Search

Sang-Mi Kim,1 Hyun-Seung Lee,1 Na-Young Hwang,2 Kyunga Kim,2 Hyung-Doo Park,1 Soo-Youn Lee1,3,4 1Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 2Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea; 3Department of Clinical Pharmacology & Therapeutics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 4Department of Health Science and Technology, Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, Seoul, KoreaCorrespondence: Soo-Youn LeeDepartment of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Ilwon-ro, Gangnam-gu, Seoul, 06351, KoreaTel +82-2-3410-1834Fax +82-2-3410-2719Email suddenbz@skku.eduBackground: To date, outcome data with a large sample size and data regarding the clinical outcomes of pharmacokinetic-guided (PK) dosing of vancomycin are limited.Aim: We evaluated the pharmacokinetic and clinical outcomes of a PK-guided dosing advisory program, pharmacokinetic consultation service (PKCS), in vancomycin treatment.Methods: We investigated vancomycin therapeutic drug monitoring (TDM) and PKCS use through a retrospective review of patients who had serum vancomycin trough concentration data from October 2017 to November 2018. Among these patients, we selected non-critically ill adult patients satisfying our selection criteria to evaluate the effect of PKCS. Target trough attainment rate, time to target attainment, vancomycin-induced nephrotoxicity (VIN), vancomycin treatment failure rate, and duration of vancomycin therapy were compared between patients whose dosing was adjusted according to PKCS (PKCS group), and those whose dose was adjusted at the discretion of the attending physician (non-PKCS group).Results: A total of 280 patients met the selection criteria for the VIN analysis (PKCS, n=134; non-PKCS, n=146). The incidence of VIN was similar between the two groups (PKCS, n=5; non-PKCS, n=5); however, the target attainment rate was higher in the PKCS group (75% vs 60%, P = 0.012). The time to target attainment was similar between the two groups. Further exclusions yielded 112 patients for the clinical outcome evaluation (PKCS, n=51; non-PKCS, n=61). The treatment failure rate was similar, and the duration of vancomycin therapy was longer in the PKCS group (12 vs 8 days, P = 0.008).Conclusion: In non-critically ill patients, an increase in target trough achieved by PKCS did not lead to decreased vancomycin treatment failures, shorter vancomycin treatment, or decreased nephrotoxicity in vancomycin treatment. Considering the excessive amount of effort currently put into vancomycin dosing and monitoring, more selective criteria for individualized pharmacokinetic-guided dosing needs to be applied.Keywords: vancomycin, pharmacokinetics, dosing, therapeutic drug monitoring, trough concentration, nephrotoxicity

Rihwa Choi,1,2 Hye In Woo,1 Hyung-Doo Park,1 Soo-Youn Lee1,31Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 2Department of Laboratory Medicine, Green Cross Laboratories, Yongin, Gyeonggi, Republic of Korea; 3Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaPurpose: The current status of therapeutic drug monitoring (TDM) assay utilization by clinical laboratories in South Korea remains little known. We investigated the TDM status of five antibiotics known for nephrotoxicity (vancomycin, amikacin, gentamicin, tobramycin, and teicoplanin) for the improvement of TDM in South Korea among patients with infectious diseases using a cross-sectional nationwide survey.Patients and methods: We developed an online questionnaire and collected responses using a user-friendly web-based platform. The survey included questions about laboratory characteristics, implementation and operation of drug assays, implementation and operation of TDM consulting services, patient needs, and barriers to providing better TDM service including expectations and concerns about other platform-based drug assays.Results: Among a total of 235 clinical laboratories, 112 (47.7%) responded, and 62 of the responding laboratories (55.4%) possessed drug assay facilities. Only 41.2% to 58.1% of respondents were providing TDM consulting services for each antibiotic. Respondents indicated that there are unmet needs regarding drug assays and TDM consultation as well as barriers to TDM utilization including high operating costs, lack of knowledge about TDM, lack of user-friendly software, lack of medical and laboratory information systems that can access patient information critical for TDM dose calculation, and reimbursement issues.Conclusion: This study, the first nationwide survey addressing these questions, showed that there are barriers against the utilization of TDM in South Korea. These barriers may be addressed by improving drug assays and TDM consulting services with the goals of new analytical method development, better interpretation of results, consultation services, and quality control.Keywords: questionnaire, TDM service, TDM consulting, point-of-care

Background: Healthcare 4.0. refers to the integration of advanced technologies, such as artificial intelligence (AI) and big data analysis, into the healthcare sector. Recognizing the impact of Healthcare 4.0 technologies in laboratory medicine (LM), we seek to assess the overall awareness and implementation of Healthcare 4.0 among members of the Korean Society for Laboratory Medicine (KSLM)., Methods: A web-based survey was conducted using an anonymous questionnaire. The survey comprised 36 questions covering demographic information (seven questions), big data (10 questions), and AI (19 questions)., Results: In total, 182 (17.9%) of 1,017 KSLM members participated in the survey. Thirty-two percent of respondents considered AI to be the most important technology in LM in the era of Healthcare 4.0, closely followed by 31% who favored big data. Approximately 80% of respondents were familiar with big data but had not conducted research using it, and 71% were willing to participate in future big data research conducted by the KSLM. Respondents viewed AI as the most valuable tool in molecular genetics within various divisions. More than half of the respondents were open to the notion of using AI as assistance rather than a complete replacement for their roles., Conclusions: This survey highlighted KSLM members' awareness of the potential applications and implications of big data and AI. We emphasize the complexity of AI integration in healthcare, citing technical and ethical challenges leading to diverse opinions on its impact on employment and training. This highlights the need for a holistic approach to adopting new technologies.

Spinal cord injury (SCI) pathology and pathophysiology can be attributed to both primary physical injury and secondary injury cascades. Secondary injury cascades involve dysregulated metabolism and energetic deficits directly linked to compromised mitochondrial bioenergetics. Rescuing mitochondrial function and reducing oxidative stress are associated with neuroprotection. In this regard, ketosis after traumatic brain injury (TBI), or after SCI, improves secondary neuropathology by decreasing oxidative stress, increasing antioxidants, reducing inflammation, and improving mitochondrial bioenergetics. Here, we follow up on our previous study and have used an exogenous ketone monoester, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE), as an alternative to a ketogenic diet, focusing on mitochondrial function between 1 and 14 days after injury. Starting 3 h following a cervical level 5 (C5) hemi-contusion injury, animals were fed either a standard control diet (SD) or a ketone ester diet (KED) combined with KE administered orally (OKE). We found that mitochondrial function was reduced after SCI at all times post-SCI, accompanied by reduced expression of most of the components of the electron transport chain (ETC). The KE rescued some of the bioenergetic parameters 1 day after SCI when D-β-Hydroxybutyrate (BHB) concentrations were ~2 mM. Still, most of the beneficial effects were observed 14 days after injury, with BHB concentrations reaching values of 4-6 mM. To our knowledge, this is the first report to show the beneficial effects of KE in rescuing mitochondrial function after SCI and demonstrates the suitability of KE in ameliorating the metabolic dysregulation that occurs after traumatic SCI without requiring a restrictive dietary regime.

Bacteria belonging to the order Fimbriimonadales are frequently detected in anammox reactors. However, the principal functions of these bacteria and their potential contribution to nitrogen removal remain unclear. In this study, we aimed to systematically validate the roles of Fimbriimonadales in an anammox reactor fed with synthetic wastewater. High-throughput 16S rRNA gene sequencing analysis revealed that heterotrophic denitrifying bacteria (HDB) were the most abundant bacterial group at the initial stage of reactor operation and the abundance of Fimbriimonadales members gradually increased to reach 38.8 % (day 196). At the end of reactor operation, Fimbriimonadales decreased to 0.9 % with an increase in anammox bacteria. Correlation analysis demonstrated nitrate competition between Fimbriimonadales and HDB during reactor operation. Based on the phylogenetic analysis, the Fimbriimonadales sequences acquired from the reactor were clustered into three distinct groups, which included the sequences obtained from other anammox reactors. Metagenome-assembled genome analysis of Fimbriimonadales allowed the identification of the genes narGHI and nrfAH, responsible for dissimilatory nitrate reduction to ammonium (DNRA), and nrt and nasA, responsible for nitrate and nitrite transport. In a simulation based on mass balance equations and quantified bacterial groups, the total nitrogen concentrations in the effluent were best predicted when Fimbriimonadales was assumed to perform DNRA (R 2 = 0.70 and RMSE = 18.9). Moreover, mass balance analysis demonstrated the potential contribution of DNRA in enriching anammox bacteria and promoting nitrogen removal. These results prove that Fimbriimonadales compete with HDB for nitrate utilization through DNRA in the anammox reactor under non-exogenous carbon supply conditions. Overall, our findings suggest that the DNRA pathway in Fimbriimonadales could enhance anammox enrichment and nitrogen removal by providing substrates (nitrite and/or ammonium) for anammox bacteria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Heterotrophic microorganisms are frequently observed in hydrogenotrophic denitrification systems and are presumed to contribute to their improved performance. However, their roles and metabolic pathways in the hydrogen-based membrane biofilm reactor (H 2- MBfR) system remain unclear. The objective of this study was to elucidate the underlying mechanisms driving heterotrophic denitrification. For this purpose, metagenomic analysis was conducted on an H 2- MBfR showing higher denitrification performance, focusing on the metabolic function of the microbial community. Functional genes related to H 2 oxidation, organic carbon metabolism, and denitrification were the major targets of interest. This analysis revealed a substantial number of genes associated with the oxidation of organic carbon compounds in the biofilm, suggesting its potential for heterotrophic denitrification. Investigation of the genes of interest in metagenome-assembled genomes (MAGs) has demonstrated a predominance of mixotrophs or heterotrophs rather than obligate autotrophs. Notably, MAGs exhibiting the highest abundance of genes of interest were affiliated with Hydrogenophaga and Thauera, implying their significant role in denitrifying the H 2- MBfR as mixotrophs utilizing both H 2 and organic substrates. The identification of 11 MAGs, presumed to originate from homoacetogens suggested that acetate might contribute to the proliferation of heterotrophs. Based on these metagenomic findings, possible metabolic pathways were identified to explain heterotrophic denitrification within the H 2- MBfR biofilms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hair growth cycles are mainly regulated by human dermal papilla cells (hDPCs) and human outer root sheath cells (hORSCs). Protecting hDPCs from excessive oxidative stress and hORSCs from glycogen phosphorylase (PYGL) is crucial to maintaining the hair growth phase, anagen. In this study, we developed a new PYGL inhibitor, Hydroxytrimethylpyridinyl Methylindolecarboxamide (HTPI) and assessed its potential to prevent hair loss. HTPI reduced oxidative damage, preventing cell death and restored decreased level of anagen marker ALP and its related genes induced by hydrogen peroxide in hDPCs. Moreover, HTPI inhibited glycogen degradation and induced cell survival under glucose starvation in hORSCs. In ex-vivo culture, HTPI significantly enhanced hair growth compared to the control with minoxidil showing comparable results. Overall, these findings suggest that HTPI has significant potential as a therapeutic agent for the prevention and treatment of hair loss.

Krabbe disease (KD) is an autosomal recessive neurodegenerative disorder caused by deficiency of the galactocerebrosidase (GALC) due to variants in the GALC gene. Here, we provide the first and the largest comprehensive analysis of clinical and genetic characteristics, and genotype-phenotype correlations of KD in Korean in comparison with other ethnic groups. From June 2010 to June 2023, 10 patients were diagnosed with KD through sequencing of GALC. Clinical features, and results of GALC sequencing, biochemical test, neuroimaging, and neurophysiologic test were obtained from medical records. An additional nine previously reported Korean KD patients were included for review. In Korean KD patients, the median age of onset was 2 years (3 months-34 years) and the most common phenotype was adult-onset (33%, 6/18) KD, followed by infantile KD (28%, 5/18). The most frequent variants were c.683_694delinsCTC (23%) and c.1901T>C (23%), while the 30-kb deletion was absent. Having two heterozygous pathogenic missense variants was associated with later-onset phenotype. Clinical features were similar to those of other ethnic groups. In Korean KD patients, the most common phenotype was the adult-onset type and the GALC variant spectrum was different from that of the Caucasian population. This study would further our understanding of KD., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Inflammatory bowel disease (IBD) is characterized by abnormal immune responses, including elevated proinflammatory cytokines, such as tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) in the gastrointestinal (GI) tract. This study presents the synthesis and anti-inflammatory evaluation of 2,4,5-trimethylpyridin-3-ol analogues, which exhibit dual inhibition of TNFα- and IL-6-induced inflammation. Analysis using in silico methods, including 3D shape-based target identification, modeling, and docking, identified G protein-coupled estrogen receptor 1 (GPER) as the molecular target for the most effective analogue, 6 - 26 , which exhibits remarkable efficacy in ameliorating inflammation and restoring colonic mucosal integrity. This was further validated by surface plasmon resonance (SPR) assay results, which showed direct binding to GPER, and by the results showing that GPER knockdown abolished the inhibitory effects of 6 - 26 on TNFα and IL-6 actions. Notably, 6 - 26 displayed no cytotoxicity, unlike G1 and G15, a well-known GPER agonist and an antagonist, respectively, which induced necroptosis independently of GPER. These findings suggest that the GPER-selective compound 6 - 26 holds promise as a therapeutic candidate for IBD.

Prostaglandin E 2 (PGE 2 ) is known to be effective in regenerating tissues, and bimatoprost, an analog of PGF 2α , has been approved by the FDA as an eyelash growth promoter and has been proven effective in human hair follicles. Thus, to enhance PGE 2 levels while improving hair loss, we found dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), using DeepZema ® , an AI-based drug development program. Here, we investigated whether DPP improved hair loss in human follicle dermal papilla cells (HFDPCs) damaged by dihydrotestosterone (DHT), which causes hair loss. We found that DPP enhanced wound healing and the expression level of alkaline phosphatase in DHT-damaged HFDPCs. We observed that DPP significantly down-regulated the generation of reactive oxygen species caused by DHT. DPP recovered the mitochondrial membrane potential in DHT-damaged HFDPCs. We demonstrated that DPP significantly increased the phosphorylation levels of the AKT/ERK and activated Wnt signaling pathways in DHT-damaged HFDPCs. We also revealed that DPP significantly enhanced the size of the three-dimensional spheroid in DHT-damaged HFDPCs and increased hair growth in ex vivo human hair follicle organ culture. These data suggest that DPP exhibits beneficial effects on DHT-damaged HFDPCs and can be utilized as a promising agent for improving hair loss.

Here, we aimed to isolate an acetic acid bacterium that is suitable for the production of unripe Citrus unshiu vinegar from traditional fermented vinegars. We compared the halo sizes of isolates to select a strain with superior acetic acid production capabilities and selected Komagataeibacter kakiaceti P6 (P6) as the final strain. Using Acetobacter pasteurianus CY (CY) and A. pasteurianus KACC 17058 (KACC 17058) as controls, we analyzed the total phenolic compounds, total flavonoid content, antioxidant activities, and organic acids of the selected strain to verify its suitability for acetic acid fermentation. On the 30th day of the fermentation period, P6 showed a total acidity of 4.86%, which was higher than that of control groups (CY, 4.16%; KACC 17058, 4.01%). The total phenolic compounds, total flavonoid content, 1,1-diphenyl-2-picrylhydrazyl scavenging activity, and ferric ion reducing antioxidant power values significantly increased during fermentation with P6 compared with the initial C. unshiu wine, and no significant differences were observed from the vinegars produced by CY and KACC 17058. Moreover, organic acid analysis revealed that the unripe C. unshiu vinegar produced with P6 had an acetic acid content of 26.15 mg/mL, which was significantly higher than those produced with CY and KACC 17058, indicating that the P6 strain effectively produces acetic acid without adversely affecting other quality aspects during fermentation. In conclusion, the novel P6 strain is expected to be used as a starter for fermenting unripe C. unshiu vinegar, and its excellent acetic acid production capabilities suggest potential applications for other vinegars., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest., (Copyright © 2024 by The Korean Society of Food Science and Nutrition.)

Until now, bacteria able to degrade, 3,3'-iminodipropionitrile (IDPN), a neurotoxin that destroys vestibular hair cells, causing ototoxicity, culminating in irreversible movement disorders, had never been isolated. The aim of this study was to isolate a novel IDPN-biodegrading microorganism and characterize its metabolic pathway. Enrichment was performed by inoculating activated sludge from a wastewater treatment bioreactor that treated IDPN-contaminated wastewater in M9 salt medium, with IDPN as the sole carbon source. A bacterial strain with a spherical morphology that could grow at high concentrations was isolated on a solid medium. Growth of the isolated strain followed the Monod kinetic model. Based on the 16S rRNA gene, the isolate was Paracoccus communis. Whole-genome sequencing revealed that the isolated P. communis possessed the expected full metabolic pathway for IDPN biodegradation. Transcriptome analyses confirmed the overexpression of the gene encoding hydantoinase/oxoprolinase during the exponential growth phase under IDPN-fed conditions, suggesting that the enzyme involved in cleaving the imine bond of IDPN may promote IDPN biodegradation. Additionally, the newly discovered P. communis isolate seems to metabolize IDPN through cleavage of the imine bond in IDPN via nitrilase, nitrile hydratase, and amidase reactions. Overall, this study lays the foundation for the application of IDPN-metabolizing bacteria in the remediation of IDPN-contaminated environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: This study evaluates the HYDRASHIFT assay's effectiveness in mitigating daratumumab interference on serum protein tests during multiple myeloma (MM) treatment, aiming to ensure an accurate assessment of treatment response., Methods: We analyzed 113 serum samples from 68 MM patients undergoing daratumumab treatment, employing both standard IF and the HYDRASHIFT assay. The assay's precision was determined through intra-day and inter-day variability assessments, while its specificity was verified using serum samples devoid of daratumumab. Comparative analysis of IF results, before and after the application of the HYDRASHIFT assay, facilitated the categorization of treatment responses in alignment with the International Myeloma Working Group's response criteria., Results: The precision underscored the assay's consistent repeatability and reproducibility, successfully eliminating interference of daratumumab-induced Gκ bands. Specificity assessments demonstrated the assay's capability to distinguish daratumumab from both isatuximab and naturally occurring M-proteins. Of the analyzed cases, 91 exhibited successful migration of daratumumab-induced Gκ bands, thereby enhancing the accuracy of treatment response classification. The remaining 22 cases did not show a visible migration complex, likely due to the low concentration of daratumumab in the serum. These findings underscore the assay's critical role in distinguishing daratumumab from endogenous M-protein, particularly in samples with a single Gκ band on standard IF, where daratumumab and endogenous M-protein had co-migrated., Conclusions: The HYDRASHIFT assay demonstrates high precision, specificity, and utility in the accurate monitoring of treatment responses in MM patients receiving daratumumab. This assay represents a significant advancement in overcoming the diagnostic challenges posed by daratumumab interference., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Grid cells in the entorhinal cortex (EC) encode an individual's location in space, integrating both environmental and multisensory bodily cues. Notably, body-derived signals are also primary signals for the sense of self. While studies have demonstrated that continuous application of visuo-tactile bodily stimuli can induce perceptual shifts in self-location, it remains unexplored whether these illusory changes suffice to trigger grid cell-like representation (GCLR) within the EC, and how this compares to GCLR during conventional virtual navigation. To address this, we systematically induced illusory drifts in self-location toward controlled directions using visuo-tactile bodily stimulation, while maintaining the subjects' visual viewpoint fixed (absent conventional virtual navigation). Subsequently, we evaluated the corresponding GCLR in the EC through functional MRI analysis. Our results reveal that illusory changes in perceived self-location (independent of changes in environmental navigation cues) can indeed evoke entorhinal GCLR, correlating in strength with the magnitude of perceived self-location, and characterized by similar grid orientation as during conventional virtual navigation in the same virtual room. These data demonstrate that the same grid-like representation is recruited when navigating based on environmental, mainly visual cues, or when experiencing illusory forward drifts in self-location, driven by perceptual multisensory bodily cues., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Adenosine deaminase (ADA) is a useful biomarker for the diagnosis of tuberculous pleurisy (TBP). However, pleural effusions with high ADA can also be caused by other diseases, particularly hematologic malignant pleural effusion (hMPE). This study aimed to investigate the features that could differentiate TBP and hMPE in patients with pleural effusion ADA ≥ 40 IU/L., Methods: This was a retrospective observational study of patients with pleural effusion ADA ≥ 40 IU/L, conducted at a Korean tertiary referral hospital with an intermediate tuberculosis burden between January 2010 and December 2017. Multivariable logistic regression analyses were performed to investigate the features associated with TBP and hMPE, respectively., Results: Among 1134 patients with ADA ≥ 40 IU/L, 375 (33.1%) and 85 (7.5%) were diagnosed with TBP and hMPE, respectively. TBP and hMPE accounted for 59% (257/433) and 6% (27/433) in patients with ADA between 70 and 150 IU/L, respectively. However, in patients with ADA ≥ 150 IU/L, they accounted for 7% (9/123) and 19% (23/123), respectively. When ADA between 40 and 70 IU/L was the reference category, ADA between 70 and 150 IU/L was independently associated with TBP (adjusted odds ratio [aOR], 3.11; 95% confidence interval [CI], 1.95-4.95; P < 0.001). ADA ≥ 150 IU/L was negatively associated with TBP (aOR, 0.35; 95% CI, 0.14-0.90; P = 0.029) and positively associated with hMPE (aOR, 13.21; 95% CI, 5.67-30.79; P < 0.001). In addition, TBP was independently associated with lymphocytes ≥ 35% and a lactate dehydrogenase (LD)/ADA ratio < 18 in pleural effusion. hMPE was independently associated with pleural polymorphonuclear neutrophils < 50%, thrombocytopenia, and higher serum LD. A combination of lymphocytes ≥ 35%, LD/ADA < 18, and ADA < 150 IU/L demonstrated a sensitivity of 0.824 and specificity of 0.937 for predicting TBP., Conclusion: In patients with very high levels of pleural effusion ADA, hMPE should be considered. Several features in pleural effusion and serum may help to more effectively differentiate TBP from hMPE., (© 2023. The Author(s).)

Biofouling, caused by microbial biofilm formation on the membrane surface and in pores, is a major operational problem in membrane bioreactors (MBR). Many quorum quenching (QQ) bacteria have been isolated and applied to MBR to reduce biofouling. However, for more effective MBR biofouling control, novel approaches for isolating QQ bacteria and applying them in MBR are needed. Therefore, Listeria grayi (HEMM-2) was isolated using a mixture of different N-acyl homoserine lactones (AHLs). HEMM-2 degraded various AHLs, regardless of the length and oxo group in the carbon chain, with quorum sensing (QS) inhibition ratios of 47-61%. This QQ activity was attributed to extracellular substances in HEMM-2 cell-free supernatant (CFS). Furthermore, the HEMM-2 CFS negatively regulated QS-related gene expression, inhibiting Pseudomonas aeruginosa and activated sludge-biofilm formation by 53-75%. Surprisingly, when the HEMM-2 CFS was directly injected into a laboratory-scale MBR system, biofouling was not significantly affected. Biofouling was only controlled by cell suspension (CS) of HEMM-2, indicating the importance of QQ bacteria in MBR. The HEMM-2 CS increased operation time to reach 0.4 bar, a threshold transmembrane pressure for complete biofouling, from 315 h to 371 h. Taken together, HEMM-2, which is effective in the degradation of various AHLs, and its applicable method to MBR may be considered a potent approach for controlling biofouling and understanding the behavior of QQ bacteria in MBR systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Chemokine-like receptor 1 (CMKLR1)─a G protein-coupled receptor─has functional roles in the immune system and related diseases, including psoriasis and metabolic diseases. Psoriasis is a chronic inflammatory disease characterized by skin redness, scaliness, and itching. In this study, we sought to develop novel CMKLR1 antagonists by screening our in-house GPCR-targeting compound library. Moreover, we optimized a phenylindazole-based hit compound with antagonistic activities and evaluated its oral pharmacokinetic properties in a murine model. A structure-based design on the human CMKLR1 homology model identified S - 26d as an optimized compound that serves as a potent and orally available antagonist with a pIC 50 value of 7.44 in h CMKLR1-transfected CHO cells. Furthermore, in the imiquimod-induced psoriasis-like mouse model, oral administration of S - 26d for 1 week significantly alleviated modified psoriasis area and severity index scores (severity of erythema, scaliness, skin thickness) compared with the control group.

Background: Serum cystatin C (cysC), which is less affected by sex, race, and muscle mass than creatinine, is a useful biomarker of the estimated glomerular filtration rate (eGFR). The standardization of cysC measurements remains controversial, although a certified reference material (ERM-DA471/IFCC) is available. Moreover, the effect of combinations of cysC reagents and equations for eGFR is unclear., Methods: We conducted a simulation analysis of cysC measured using two reagents standardized against ERM-DA471/IFCC-Gentian cystatin C immunoassay (Gentian cys ; GentianAS, Moss, Norway) and Roche Tina-quant Cystatin C Gen.2 (Roche cys ; Roche, Mannheim, Germany)-on a Cobas c702 system (Roche) and eGFR generated by eight combinations of four equations: 2012 cystatin C-based Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI cys ); the Caucasian, Asian, pediatric, and adult equation (CAPA eq ); full age spectrum equation (FAS eq ); and 2023 cystatin C-based European Kidney Function Consortium equation (EKFC cys )., Results: A total of 148 participants (mean age, 60.5±14.5 years; 43% female) were enrolled. The mean cysC was 1.72±1.44 mg/L for Gentian cys and 1.71±1.35 mg/L for Roche cys . Regression analysis showed concordance between the reagents within 0.85-4.40 mg/L when using ±7.61% total allowable error. Lin's concordance correlation coefficient of eGFR, by combining the measuring system and equation, varied from 0.73 to 1.00., Conclusions: The equivalence of cysC values at low concentrations (<0.85 mg/L) between the two reagents was unsatisfactory. Results obtained with different measurement systems could lead to larger differences in eGFR varying with the combination.

The coronavirus disease 2019 pandemic has posed a significant threat not only to health outcomes but also to other societal sectors, including the educational system. Apart from youth education, colleges and universities are characterized by the integration of in-depth theoretical and practical knowledge in young adulthood. Our observations in this study suggest that college fairs, sports matches, and extracurricular activities can be safely resumed when population-level immunity has reached herd protection., Competing Interests: No conflict of interest, (Copyright © 2023 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Background: To ensure valid results of big data research in the medical field, the input laboratory results need to be of high quality. We aimed to establish a strategy for evaluating the quality of laboratory results suitable for big data research., Methods: We used Korean Association of External Quality Assessment Service (KEQAS) data to retrospectively review multicenter data. Seven measurands were analyzed using commutable materials: HbA1c, creatinine (Cr), total cholesterol (TC), triglyceride (TG), alpha-fetoprotein (AFP), prostate-specific antigen (PSA), and cardiac troponin I (cTnI). These were classified into three groups based on their standardization or harmonization status. HbA1c, Cr, TC, TG, and AFP were analyzed with respect to peer group values. PSA and cTnI were analyzed in separate peer groups according to the calibrator type and manufacturer, respectively. The acceptance rate and absolute percentage bias at the medical decision level were calculated based on biological variation criteria., Results: The acceptance rate (22.5%-100%) varied greatly among the test items, and the mean percentage biases were 0.6%-5.6%, 1.0%-9.6%, and 1.6%-11.3% for all items that satisfied optimum, desirable, and minimum criteria, respectively., Conclusions: The acceptance rate of participants and their external quality assessment (EQA) results exhibited statistically significant differences according to the quality grade for each criterion. Even when they passed the EQA standards, the test results did not guarantee the quality requirements for big data. We suggest that the KEQAS classification can serve as a guide for building big data.

Although detection of gram-negative bacteria (GNB) in body fluids is important for clinical purpose, traditional gram staining and other recently developed methods have inherent limitations in terms of accuracy, sensitivity, and convenience. To overcome the weakness, this study proposed a method detecting GNB based on specific binding of polymyxin B (PMB) to lipopolysaccharides (LPS) of GNB. Fluorescent microscopy demonstrated that surface immobilized PMB using a silane coupling agent was possible to detect fluorescent signal produced by a single Escherichia coli (a model GNB) cell. Furthermore, the signal was selective enough to differentiate between GNB and gram-positive bacteria. The proposed method could detect three cells per ml within one hour, indicating the method was very sensitive and the sensing was rapid. These results suggest that highly multifold PMB binding on each GNB cell occurred, as millions of LPS are present on cell wall of a GNB cell. Importantly, the principle used in this study was realized in a microfluidic chip for a sample containing E. coli cells suspended in porcine plasma, demonstrating its potential application to practical uses. In conclusion, the proposed method was accurate, sensitive, and convenient for detecting GNB, and could be applied clinically., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The risk of acute kidney injury (AKI) after liver transplantation was lower in patients with serum albumin levels ≥3.0 mg/dL during surgery. We tested whether intraoperative infusion of 20% albumin affects neutrophil gelatinase-associated lipocalin (NGAL) level, a reliable indicator of AKI. We randomly assigned 134 patients undergoing liver transplantation into albumin group (n=70, 20% albumin 200 mL) and the control group (n=66, crystalloid solution 200 mL). The 2 study fluids were infused at 100 mL/h from the start of the anhepatic phase. The primary outcome was plasma NGAL level at 1 hour after graft reperfusion. Albumin level at the start of graft reperfusion was significantly greater in albumin group than in the control group [2.9 (2.4-3.3) g/dL vs. 2.3 (2.0-2.7) g/dL, p <0.001]. The NGAL level at 1 hour after graft reperfusion was not significantly different between the 2 groups [100.2 (66.7-138.8) ng/mL vs. 92.9 (70.8-120.6) ng/mL, p =0.46], and the AKI risk was not either (63.9% vs. 67.8%, adjusted p =0.73). There were no significant differences between the 2 groups regarding hospital readmission within 30 days/90 days after transplantation (32.6% vs. 41.5%, adjusted p =0.19 and 55.0% vs. 55.7%, adjusted p =0.87). Graft survival probability at 30 days/90 days/1 year after transplantation was 90.0%/84.3%/78.6% in albumin group and 97.0%/90.9%/89.4% in the control group [HR=1.6 (0.6-4.0), adjusted p =0.31]. In conclusion, intraoperative infusion of 20% albumin 200 mL increased the albumin level but failed to maintain serum albumin ≥3.0 mg/dL during surgery. The hypertonic albumin therapy did not significantly affect plasma NGAL level and clinical outcomes including AKI., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: Medications influencing the risk of fall-related injuries (FRIs) in older adults have been inconsistent in previous guidelines. This study employed case-control design to assess the association between FRIs and medications, and an additional case-crossover design was conducted to examine the consistency of the associations and the transient effects of the medications on FRIs., Methods: This study was conducted using a national claims database (2002-2015) in Korea. Older adults (≥ 65 years) who had their first FRI between 2007 and 2015 were matched with non-cases in 1:2 ratio. Drug exposure was examined for 60 days prior to the date of the first FRI (index date) in the case-control design. The hazard period (1-60 days) and two control periods (121-180 and 181-240 days prior to the index date) were investigated in the case-crossover design. The risk of FRIs with 32 medications was examined using conditional logistic regression after adjusting for other medications that were significant in the univariate analysis. In the case-crossover study, the same conditional model was applied., Results: In the case-control design, the five medications associated with the highest risk of FRIs were muscle relaxants (adjusted odd ratio(AOR) = 1.35, 95% confidence interval (CI) = 1.31-1.39), anti-Parkinson agents (AOR = 1.30, 95%CI = 1.19-1.40), opioids (AOR = 1.23, 95%CI = 1.19-1.27), antiepileptics (AOR = 1.19, 95%CI = 1.12-1.26), and antipsychotics (AOR = 1.16, 95%CI = 1.06-1.27). In the case-crossover design, the five medications associated with the highest risk of FRIs were angiotensin II antagonists (AOR = 1.87, 95%CI = 1.77-1.97), antipsychotics (AOR = 1.63, 95%CI = 1.42-1.83), anti-Parkinson agents (AOR = 1.58, 95%CI = 1.32-1.85), muscle relaxants (AOR = 1.42, 95%CI = 1.35-1.48), and opioids (AOR = 1.35, 95%CI = 1.30-1.39)., Conclusions: Anti-Parkinson agents, opioids, antiepileptics, antipsychotics, antidepressants, hypnotics and sedatives, anxiolytics, muscle relaxants, and NSAIDs/antirheumatic agents increased the risk of FRIs in both designs among older adults. Medications with a significant risk only in the case-crossover analysis, such as antithrombotic agents, calcium channel blockers, angiotensin II antagonists, lipid modifying agents, and benign prostatic hypertrophy agents, may have transient effects on FRIs at the time of initiation. Corticosteroids, which were only associated with risk of FRIs in the case-control analysis, had more of cumulative than transient effects on FRIs., (© 2023. The Author(s).)

Cystinuria is a genetic disorder caused by defects in the b 0,+ transporter system, which is composed of rBAT and b 0,+ AT coded by SLC3A1 and SLC7A9, respectively. Variants in SLC3A1 and SLC7A9 follow autosomal recessive inheritance and autosomal dominant inheritance with reduced penetrance, respectively, which complicates the interpretation of cystinuria-related variants. Here, we report seven different SLC3A1 variants and six different SLC7A9 variants. Among these variants were two novel variants previously not reported: SLC3A1 c.223C > T and SLC7A9 c.404A > G. In silico analysis using REVEL correlated well with the functional loss upon SLC7A9 variants with scores of 0.8560-0.9200 and 0.4970-0.5239 for severe and mild decrease in transport activity, respectively. In addition, DynaMut2 was able to predict a decreased protein expression level resulting from the SLC7A9 variant c.313G > A with a ΔΔG Stability -2.93 kcal/mol. Our study adds to the literature as additional cases of a variant allow applying the PM3 criterion with higher strength level. In addition, we suggest the clinical utility of REVEL and DynaMut2 in interpreting SLC3A1 and SLC7A9 variants. While a decreased protein expression level is not embraced in the current variant interpretation guidelines, we believe in silico protein stability predicting tools could serve as evidence of protein function loss., (© 2023. The Author(s).)

Global navigation satellite systems (GNSSs) provide a common positioning method that utilizes satellite signals to determine the spatial location of a receiver. However, there are several error factors in standalone GNSS positioning due to instrumental, procedural, and environmental factors that arise during the signal transmission process, and the final positioning error can be up to several meters or greater in length. Thus, real-time kinematic (RTK) correction and post-mission precise point positioning (PPP) processing technologies are proposed to improve accuracy and accomplish precise position measurements. To evaluate the geolocation accuracy of mosaicked UAV images of an abandoned mine site, we compared each orthomosaic image and digital elevation model obtained using standalone GNSS positioning, differential (RTK) GNSS positioning, and post-mission PPP processing techniques. In the three types of error evaluation measure (i.e., relative camera location error, ground control points-based absolute image mapping error, and volumetric difference of mine tailings), we found that the RTK GNSS positioning method obtained the best performance in terms of the relative camera location error and the absolute image mapping error evaluations, and the PPP post-processing correction effectively reduced the error (69.5% of the average total relative camera location error and 59.3% of the average total absolute image mapping error) relative to the standalone GNSS positioning method. Although differential (RTK) GNSS positioning is widely used in positioning applications that require very high accuracy, post-mission PPP processing can also be used in various fields in which it is either not feasible to operate expensive equipment to receive RTK GNSS signals or network RTK services are unavailable.

Biofilms consist of single or multiple species of bacteria embedded in extracellular polymeric substances (EPSs), which affect the increase in antibiotic resistance by restricting the transport of antibiotics to the bacterial cells. An alternative approach to treatment with antimicrobial agents is using biofilm inhibitors that regulate biofilm development without inhibiting bacterial growth. In this study, we found that citrus peel extract from Jeju Island (CPEJ) can inhibit bacterial biofilm formation. According to the results, CPEJ concentration-dependently reduces biofilm formation without affecting bacterial growth. Additionally, CPEJ decreased the production of extracellular polymeric substances but increased bacterial swarming motility. These results led to the hypothesis that CPEJ can reduce intracellular bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) concentration. The results showed that CPEJ significantly reduced the c-di-GMP level through increased phosphodiesterase activity. Altogether, these findings suggest that CPEJ as a biofilm inhibitor has new potential for pharmacological (e.g. drug and medication) and industrial applications (e.g. ship hulls, water pipes, and membrane processes biofouling control)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We characterized the potential functioning and composition of the bacterial and fungal communities in the O and A horizons of forest soils using community-level physiological profile (CLPP) based on BIOLOG analysis, and polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis of 16S and 18S rDNA fragments, respectively. In addition, relationships between the potential functioning and the community composition in each horizon, and between the O and A horizons, were assessed using Procrustes analysis. For the bacterial and fungal communities, the CLPP and DGGE profile were clearly separated between the O and A horizons in a principal coordinate analysis except for the fungal CLPP. No significant links for CLPP and DGGE profile between the O and A horizons were observed for either bacterial or fungal communities, suggesting that different factors had considerable influence on the microbial communities between the O and A horizons. Significant couplings between bacterial and fungal DGGE profiles (p <0.05 for O horizon; p <0.01 for A horizon), and between bacterial and fungal CLPPs (p = 0.001 for O horizon; p <0.01 for A horizon), were observed in the O and A horizons, implying that common factors strongly influenced the bacterial and fungal communities in each horizon. Although a significant correlation was observed between bacterial community composition and the potential functioning in the A horizon (p <0.01), such a correlation was not observed for the fungal community in the A horizon, and for the bacterial and fungal communities in the O horizon. This finding suggested that potential functioning, which would reflect only rapidly growing microorganisms, was not strongly associated with the composition of the entire microbial community. Further studies are needed to unravel the factors shaping the composition and functioning of microbial communities in forest soils., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kunito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In a hydrogen-based membrane biofilm reactor (H 2 -MBfR), the biofilm thickness is considered to be one of the most important factors for denitrification. Thick biofilms in MBfRs are known for low removal fluxes owing to their resistance to substrate transport. In this study, the H 2 -MBfR was operated under various loading rates of oxyanions, such as NO 3 -N, SO 4 -S, and ClO 4 - at an H 2 flux of 1.06 e - eq/m 2 -d. The experiment was initiated with NO 3 -N, SO 4 -S, and ClO 4 - loadings of 0.464, 0.026, and 0.211 e - eq/m 2 -d, respectively, at 20 °C. Under the most stressful conditions, the loading rates increased simultaneously to 1.911, 0.869, and 0.108 e - eq/m 2 -d, respectively, at 10 °C. We observed improved performance in significantly thicker biofilms (approximately 2.7 cm) compared to previous studies using a denitrifying H 2 -MBfR for 120 days. Shock oxyanion loadings led to a decrease in total nitrogen (TN) removal by 20 to 30%, but TN removal returned to 100% within a few days. Similarly, complete denitrification was observed, even at 10 °C. The protective function and microbial diversity of the thick biofilm may allow stable denitrification despite stress-imposing conditions. In the microbial community analysis, heterotrophs were dominant and acetogens accounted for 11% of the biofilm. Metagenomic results showed a high abundance of functional genes involved in organic carbon metabolism and homoacetogenesis. Owing to the presence of organic compounds produced by acetogens and autotrophs, heterotrophic denitrification may occur simultaneously with autotrophic denitrification. As a result, the total removal flux of oxyanions (1.84 e - eq/m 2 -d) far exceeded the H 2 flux (1.06 e - eq/m 2 -d). Thus, the large accumulation of biofilms could contribute to good resilience and enhanced removal fluxes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Despite the popularity of the NeoBase 2 Non-derivatized MSMS assay (PerkinElmer, Turku, Finland), there are no reports of its comprehensive evaluation, including the ability to distinguish transient tyrosinemia of the newborn (TTN) from tyrosinemia type 1 (TYR 1) using succinylacetone (SUAC). No newborn screening (NBS) cutoffs for preterm neonates in the Korean population have been suggested. We evaluated the NeoBase 2 assay and identified analytes requiring different cutoffs in preterm neonates., Methods: Residual NBS dried blood spot samples and proficiency testing (PT) materials of the Newborn Screening Quality Assurance Program and the Korean Association of External Quality Assessment Service were used. Precision, accuracy, limit of detection (LOD), lower limit of quantification (LLOQ), linearity, recovery, carryover, and performance of SUAC were evaluated. Cutoffs were determined, and analytes requiring different cutoffs in preterm neonates were investigated., Results: Mean CVs for within-run and between-day precision were within 15%. Accuracy analysis indicated high agreement with in-house derivatized assay results and results of other PT participants. All analytes demonstrated acceptable LOD, LLOQ, and linearity. Recoveries were acceptable, except for SUAC. Carryover was negligible. Cutoffs were established for all analytes; Tyr, adenosine, and C20:0-lysophosphatidylcholine required different cutoffs in preterm neonates. Differential diagnosis of TYR 1 and TTN was successful with simultaneous Tyr and SUAC measurement., Conclusions: The NeoBase 2 assay demonstrated satisfactory performance. The additional analytes provide a wider diagnostic coverage, and the simultaneous measurement of Tyr and SUAC is efficient in excluding TYR 1. The new cutoffs for preterm neonates may decrease false-positive rates, without compromising diagnostic sensitivity.

A novel series of aminotrimethylpyridinol and aminodimethylpyrimidinol derivatives were designed and synthesised for FGFR4 inhibitors. Structure-activity relationship on the FGFR4 inhibitory activity of the new compounds was clearly elucidated by an intensive molecular docking study. Anti-cancer activity of the compounds was evaluated using hepatocellular carcinoma (HCC) cell lines and a chick chorioallantoic membrane (CAM) tumour model. Compound 6O showed FGFR4 inhibitory activity over FGFR1 - 3. Compared to the positive control BLU9931, compound 6O exhibited at least 8 times higher FGFR4 selectivity. Strong anti-proliferative activity of compound 6O was observed against Hep3B, an HCC cell line which was a much more sensitive cell line to BLU9931. In vivo anti-tumour activity of compound 6O against Hep3B-xenografted CAM tumour model was almost similar to BLU9931. Overall, compound 6O , a novel derivative of aminodimethylpyrimidinol, was a selective FGFR4 kinase inhibitor blocking HCC tumour growth.

Backgruound: Thyroxine-binding globulin (TBG) is a major transporter protein for thyroid hormones. The serpin family A member 7 (SERPINA7) gene codes for TBG, and mutations of the SERPINA7 gene result in TBG deficiency. Although more than 40 mutations have been reported in several countries, only a few studies of TBG deficiency and SERPINA7 gene mutation have been performed in Korea. The aim of this study is to review the clinical presentations and laboratory findings of patients with TBG deficiency and to investigate the types of SERPINA7 gene mutation., Methods: Five unrelated Korean adults with TBG deficiency attending endocrinology clinic underwent SERPINA7 gene sequencing. Four patients harbored a SERPINA7 gene mutation. Serum thyroid hormones, anti-microsomal antibodies, and TBG were measured. Genomic DNA was extracted from whole blood. All exons and intron-exon boundaries of the TBG gene were amplified and sequencing was performed., Results: Two patients were heterozygous females, and the other two were hemizygous males. One heterozygous female had coexisting hypothyroidism. The other heterozygous female was erroneously prescribed levothyroxine at a local clinic. One hemizygous male harbored a novel mutation, p.Phe269Cysfs*18, which caused TBG partial deficiency. Three patients had the p.Leu372Phefs*23 mutation, which is known as TBG-complete deficiency Japan (TBG-CDJ) and was also presented in previous mutation analyses in Korea., Conclusion: This study presents four patients diagnosed with TBG deficiency and provides the results of SERPINA7 gene sequencing. One novel mutation, p.Phe269Cysfs*18, causing TBD-partial deficiency and three cases of TBG-CDJ were demonstrated. It is necessary to identify TBG deficiency to prevent improper treatment. Also, sequencing of the SERPINA7 gene would provide valuable information about the TBG variants in Korea.

Previous research has suggested that bodily signals from internal organs are associated with diverse cortical and subcortical processes involved in sensory-motor functions, beyond homeostatic reflexes. For instance, a recent study demonstrated that the preparation and execution of voluntary actions, as well as its underlying neural activity, are coupled with the breathing cycle. In the current study, we investigated whether such breathing-action coupling is limited to voluntary motor action or whether it is also present for mental actions not involving any overt bodily movement. To answer this question, we recorded electroencephalography (EEG), electromyography (EMG), and respiratory signals while participants were conducting a voluntary action paradigm including self-initiated motor execution (ME), motor imagery (MI), and visual imagery (VI) tasks. We observed that the voluntary initiation of ME, MI, and VI are similarly coupled with the respiration phase. In addition, EEG analysis revealed the existence of readiness potential (RP) waveforms in all three tasks (i.e., ME, MI, VI), as well as a coupling between the RP amplitude and the respiratory phase. Our findings show that the voluntary initiation of both imagined and overt action is coupled with respiration, and further suggest that the breathing system is involved in preparatory processes of voluntary action by contributing to the temporal decision of when to initiate the action plan, regardless of whether this culminates in overt movements., Competing Interests: Declaration of Competing Interest H.D.P., O.A.K. and O.B. are inventors on a provisional patent application PCT/IB2020/050858 (Title: Method and system for determining the intention of performing a voluntary action) held by the Swiss Federal Institute (EPFL). O.B. is cofounder and shareholder of Metaphysiks Engineering SA. O.B. is member of the board and shareholder of Mindmaze SA., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The production of polyethylene terephthalate (PET) has drastically increased in the past half-century, reaching 30 million tons every year. The accumulation of this recalcitrant waste now threatens diverse ecosystems. Despite efforts to recycle PET wastes, its rate of recycling remains limited, as the current PET downcycling is mostly unremunerative. To address this problem, PET bio-upcycling, which integrates microbial depolymerization of PET followed by repolymerization of PET-derived monomers into value-added products, has been suggested. This article critically reviews current understanding of microbial PET hydrolysis, the metabolic mechanisms involved in PET degradation, PET hydrolases, and their genetic improvement. Furthermore, this review includes the use of meta-omics approaches to search PET-degrading microbiomes, microbes, and putative hydrolases. The current development of biosynthetic technologies to convert PET-derived materials into value-added products is also comprehensively discussed. The integration of various depolymerization and repolymerization biotechnologies enhances the prospects of a circular economy using waste PET., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Direct interspecies electron transfer (DIET) is a syntrophic mechanism for electron transfer between exo- and endoelectrogens. Previous studies have demonstrated that methanogenesis performance was significantly improved via the DIET mechanism through conductive materials (CMs) under batch conditions with a single substrate, while that under continuous condition is still under investigation. To investigate how the DIET via CM on methanogenesis performance was changed in response to the different substrates (acetate versus glucose)-fed in continuous anaerobic bioreactors, continuous bioreactors were operated by cross-feeding with acetate and glucose. Acetate-fed conditions showed 0.40 day shorten lagtime, 1.88- and 1.22-folds higher methane production rate, and ultimate methane production than glucose-fed conditions, respectively. Burkholderiaceae- and Anaerolineaceae-related exo-electrogenic populations were enriched with low abundance of Geobacter species in batch reactors. Furthermore, influent substrates affected the distribution of the enriched populations. Taken together, the results suggested that different syntrophic associations contributed methane production by DIET in continuous bioreactors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Mucopolysaccharidosis type IVA (MPS IVA; Morquio syndrome type A) is an autosomal recessive disorder caused by defects in the lysosomal hydrolase N-acetylgalactosamine-6-sulfatase (GALNS) gene, leading to progressive systemic skeletal dysplasia. Early diagnosis and early intervention with enzyme replacement therapy are crucial for improving outcomes in these patients. However, a relatively high number of patients are genetically undiagnosed due to high allelic heterogeneity and the absence of robust functional evidence for most variants of the GALNS gene. Herein, we report a novel intronic variant identified with RNA analysis and an allele dropout (ADO) event caused by a common benign variant in the primer-binding site in a Korean boy with MPS IVA. A 28-month-old boy presented with pectus carinatum, kyphoscoliosis, and joint hypermobility with multiple skeletal dysplasia involving the vertebrae and hip joint. Total urinary glycosaminoglycans were elevated with a predominant keratan sulfate fraction, and GALNS (EC 3.1.6.4) activity was significantly decreased in leukocytes. Sanger sequencing was performed; however, only one heterozygous intronic variant with uncertain clinical significance, c.566+3A > T (p.(?)), was identified. As the patient exhibited clinical and biochemical features of MPS IVA, we conducted whole genome sequencing (WGS) of the patient and his family to clarify the molecular diagnosis. WGS revealed a compound heterozygous genotype, c.1019G > A (p.(Gly340Asp)) and c.566+3A > T (p.(?)), in the GALNS gene. On mRNA sequencing, c.566+3A > T, was confirmed to cause exon 5 skipping and a premature stop codon. With subsequent investigation, we discovered that the variant, c.1019G > A, was undetected on initial sequencing because of ADO due to a common benign variant (rs3859024:G > C) at the primer annealing location. We present a novel intronic variant with a splicing defect in the GALNS gene and suggest that clinicians review primer sequences in cases not diagnosed on Sanger sequencing before progressing to diagnostic steps such as WGS., (© 2022 John Wiley & Sons Ltd/University College London.)

Purpose: To find pharmacokinetic/pharmacodynamic parameters of vancomycin associated with the optimal outcome of severe infection due to Enterococcus species., Methods: We retrospectively reviewed enterococcal bacteremia cases treated with vancomycin from January 2015 to December 2020. The primary outcome was 30-day mortality. We calculated cutoff values of the ratio of vancomycin area under the concentration-time curve over 24 h to the minimum inhibitory concentration (AUC 24 /MIC) and trough concentration (C trough ) during the initial 72 h of treatment. The optimal cutoff value was determined using the Youden index. Binary variables created based on these cutoffs were further assessed using multivariable analysis., Results: A total of 65 patients were included. The majority (87.7%) had solid or hematologic malignancies. Thirty-day mortality and nephrotoxicity occurred in nine (13.4%) and 14 (21.5%) patients, respectively. Both vancomycin AUC 24 /MIC and C trough showed fair performance in predicting 30-day mortality (AUC of receiver-operator curve for AUC 24 /MIC, 0.712; 95% confidence interval [CI] 0.539-0.886; AUC for C trough , 0.760; 95% CI 0.627-0.892; pairwise AUC comparison: p = 0.570). C trough  ≥ 13.94 μg/mL, but not AUC 24 /MIC ≥ 504, had a significant association with 30-day mortality after adjusting for confounders (odds ratio, 8.40; 95% CI 1.60-86.62; p = 0.010)., Conclusion: Mean C trough  ≥ 13.94 μg/mL during the initial 72 h was associated with higher 30-day mortality in enterococcal bacteremia. Further studies are warranted to elucidate optimal pharmacokinetic targets for enterococcal bacteremia., (© 2022. The Author(s).)

Blood gas, electrolyte, glucose, and lactate level measurement have an immediate and critical impact on patient care. We evaluated the performance of i-SmartCare 10 (i-SENS Inc., Seoul, Korea) and conducted a method comparison study of five point-of-care (POC) analyzers with i-SmartCare 10 as the comparator, according to the CLSI guidelines. Ten analytes (pH, pCO 2 , pO 2 , Na + , K + , Cl - , iCa 2+ , glucose, lactate, and Hct) were tested on six analyzers: i-SmartCare 10, ABL90 FLEX PLUS (Radiometer Medical ApS, Copenhagen, Denmark), i-Stat (Abbott Point of Care Inc., Princeton, NJ, USA), RapidLab 1265 (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA), Stat Profile pHOx Ultra (Nova Biomedical, Waltham, MA, USA), and Gem Premier 5000 (Instrumentation Laboratory, Bedford, MA, USA). The total imprecision and linearity (r 2 >0.99) were excellent, except for a few analytes that narrowly escaped the preset criteria. Interference was noted for Na + in the presence of a high K + level and for iCa 2+ in the presence of high K + and Mg 2+ levels. Forty of 48 items demonstrated either a proportional or systematic difference in regression analysis; the relative mean difference (%) of 14/48 items escaped the allowable total error in the difference plot analysis. i-SmartCare 10 shows acceptable performance, and using a single POC blood gas analyzer is recommended for monitoring.

A growing number of studies have focused on identifying cognitive processes that are modulated by interoceptive signals, particularly in relation to the respiratory or cardiac cycle. Considering the fundamental role of interoception in bodily self-consciousness, we here investigated whether interoceptive signals also impact self-voice perception. We applied an interactive, robotic paradigm associated with somatic passivity (a bodily state characterized by illusory misattribution of self-generated touches to someone else) to investigate whether somatic passivity impacts self-voice perception as a function of concurrent interoceptive signals. Participants' breathing and heartbeat signals were recorded while they performed two self-voice tasks (self-other voice discrimination and loudness perception) and while simultaneously experiencing two robotic conditions (somatic passivity condition; control condition). Our data reveal that respiration, but not cardiac activity, affects self-voice perception: participants were better at discriminating self-voice from another person's voice during the inspiration phase of the respiration cycle. Moreover, breathing effects were prominent in participants experiencing somatic passivity and a different task with the same stimuli (i.e., judging the loudness and not identity of the voices) was unaffected by breathing. Combining interoception and voice perception with self-monitoring framework, these data extend findings on breathing-dependent changes in perception and cognition to self-related processing., (© 2022 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Streptococcus mutans is a representative biofilm-forming bacterium that causes dental caries through glucosyltransferase (GTF) activity. Glucans are synthesized from sucrose by GTFs and provide binding sites for S. mutans to adhere tightly to the tooth enamel. Therefore, if a novel compound that interferes with GTF function is developed, biofilm formation control in S. mutans would be possible. We discovered that raffinose, an oligosaccharide from natural products, strongly inhibited biofilm formation, GTF-related gene expression, and glucan production. Furthermore, biofilm inhibition on saliva-coated hydroxyapatite discs through the reduction of bacterial adhesion indicated the applicability of raffinose in oral health. These effects of raffinose appear to be due to its ability to modulate GTF activity in S. mutans. Hence, raffinose may be considered an antibiofilm agent for use as a substance for oral supplies and dental materials to prevent dental caries. IMPORTANCE Dental caries is the most prevalent infectious disease and is expensive to manage. Dental biofilms can be eliminated via mechanical treatment or inhibited using antibiotics. However, bacteria that are not entirely removed or are resistant to antibiotics can still form biofilms. In this study, we found that raffinose inhibited biofilm formation by S. mutans, a causative agent of dental caries, possibly through binding to GtfC. Our findings support the notion that biofilm inhibition by raffinose can be exerted by interference with GTF function, compensating for the shortcomings of existing commercialized antibiofilm methods. Furthermore, raffinose is an ingredient derived from natural products and can be safely utilized in humans; it has no smell and tastes sweet. Therefore, raffinose, which can control S. mutans biofilm formation, has been suggested as a substance for oral supplies and dental materials to prevent dental caries.

Grid cells in entorhinal cortex (EC) encode an individual's location in space and rely on environmental cues and self-motion cues derived from the individual's body. Body-derived signals are also primary signals for the sense of self and based on integrated sensorimotor signals (proprioceptive, tactile, visual, motor) that have been shown to enhance self-centered processing. However, it is currently unknown whether such sensorimotor signals that modulate self-centered processing impact grid cells and spatial navigation. Integrating the online manipulation of bodily signals, to modulate self-centered processing, with a spatial navigation task and an fMRI measure to detect grid cell-like representation (GCLR) in humans, we report improved performance in spatial navigation and decreased GCLR in EC. This decrease in entorhinal GCLR was associated with an increase in retrosplenial cortex activity, which was correlated with participants' navigation performance. These data link self-centered processes during spatial navigation to entorhinal and retrosplenial activity and highlight the role of different bodily factors at play when navigating in VR., (© 2022. The Author(s).)

To apply the anammox processes into the mainstream of domestic wastewater treatment plants, two laboratory-scale sequence batch reactors have been developed and used with two different activated sludges seeded in each sequence batch reactors with gradually increases influent total nitrogen concentrations under low nitrogen loading rates. During 320 days of operation, both sequence batch reactors showed high specific anammox activity (0.68 - 0.75 kgN kg -1 VSS d -1 ) and a nitrogen removal efficiency of 97.50%. To monitor changes in microbial community dynamics during enrichment, high-throughput sequencing analysis was performed. Members taxonomically affiliated with Candidatus Jettenia were markedly enriched and predominant in both sequence batch reactors in response to the increasing influent total nitrogen concentrations. These results suggest that Candidatus Jettenia might be a prominent anammox genus under low nitrogen loading rate with high total nitrogen concentration conditions and could be suitably applied to the mainstream process of domestic wastewater treatment systems., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The Lake Suwa (Japan) has a history of non-N-fixing Microcystis blooms. Lake Kinneret (Israel) experienced multiannual periods of sole domination by the dinoflagellate Peridinium gatunense and periods dominated seasonally by P. gatunense or cyanobacteria. Extensive studies have been carried out in both lakes regarding the role of dissolved inorganic nitrogen and phosphorus as drivers of primary productivity. There is growing evidence that dissolved organic nitrogen (DON) compounds also influence not only biomass and structure of phytoplankton communities but also microcystin production. This study focuses on relationships of DON with: (1) population dynamics of Microcystis spp. and concentrations of microcystins in Lake Suwa, and (2) population dynamics of P. gatunense as well as N- and non-N-fixing cyanobacteria in Lake Kinneret. Modelling results for historical data of Lake Suwa by means of the hybrid evolutionary algorithm HEA revealed that the prediction of abundances of four Microcystis species and concentrations of cyanotoxins achieved higher coefficients of correlation when DON/DIN-ratios were included as drivers. Population dynamics of P. gatunense in Lake Kinneret appeared to have a strong inverse relationships with DON/DIN-ratios reflected by inferential models of HEA with higher coefficients of correlation when driven by DON/DIN-ratios. When DON/DIN-ratios were included as drivers, models of Microcystis spp. in Lake Kinneret performed higher coefficients of determination compared to models of N-fixing cyanobacteria. The study highlights the need to consider DON for improved understanding and management of population dynamics of cyanobacteria and dinoflagellates in freshwater lakes., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Mucopolysaccharidosis type III (MPS III) is an autosomal recessive lysosomal storage disorder characterised by progressive neurocognitive deterioration. MPS III subtypes are clinically indistinguishable, with a wide range of symptoms and variable severity. The natural history of this disorder within an Asian population has not yet been extensively studied. This study investigated the natural history of Korean patients with MPS III., Methods: Thirty-four patients from 31 families diagnosed with MPS III from January 1997 to May 2020 in Samsung Medical Centre were enrolled. Clinical, molecular, and biochemical characteristics were retrospectively collected from the patients' medical records and via interviews., Results: 18 patients had MPS IIIA, 14 had IIIB, and two had IIIC. Twenty (58.9%) patients were male. Mean age at symptom onset was 2.8 ± 0.8 years and at diagnosis was 6.3 ± 2.2 years. All patients with MPS IIIA and IIIB were classified into the rapidly progressing (RP) phenotype. The most common symptom at diagnosis was language retardation (88.2%), followed by motor retardation (76.5%), general retardation (64.7%), and hyperactivity (41.2%). Language retardation was more predominant in IIIA, and motor retardation was more predominant in IIIB. The mean age of the 13 deceased patients at the time of the study was 14.4 ± 4.1 years. The age at diagnosis and lag time were significantly older and longer in the non-survivor group compared with the survivor group ( p = 0.029 and 0.045, respectively). Genetic analysis was performed in 24 patients with MPS III and identified seven novel variants and three hot spots., Conclusion: This study is the first to analyse the genetic and clinical characteristics of MPS III patients in Korea. Better understanding of the natural history of MPS III might allow early diagnosis and timely management of the disease and evaluation of treatment outcomes in future clinical trials for MPS III.

Background: Electrolytes are measured regularly in a variety of clinical settings because electrolyte imbalance can be life-threatening. Although arterial blood-gas analysis reports electrolyte levels, the result often is discrepant with results from serum and plasma samples. Since prompt and accurate measurement of serum electrolyte levels could allow early treatment, point-of-care (POC) electrolyte analyzers would be beneficial. We evaluated a POC electrolyte analyzer cartridge based on the Clinical and Laboratory Standard Institute (CLSI) guidelines., Methods: Precision and linearity were assessed according to the CLSI EP05-A3 and EP06-A guidelines, respectively. A comparison study was conducted with both serum and plasma samples according to the CLSI EP09-A3. For serum, results from the i-Smart 300E analyzer were compared with results from the Nova 8 and i-Smart 30 analyzers. For plasma, results were compared among the i-Smart 300E, Nova 8, i-Smart 30, and Cobas c702 analyzers., Results: Coefficients of variation in the precision analysis were all less than 5%. Linearity assessment demonstrated a coefficient of determination between 0.999 and 1.000 for all analytes. The comparison study showed a high Pearson's correlation coefficient greater than 0.9 for all analytes, instruments, and specimens., Conclusions: The i-Smart 300E demonstrated good analytical performance. Its use could be beneficial in terms of both efficiency and clinical outcome in point-of-care testing (POCT) for electrolyte levels from serum and plasma samples., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Pseudomonas &nbsp; aeruginosa ( P . aeruginosa ) is an opportunistic gram-negative pathogen that can cause various infections, particularly in patients with compromised host defenses. P . aeruginosa forms biofilms and produces virulence factors through quorum sensing (QS) network, resulting in resistance to antibiotics. RhlI/RhlR, one of key QS systems in P . aeruginosa , is considered an attractive target for inhibiting biofilm formation and attenuating virulence factors. Several recent studies examined small molecules targeting the RhlI/RhlR system and their in vitro and in vivo biological activities. In this review, RhlR-targeted modulators, including agonists and antagonists, are discussed with particular focus on structure-activity relationship studies and outlook for next-generation anti-biofilm agents.