Reliable detection of generalized convulsive seizures using an off-the-shelf digital watch: A multisite phase 2 study.

OBJECTIVE: The aim of this study was to develop a machine learning algorithm using an off-the-shelf digital watch, the Samsung watch (SM-R800), and evaluate its effectiveness for the detection of generalized convulsive seizures (GCS) in persons with epilepsy. METHODS: This multisite epilepsy monitoring unit (EMU) phase 2 study included 36 adult patients. Each patient wore a Samsung watch that contained accelerometer, gyroscope, and photoplethysmographic sensors. Sixty-eight time and frequency domain features were extracted from the sensor data and were used to train a random forest algorithm. A testing framework was developed that would better reflect the EMU setting, consisting of (1) leave-one-patient-out cross-validation (LOPO CV) on GCS patients, (2) false alarm rate (FAR) testing on nonseizure patients, and (3) "fixed-and-frozen" prospective testing on a prospective patient cohort. Balanced accuracy, precision, sensitivity, and FAR were used to quantify the performance of the algorithm. Seizure onsets and offsets were determined by using video-electroencephalographic (EEG) monitoring. Feature importance was calculated as the mean decrease in Gini impurity during the LOPO CV testing. RESULTS: LOPO CV results showed balanced accuracy of .93 (95% confidence interval [CI] = .8-.98), precision of .68 (95% CI = .46-.85), sensitivity of .87 (95% CI = .62-.96), and FAR of .21/24 h (interquartile range [IQR] = 0-.90). Testing the algorithm on patients without seizure resulted in an FAR of .28/24 h (IQR = 0-.61). During the "fixed-and-frozen" prospective testing, two patients had three GCS, which were detected by the algorithm, while generating an FAR of .25/24 h (IQR = 0-.89). Feature importance showed that heart rate-based features outperformed accelerometer/gyroscope-based features. SIGNIFICANCE: Commercially available wearable digital watches that reliably detect GCS, with minimum false alarm rates, may overcome usage adoption and other limitations of custom-built devices. Contingent on the outcomes of a prospective phase 3 study, such devices have the potential to provide non-EEG-based seizure surveillance and forecasting in the clinical setting.

Integrated 4D Analysis of Intramuscular Fat Deposition: Quantitative Proteomic and Transcriptomic Studies in Wannanhua Pig Longissimus Dorsi Muscle.

Wannanhua (WH) is a pig breed indigenous to Anhui Province, China. This breed has a high intramuscular fat (IMF) content, making it an ideal model for investigating lipid deposition mechanisms in pigs. IMF content is one of the main indicators of meat quality in pigs and is regulated by multiple genes and metabolic pathways. Building upon our prior transcriptomic investigation, the present study focused on the longissimus dorsi muscle tissue of Wannanhua (WH) pigs in the rapid fat-deposition stages (120 and 240 days of age). Employing 4D label-free quantitative proteomic analysis, we identified 106 differentially expressed proteins (DEPs). Parallel reaction monitoring (PRM) technology was used to verify the DEPs, and the results showed that the 4D label-free results were reliable and valid. Functional enrichment and protein-protein interaction analyses showed that the DEPs were mainly involved in the skeletal-muscle-associated structural proteins, mitochondria, energy metabolism, and fatty acid metabolism. By integrating transcriptomic data, we identified seven candidate genes including ACADL, ACADM, ANKRD2, MYOZ2, TNNI1, UCHL1, and ART3 that play a regulatory role in fat deposition and muscle development. These findings establish a theoretical foundation for future analyses of lipid deposition traits, contributing to potential enhancements in pig meat quality during breeding and advancing the selection process for Chinese indigenous breeds.

From inflammation to pyroptosis: Understanding the consequences of cadmium exposure in chicken liver cells.

Hepatotoxicity is frequently observed following acute cadmium (Cd) exposure in chicken. Oxidative stress and subsequent inflammation are regarded as the main reasons for cadmium-induced liver injury. NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome-induced pyroptosis is involved in various inflammatory diseases, including liver injury. Poultry are more susceptible to harmful effects of heavy metals. However, the mechanism of cadmium-induced liver injury in chicken is still elusive. In this study, the effect of cadmium on chicken liver cells and the underlying mechanisms were investigated. The results showed mitochondria was damaged and excessive reactive oxygen species (ROS) were generated in chicken liver cell line LMH after cadmium exposure. Furthermore, cadmium-induced NLRP3 inflammasome activation and the cell membrane rupture indicated LMH cells pyroptosis. The ROS scavengers, acetylcysteine (NAC) and Mito-TEMPO prevented pyroptosis in LMH cells, suggesting that ROS were responsible for the activation of the NLRP3 inflammasome induced by cadmium. Additionally, anti-oxidative transcription factor Nrf2 was inhibited after cadmium exposure, explaining the excessive ROS generation. In summary, our study showed that cadmium leads to ROS generation by inducing mitochondrial damage and inhibiting Nrf2 activity, which promotes NLRP3 inflammasome activation and eventually induces pyroptosis in LMH cells.

Acetylenic spiroketal enol ethers from Artemisia rupestris and their synergistic antibacterial effects on methicillin-resistant Staphylococcus aureus.

Synergistic bioassay-guided isolation of the extracts of Artemisia rupestris L, which belongs to the family Asteraceae, afforded two acetylenic spiroketal enol ethers, namely rupesdiynes A (1) and B (2). Their structures were determined based on spectroscopic analysis and experimental and calculated ECD investigations. The two compounds exhibited synergistic activity and were able to reduce the minimum inhibitory concentration (MIC) of oxacillin four-fold, with a fractional inhibitory concentration index (FICI) of 0.5 in combination with oxacillin against the oxacillin-resistant EMRSA-16. Biofilm formation inhibitory and Ethidium bromide (EtBr) efflux assay were further employed to verify the possible mechanism of the synergistic antibacterial effect. Additionally, molecular docking studies were conducted to investigate the binding affinities of the two compounds with penicillin-binding protein 2a (PBP2a) of EMRSA-16. Taken together, rupesdiynes A (1) and rupesdiyne B (2) showed moderate synergistic activity against EMRSA-16 with oxacillin via inhibiting biofilm formation and efflux pump activity, respectively.

Effects of Boron on Fat Synthesis in Porcine Mammary Epithelial Cells.

This study aimed to investigate the effect of boron on porcine mammary epithelial cells (PMECs) survival, cell cycle, and milk fat synthesis. PMECs from boron-treated groups were exposed to 0-80 mmol/L boric acid concentrations. Cell counting kit-8 and flow cytometry assays were performed to assess cell survival and the cell cycle, respectively. Triacylglycerol (TAG) levels in PMECs and culture medium were determined by a triacylglycerol kit while PMECs lipid droplet aggregation was investigated via oil red staining. Milk fat synthesis-associated mRNA levels were determined by quantitative real-time polymerase chain reaction (qPCR) while its protein expressions were determined by Western blot. Low (0.2, 0.3, 0.4 mmol/L) and high (> 10 mmol/L) boron concentrations significantly promoted and inhibited cell viabilities, respectively. Boron (0.3 mmol/L) markedly elevated the abundance of G2/M phase cells. Ten mmol/L boron significantly increased the abundances of G0/G1 and S phase cells, but markedly suppressed G2/M phase cell abundance. At 0.3 mmol/L, boron significantly enhanced ERK phosphorylation while at 0.4, 0.8, 1, and 10 mmol/L, it markedly decreased lipid droplet diameters. Boron (10 mmol/L) significantly suppressed ACACA and SREBP1 protein expressions. The FASN protein levels were markedly suppressed by 0.4, 0.8, 1, and 10 mmol/L boron. Both 1 and 10 mmol/L markedly decreased FASN and SREBP1 mRNA expressions. Ten mmol/L boron significantly decreased PPARα mRNA levels. Low concentrations of boron promoted cell viability, while high concentrations inhibited PMECS viabilities and reduced lipid droplet diameters, which shows the implications of boron in pregnancy and lactation.

Transcriptome-wide map of N6-methyladenosine (m6A) profiling in coronary artery disease (CAD) with clopidogrel resistance.

BACKGROUND: Clopidogrel resistance profoundly increases the risk of major cardiovascular events in coronary artery disease (CAD) patients. Here, we comprehensively analyse global m6A modification alterations in clopidogrel-resistant (CR) and non-CR patients. METHODS: After RNA isolation, the RNA transcriptome expression (lncRNA, circRNA, and mRNA) was analysed via RNA-seq, and m6A peaks were identified by MeRIP-seq. The altered m6A methylation sites on mRNAs, lncRNAs, and circRNAs were identified, and then, GO and KEGG pathway analyses were performed. Through joint analysis with RNA-seq and MeRIP-seq data, differentially expressed mRNAs harbouring differentially methylated sites were identified. The changes in m6A regulator levels and the abundance of differentially methylated sites were measured by RT-PCR. The identification of m6A-modified RNAs was verified by m6A-IP-qPCR. RESULTS: The expression of 2919 hypermethylated and 2519 hypomethylated mRNAs, 192 hypermethylated and 391 hypomethylated lncRNAs, and 375 hypermethylated and 546 hypomethylated circRNAs was shown to be altered in CR patients. The m6A peaks related to CR indicated lower mark density at the CDS region. Functional enrichment analysis revealed that inflammatory pathways and insulin signalling pathways might be involved in the pathological processes underlying CR. The expression of mRNAs (ST5, KDM6B, GLB1L2, and LSM14B), lncRNAs (MSTRG.13776.1 and ENST00000627981.1), and circRNAs (hsa_circ_0070675_CBC1, hsa-circRNA13011-5_CBC1, and hsa-circRNA6406-3_CBC1) was upregulated in CR patients, while the expression of mRNAs (RPS16 and CREG1), lncRNAs (MSTRG.9215.1), and circRNAs (hsa_circ_0082972_CBC1) was downregulated in CR patients. Moreover, m6A regulators (FTO, YTHDF3, and WTAP) were also differentially expressed. An additional combined analysis of gene expression and m6A peaks revealed that the expression of mRNAs (such as ST5, LYPD2, and RPS16 mRNAs) was significantly altered in the CR patients. CONCLUSION: The expression of m6A regulators, the RNA transcriptome, and the m6A landscape was altered in CR patients. These findings reveal epitranscriptomic regulation in CR patients, which might be novel therapeutic targets in future.

[Correlation between rhizosphere environment and content of medicinal components of Arnebia euchroma].

This study aimed to explore the correlation between rhizosphere soil microorganisms of wild Arnebia euchroma and the content of medicinal components to provide guidance for the selection of the ecological planting base. The total DNA of rhizosphere soil microorganisms of wild A. euchroma was extracted, and the microbial community structure of rhizosphere soil microorganisms was analyzed by IlluminaMiseq high-throughput sequencing technology. The content of total hydroxynaphthoquinone pigment and ß,ß'-dimethylacrylalkannin in medicinal materials was determined by high-performance liquid chromatography(HPLC). The physicochemical pro-perties of rhizosphere soil of wild A. euchroma in main producing areas were determined, and the correlation of soil microbial abundance with index component content and soil physicochemical properties was analyzed by SPSS software. The results showed that the species composition of rhizosphere fungi and bacteria in A. euchroma from different habitats was similar at the phylum and genus levels, but their relative abundance, richness index(Chao1), and community diversity(Simpson) index were different. Correlation analysis showed that the content of available phosphorus in soil was positively correlated with the content of total hydroxynaphthoquinone pigment and ß,ß'-dimethylacrylalkannin, and the abundance of five fungal genera such as Solicoccozyma and six bacterial genera such as Pseudo-nocardia and Bradyrhizobium was positively correlated with the content of medicinal components in medicinal materials. The abundance of Bradyrhizobium was significantly positively correlated with the content of ß,ß'-dimethylacrylalkanin. The abundance of fungi such as Archaeorhizomyces was significantly positively correlated with the content of available phosphorus in rhizosphere soil, and Bradyrhizobium was significantly negatively correlated with soil pH. Therefore, the abundance of fungi and bacteria in the rhizosphere of A. euchroma has a certain correlation with the medicinal components and the physicochemical properties of the rhizosphere soil, which can provide a scientific basis for the selection of ecological planting bases in the later stage.

Transcriptome profiling of Madin-Darby bovine kidney cells uncover differences in the susceptibility of cattle to Toxoplasma gondii and Neospora caninum.

Toxoplasma gondii and Neospora caninum are two major apicomplexan protozoan parasites with heteroxenous life cycles and worldwide distributions. The transplacental transmission of N. caninum causes bovine abortion, which resulting in serious economic losses to the dairy industry. Although T. gondii was also reported to cause abortions in pregnant woman and small ruminants, scarce cases about the symptom to the host cattle and the causality remains unknown. In this study, transcriptome analysis of Madin Darby bovine kidney (MDBK) cells infected with T. gondii and N. caninum was performed to uncover the differences in susceptibility of cattle to the two parasites. The results showed that 256 and 2225 differentially expressed genes (DEGs) were detected in cells infected with N. caninum and T. gondii, respectively. Moreover, significant biological differences were revealed by the functional analysis including GO and KEGG enrichment. One serpin peptidase inhibitor (SEPRINA14), which is associated with immunosuppression during pregnancy, was found to significantly decrease in cells infected with N. caninum and increase in cells infected with T. gondii-infected cells. Pattern recognition receptors TLR3 and NOD2 were also significantly upregulated in N. caninum-infected MDBK cells, but not in T. gondii. They could induce an increased inflammatory response leading to severe tissue damage. In addition, the interleukin 12 receptor subunit beta 2 (IL12ß2), which plays an essential role in Th1 and Th2 cell differentiation and inflammatory bowel disease, was also markedly upregulated in the N. caninum infected cells, which led to an imbalance in the Th1 and Th2 cells by promoting the Th1 cellular response. Altogether, our findings recognized a new understanding on the differences between T. gondii and N. caninum infection of MDBK cells, where SEPRINA14, TLR3, NOD2, and IL12ß2 may be the key genes that affect the difference in susceptibility of cattle to T. gondii and N. caninum, especially in pregnant animals. This study provides more clues as to why N. caninum is more likely to cause abortions in cattle.

[Construction of a stable centromere protein F overexpression cell model of hepatocellular carcinoma using CRISPR activation system].

Current studies have shown that centromere protein F (CENPF) was overexpressed in hepatocellular carcinoma (HCC) and might be involved in the pathogenesis of HCC. Specifically, due to the very large molecular weight (358 kDa) of CENPF full length protein, only CENPF knock-down, but not overexpression models, were applied currently to explore the carcinogenicity of CENPF in HCC. Whether CENPF overexpression is a cause or an effect in HCC remains to be illustrated. We aimed to establish a CENPF overexpression cell model using CRISPR/dCas9 synergistic activation mediator (SAM) system with lentiMPHv2 and lentiSAMv2 vectors to explore the role of CENPF overexpression in HCC. Single guide RNAs (sgRNAs) that specifically identify the transcription initiation site of CENPF gene were synthesized and inserted into the lentiSAMv2 plasmid. Huh-7 and HCCLM3 cells were first transduced with lentiMPHv2 and then selected with hygromycin B. The cells were then transduced with lentiSAMv2 carrying specific sgRNA for CENPF gene, followed by blasticidin S selection. The mRNA and protein detection results of Huh-7 and HCCLM3 cells screened by hygromycin B and blasticidin S showed that the endogenous overexpression of CENPF can be induced by sgRNA1 and sgRNA4, especially by sgRNA4. By using the CRISPR/dCas9 technique, stable cell models with overexpressed CENPF were successfully constructed to explore the role of CENPF in tumorigenesis, which provides a reference for the construction of cell models overexpressing large molecular weight protein.

Customizing Catalyst/Ionomer Interface for High-Durability Electrode of Proton Exchange Membrane Fuel Cells.

Commercialization applications of proton exchange membrane fuel cells (PEMFCs) are throttled by the durability issues of the electrodes prepared by using catalyst inks. Probing into a desirable catalyst/ionomer interface by adjusting the catalyst inks is an effective way for obtaining high-durability electrodes. The present study investigated quantitatively the catalyst/ionomer interfaces based on the viscosity (η) property of the isopropyl alcohol (IPA) and dipropylene glycol (DPG) nonaqueous mixture solvent for the first time. Accelerated stress test (AST) showed that η as one of the characteristic parameters of the solvent had a threshold effect on the durability of electrodes. The electrodes in the half-cell and single cell all exhibited the highest durability using IPA:DPG = 2:6 (η = 27.00 cP) as the dispersion solvent in this work, embodied by its ECSA loss rate, and the cell potential loss was minimum after AST. The ECSA loss mechanism showed that a fine catalyst/ionomer interface structure was created for the highest durability electrode by regulating the η values of the solvent, and the carbon corrosion loss (le) and Pt particle dissolution loss (ld) were weakened. Based on the molecular dynamics (MD) simulation and 19F NMR spectra results, the solvent ratio (various η and similar ε and δ) affected the dispersion states of the ionomer. For the catalyst inks with the highest durability (IPA:DPG = 2:6), the Nafion backbone and side chain presented a higher mobility behavior in the solvent and tended to show the structure of extension separation and the respective aggregation of hydrophilic/hydrophobic phases. Meanwhile, Pt slab models suggested that the side chain of Nafion more easily adhered to the Pt interface zone, while the backbone was pushed toward the carbon support interface zone as more DPG molecules distributed on the Pt surface, which reduced the dissolution of Pt particles and the corrosion of the carbon support. These catalyst/ionomer interface structures tailored by regulating the solvent η values provide insights into improving the electrode durability.

Transcriptomic Profiling of Meat Quality Traits of Skeletal Muscles of the Chinese Indigenous Huai Pig and Duroc Pig.

The Huai pig is a well-known indigenous pig breed in China. The main advantages of Huai pigs over Western commercial pig breeds include a high intramuscular fat (IMF) content and good meat quality. There are significant differences in the meat quality traits of the same muscle part or different muscle parts of the same variety. To investigate the potential genetic mechanism underlying the meat quality differences in different pig breeds or muscle groups, longissimus dorsi (LD), psoas major (PM), and biceps femoris (BF) muscle tissues were collected from two pig breeds (Huai and Duroc). There were significant differences in meat quality traits and amino acid content. We assessed the muscle transcriptomic profiles using high-throughput RNA sequencing. The IMF content in the LD, PM, and BF muscles of Huai pigs was significantly higher than that in Duroc pigs (p < 0.05). Similarly, the content of flavor amino acids in the three muscle groups was significantly higher in Huai pigs than that in Duroc pigs (p < 0.05). We identified 175, 110, and 86 differentially expressed genes (DEGs) between the LD, PM, and BF muscles of the Huai and Duroc pigs, respectively. The DEGs of the different pig breeds and muscle regions were significantly enriched in the biological processes and signaling pathways related to muscle fiber type, IMF deposition, lipid metabolism, PPAR signaling, cAMP signaling, amino acid metabolism, and ECM-receptor interaction. Our findings might help improve pork yield by using the obtained DEGs for marker-assisted selection and providing a theoretical reference for evaluating and improving pork quality.

Proteomic Analysis of Rat Duodenum Reveals the Modulatory Effect of Boron Supplementation on Immune Activity.

The proper supplementation of boron, an essential trace element, can enhance animal immune function. We utilized the method of TMT peptide labeling in conjunction with LC-MS/MS quantitative proteomics for the purpose of examining the effects of boric acid on a rat model and analyzing proteins from the duodenum. In total, 5594 proteins were obtained from the 0, 10, and 320 mg/L boron treatment groups. Two hundred eighty-four proteins that exhibit differential expression were detected. Among the comparison, groups of 0 vs. 10 mg/L, 0 vs. 320 mg/L, and 10 vs. 320 mg/L of boron, 110, 32, and 179 proteins, respectively, demonstrated differential expression. The results revealed that these differential expression proteins (DEPs) mainly clustered into two profiles. GO annotations suggested that most of the DEPs played a role in the immune system process, in which 2'-5'-oligoadenylate synthetase-like, myxovirus resistance 1, myxovirus resistance 2, dynein cytoplasmic 1 intermediate chain 1, and coiled-coil domain containing 88B showed differential expression. The DEPs had demonstrated an augmentation in the signaling pathways, which primarily include phagosome, antigen processing, and presentation, as well as cell adhesion molecules (CAMs). Our study found that immune responses in the duodenum were enhanced by lower doses of boron and that this effect is likely mediated by changes in protein expression patterns in related signaling pathways. It offers an in-depth understanding of the underlying molecular mechanisms that lead to immune modulation in rats subjected to dietary boron treatment.

An ontology-based approach for harmonization and cross-cohort query of Alzheimer's disease data resources.

BACKGROUND: In the United States, the National Alzheimer's Coordinating Center (NACC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) are two major data sharing resources for Alzheimer's Disease (AD) research. NACC and ADNI strive to make their data more FAIR (findable, interoperable, accessible and reusable) for the broader research community. However, there is limited work harmonizing and supporting cross-cohort interoperability of the two resources. METHOD: In this paper, we leverage an ontology-based approach to harmonize data elements in the two resources and develop a web-based query system to search patient cohorts across the two resources. We first mapped data elements across NACC and ADNI, and performed value harmonization for the mapped data elements with inconsistent permissible values. Then we built an Alzheimer's Disease Data Element Ontology (ADEO) to model the mapped data elements in NACC and ADNI. We further developed a prototype cross-cohort query system to search patient cohorts across NACC and ADNI. RESULTS: After manual review, we found 172 mappings between NACC and ADNI. These 172 mappings were further used to construct common concepts in ADEO. Our data element mapping and harmonization resulted in five files storing common concepts, variables in NACC and ADNI, mappings between variables and common concepts, permissible values of categorical type data elements, and coding inconsistency harmonization, respectively. Our cross-cohort query system consists of three core architectural elements: a web-based interface, an advanced query engine, and a backend MongoDB database. CONCLUSIONS: In this work, ADEO has been specifically designed to facilitate data harmonization and cross-cohort query of NACC and ADNI data resources. Although our prototype cross-cohort query system was developed for exploring NACC and ADNI, its backend and frontend framework has been designed and implemented to be generally applicable to other domains for querying patient cohorts from multiple heterogeneous data sources.

Genome-wide detection of CNV regions between Anqing six-end-white and Duroc pigs.

BACKGROUND: Anqing six-end-white pig is a native breed in Anhui Province. The pigs have the disadvantages of a slow growth rate, low proportion of lean meat, and thick back fat, but feature the advantages of strong stress resistance and excellent meat quality. Duroc pig is an introduced pig breed with a fast growth rate and high proportion of lean meat. With the latter breed featuring superior growth characteristics but inferior meat quality traits, the underlying molecular mechanism that causes these phenotypic differences between Chinese and foreign pigs is still unclear. RESULTS: In this study, copy number variation (CNV) detection was performed using the re-sequencing data of Anqing Six-end-white pigs and Duroc pigs, A total of 65,701 CNVs were obtained. After merging the CNVs with overlapping genomic positions, 881 CNV regions (CNVRs) were obtained. Based on the obtained CNVR information combined with their positions on the 18 chromosomes, a whole-genome map of the pig CNVs was drawn. GO analysis of the genes in the CNVRs showed that they were primarily involved in the cellular processes of proliferation, differentiation, and adhesion, and primarily involved in the biological processes of fat metabolism, reproductive traits, and immune processes. CONCLUSION: The difference analysis of the CNVs between the Chinese and foreign pig breeds showed that the CNV of the Anqing six-end-white pig genome was higher than that of the introduced pig breed Duroc. Six genes related to fat metabolism, reproductive performance, and stress resistance were found in genome-wide CNVRs (DPF3, LEPR, MAP2K6, PPARA, TRAF6, NLRP4).

Recent COVID-19 infection is associated with increased mortality in the ambulatory surgery population.

BACKGROUND: The effect of COVID-19 infection on post-operative mortality and the optimal timing to perform ambulatory surgery from diagnosis date remains unclear in this population. Our study was to determine whether a history of COVID-19 diagnosis leads to a higher risk of all-cause mortality following ambulatory surgery. METHODS: This cohort constitutes retrospective data obtained from the Optum dataset containing 44,976 US adults who were tested for COVID-19 up to 6 months before surgery and underwent ambulatory surgery between March 2020 to March 2021. The primary outcome was the risk of all-cause mortality between the COVID-19 positive and negative patients grouped according to the time interval from COVID-19 testing to ambulatory surgery, called the Testing to Surgery Interval Mortality (TSIM) of up to 6 months. Secondary outcome included determining all-cause mortality (TSIM) in time intervals of 0-15 days, 16-30 days, 31-45 days, and 46-180 days in COVID-19 positive and negative patients. RESULTS: 44,934 patients (4297 COVID-19 positive, 40,637 COVID-19 negative) were included in our analysis. COVID-19 positive patients undergoing ambulatory surgery had higher risk of all-cause mortality compared to COVID-19 negative patients (OR = 2.51, p < 0.001). The increased risk of mortality in COVID-19 positive patients remained high amongst patients who had surgery 0-45 days from date of COVID-19 testing. In addition, COVID-19 positive patients who underwent colonoscopy (OR = 0.21, p = 0.01) and plastic and orthopedic surgery (OR = 0.27, p = 0.01) had lower mortality than those underwent other surgeries. CONCLUSIONS: A COVID-19 positive diagnosis is associated with significantly higher risk of all-cause mortality following ambulatory surgery. This mortality risk is greatest in patients that undergo ambulatory surgery within 45 days of testing positive for COVID-19. Postponing elective ambulatory surgeries in patients that test positive for COVID-19 infection within 45 days of surgery date should be considered, although prospective studies are needed to assess this.

Data Mining Pipeline for COVID-19 Vaccine Safety Analysis Using a Large Electronic Health Record.

We developed a novel data mining pipeline that automatically extracts potential COVID-19 vaccine-related adverse events from a large Electronic Health Record (EHR) dataset. We applied this pipeline to Optum® de-identified COVID-19 EHR dataset containing COVID-19 vaccine records between December 11, 2020 and January 20, 2022. We compared post-vaccination diagnoses between the COVID-19 vaccine group and the influenza vaccine group among 553,682 individuals without COVID-19 infection. We extracted 1,414 ICD-10 diagnosis categories (first three ICD10 digits) within 180 days after the first dose of the COVID-19 vaccine. We then ranked the diagnosis codes using the adverse event rates and adjusted odds ratio based on the self-controlled case series analysis. Using inverse probability of censoring weighting, we estimated the right-censored time-to-event records. Our results show that the COVID-19 vaccine has a similar adverse events rate to the influenza vaccine. We found 20 types of potential COVID-19 vaccine-related adverse events that may need further investigation.

A Query Engine for Self-controlled Case Series, with an application to COVID-19 EHR data.

Self-controlled case series (SCCS) is a statistical method in epidemiological study design that uses individuals as their own controls, with comparisons made within the same individuals at different time points of observation. SCCS has been applied in settings where it is difficult to identify comparison or control groups. To provide computational support for SCCS, we introduce a query engine called Self-Controlled Case Query (SCCQ) and use it to extract cohorts of self-controlled case series from a large-scale COVID-19 Electronic Health Records (EHR) dataset. Visual summary of the queried population through the R-Shiny visualization framework offers SCCQ's query result dashboard to the researcher. SCCQ allows the export of query-generated raw data files with a portable format that researchers can extend to create more intricate and robust visualization capabilities without needing a high-level of technical or statistical background. Our validation and evaluation experiments uncovered COVID-19 outcomes to be consistent with existing research findings. With SCCQ, cohort exploration, data extraction, and information visualization can be provided for structured EHR data to lower the barrier for clinical and epidemiological research.

Interictal respiratory variability predicts severity of hypoxemia after generalized convulsive seizures.

OBJECTIVE: Severe respiratory dysfunction induced by generalized convulsive seizures (GCS) is now thought to be a common mechanism for sudden unexpected death in epilepsy (SUDEP). In a mouse model of seizure-induced death, increased interictal respiratory variability was reported in mice that later died of respiratory arrest after GCS. We studied respiratory variability in epilepsy patients as a predictive tool for severity of postictal hypoxemia, a potential biomarker for SUDEP risk. We then explored the relationship between respiratory variability and central CO2 drive, measured by the hypercapnic ventilatory response (HCVR). METHODS: We reviewed clinical, video-electroencephalography, and respiratory (belts, airflow, pulse oximeter, and HCVR) data of epilepsy patients. Mean, SD, and coefficient of variation (CV) of interbreath interval (IBI) were calculated. Primary outcomes were: (1) nadir of capillary oxygen saturation (SpO2 ) and (2) duration of oxygen desaturation. Poincaré plots of IBI were created. Covariates were evaluated in univariate models, then, based on Akaike information criteria (AIC), multivariate regression models were created. RESULTS: Of 66 GCS recorded in 131 subjects, 30 had interpretable respiratory data. In the multivariate model with the lowest AIC value, duration of epilepsy was a significant predictor of duration of oxygen desaturation. Duration of tonic phase and CV of IBI during the third postictal minute correlated with SpO2 nadir, whereas CV of IBI during non-rapid eye movement sleep had a negative correlation. Poincaré plots showed that long-term variability was significantly greater in subjects with ≥200 s of postictal oxygen desaturation after GCS compared to those with <200 s desaturation. Finally, HCVR slope showed a negative correlation with measures of respiratory variability. SIGNIFICANCE: These results indicate that interictal respiratory variability predicts severity of postictal oxygen desaturation, suggesting its utility as a potential biomarker. They also suggest that interictal respiratory control may be abnormal in some patients with epilepsy.

Identification of novel serum autoantibody biomarkers for early esophageal squamous cell carcinoma and high-grade intraepithelial neoplasia detection.

Background: Early diagnosis of esophageal squamous cell carcinoma (ESCC) is critical for effective treatment and optimal prognosis; however, less study on serum biomarkers for the early ESCC detection has been reported. The aim of this study was to identify and evaluate several serum autoantibody biomarkers in early ESCC. Methods: We initially screened candidate tumor-associated autoantibodies (TAAbs) associated with ESCC by serological proteome analysis (SERPA) combined with nanoliter-liquid chromatography combined with quadrupole time of flight tandem mass spectrometry (nano-LC-Q-TOF-MS/MS), and the TAAbs were further subjected to analysis by Enzyme-linked immunosorbent assay (ELISA) in a clinical cohort (386 participants, including 161 patients with ESCC, 49 patients with high-grade intraepithelial neoplasia [HGIN] and 176 healthy controls [HC]). Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic performance. Results: The serum levels of CETN2 and POFUT1 autoantibodies which were identified by SERPA were statistically different between ESCC or HGIN patients and HC in ELISA analysis with the area under the curve (AUC) values of 0.709 (95%CI: 0.654-0.764) and 0.741 (95%CI: 0.689-0.793), 0.717 (95%CI: 0.634-0.800) and 0.703 (95%CI: 0.627-0.779) for detection of ESCC and HGIN, respectively. Combining these two markers, the AUCs were 0.781 (95%CI: 0.733-0.829), 0.754 (95%CI: 0.694-0.814) and 0.756 (95%CI: 0.686-0.827) when distinguishing ESCC, early ESCC and HGIN from HC, respectively. Meanwhile, the expression of CETN2 and POFUT1 was found to be correlated with ESCC progression. Conclusions: Our data suggest that CETN2 and POFUT1 autoantibodies have potential diagnostic value for ESCC and HGIN, which may provide novel insights for early ESCC and precancerous lesions detection.

Transcriptome Profiling of Different Developmental Stages on Longissimus Dorsi to Identify Genes Underlying Intramuscular Fat Content in Wannanhua Pigs.

Intramuscular fat (IMF) is a key index to measure the tenderness and flavor of pork. Wannanhua pig, a famous indigenous pig breed in Anhui Province, is renowned for its high lipid deposition and high genetic divergence, making it an ideal model for investigating the lipid position trait mechanisms in pigs. However, the regulatory mechanisms of lipid deposition and development in pigs remain unclear. Furthermore, the temporal differences in gene regulation are based on muscle growth and IMF deposition. The purpose of this study was to study the expression changes of longissimus dorsi (LD) at different growth stages of WH pigs at the molecular level, to screen the candidate genes and signaling pathways related to IMF during development by transcriptome sequencing technology, and to explore the transcriptional regulation mechanism of IMF deposition-related genes at different development stages. In total, 616, 485, and 1487 genes were differentially expressed between LD60 and LD120, LD120 and LD240, and LD60 and LD240, respectively. Numerous differentially expressed genes (DEGs) associated with lipid metabolism and muscle development were identified, and most of them were involved in IMF deposition and were significantly up-regulated in LD120 and LD240 compared to LD60. STEM (Short Time-series Expression Miner) analysis indicated significant variations in the mRNA expression across distinct muscle development stages. The differential expression of 12 selected DEGs was confirmed by RT-qPCR. The results of this study contribute to our understanding of the molecular mechanism of IMF deposition and provide a new way to accelerate the genetic improvement of pork quality.