Screening miRNAs for early diagnosis of colorectal cancer by small RNA deep sequencing and evaluation in a Chinese patient population

Purpose: This study aims to screen microRNAs (miRNAs), for an early diagnosis of colorectal cancer, by deep sequencing and evaluation of total miRNAs using clinical samples from a Chinese patient population. Methods: Total small RNAs from normal colonic mucosa, colonic adenomas, and colorectal cancer tissues were prepared for miRNA analysis by deep sequencing. The sequencing data were then analyzed by bioinformatics for candidate diagnostic miRNAs, which were further validated for their up- or downregulation status. Results: Comparison of cancer tissues with normal mucosa identified 99 upregulated and 90 downregulated miRNAs. Comparison of adenomas and normal mucosa found 114 upregulated and 107 downregulated miRNAs. Comparison of cancer and adenoma tissues found 70 upregulated and 27 downregulated miRNAs. Selected up- and downregulated miRNAs were validated for their expressions in 12 cases of patients with cancer and polyps. Specifically, for the upregulated miRNAs, miR-18a-5p and miR-21-3p were significantly upregulated in adenomas and cancer tissues, compared with the normal mucosa; miR-135b-5p, miR-17-5p, miR-182-5p, miR-200a-5p, and miR-200c-3p were significantly upregulated in cancer tissues compared to the normal mucosa, but their differential expression was not significant in adenoma tissues when compared with the normal mucosa. miR-183-5p and miR-96-5p were significantly upregulated in adenoma tissues when compared with normal mucosa, but these differences were not significant in cancer tissues when compared to normal mucosa. For the downregulated miRNAs, miR-133a-3p was significantly downregulated in both adenoma and cancer tissues when compared to normal mucosa; miR-204-5p, miR-125b-5p, miR-139-5p, miR-100-5p, and miR-30a-5p were significantly downregulated in cancer tissues compared to the normal mucosa, but their differential expression was not significant in adenoma tissue compared to normal mucosa. Conclusion: The findings of this study show that a number of miRNAs might be important in the diagnosis and prognosis of colorectal cancer in Chinese patients using the method of small RNA deep sequencing. Upregulation of miR-18a-5p and miR-21-3p or downregulation of miR-133a-3p in adenoma and cancer tissues may serve as an index for early screening of colorectal cancer. Other miRNAs, such as miR-135b-5p, miR-17-5p, miR-182-5p, miR-200a-5p, miR-200c-3p, miR-183-5p, and miR-96-5p, which were either up- or downregulated, in cancer tissues, but not in adenoma tissues, have limited significance in early diagnosis. Further study is needed to determine a screening index with diagnostic value

Identification of a polyamine-related signature and six novel prognostic biomarkers in oral squamous cell carcinoma

Elevated polyamine levels are required for tumor transformation and development; however, expression patterns of polyamines and their diagnostic potential have not been investigated in oral squamous cell carcinoma (OSCC), and its impact on prognosis has yet to be determined. A total of 440 OSCC samples and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Consensus clustering was conducted to classify OSCC patients into two subgroups based on the expression of the 17 polyamine regulators. Polyamine-related differentially expressed genes (PARDEGs) among distinct polyamine clusters were determined. To create a prognostic model, PARDEGs were examined in the training cohorts using univariate-Lasso-multivariate Cox regression analyses. Six prognostic genes, namely, “CKS2,” “RIMS3,” “TRAC,” “FMOD,” CALML5,” and “SPINK7,” were identified and applied to develop a predictive model for OSCC. According to the median risk score, the patients were split into high-risk and low-risk groups. The predictive performance of the six gene models was proven by the ROC curve analysis of the training and validation cohorts. Kaplan–Meier curves revealed that the high-risk group had poorer prognosis. Furthermore, the low-risk group was more susceptible to four chemotherapy drugs according to the IC50 of the samples computed by the “pRRophetic” package. The correlation between the risk scores and the proportion of immune cells was calculated. Meanwhile, the tumor mutational burden (TMB) value of the high-risk group was higher. Real-time quantitative polymerase chain reaction was applied to verify the genes constructing the model. The possible connections of the six genes with various immune cell infiltration and therapeutic markers were anticipated. In conclusion, we identified a polyamine-related prognostic signature, and six novel biomarkers in OSCC, which may provide insights to identify new treatment targets for OSCC

Short-Term Speed Prediction Using Remote Microwave Sensor Data: Machine Learning versus Statistical Model

Recently, a number of short-term speed prediction approaches have been developed, in which most algorithms are based on machine learning and statistical theory. This paper examined the multistep ahead prediction performance of eight different models using the 2-minute travel speed data collected from three Remote Traffic Microwave Sensors located on a southbound segment of 4th ring road in Beijing City. Specifically, we consider five machine learning methods: Back Propagation Neural Network (BPNN), nonlinear autoregressive model with exogenous inputs neural network (NARXNN), support vector machine with radial basis function as kernel function (SVM-RBF), Support Vector Machine with Linear Function (SVM-LIN), and Multilinear Regression (MLR) as candidate. Three statistical models are also selected: Autoregressive Integrated Moving Average (ARIMA), Vector Autoregression (VAR), and Space-Time (ST) model. From the prediction results, we find the following meaningful results: (1) the prediction accuracy of speed deteriorates as the prediction time steps increase for all models; (2) the BPNN, NARXNN, and SVM-RBF can clearly outperform two traditional statistical models: ARIMA and VAR; (3) the prediction performance of ANN is superior to that of SVM and MLR; (4) as time step increases, the ST model can consistently provide the lowest MAE comparing with ARIMA and VAR

Screening miRNAs for early diagnosis of colorectal cancer by small RNA deep sequencing and evaluation in a Chinese patient population

Purpose: This study aims to screen microRNAs (miRNAs), for an early diagnosis of colorectal cancer, by deep sequencing and evaluation of total miRNAs using clinical samples from a Chinese patient population. Methods: Total small RNAs from normal colonic mucosa, colonic adenomas, and colorectal cancer tissues were prepared for miRNA analysis by deep sequencing. The sequencing data were then analyzed by bioinformatics for candidate diagnostic miRNAs, which were further validated for their up-or downregulation status. Results: Comparison of cancer tissues with normal mucosa identified 99 upregulated and 90 downregulated miRNAs. Comparison of adenomas and normal mucosa found 114 upregulated and 107 downregulated miRNAs. Comparison of cancer and adenoma tissues found 70 upregulated and 27 downregulated miRNAs. Selected up-and downregulated miRNAs were validated for their expressions in 12 cases of patients with cancer and polyps. Specifically, for the upregulated miRNAs, miR-18a-5p and miR-21-3p were significantly upregulated in adenomas and cancer tissues, compared with the normal mucosa; miR-135b-5p, miR-17-5p, miR-182-5p, miR-200a-5p, and miR-200c-3p were significantly upregulated in cancer tissues compared to the normal mucosa, but their differential expression was not significant in adenoma tissues when compared with the normal mucosa. miR-183-5p and miR-96-5p were significantly upregulated in adenoma tissues when compared with normal mucosa, but these differences were not significant in cancer tissues when compared to normal mucosa. For the downregulated miRNAs, miR-133a-3p was significantly downregulated in both adenoma and cancer tissues when compared to normal mucosa; miR-204-5p, miR-125b-5p, miR-139-5p, miR-100-5p, and miR-30a-5p were significantly downregulated in cancer tissues compared to the normal mucosa, but their differential expression was not significant in adenoma tissue compared to normal mucosa. Conclusion: The findings of this study show that a number of miRNAs might be important in the diagnosis and prognosis of colorectal cancer in Chinese patients using the method of small RNA deep sequencing. Upregulation of miR-18a-5p and miR-21-3p or downregulation of miR-133a-3p in adenoma and cancer tissues may serve as an index for early screening of colorectal cancer. Other miRNAs, such as miR-135b-5p, miR-17-5p, miR-182-5p, miR-200a-5p, miR-200c-3p, miR-183-5p, and miR-96-5p, which were either up-or downregulated, in cancer tissues, but not in adenoma tissues, have limited significance in early diagnosis. Further study is needed to determine a screening index with diagnostic value.National Science Foundation of China [30572447, 30973837, 81273944]; Jiangsu National Science Foundation [BK20151081]; Nanjing Science Fundation [201402041]; Nanjing Medical Science Foundation [YKK14140]SCI(E)[email protected]

SpeechNet: Weakly Supervised, End-to-End Speech Recognition at Industrial Scale

End-to-end automatic speech recognition systems represent the state of the art, but they rely on thousands of hours of manually annotated speech for training, as well as heavyweight computation for inference. Of course, this impedes commercialization since most companies lack vast human and computational resources. In this paper, we explore training and deploying an ASR system in the label-scarce, compute-limited setting. To reduce human labor, we use a third-party ASR system as a weak supervision source, supplemented with labeling functions derived from implicit user feedback. To accelerate inference, we propose to route production-time queries across a pool of CUDA graphs of varying input lengths, the distribution of which best matches the traffic's. Compared to our third-party ASR, we achieve a relative improvement in word-error rate of 8% and a speedup of 600%. Our system, called SpeechNet, currently serves 12 million queries per day on our voice-enabled smart television. To our knowledge, this is the first time a large-scale, Wav2vec-based deployment has been described in the academic literature.Comment: Accepted to EMNLP 2022 Industry Track; 9 pages, 7 figure

Comparison analysis of microRNAs in response to EV71 and CA16 infection in human bronchial epithelial cells by high-throughput sequencing to reveal differential infective mechanisms

AbstractHand, foot, and mouth disease (HFMD) mainly caused by Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) infections which presented significantly different clinical manifestations. Nevertheless, the factors underlying these differences remain unclear. Recently, the functions of microRNAs (miRNAs) in pathogen-host interactions have been highlighted. Here, we performed comprehensive miRNA profiling in EV71- and CA16-infected human bronchial epithelial (16HBE) cells at multiple time points using high-throughput sequencing. The results showed that 154 known and 47 novel miRNAs exhibited remarkable differences in expression. Of these, 65 miRNAs, including 58 known and 7 novel miRNAs, presented opposite trends in EV71- and CA16-infected samples. Subsequently, we mainly focused on the 56 known differentially expressed miRNAs by further screening for targets prediction. GO and pathway analysis of these targets demonstrated that 18 biological processes, 7 molecular functions, 1 cellular component and 123 pathways were enriched. Among these pathways, Cadherin signalling pathway, Wnt signalling pathway and angiogenesis showed significant alterations. The regulatory networks of these miRNAs with predicted targets, GOs, pathways and transcription factors were determined, which suggested that miRNAs displayed intricate regulatory mechanisms during the infection phase. Consequently, we specifically analysed the hierarchical GO categories of the predicted targets involved in adhesion. The results indicated that the distinct changes induced by EV71 and CA16 infection may be partly linked to airway epithelial barrier function. Taken together, our data provide useful insights that help elucidate the different host-pathogen interactions following EV71 and CA16 infection and might offer novel therapeutic targets for these infections

Optimizing Peer Distribution of Syphilis Self-Testing Among Men Who Have Sex with Men in China: A Multi-City Pragmatic Randomized Controlled Trial

Syphilis testing uptake is low among men who have sex with men (MSM) around the world. Syphilis self-testing (SST) may complement facility-based testing; the distribution model is yet to be explored. This study aimed to investigate the effectiveness of peer distribution of syphilis self-testing on promoting syphilis testing. We conducted a three-arm, unblinded, parallel individually randomized controlled trial among MSM in three cities in Guangdong, China. Inclusion criteria were: men who were born biologically male, aged 18 or above, have ever had sex with a man, will refer the interventions to peers, and will take the three-month follow-up survey. Enrolled indexes were randomly assigned in a 1:1:1 ratio into standard-of-care arm (SOC arm), standard SST delivery arm (S-SST arm), and a web-based referral link SST delivery arm (RL-SST arm). The primary outcome was the number of returned photograph-verified syphilis testing results per index. A total number of 300 indexes were enrolled, with 100 indexes in each arm. The number of verified syphilis tests per index conducted by alters was 0.05 in the control arm, 0.51 in the S-SST arm, and 0.31 in the RL-SST arm. The cost per alter tested was $760.60 for SOC,$83.78 for S-SST, and $93.10 for RL-SST. Minimal adverse event was reported among both indexes and alters during the study. This study showed that peer distribution of SST could improve syphilis testing uptake among MSM in China compared to facility-based testing. This approach warrants further consideration as part of expanding syphilis self-testing

Sexualized Drug Use Among Female Sex Workers from Eight Cities in China: A Cross-Sectional Study.

There is a rich literature on sexualized drug use (i.e., drug use before or during sex) for men who have sex with men but less data from female sex workers (FSW), particularly from low- and middle-income countries. We describe the sexual and reproductive health outcomes in FSW reporting sexualized drug use. In 2019, we conducted a cross-sectional study in eight cities from seven provinces in China. We recruited FSW through community organizations working with sex workers and included those aged 18 years or above, exchanged sex at least once for money or goods in the past three months, and had traded sex for longer than a year. Multivariable logistic regression models were used. In total, 650 women participated: average age was 38.8 years (SD 10.2), 57.1% reported a monthly income over 5000 RMB ($USD 707), and 12.8% completed high school or above. Among participants, 65 (10.0%, 95% confidence interval (CI) 7.8-12.6) reported a history of sexualized drug use. Compared to FSW who never reported a history of sexualized drug use, FSW who reported a history of sexualized drug use had greater odds of working for a manager compared to being self-employed (adjusted odds ratio (AOR) 4.04, 95% CI 2.12-7.69), work in a sauna (AOR 2.43, 95% CI 1.09-5.41), charging a higher price for vaginal sex (AOR 2.15, 95% CI 1.14-4.06), and ever diagnosed with STIs (AOR 4.51, 95% CI 2.61-7.80). One in ten FSW reported sexualized drug use. Although they had similar risk profiles in terms of consistency of condom use and reproductive health outcomes, these women were more likely to report past STIs than those who reported no sexualized drug use. Health workers who work with substance users should devote attention to the sexual practices of their clients to make sure that they have safer sex

Case Report: Chronic hepatitis E virus Infection in an individual without evidence for immune deficiency

Chronic hepatitis E virus (HEV) infection occurs mainly in immunosuppressed populations. We describe an investigation of chronic HEV infection of genotype 3a in an individual without evidence for immune deficiency who presented hepatitis with significant HEV viremia and viral shedding. We monitored HEV RNA in plasma and stools, and assessed anti-HEV specific immune responses. The patient was without apparent immunodeficiency based on quantified results of white blood cell, lymphocyte, neutrophilic granulocyte, CD3+ T cell, CD4+ T cell, and CD8+ T cell counts and CD4/CD8 ratio, as well as total serum IgG, IgM, and IgA, which were in the normal range. Despite HEV specific cellular response and strong humoral immunity being observed, viral shedding persisted up to 109 IU/mL. After treatment with ribavirin combined with interferon, the indicators of liver function in the patient returned to normal, accompanied by complete suppression and clearance of HEV. These results indicate that HEV chronicity can also occur in individuals without evidence of immunodeficiency