of TCR V? subfamily of T cells in cord blood stimulated by K562 cells / 第三军医大学学报

Objective To investigate the effect of cimetidine on the clonal expansion of TCR V? subfamily of T cells in cord blood after the stimulation by K562 cells in vitro.Methods Cimetidine(1?10-5 mol/L) or K562 cells(1?106/ml) or both of them were respectively cultured with mononuclear cells(MNC) isolated from normal human cord blood for 2 weeks.After the induction,specific cytotoxicity of the proliferated T cells were detected with K562 cells as the target cells.The selective usages and clonal expansion of TCR V? subfa-mily of T cells were analyzed by RT-PCR and genescan technique.Results After induction for 2 weeks,the 3 groups showed the increased cell proliferation,in which specific cytotoxicity of T cells induced by both cimetidine and K562 cells against K562 cells was enhanced significantly compared with the other 2 groups(P

A Clinical Study of 2788 Newborns Screened for Hearing and Gene / 听力学及言语疾病杂志

G mutation were intervened and avoided the occurrence of deafness,1 babies with 235delC homozygote was confirmed severe sensorineural hearing loss in the hearing screening.Conclusion Newborn gene screening make up the defects of missed diagnosis in simple hearing screening in finding the newborn babies with late-onset deafness or the high risk as well as the pathogenic carriers.So the hearing and gene screening were necessary in the current situation,and this screening strategy would be developed further in Henan province.