The FUTUREPAIN study develops a short general-purpose questionnaire, based on the biopsychosocial model, to predict the probability of developing or maintaining moderate-to-severe chronic pain 7-10 ...years into the future.
This is a retrospective cohort study. Two-thirds of participants in the National Survey of Midlife Development in the United States were randomly assigned to a training cohort used to train a predictive machine learning model based on the least absolute shrinkage and selection operator (LASSO) algorithm, which produces a model with minimal covariates. Out-of-sample predictions from this model were then estimated using the remaining one-third testing cohort to determine the area under the receiver operating characteristic curve (AUROC). An optimal cut-point that maximized sensitivity and specificity was determined.
The LASSO model using 82 variables in the training cohort, yielded an 18-variable model with an out-of-sample AUROC of 0.85 (95% Confidence Interval (CI): 0.80, 0.91) in the testing cohort. The sum of sensitivity (0.88) and specificity (0.76) was maximized at a cut-point of 17 (95% CI: 15, 18) on a 0-100 scale where the AUROC was 0.82.
We developed a short general-purpose questionnaire that predicts the probability of an adult having moderate-to-severe chronic pain in 7-to-10 years. It has diagnostic ability greater than 80% and can be used regardless of whether a patient is currently experiencing chronic pain. Knowing which patients are likely to have moderate-to-severe chronic pain in the future allows clinicians to target preventive treatment.
Water electrolysis technology is required to overcome the intermittency of renewable energy sources. Among various water electrolysis methods, the proton exchange membrane water electrolysis (PEMWE) ...cell has the advantages of a fast response and high current density. However, high capital costs have hindered the commercialization of PEMWE; therefore, it is important to lower the price of bipolar plates, which make PEMWE expensive. In addition, since the flow field inscribed in the bipolar plate significantly influences the performance, it is necessary to design the enhanced pattern. A three-dimensional two-phase flow model was used to analyze the two-phase flow and electrochemical reactions of the PEMWE anode. In order to compare the experimental results with the simulation, experiments were conducted according to the flow rate, and the results were in good agreement. First, as a result of comparing the performance of the channel and PTL (porous transport layer) flow fields, the channel flow field showed better performance than the PTL flow field. For the channel flow field, the higher the ratio of the channel width-to-rib width and the permeability of PTL, the performance got better. In the case of the PTL flow field, with the increased capillary pressure, the performance improved even if the PTL permeability decreased. Next, the direction of gravity affected the performance only when the channel flow field was used, and the X+ and Z+ directions were optimal for the performance. Finally, increasing the inlet flow rate could reduce the difference in performance between the channel and PTL flow fields, but the pressure drop gradually increased.
Water electrolysis is an eco-friendly method for the utilization of renewable energy sources which provide intermittent power supply. Proton exchange membrane water electrolysis (PEMWE) has a high ...efficiency in this regard. However, the two-phase flow of water and oxygen at the anode side causes performance degradation, and various operating conditions affect the performance of PEMWE. In this study, the effects of four control parameters (operating temperature, flow rate, cell orientation, and pattern of the channel) on the performance of PEMWE were investigated. The effects of the operating conditions on its performance were examined using a 25 cm2 single-cell. Evaluation tests were conducted using in situ methods such as polarization curves and electrochemical impedance spectroscopy. The results demonstrated that a high operating temperature and low flow rate reduce the activation and ohmic losses, and thereby enhance the performance of PEMWE. Additionally, the cell orientation affects the performance of PEMWE owing to the variation in the two-phase flow regime. It was observed that the slope of specific sections in the polarization curve rapidly increases at a specific cell voltage.
Metal-metal contacts, though not yet widely realized, may provide exciting opportunities to serve as tunable and functional interfaces in single-molecule devices. One of the simplest components which ...might facilitate such binding interactions is the ferrocene group. Notably, direct bonds between the ferrocene iron center and metals such as Pd or Co have been demonstrated in molecular complexes comprising coordinating ligands attached to the cyclopentadienyl rings. Here, we demonstrate that ferrocene-based single-molecule devices with Fe-Au interfacial contact geometries form at room temperature in the absence of supporting coordinating ligands. Applying a photoredox reaction, we propose that ferrocene only functions effectively as a contact group when oxidized, binding to gold through a formal Fe
center. This observation is further supported by a series of control measurements and density functional theory calculations. Our findings extend the scope of junction contact chemistries beyond those involving main group elements, lay the foundation for light switchable ferrocene-based single-molecule devices, and highlight new potential mechanistic function(s) of unsubstituted ferrocenium groups in synthetic processes.
Salmonella infections represent an important public health problem. In 2018, a multistate outbreak of S. enterica subsp. enterica serovar Thompson infection associated with contaminated chocolate ...cakes in schools was reported in South Korea. In this study, we sequenced the 37 S. Thompson strains isolated from chocolate cakes, egg whites, preserves, and cookware associated with the outbreak. In addition, we analyze the genomic sequences of 61 S. Thompson strains (37 chocolate cake-related outbreak strains, 4 strains isolated from outbreaks in South Korea and 20 strains available in the National Center for Biotechnology Information) to assess the genomic characteristics of outbreak-related strains by comparative genomics and phylogenetic analysis. The results showed that identically classified clusters divided strains into two clusters, sub-clusters A & I (with strains from 2018 in South Korea) and sub-clusters B & II (with strains from 2014 to 2015 in South Korea). S. Thompson isolated from South Korea were accurately distinguished from publicly-available strains. Unlike other S. Thompson genomes, those of chocolate cake outbreak-related strains had three Salmonella phages (SEN8, vB SosS Oslo, and SI7) integrated into their chromosome. Comparative genomics revealed several genes responsible for the specific genomic features of chocolate cake outbreak-related strains and three bacteriophages that may contribute to the pathogenicity of other S. Thompson strains.
Hybrid strains Escherichia coli acquires genetic characteristics from multiple pathotypes and is speculated to be more virulent; however, understanding their pathogenicity is elusive. Here, we ...performed genome-based characterization of the hybrid of enteropathogenic (EPEC) and enterotoxigenic E. coli (ETEC), the strains that cause diarrhea and mortality in children. The virulence genes in the strains isolated from different sources in the South Korea were identified, and their phylogenetic positions were analyzed. The EPEC/ETEC hybrid strains harbored eae and est encoding E. coli attaching and effacing lesions and heat-stable enterotoxins of EPEC and ETEC, respectively. Genome-wide phylogeny revealed that all hybrids (n = 6) were closely related to EPEC strains, implying the potential acquisition of ETEC virulence genes during ETEC/EPEC hybrid emergence. The hybrids represented diverse serotypes (O153:H19 (n = 3), O49:H10 (n = 2), and O71:H19 (n = 1)) and sequence types (ST546, n = 4; ST785, n = 2). Furthermore, heat-stable toxin-encoding plasmids possessing estA and various other virulence genes and transporters, including nleH2, hlyA, hlyB, hlyC, hlyD, espC, espP, phage endopeptidase Rz, and phage holin, were identified. These findings provide insights into understanding the pathogenicity of EPEC/ETEC hybrid strains and may aid in comparative studies, virulence characterization, and understanding evolutionary biology.
The predominant hybrid pathogenic
, enterohemorrhagic
(EHEC), combines characteristics of Shiga toxin-producing
(STEC) and enteropathogenic
(EPEC), contributing to global outbreaks with severe ...symptoms including fatal consequences. Since EHEC infection was designated as a notifiable disease in 2000 in South Korea, around 2000 cases have been reported, averaging approximately 90 cases annually.
In this work, genome-based characteristic analysis and cell-based assay of hybrid STEC/aEPEC strains isolated from livestock feces, animal source foods, and water in South Korea was performed.
To identify the virulence and antimicrobial resistance genes, determining the phylogenetic position of hybrid STEC/aEPEC strains isolated in South Korea, a combination of real-time PCR and whole-genome sequencing (WGS) was used. Additionally, to assess the virulence of the hybrid strains and compare them with genomic characterization, we performed a cell cytotoxicity and invasion assays.
The hybrid STEC/aEPEC strains harbored
and
genes, encoding Shiga toxins and
attachment/effacement related protein of STEC and EPEC, respectively. Furthermore, all hybrid strains harbored plasmid-carried enterohemolysin(
), a key virulence factor in prevalent pathogenic
infections, such as diarrheal disease and hemolytic-uremic syndrome (HUS). Genome-wide phylogenetic analysis revealed a close association between all hybrid strains and specific EPEC strains, suggesting the potential acquisition of Stx phages during STEC/aEPEC hybrid formation. Some hybrid strains showed cytotoxic activity against HeLa cells and invasive properties against epithelial cells. Notably, all STEC/aEPEC hybrids with sequence type (ST) 1,034 (
= 11) exhibited higher invasiveness than those with E2348/69. This highlights the importance of investigating potential correlations between STs and virulence characteristics of
hybrid strains.
Through genome-based characterization, we confirmed that the hybrid STEC/aEPEC strains are likely EPEC strains that have acquired STEC virulence genes via phage. Furthermore, our results emphasize the potential increased danger to humans posed by hybrid STEC/aEPEC strains isolated in South Korea, containing both
and
, compared to STEC or EPEC alone.
Eukaryotic algae and cyanobacteria produce hydrogen under anaerobic and limited aerobic conditions. Here we show that novel microalgal strains (Chlorella vulgaris YSL01 and YSL16) upregulate the ...expression of the hydrogenase gene (HYDA) and simultaneously produce hydrogen through photosynthesis, using CO2 as the sole source of carbon under aerobic conditions with continuous illumination. We employ dissolved oxygen regimes that represent natural aquatic conditions for microalgae. The experimental expression of HYDA and the specific activity of hydrogenase demonstrate that C. vulgaris YSL01 and YSL16 enzymatically produce hydrogen, even under atmospheric conditions, which was previously considered infeasible. Photoautotrophic H2 production has important implications for assessing ecological and algae-based photolysis.
Detecting and identifying the origins of foodborne pathogen outbreaks is a challenging. The Next-Generation Sequencing (NGS) panel method offers a potential solution by enabling efficient screening ...and identification of various bacteria in one reaction. In this study, new NGS panel primer sets that target 18 specific virulence factor genes from six target pathogens (
,
,
,
,
, and
) were developed and optimized. The primer sets were validated for specificity and selectivity through singleplex PCR, confirming the expected amplicon size. Crosscheck and multiplex PCR showed no interference in the primer set or pathogenic DNA mixture. The NGS panel analysis of spiked water samples detected all 18 target genes in a single reaction, with pathogen concentrations ranging from 10
to 10
colony-forming units (CFUs) per target pathogen. Notably, the total sequence read counts from the virulence factor genes showed a positive association with the CFUs per target pathogen. However, the method exhibited relatively low sensitivity and occasional false positive results at low pathogen concentrations of 10
CFUs. To validate the detection and identification results, two sets of quantitative real-time PCR (qPCR) analyses were independently performed on the same spiked water samples, yielding almost the same efficiency and specificity compared to the NGS panel analysis. Comparative statistical analysis and Spearman correlation analysis further supported the similarity of the results by showing a negative association between the NGS panel sequence read counts and qPCR cycle threshold (Ct) values. To enhance NGS panel analysis for better detection, optimization of primer sets and real-time NGS sequencing technology are essential. Nonetheless, this study provides valuable insights into applying NGS panel analysis for multiple foodborne pathogen detection, emphasizing its potential in ensuring food safety.
To unravel metabolic determinats of insulin resistance, we performed a targeted metabolomics analysis in Korean Children-Adolescent Cohort Study (KoCAS, n = 430). Sixty-seven metabolites were ...associated with insulin resistance in adolescents and the association also found in an adult population (KoGES, n = 2,485). Functional interactions of metabolites with gene/proteins using biological pathway with insulin resistance were not identified biological significance and regulatory effects of asymmetric dimethylarginine (ADMA). However, ADMA showed a higher association with adolescent obesity (P < 0.001) and adult diabetes (P = 0.007) and decreased after obesity intervention program. Functional studies in cellular and mouse models demonstrated that an accumulation of ADMA is associated with the regulation of obesity-induced insulin resistance in skeletal muscle. ADMA treatment inhibited dimethylarginine-dimethylaminohydrolase (DDAH) activity and mRNA expression in insulin resistance muscle cell. Moreover, the treatment led to decrease of phosphorylation of insulin receptor (IR), AKT, and GLUT4 but increase of protein-tyrosine phosphatase 1B (PTP1B). Accordingly, increased ADMA significantly inhibited glucose uptake in myotube cell. We suggest that accumulation of ADMA is associated with modulation of insulin signaling and insulin resistance. ADMA might expand the possibilities of new therapeutic target for functional and clinical implications in the control of energy and metabolic homeostasis in humans.