MF-MNER: Multi-models Fusion for MNER in Chinese Clinical Electronic Medical Records.

To address the problem of poor entity recognition performance caused by the lack of Chinese annotation in clinical electronic medical records, this paper proposes a multi-medical entity recognition method F-MNER using a fusion technique combining BART, Bi-LSTM, and CRF. First, after cleaning, encoding, and segmenting the electronic medical records, the obtained semantic representations are dynamically fused using a bidirectional autoregressive transformer (BART) model. Then, sequential information is captured using a bidirectional long short-term memory (Bi-LSTM) network. Finally, the conditional random field (CRF) is used to decode and output multi-task entity recognition. Experiments are performed on the CCKS2019 dataset, with micro avg Precision, macro avg Recall, weighted avg Precision reaching 0.880, 0.887, and 0.883, and micro avg F1-score, macro avg F1-score, weighted avg F1-score reaching 0.875, 0.876, and 0.876 respectively. Compared with existing models, our method outperforms the existing literature in three evaluation metrics (micro average, macro average, weighted average) under the same dataset conditions. In the case of weighted average, the Precision, Recall, and F1-score are 19.64%, 15.67%, and 17.58% higher than the existing BERT-BiLSTM-CRF model respectively. Experiments are performed on the actual clinical dataset with our MF-MNER, the Precision, Recall, and F1-score are 0.638, 0.825, and 0.719 under the micro-avg evaluation mechanism. The Precision, Recall, and F1-score are 0.685, 0.800, and 0.733 under the macro-avg evaluation mechanism. The Precision, Recall, and F1-score are 0.647, 0.825, and 0.722 under the weighted avg evaluation mechanism. The above results show that our method MF-MNER can integrate the advantages of BART, Bi-LSTM, and CRF layers, significantly improving the performance of downstream named entity recognition tasks with a small amount of annotation, and achieving excellent performance in terms of recall score, which has certain practical significance. Source code and datasets to reproduce the results in this paper are available at https://github.com/xfwang1969/MF-MNER .

The Long COVID Symptoms and Severity Score: Development, Validation, and Application.

OBJECTIVES: The primary focus of this research is the proposition of a methodological framework for the clinical application of the long COVID symptoms and severity score (LC-SSS). This tool is not just a self-reported assessment instrument developed and validated but serves as a standardized, quantifiable means to monitor the diverse and persistent symptoms frequently observed in individuals with long COVID. METHODS: A 3-stage process was used to develop, validate, and establish scoring standards for the LC-SSS. Validation measures included correlations with other patient-reported measures, confirmatory factor analysis, Cronbach's α for internal consistency, and test-retest reliability. Scoring standards were determined using K-means clustering, with comparative assessments made against hierarchical clustering and the Gaussian Mixture Model. RESULTS: The LC-SSS showed correlations with EuroQol 5-Dimension 5-Level (rs = -0.55), EuroQol visual analog scale (rs = -0.368), Patient Health Questionnaire-9 (rs = 0.538), Beck Anxiety Inventory (rs = 0.689), and Insomnia Severity Index (rs = 0.516), confirming its construct validity. Structural validity was good with a comparative fit index of 0.969, with Cronbach's α of 0.93 indicating excellent internal consistency. Test-retest reliability was also satisfactory (intraclass correlation coefficient 0.732). K-means clustering identified 3 distinct severity categories in individuals living with long COVID, providing a basis for personalized treatment strategies. CONCLUSIONS: The LC-SSS provides a robust and valid tool for assessing long COVID. The severity categories established via K-means clustering demonstrate significant variation in symptom severity, informing personalized treatment and improving care quality for patients with long COVID.

Coxsackievirus B3 HFMD animal models in Syrian hamster and rhesus monkey.

Coxsackievirus B3 (CVB3) is the pathogen causing hand, foot and mouth disease (HFMD), which manifests across a spectrum of clinical severity from mild to severe. However, CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis, failing to replicate human HFMD symptoms. Although several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys, there is no comprehensive data on CVB3. In this study, we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different routes. The results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip, leading to nasopharyngeal colonization, acute severe pathological injury, and typical HFMD symptoms. Notably, the nasal drip group exhibited a longer viral excretion cycle and more severe pathological damage. In the subsequent study, rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms, viral excretion, serum antibody conversion, viral nucleic acids and antigens, and the specific organ damages, particularly in the heart. Surprisingly, there were no significant differences in myocardial enzyme levels, and the clinical symptoms resembled those often associated with common, mild infections. In summary, the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced HFMD. These models could serve as a basis for understanding the disease pathogenesis, conducting pre-trial prevention and evaluation, and implementing post-exposure intervention.

Molecular characterization of a novel clade echovirus 3 isolated from patients with hand-foot-and-mouth disease in southwest China.

Echovirus 3 (E3) belongs to the species Enterovirus B. Currently, three nearly whole-genome sequences of E3 are available in GenBank in China. In this study, we determined the whole genomic sequences of six E3 strains isolated from the stools of patients with hand-foot-and-mouth disease in Southwest China in 2022. Their nucleotide and amino acid sequences shared 82.1%-86.4% and 96.6%-97.2% identity with the prototype Morrisey strain, respectively, and showed 87.1% and 97.2% mutual identity. The six E3 strains are not clustered with other Chinese strains and formed a novel subgenotype (C6) with the recent American and British strains. Recombination analyses revealed that intertype recombination had occurred in the 2 C and 3D regions of the six E3 strains with coxsackieviruses B5 and B4, respectively. This study augments the nearly whole-genome sequences of E3 in the GenBank database and extends the molecular characterization of this virus in China.

Complete genome analysis of echovirus 30 strains isolated from hand-foot-and-mouth disease in Yunnan province, China.

BACKGROUND: Echovirus 30 is prone to cause hand-foot-and-mouth disease in infants and children. However, molecular epidemiologic information on the spread of E30 in southwestern China remains limited. In this study, we determined and analyzed the whole genomic sequences of E30 strains isolated from the stools of patients with hand-foot-and-mouth disease in Yunnan Province, China, in 2019. METHODS: E30 isolates were obtained from fecal samples of HFMD patients. The whole genomes were sequenced by segmented PCR and analyzed for phylogeny, mutation and recombination. MEGA and DNAStar were used to align the present isolates with the reference strains. The VP1 sequence of the isolates were analyzed for selection pressure using datamonkey server. RESULTS: The complete genome sequences of four E30 were obtained from this virus isolation. Significant homologous recombination signals in the P2-3'UTR region were found in all four isolates with other serotypes. Phylogenetic analysis showed that the four E30 isolates belonged to lineage H. Comparison of the VP1 sequences of these four isolates with other E30 reference strains using three selection pressure analysis models FUBAR, FEL, and MEME, revealed a positive selection site at 133rd position. CONCLUSIONS: This study extends the whole genome sequence of E30 in GenBank, in which mutations and recombinations have driven the evolution of E30 and further improved and enriched the genetic characteristics of E30, providing fundamental data for the prevention and control of diseases caused by E30. Furthermore, we demonstrated the value of continuous and extensive surveillance of enterovirus serotypes other than the major HFMD-causing viruses.

Abnormal grey matter structural changes in patients with end-stage kidney disease and mild cognitive impairment: correlations with clinical features.

End-stage kidney disease and mild cognitive impairment (ESKD-MCI) affect the quality of life and long-term treatment outcomes of patients affected by these diseases. Clarifying the morphological changes from brain injuries in ESKD-MCI and their relationship with clinical features is helpful for the early identification and intervention of MCI before it progresses to irreversible dementia. This study gathered data from 23 patients with ESKD-MCI, 24 patients with ESKD and non-cognitive impairment (NCI), and 27 health controls (HCs). Structural magnetic resonance studies, cognitive assessments, and general clinical data were collected from all participants. Voxel-based morphometry analysis was performed to compare grey matter (GM) volume differences between the groups. The patients' GM maps and clinical features were subjected to univariate regression to check for possible correlations. Patients with ESKD-MCI displayed significantly more impairments in multiple cognitive domains, including global cognition, visuospatial and executive function, and memory, compared to patients with ESKD-NCI. Using a more liberal threshold (P < 0.001, uncorrected), we found that compared to patients with ESKD-NCI, patients with ESKD-MCI exhibited clusters of regions with lower GM volumes, including the right hippocampus (HIP), parahippocampal gyrus (PHG), Rolandic operculum, and supramarginal gyrus. The volumes of the right HIP and PHG were negatively correlated with serum calcium levels. ESKD-MCI was associated with a subtle volume reduction of GM in several brain areas known to be involved in memory, language, and auditory information processing. We speculate that these slight morphometric impairments may be associated with disturbed calcium metabolism.

The influence of confirmatory psychology on consumers' purchase of sports goods on an e-commerce platform / La influencia de la psicología confirmatoria en la compra de artículos deportivos por parte de los consumidores en una plataforma de comercio electrónico

This study examines the impact of confirmatory psychology (CP) on the e-commerce (EC) platform purchasing of sporting products by consumers. The evolution of network communication technologies has produced EC. This study used literature and mathematical statistics to assess the consumption data of sports products purchased by consumers who purchase sports products. By descriptive analysis, variables such as CP are partitioned into dimensions, and hypotheses regarding the relationship between variables are formulated. The study found significant positive associations (P< 0.01) between normative conformity and customers' purchase intentions and between informational conformity and consumers' buying intentions. The interaction variable significantly benefits purchase intent (coefficient standard = 0.045, P< 0.001). Interaction elements showed a statistically significant positive impact on purchase intent (coefficient standard = 0.18, P <0.001). The study has theoretical ramifications that contribute to the body of knowledge. Moreover, the practical consequences of this research are essential for improving the EC platform offerings.(AU)

Screening of a new candidate coxsackievirus B1 vaccine strain based on its biological characteristics.

Coxsackievirus B1 (CVB1) is one of the significant pathogens causing viral myocarditis, hand, foot, and mouth disease (HFMD), and aseptic meningitis, and it has been associated with type 1 diabetes (T1DM). No effective antiviral drugs against CVB1 infection or preventive vaccines are available. Due to the success of two inactivated vaccines against enterovirus 71 and poliovirus, an inactivated Vero cell-based CVB1 vaccine could be developed. In this study, we isolated a high-growth CVB1 virus strain KM7 in Vero cells and developed a Vero-adapted vaccine candidate strain KM7-X29 via three rounds of plaque purification and serial passages. The KM7-X29 strain was grouped into the GII sub-genotype, which belonged to the Chinese epidemic strain and grew to a titer of more than 107 CCID50/ml in Vero cells. The inactivated CVB1 vaccine produced by the KM7-X29 strain induced an effective neutralizing antibody response in BALB/c mice, and maternal antibodies were able to provide a 100% protective effect against lethal challenges with a CVB1 strain in suckling BALB/c mice. Thus, the KM7-X29 strain might be used as a new candidate coxsackievirus B1 vaccine strain. The neonatal murine model of CVB1 infection will contribute to the development of the CVB1 vaccine.

Coxsackievirus B: The important agent of hand, foot, and mouth disease.

Hand, foot, and mouth disease (HFMD) is a common pediatric infectious illness caused by enteroviruses (EVs). EV-A serotypes are the main pathogens associated with HFMD. In this study, 213 stool samples from 213 children with severe HFMD in Yunnan, China in 2013, 2015, and 2016 were further analyzed retrospectively for EV-B infection. A total of 70.0% of the specimens tested positive for EV.20 EV serotypes were detected. The predominant serotype was enterovirus A71 (EV-A71, 27.7%), followed by coxsackievirus B4 (CV-B4, 16.4%), CV-A16 (9.9%), CV-B5 (6.6%), and Echovirus 9 (E-9,4.7%). EV-A and EV-B accounted for 45.1% and 41.3%, respectively. Among the positive specimens, 28.6% were CV-Bs. Co-infection was present in 19.3% of these cases. In the study, CV-B5 and the majority of CV-B4 isolates belonged to genotypes VI and C3, respectively. This result indicates that EV-B, especially CV-Bs, might be the important agents associated with HFMD and this knowledge will contribute to the prevention and treatment of the disease.

Comprehensive research on the distribution of HLA-DRB1 in Chinese populations.

By presenting antigen peptides, HLA-DRB1 plays an important role in the immune system. However, the allele frequency of HLA-DRB1 exon 2 across China has not been comprehensively studied, especially in minority populations. We sampled 3757 individuals from 59 population. The HLA-DRB1 region from 212 to 463 bp (NM_002124.4 exon 2) in each population was sequenced by Sanger sequencing and genotyped via SBTengine® software, and the allele frequency was calculated by GenAlEx 6.5. Eighty-two DRB1 alleles were identified. The expected heterozygosity of DRB1 was lower in the south than in the north, which was inconsistent with the Y chromosome and mitochondrial DNA results. The Mantel test and nonparametric correlation analysis showed that the correlations of the genetic distance with geographical distance and of DRB1 allele frequencies with latitude weakened after the southern and northern groups were considered separately. Principal coordinate analysis showed that populations speaking the same languages were not codistributed. Compared with other genetic markers, the distribution of DRB1 seems less affected by geographic distance and ethnic origin. Local factors such as gene flow with neighbouring populations, geographic isolation or natural selection are important forces shaping the DRB1 gene pool of local populations.

Reversal of neurovascular decoupling and cognitive impairment in patients with end-stage renal disease during a hemodialysis session: Evidence from a comprehensive fMRI analysis.

Neurovascular (NV) decoupling is a potential neuropathologic mechanism of cognitive impairment in patients with end-stage renal disease (ESRD). Hemodialysis improves cognitive impairment at 24 h post-dialysis, which suggests a potential neuroprotective effect of hemodialysis treatment on the brain. We investigated the effects of hemodialysis treatment on the reversal of NV decoupling associated with cognitive improvement. A total of 39 patients with ESRD and 39 healthy controls were enrolled. All patients were imaged twice during a dialysis session: before hemodialysis (T1pre-dialysis ) and at 24 h after dialysis (T2post-dialysis ). The healthy controls were imaged once. NV coupling was characterized based on correlation coefficients between four types of blood oxygen level-dependent signals and cerebral blood flow (CBF). A battery of neuropsychological and blood tests was performed before the imaging. Patients with ESRD showed improvements in memory and executive function at T2post-dialysis compared with that at T1pre-dialysis . At both T1pre-dialysis and T2post-dialysis , patients with ESRD had lower amplitude of low-frequency fluctuation (ALFF)-CBF coupling than healthy controls. Additionally, patients with ESRD had higher ALFF-CBF coupling at T2post-dialysis than at T1pre-dialysis . Higher memory scores, higher hemoglobin level, lower total plasma homocysteine level, lower systolic blood pressure variance, and lower ultrafiltration volume were associated with higher ALFF-CBF coupling in patients with ESRD after a hemodialysis session. These findings indicate that partial correction of anemia and hyperhomocysteinemia, stable systolic blood pressure, and fluid restriction may be closely linked to the reversal of NV decoupling and improvement in cognition in patients with ESRD.

Reduced cortical complexity in patients with end-stage kidney disease prior to dialysis initiation.

End-stage kidney disease (ESKD) is associated with cognitive impairment (CI) and affects different aspects of cortical morphometry, but where these changes converge remains unclear. Fractal dimension (FD) is used to represent cortical complexity (CC), which describes the structural complexity of the cerebral cortex by integrating different cortical morphological measures. This study aimed to investigate changes in CC in patients with ESKD prior to initiation of dialysis and to evaluate the relationship between changes in CC, cognitive performance, and uremic toxins. Forty-nine patients with ESKD naive to dialysis and 31 healthy controls (HCs) were assessed using structural magnetic resonance imaging (MRI) and cognitive tests, including evaluations of global cognitive function, memory, and executive function. Clinical laboratory blood tests were performed on all patients with ESKD, including measurement of nine uremic toxin-related indices. CC was measured using MRI data to determine regional FD values. We estimated the association between cognitive performance, uremic toxin levels, and CC changes. Compared to HCs, patients with ESKD showed significantly lower CC in the left precuneus (p = 0.006), left middle temporal cortex (p = 0.010), and left isthmus cingulate cortex (p = 0.018). Furthermore, lower CC in the left precuneus was associated with impaired long-term delayed memory (Pearson r = 0.394, p = 0.042) in patients with ESKD. Our study suggests that regional decreases in CC are an additional characteristic of patients with ESKD naive to dialysis, related to impaired long-term memory performance. These findings may help further understand the underlying neurobiological mechanisms between brain structural changes and CI in patients with ESKD.

Post-script-Retail forecasting: Research and practice.

This note updates the 2019 review article "Retail forecasting: Research and practice" in the context of the COVID-19 pandemic and the substantial new research on machine-learning algorithms, when applied to retail. It offers new conclusions and challenges for both research and practice in retail demand forecasting.

The prevalence and influencing factors of the oropharyngeal carriage of Haemophilus influenzae in healthy children in a high-altitude area of China: A cross-sectional study.

Haemophilus influenzae is a common commensal organism of the human upper respiratory tract and an important cause of human disease. No data on H influenzae carriage rate has been carried out on the Qinghai-Tibet Plateau of China. This study aims to present the H influenzae carriage rate and influencing factors of H influenzae in healthy children <15 years of age in Qinghai Province, an area located on the Qinghai-Tibet Plateau in China. Oropharyngeal swabs for the detection of H influenzae DNA were collected between September and October 2019. Taqman real-time polymerase chain reaction was used to detect the nucleic acids from the oropharyngeal swabs. Self-designed questionnaires were used to investigate the related information among this group of children. A number of 284 children were enrolled in this study. The carriage rate of H influenzae was 44.7%. The carriage rate in cities was 47.5%, in rural areas was 21.9%, and in pastoral areas was 52.8%. The carriage rate was found to be higher among children of minority ethnic groups than those of Han ethnicity (55.6% vs 38.1%). H influenzae carriage rate was influenced by tobacco smoke exposure (adjusted odds ratio [aOR] = 2.31, 95% CI [confidence interval]: 1.14-4.70), having siblings <5 years of age (aOR = 2.36, 95% CI: 1.21-4.59), respiratory infections during the last 30 days (aOR = 2.37, 95% CI: 1.11-5.06), and parent/guardian education level (aOR = 0.08, 95% CI: 0.02-0.27). H influenzae was highly prevalent in healthy children in Qinghai Province, especially among children of minority ethnicities and those living in pastoral areas. Tobacco smoke exposure, having siblings <5 years of age, and respiratory infections during the last 30 days were risk factors for H influenzae carriage. Parents or guardians having education levels of college or higher was a protective factor for H influenzae carriage. It is of critical importance that the government take effective measures to reduce the carriage rate and the occurrence of H influenzae related diseases in susceptible populations.

Co-infection and enterovirus B: post EV-A71 mass vaccination scenario in China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common child infectious disease caused by more than 20 enterovirus (EV) serotypes. In recent years, enterovirus A71 (EV-A71) has been replaced by Coxsackievirus A6 (CV-A6) to become the predominant serotype. Multiple EV serotypes co-circulate in HFMD epidemics, and this study aimed to investigate the etiological epidemic characteristics of an HFMD outbreak in Kunming, China in 2019. METHODS: The clinical samples of 459 EV-associated HFMD patients in 2019 were used to amplify the VP1 gene region by the three sets of primers and identify serotypes using the molecular biology method. Phylogenetic analyses were performed based on the VP1 gene. RESULTS: Three hundred and forty-eight cases out of 459 HFMD patients were confirmed as EV infection. Of these 191 (41.61%) were single EV infections and 34.20% had co-infections. The EVs were assigned to 18 EV serotypes, of which CV-A6 was predominant (11.33%), followed by CV-B1 (8.93%), CV-A4 (5.23%), CV-A9 (4.58%), CV-A 16 (3.49%) and CV-A10 and CVA5 both 1.96%. Co-infection of CV-A6 with other EVs was present in 15.25% of these cases, followed by co-infection with CV-A16 and other EVs. The VP1 sequences used in the phylogenetic analyses showed that the CV-A6, CV-B1 and CV-A4 sequences belonged to the sub-genogroup D3 and genogroups F and E, respectively. CONCLUSION: Co-circulation and co-infection of multiple serotypes were the etiological characteristic of the HFMD epidemic in Kunming China in 2019 with CV-A-6, CV-B1 and CV-A4 as the predominant serotypes. This is the first report of CV-B1 as a predominant serotype in China and may provide valuable information for the diagnosis, prevention and control of HFMD.

Epidemiological and etiological characteristics of viral meningitis for hospitalized pediatric patients in Yunnan, China.

BACKGROUND: Viral infection is the most common cause of aseptic meningitis. The purpose of this study was to identify the viruses responsible for aseptic meningitis to better understand the clinical presentations of this disease. METHOD: Between March 2009 and February 2010, we collected 297 cerebrospinal fluid specimens from children with aseptic meningitis admitted to a pediatric hospital in Yunnan (China). Viruses were detected by using "in house" real-time quantitative polymerase chain reaction or reverse-transcription real-time quantitative polymerase chain reaction from these samples. Phylogenetic analyses were conducted using the Molecular Evolutionary Genetic Analysis version 7.0 software, with the neighbor-joining method. RESULTS: Viral infection was diagnosed in 35 of the 297 children (11.8%). The causative viruses were identified to be enteroviruses in 25 cases (71.4%), varicella-zoster virus in 5 cases (14.3%), herpes simplex virus 1 in 2 cases (5.7%), and herpes simplex virus 2, Epstein-Barr virus, and human herpesvirus 6 in 1 case each (2.9% each). Of the enteroviruses, coxsackievirus B5 was the most frequently detected serotype (10/25 cases; 40.0%) and all coxsackievirus B5 strains belonged to C group. CONCLUSIONS: In the study, a causative virus was only found in the minority of cases, of them, enteroviruses were the most frequently detected viruses in patients with viral meningitis, followed by varicella-zoster virus and herpes simplex virus. Our findings underscore the need for enhanced surveillance and etiological study of aseptic meningitis.

Pathogenic analysis of coxsackievirus A10 in rhesus macaques.

Coxsackievirus A10 (CV-A10) is one of the etiological agents associated with hand, foot and mouth disease (HFMD) and also causes a variety of illnesses in humans, including pneumonia, and myocarditis. Different people, particularly young children, may have different immunological responses to infection. Current CV-A10 infection animal models provide only a rudimentary understanding of the pathogenesis and effects of this virus. The characteristics of CV-A10 infection, replication, and shedding in humans remain unknown. In this study, rhesus macaques were infected by CV-A10 via respiratory or digestive route to mimic the HFMD in humans. The clinical symptoms, viral shedding, inflammatory response and pathologic changes were investigated in acute infection (1-11 day post infection) and recovery period (12-180 day post infection). All infected rhesus macaques during acute infection showed obvious viremia and clinical symptoms which were comparable to those observed in humans. Substantial inflammatory pathological damages were observed in multi-organs, including the lung, heart, liver, and kidney. During the acute period, all rhesus macaques displayed clinical signs, viral shedding, normalization of serum cytokines, and increased serum neutralizing antibodies, whereas inflammatory factors caused some animals to develop severe hyperglycemia during the recovery period. In addition, there were no significant differences between respiratory and digestive tract infected animals. Overall, all data presented suggest that the rhesus macaques provide the first non-human primate animal model for investigating CV-A10 pathophysiology and assessing the development of potential human therapies.

A novel splice site variant in the POPDC3 causes autosomal recessive limb-girdle muscular dystrophy type 26.

Limb-Girdle muscular dystrophy (LGMD) is a group of muscle disorders with highly heterogeneous genetic patterns and clinical phenotypes, and this group includes multiple subtypes. Different LGMD subtypes have similar phenotypes and clinical overlaps, these subtypes are difficult to distinguish by clinical symptoms alone and can only be accurately diagnosed by analysis in combination with definitive genetic test results. Here, we report a female presenting features of LGMD. After analysis of whole-exome sequencing data, a novel homozygous POPDC3 variant c.486-1G>A (rs113419658) located in the acceptor splice site of intron 2 was identified in the proband. The variant effect on splicing were analyzed by genetic analysis based on cDNA synthesized by the patient's RNA. cDNA analysis indicated that the novel homozygous POPDC3 splice variant disrupted original acceptor splice site, which can cause a frameshift in the mRNA of the POPDC3 gene, thereby producing a truncated POPDC3 protein and ultimately affecting its normal function. POPDC3 variant was recently associated with recessive limb-girdle muscular dystrophy type 26 (LGMDR26). Based on the above results, we hypothesize that this variant is probably a pathogenic variant, and expand the gene variant spectrum of POPDC3.

Molecular characterization of echovirus 9 strains isolated from hand-foot-and-mouth disease in Kunming, Yunnan Province, China.

Echovirus 9 (E9) belongs to the species Enterovirus B. So far, 12 whole genome sequences of E9 are available in GenBank. In this study, we determined the whole genomic sequences of five E9 strains isolated from the stools of patients with hand-foot-and-mouth disease in Kunming, Yunnan Province, China, in 2019. Their nucleotide and amino acid sequences shared 80.8-80.9% and 96.4-96.8% identity with the prototype Hill strain, respectively, and shared 99.3-99.9% and 99.1-99.8% mutual identity, respectively. Recombination analyses revealed that intertype recombination had occurred in the 2C and 3D regions of the five Yunnan E9 strains with coxsackieviruses B5 and B4, respectively. This study augmented the whole genome sequences of E9 in the GenBank database and extended the molecular characterization of this virus in China.