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Globally, since the outbreak of the Omicron variant in November 2021, the number of confirmed cases of COVID-19 has continued to increase, posing a tremendous challenge to the prevention and control of this infectious disease in many countries. The global daily confirmed cases of COVID-19 between November 1, 2021, and February 17, 2022, were used as a database for modeling, and the ARIMA, MLR, and Prophet models were developed and compared. The prediction performance was evaluated using mean absolute error (MAE), mean absolute percentage error (MAPE), and root mean square error (RMSE). The study showed that ARIMA (7, 1, 0) was the optimum model, and the MAE, MAPE, and RMSE values were lower than those of the MLR and Prophet models in terms of fitting performance and forecasting performance. The ARIMA model had superior prediction performance compared to the MLR and Prophet models. In real-world research, an appropriate prediction model should be selected based on the characteristics of the data and the sample size, which is essential for obtaining more accurate predictions of infectious disease incidence.

Multiple morphological abnormalities of the sperm flagella (MMAF) is a specific type of asthenoteratozoospermia, presenting with multiple morphological anomalies in spermatozoa, such as absent, bent, coiled, short, or irregular caliber flagella. Previous genetic studies revealed pathogenic mutations in genes encoding cilia and flagella-associated proteins (CFAPs; e.g., CFAP43, CFAP44, CFAP65, CFAP69, CFAP70, and CFAP251) responsible for the MMAF phenotype in infertile men from different ethnic groups. However, none of them have been identified in infertile Pakistani males with MMAF. In the current study, two Pakistani families with MMAF patients were recruited. Whole-exome sequencing (WES) of patients and their parents was performed. WES analysis reflected novel biallelic loss-of-function mutations in CFAP43 in both families (Family 1: ENST00000357060.3, p.Arg300Lysfs*22 and p.Thr526Serfs*43 in a compound heterozygous state; Family 2: ENST00000357060.3, p.Thr526Serfs*43 in a homozygous state). Sanger sequencing further confirmed that these mutations were segregated recessively in the families with the MMAF phenotype. Semiquantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was carried out to detect the effect of the mutation on mRNA of the affected gene. Previous research demonstrated that biallelic loss-of-function mutations in CFAP43 accounted for the majority of all CFAP43-mutant MMAF patients. To the best of our knowledge, this is the first study to report CFAP43 biallelic loss-of-function mutations in a Pakistani population with the MMAF phenotype. This study will help researchers and clinicians to understand the genetic etiology of MMAF better.

Male infertility is a prevalent disorder distressing an estimated 70 million people worldwide. Despite continued progress in understanding the causes of male infertility, idiopathic sperm abnormalities such as multiple morphological abnormalities of sperm flagella (MMAF) still account for about 30% of male infertility. Recurrent mutations in DNAH1 have been reported to cause MMAF in various populations, but the underlying mechanism is still poorly explored. This study investigated the MMAF phenotype of two extended consanguineous Pakistani families without manifesting primary ciliary dyskinesia symptoms. The transmission electron microscopy analysis of cross-sections of microtubule doublets revealed a missing central singlet of microtubules and a disorganized fibrous sheath. SPAG6 staining, a marker generally used to check the integration of microtubules of central pair, further confirmed the disruption of central pair in the spermatozoa of patients. Thus, whole-exome sequencing (WES) was performed, and WES analysis identified two novel mutations in the DNAH1 gene that were recessively co-segregating with MMAF phenotype in both families. To mechanistically study the impact of identified mutation, we generated Dnah1 mice models to confirm the in vivo effects of identified mutations. Though Dnah1 △iso1/△iso1 mutant mice represented MMAF phenotype, no significant defects were observed in the ultrastructure of mutant mice spermatozoa. Interestingly, we found DNAH1 isoform2 in Dnah1 △iso1/△iso1 mutant mice that may be mediating the formation of normal ultrastructure in the absence of full-length protein. Altogether we are first reporting the possible explanation of inconsistency between mouse and human DNAH1 mutant phenotypes, which will pave the way for further understanding of the underlying pathophysiological mechanism of MMAF.

Background and objective Tuberculosis (Tuberculosis, TB) is a public health problem in China, which not only endangers the population’s health but also affects economic and social development. It requires an accurate prediction analysis to help to make policymakers with early warning and provide effective precautionary measures. In this study, ARIMA, GM(1,1), and LSTM models were constructed and compared, respectively. The results showed that the LSTM was the optimal model, which can be achieved satisfactory performance for TB cases predictions in mainland China. Methods The data of tuberculosis cases in mainland China were extracted from the National Health Commission of the People’s Republic of China website. According to the TB data characteristics and the sample requirements, we created the ARIMA, GM(1,1), and LSTM models, which can make predictions for the prevalence trend of TB. The mean absolute error (MAE), root mean square error (RMSE), and mean absolute percentage error (MAPE) were applied to evaluate the effects of model fitting predicting accuracy. Results There were 3,021,995 tuberculosis cases in mainland China from January 2018 to December 2020. And the overall TB cases in mainland China take on a downtrend trend. We established ARIMA, GM(1,1), and LSTM models, respectively. The optimal ARIMA model is the ARIMA (0,1,0) × (0,1,0)12. The equation for GM(1,1) model was X(k+1) = -10057053.55e(-0.01k) + 10153178.55 the Mean square deviation ratio C value was 0.49, and the Small probability of error P was 0.94. LSTM model consists of an input layer, a hidden layer and an output layer, the parameters of epochs, learning rating are 60, 0.01, respectively. The MAE, RMSE, and MAPE values of LSTM model were smaller than that of GM(1,1) and ARIMA models. Conclusions Our findings showed that the LSTM model was the optimal model, which has a higher accuracy performance than that of ARIMA and GM (1,1) models. Its prediction results can act as a predictive tool for TB prevention measures in mainland China.

Serine/threonine kinases domain-containing proteins are known to play important functions in sperm flagella and male fertility. However, the roles of these proteins in human reproduction remain poorly understood and whether their variants are associated with human asthenozoospermia have not been reported. Here, we recruited a Pakistani family having four infertile patients diagnosed with idiopathic asthenozoospermia without any ciliary-related symptoms. Whole-exome sequencing identified a novel homozygous frameshift mutation (c.1235del, p.T412Kfs*14) in serine/threonine kinase 33 (STK33), which displays a highly conserved and predominant expression in testis in humans. This variant led to a dramatic reduction of STK33 messenger RNA (mRNA) in the patients. Patients homozygous for the STK33 variant presented reduced sperm motility, frequent morphological abnormalities of sperm flagella and completely disorganized flagellar ultrastructures, which are typical for multiple morphological abnormalities of the flagella (MMAF) phenotypes. Overall, these findings present evidence establishing that STK33 is an MMAF-related gene and provide new insights for understanding the role of serine/threonine kinases domain-containing proteins in human male reproduction.

Hepatitis B virus infection is a major global public health concern. This study explored the epidemic characteristics and tendency of hepatitis B in 31 provinces of mainland China, constructed a SARIMA model for prediction, and provided corresponding preventive measures.Monthly hepatitis B case data from mainland China from 2013 to 2020 were obtained from the website of the National Health Commission of the People's Republic of China. Monthly data from 2013 to 2020 were used to build the SARIMA model and data from 2021 were used to test the model.Between 2013 and 2020, 9,177,313 hepatitis B cases were reported in mainland China. SARIMA(1,0,0)(0,1,1)12 was the optimal model and its residual was white noise. It was used to predict the number of hepatitis B cases from January to December 2021, and the predicted values for 2021 were within the 95% confidence interval.This study suggests that the SARIMA model simulated well based on epidemiological trends of hepatitis B in mainland China. The SARIMA model is a feasible tool for monitoring hepatitis B virus infections in mainland China.

With the advances of next-generation sequencing technology, the field of disease research has been revolutionized. However, pinpointing the disease-causing variants from millions of revealed variants is still a tough task. Here, we have reviewed the existing linkage analysis tools and presented PedMiner, a web-based application designed to narrow down candidate variants from family based whole-exome sequencing (WES) data through linkage analysis. PedMiner integrates linkage analysis, variant annotation and prioritization in one automated pipeline. It provides graphical visualization of the linked regions along with comprehensive annotation of variants and genes within these linked regions. This efficient and comprehensive application will be helpful for the scientific community working on Mendelian inherited disorders using family based WES data.