Pure tone audiogram classification using deep learning techniques.

OBJECTIVE: Pure tone audiometry has played a critical role in audiology as the initial diagnostic tool, offering vital insights for subsequent analyses. This study aims to develop a robust deep learning framework capable of accurately classifying audiograms across various commonly encountered tasks. DESIGN, SETTING, AND PARTICIPANTS: This single-centre retrospective study was conducted in accordance with the STROBE guidelines. A total of 12 518 audiograms were collected from 6259 patients aged between 4 and 96 years, who underwent pure tone audiometry testing between February 2018 and April 2022 at Tongji Hospital, Tongji Medical College, Wuhan, China. Three experienced audiologists independently annotated the audiograms, labelling the hearing loss in degrees, types and configurations of each audiogram. MAIN OUTCOME MEASURES: A deep learning framework was developed and utilised to classify audiograms across three tasks: determining the degrees of hearing loss, identifying the types of hearing loss, and categorising the configurations of audiograms. The classification performance was evaluated using four commonly used metrics: accuracy, precision, recall and F1-score. RESULTS: The deep learning method consistently outperformed alternative methods, including K-Nearest Neighbors, ExtraTrees, Random Forest, XGBoost, LightGBM, CatBoost and FastAI Net, across all three tasks. It achieved the highest accuracy rates, ranging from 96.75% to 99.85%. Precision values fell within the range of 88.93% to 98.41%, while recall values spanned from 89.25% to 98.38%. The F1-score also exhibited strong performance, ranging from 88.99% to 98.39%. CONCLUSIONS: This study demonstrated that a deep learning approach could accurately classify audiograms into their respective categories and could contribute to assisting doctors, particularly those lacking audiology expertise or experience, in better interpreting pure tone audiograms, enhancing diagnostic accuracy in primary care settings, and reducing the misdiagnosis rate of hearing conditions. In scenarios involving large-scale audiological data, the automated classification system could be used as a research tool to efficiently provide a comprehensive overview and statistical analysis. In the era of mobile audiometry, our deep learning framework can also help patients quickly and reliably understand their self-tested audiograms, potentially encouraging timely consultations with audiologists for further evaluation and intervention.

Response mechanism of a highly efficient partial nitritation-anammox (PN/A) process under antibiotic stress: Extracellular polymers, microbial community, and functional genes.

The Partial nitritation-Anammox (PN/A) process can be restricted when treating high ammonia nitrogen wastewater containing antibiotics. This study aims to explore the response mechanism of the PN/A process under antibiotic stress. Results showed the PN/A process achieved a nitrogen removal rate higher than 1.01 ± 0.03 kg N/m3/d under long-term sulfamethazine stress. The increase of extracellular polymers from 22.52 to 43.96 mg/g VSS was conducive to resisting antibiotic inhibitory. The increase of Denitratisoma and SM1A02 abundance as well as functional genes nirS and nirK indicated denitrifiers should play an important role in the stability of the PN/A system under sulfamethazine stress. In addition, antibiotic-resistant genes (ARGs) sul1 and intI1 significantly increased by 8.78 and 5.12 times of the initial values to maintain the resistance of PN/A process to sulfamethazine stress. This study uncovers the response mechanism of the PN/A process under antibiotic stress, offering a scientific basis and guidance for further application in the future.

Single-cell RNA-seq Revealed that Altered Tumor Infiltrating Lymphocytes in Cirrhotic Liver Indicate Development of Hepatocellular Carcinoma.

Background and Aims: Cirrhosis is the precursor lesion for most hepatocellular carcinoma (HCC) cases. However, no biomarker effectively predicted HCC initiation before diagnosis by imaging. We aimed to investigate the hallmarks of immune microenvironments in healthy, cirrhotic livers and HCC tumor tissues and to identify immune biomarkers of cirrhosis-HCC transition. Methods: Expression matrices of single-cell RNA sequencing studies were downloaded and integrated with Seurat package vignettes. Clustering was performed to analyze the immune cell compositions of different sample types. Results: The cirrhotic liver and HCC tumors had distinct immune microenvironments, but the immune landscape of cirrhotic livers was not markedly modified compared with healthy livers. Two subsets of B cells and three subsets of T cells were identified in the samples. Among the T cells, naïve T cells were more prominent in the cirrhotic and healthy liver samples than in the HCC samples. In contrast, the neutrophil count was lower in cirrhotic livers. Two macrophage clusters were identified, one that actively interacted with T cells and B cells and was enriched in cirrhotic blood compared with HCC blood samples. Conclusions: Decreased naïve T cell infiltration and increased neutrophil infiltration in the liver may indicate the development of HCC in cirrhotic patients. Alterations in blood-resident immune cells may also be a sign of HCC development in cirrhotic patients. The dynamics of the immune cell subsets may serve as novel biomarkers to predict the transition from cirrhosis to HCC.

Postoperative circulating tumor DNA detection and CBLB mutations are prognostic biomarkers for gastric cancer.

BACKGROUND: Several studies have demonstrated that circulating tumor DNA (ctDNA) can be used to predict the postoperative recurrence of several cancers. However, there are few studies on the use of ctDNA as a prognosis tool for gastric cancer (GC) patients. OBJECTIVE: This study aims to determine whether ctDNA could be used as a prognostic biomarker in GC patients through multigene-panel sequencing. METHODS: Using next-generation sequencing (NGS) Multigene Panels, the mutational signatures associated with the prognosis of GC patients were identified. We calculated the survival probability with Kaplan-Meier and used the Log-rank test to compare survival curves between ctDNA-positive and ctDNA-negative groups. Potential application of radiology combined with tumor plasma biomarker analysis of ctDNA in GC patients was carried out. RESULTS: Disease progression is more likely in ctDNA-positive patients as characterized clinically by a generally higher T stage and a poorer therapeutic response (P < 0.05). ctDNA-positive patients also had worse overall-survival (OS: P = 0.203) and progression-free survival (PFS: P = 0.037). The combined analysis of ctDNA, radiological, and serum biomarkers in four patients indicated that ctDNA monitoring can be a good complement to radiological and plasma tumor markers for GC patients. Kaplan-Meier analysis using a cohort of GC patients in the TCGA database showed that patients with CBLB mutations had shorter OS and PFS than wild-type patients (OS: P = 0.0036; PFS: P = 0.0027). CONCLUSIONS: This study confirmed the utility and feasibility of ctDNA in the prognosis monitoring of gastric cancer.

Clinical features and prognosis of pediatric idiopathic sudden sensorineural hearing loss: A bi-center retrospective study.

Objective: Limited research has focused on the clinical features of sudden sensorineural hearing loss (SSNHL) in pediatric patients. This study is aimed to investigate the relationship between clinical features and the baseline hearing severity and outcomes of SSNHL in the pediatric population. Method: We conducted a bi-center retrospective observational study in 145 SSNHL patients aged no more than 18 years who were recruited between November 2013 and October 2022. Data extracted from medical records, audiograms, complete blood count (CBC) and coagulation tests have been assessed for the relationship with the severity (the thresholds of the initial hearing) and outcomes (recovery rate, hearing gain and the thresholds of the final hearing). Results: A lower lymphocyte count (P = 0.004) and a higher platelet-to-lymphocyte ratio (PLR) (P = 0.041) were found in the patient group with profound initial hearing than in the less severe group. Vertigo (ß = 13.932, 95%CI: 4.082-23.782, P = 0.007) and lymphocyte count (ß = -6.686, 95%CI: -10.919 to -2.454, P = 0.003) showed significant associations with the threshold of the initial hearing. In the multivariate logistic model, the probability of recovery was higher for patients with ascending and flat audiograms compared to those with descending audiograms (ascending: OR 8.168, 95% CI 1.450-70.143, P = 0.029; flat: OR 3.966, 95% CI 1.341-12.651, P = 0.015). Patients with tinnitus had a 3.2-fold increase in the probability of recovery (OR 3.222, 95% CI 1.241-8.907, P = 0.019), while the baseline hearing threshold (OR 0.968, 95% CI 0.936-0.998, P = 0.047) and duration to the onset of therapy (OR 0.942, 95% CI 0.890-0.977, P = 0.010) were negatively associated with the odds of recovery. Conclusions: The present study showed that accompanying tinnitus, the severity of initial hearing loss, the time elapse and the audiogram configuration might be related to the prognosis of pediatric SSNHL. Meanwhile, the presence of vertigo, lower lymphocytes and higher PLR were associated with worse severity.

Enhanced biodegradation of thiamethoxam with a novel polyvinyl alcohol (PVA)/sodium alginate (SA)/biochar immobilized Chryseobacterium sp H5.

Long-term and extensive usage of thiamethoxam, the second-generation neonicotinoid insecticide, has caused a serious threat to non-target organisms and ecological security. Efficient immobilized microorganism techniques are a sustainable solution for bioremediation of thiamethoxam contamination. A Gram-negative aerobic bacterium Chryseobacterium sp H5 with high thiamethoxam-degrading efficiencies was isolated from activated sludge. Then we developed a novel polyvinyl alcohol (PVA)/sodium alginate (SA)/biochar bead with this functional microbe immobilization to enhance the biodegradation and removal of thiamethoxam. Results indicated that the total removal and biodegradation rate of thiamethoxam with PVA/SA/biochar (0.7 %) beads with Chryseobacterium sp H5 immobilization at 30 °C and pH of 7.0 within 7 d reached about 90.47 % and 68.03 %, respectively, much higher than that using PVA/SA immobilized microbes (75.06 %, 56.05 %) and free microbes (61.72 %). Moreover, the PVA/SA/biochar (0.7 %) immobilized microbes showed increased tolerance to extreme conditions. Biodegradation metabolites of thiamethoxam were identified and two intermediates were first reported. Based on the identified biodegradation intermediates, cleavage of C-N between the 2-chlorothiazole ring and oxadiazine, dichlorination, nitrate reduction and condensation reaction would be the major biodegradation routes of thiamethoxam. Results of this work suggested the novel PVA/SA/biochar beads with Chryseobacterium sp H5 immobilization would be helpful for the effective bioremediation of thiamethoxam contamination.

Trace determination of fifteen free amino acids in drinking source water via solid-phase extraction coupled with liquid chromatography tandem mass spectrometry.

Amino acids (AAs) are important nitrogen-containing organics in water, and a large number of reports have proven that they were the precursors of many nitrogen-containing disinfection by-products, some of which have cytotoxicity and carcinogenicity. However, little has been done on their occurrence in drinking source water. Therefore, a trace determination method via solid-phase extraction coupled with ultra-high pressure liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for 15 free AAs (FAAs) was developed, which was successfully applied for drinking source water samples. For sample preparation, strong cation-exchange stationary solid-phase extraction (SPE) cartridge showed better extraction performance to that of reverse phase stationary oasis HLB SPE cartridge. The optimal water pH was determined to be 2.8 before extraction. Strong matrix effects for most FAAs were observed in this work; thus, sample extraction with SPE was recommended to eliminate the matrix effects. The developed method showed excellent linearity (R2 > 0.991), low limits of detection (LODs, 0.01-0.27 nmol/L), and good recoveries of 69.8-117.9% in drinking source water with low relative standard deviations (RSDs, 0.3-13.2%). The developed method was finally applied to eight drinking source water samples, and the top five FAAs were found to be serine, glycine, leucine, alanine, and isoleucine.

ScRNAPip: A systematic and dynamic pipeline for single-cell RNA sequencing analysis.

With the advancement of sequencing technology, cell separation, and whole-genome amplification techniques, single cell technology for genome sequencing is emerging gradually. In comparison to traditional genome sequencing at the multi-cellular level, single-cell sequencing can not only measure the gene expression level more accurately but also can detect a small amount of gene expression or rare noncoding RNA. This technology has garnered increasing interest among researchers engaged in single-cell studies in recent years. Here, we developed a reproducible computational workflow for scRNA-seq data analysis which including tasks like quality control, normalization, data correction, pseudotime analysis, copy number analysis, etc. We illustrate the application of these steps using publicly available datasets and provide practical recommendations for their implementation. This study serves as a comprehensive tutorial for researchers keen on single-cell data analysis, aiding users in constructing and refining their own analysis pipelines.

Molecular characteristics of pediatric nasopharyngeal carcinoma using whole-exome sequencing.

OBJECTIVES: While a number of genetic and epigenetic events contributing to adult nasopharyngeal carcinomas (aNPC) development has been established, the scarcity of pediatric nasopharyngeal carcinoma (pNPC) hinders the understanding of the biology of the disease and rational treatment approach. We aim to identify the molecular characteristics of pNPC. MATERIALS AND METHODS: pNPC primary tumors with paired blood samples were collected and sequenced using whole-exome sequencing. Samples were collected from four tertiary academic medical centers in China. A total of 30 patients (25 male and 5 female) with pathologically confirmed NPC under the age of 20 were enrolled. RESULTS: Several genes such as C9orf84 (20 %), ZFHX4 (16.7 %), ZC3H6 (16.7 %), RBM38 (16.7 %) were frequently mutated in pNPC. Copy number analysis revealed highly recurring gain/amplification of the HLA class II genes at 6p21.32 (63.3 %) and losses of TOLLIP at 11p15.5 (20 %). Recurrent NUTM1 (16.7 %) fusion variants were found for the first time with pNPC. We also investigated germline genomic signatures and showed 8 of 30 (26.7 %) of the pNPC patients carrying germline pathogenic and/or likely pathogenic variants in known cancer-predisposing genes. Multi-dimensional comparison suggested that pNPC might exhibit distinct genomic profile compared to aNPC. In addition, pNPC exhibited significantly elevated level of PD-L1 expression than aNPC (percent of patients with >50 % PD-L1 expression: 92.0 % vs 32.1 %), suggesting high possibility of benefit from immunotherapy. CONCLUSION: Our results provide the first insight into the molecular basis of pNPC, and might offer novel targets and therapeutic approaches such as immunotherapy for this rare disease.

Inference of emission history of neonicotinoid pesticides from marine sediment cores impacted by riverine runoff of a developed agricultural region: The Pearl River Basin, China.

Neonicotinoids (NEOs), as the most-consumed pesticides on a global scale, have posed a serious threat to human health and ecological environment. Information regarding the emission history of NEOs is of great importance to improve the prediction of their environmental loading and biological risk potential. In the present study, contamination levels and compositions of 12 NEOs were identified in 8 sediment cores from the Lingdingyang Estuary, which was impacted by agricultural emissions in riverine runoff of the Pearl River Basin for centuries. The total concentration of 12 target NEOs (∑12NEOs) ranged from 0.02 to 69.5 ng/g dw along the sediment core profile, with a mean of 12.9 ± 15.9 ng/g dw. Net deposition fluxes and concentrations of 5 parent NEOs experienced a remarkable exponential increase in the vertical profile of sediment cores, except for imidacloprid (IMI). Despite the similar exponential growth before 2012, subsequent decreased levels of IMI in historical sediment indicated its gradual replacement by other NEOs. IMI was the NEO with the highest frequency of 80.3% and the highest mean concentration of 7.66 ± 8.76 ng/g dw. The ecological risk assessment of NEOs suggests that 65.1% of sediment samples exceeded the chronic threshold for aqueous organisms using equilibrium partitioning approach. Since downward diffusion of NEOs in the Lingdingyang Estuary was rectified by their rapid desorption, the sedimentary record probably provided an accurate illustration of agricultural NEO emissions in the Pearl River Basin, China. The recent NEO inventory in the adjacent waters of core sites was estimated with a mean of 76.8 tons/yr. This study provides insights into the role of agricultural emission in riverine runoff in the environmental loads of NEOs in the historical sediment.

A risk prediction model for dysphagia in older patients: a single-center prospective study.

Surveys based on western populations have identified many risk factors for dysphagia in older people, but the potential risk factors consistent with the demographic characteristics of older, hospitalized Chinese patients require further study. This single-center prospective study aimed to determine the incidence of dysphagia in western China, and to develop and validate a model to predict the risk of dysphagia among older patients. A total of 343 inpatients (aged ≥ 65 years without dysphagia and cognitive impairment) were included. A score ≥ 2 on the Eating Assessment Tool-10 was defined as dysphagia. After a six-month follow-up, 70 (20.4%) patients were found to have dysphagia. The final model included age, wearing dentures, activities of daily living, cerebral vascular disease, coronary heart disease, and malignancy. The developed model has high predictive accuracy and can be easily implemented in daily practice.

Molecular epidemiologic study of citrin deficiency by screening for four reported pathogenic SLC25A13 variants in the Shaanxi and Guangdong provinces, China.

BACKGROUND: Citrin deficiency (CD) is an autosomal recessive disease resulting from biallelic mutations of the SLC25A13 gene. This study aimed to investigate the molecular epidemiological features of CD in the Guangdong and Shaanxi provinces of China. METHODS: A total of 3,409 peripheral blood samples from Guangdong and 2,746 such samples from Shaanxi province were collected. Four prevalent SLC25A13 mutations NG_012247.2 (NM_014251.3): c.852_855del, c.1638_1660dup, c.615+5G>A, and c.1751-5_1751-4ins(2684) were screened by using the conventional polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism and newly-developed multiplex PCR methods, respectively. The mutated SLC25A13 allele frequencies, carrier frequencies, and CD morbidity rates were calculated and then compared with the Chi-square and Fisher's exact tests. RESULTS: The mutations were detected in 68 out of 6,818 SLC25A13 alleles in Guangdong and 29 out of 5,492 alleles in the Shaanxi population. The carrier frequencies were subsequently calculated to be 1/51 and 1/95, while the CD morbidity rates were 1/10,053 and 1/35,865, in the 2 populations, respectively. When compared with the Shaanxi population, Guangdong exhibited a higher frequency of mutated SLC25A13 allele (68/6,818 vs. 29/5,492, χ2=8.570, P=0.003) in general, with higher c.852_855del (54/6,818 vs. 13/5,492, χ2=17.328, P=0.000) but lower c.1751-5_1751 -4ins(2684) (2/6,818 vs. 9/5,492, P=0.015) allele frequencies. The distribution of c.615+5G>A and c.1638_1660dup between the 2 provinces, as well as all 4 prevalent mutations among different geographic regions within the 2 provinces, did not differed significantly. CONCLUSIONS: Our findings depicted the CD molecular epidemiological features in Guangdong and Shaanxi populations, providing preliminary but significant laboratory evidences for the subsequent CD diagnosis and management in the 2 provinces of mainland China.

A computational toolset for rapid identification of SARS-CoV-2, other viruses and microorganisms from sequencing data.

In this paper, we present a toolset and related resources for rapid identification of viruses and microorganisms from short-read or long-read sequencing data. We present fastv as an ultra-fast tool to detect microbial sequences present in sequencing data, identify target microorganisms and visualize coverage of microbial genomes. This tool is based on the k-mer mapping and extension method. K-mer sets are generated by UniqueKMER, another tool provided in this toolset. UniqueKMER can generate complete sets of unique k-mers for each genome within a large set of viral or microbial genomes. For convenience, unique k-mers for microorganisms and common viruses that afflict humans have been generated and are provided with the tools. As a lightweight tool, fastv accepts FASTQ data as input and directly outputs the results in both HTML and JSON formats. Prior to the k-mer analysis, fastv automatically performs adapter trimming, quality pruning, base correction and other preprocessing to ensure the accuracy of k-mer analysis. Specifically, fastv provides built-in support for rapid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identification and typing. Experimental results showed that fastv achieved 100% sensitivity and 100% specificity for detecting SARS-CoV-2 from sequencing data; and can distinguish SARS-CoV-2 from SARS, Middle East respiratory syndrome and other coronaviruses. This toolset is available at: https://github.com/OpenGene/fastv.

Neoproterozoic rifting in the Upper Yangtze Continental Block: Constraints from granites in the Well W117 borehole, South China.

Well W117 in the Sichuan Basin reveals a suite of ~814 Ma quartz monzonites, unconformably overlain by Sinian clastic and carbonate sediments. The quartz monzonites contain no muscovite and amphibole, and are characterized by high SiO2 (72.26-77.93%), total alkali, and TFe2O3/MgO content, and low P2O5 and CaO abundance, with variable A/CNK ratio (0.93-1.19), classified as metaluminous to weakly aluminous highly fractionated I-type granites. They are preserved in the Neoproterozoic rift and exhibit restricted negative εNd(t) values (-7.0 to -5.2) and variable zircon εHf(t) values (-13.9 to 2.3), suggesting their generation via melting of both ancient and juvenile crustal materials in an extensional setting. Their parent magmas were formed in a low-temperature condition (831-650 °C) and finally emplaced at ca. 9-10 km below the surface, indicating that the intrusion underwent exhumation before the deposition of Sinian sag basin. Such geological processes, together with evidence for Neoproterozoic structures in the surrounding area, support that the Upper Yangtze craton experienced two main phases of rifting from 830-635 Ma. The Well W117 granites and its overlying sediments record a geodynamic evolution from orogenic collapse to continental rifting, and to thermal subsidence, probably related to the Rodinia supercontinent breakup.