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A revised approach to cloud microphysical processes in a commonly used bulk microphysics parameterization and the importance of correctly representing properties of cloud ice are discussed. Several modifications are introduced to more realistically simulate some of the ice microphysical processes. In addition to the assumption that ice nuclei number concentration is a function of temperature, a new and separate assumption is developed in which ice crystal number concentration is a function of ice amount. Related changes in ice microphysics are introduced, and the impact of sedimentation of ice crystals is also investigated. In an idealized thunderstorm simulation, the distribution of simulated clouds and precipitation is sensitive to the assumptions in microphysical processes, whereas the impact of the sedimentation of cloud ice is small. Overall, the modifications introduced to microphysical processes play a role in significantly reducing cloud ice and increasing snow at colder temperatures and slightly increasing cloud ice and decreasing snow at warmer temperatures. A mesoscale simulation experiment for a heavy rainfall case indicates that impact due to the inclusion of sedimentation of cloud ice is not negligible but is still smaller than that due to the microphysics changes. Together with the sedimentation of ice, the new microphysics reveals a significant improvement in high-cloud amount, surface precipitation, and large-scale mean temperature through a better representation of the ice cloud-radiation feedback. © 2004 American Meteorological Society.

Background: Namibia's antiretroviral therapy (ART) programme has been successful in achieving a high level of viral load suppression (VLS) of 91% (NAMPHIA, 2017). Sub-populations and geographic areas need approaches to [...]

Background: Water kefir is a fermented beverage using water, sugar, and cultured microorganism grains as the primary ingredients. Ethanol may be present at varying levels within the final product due to the fermentation process, so it is vital to have a validated method to meet regulatory, quality, and safety requirements. Objective: This study describes using water kefir as a matrix for the evaluation of the previously validated method employing headspace gas chromatography mass spectrometry (HS-GCMS) detection for ethanol in kombucha. The study objective is to demonstrate the method originally using kombucha is also fit for the analysis of water kefir. This method will also evaluate the determination of methanol within the water kefir samples. Method: The matrix extension study was performed as per the AOAC INTERNATIONAL guidance documents outlined in Appendix K: Guidelines for Dietary Supplements and Botanicals using HS-GCMS for ethanol determination. Ethanol determination in each water kefir sample is quantified against an external standard calibration curve. The same instrumentation is used for methanol characterization. Results: RSDr and HorRat values obtained for from the study demonstrated acceptable precision with RSDr values of 1.03 to 6.68% and HorRat values determined to be between 0.23 and 1.52 for ethanol determination within kefir samples. Similarly, acceptable values of RSDr ranging from 1.45 to 3.39% and HorRat ranging from 0.25 to 0.49 were observed with methanol determination. For methanol determination, the limit of detection (LOD) and limit of quantification (LOQ) determined for the method in this study to be 16 and 21ppm, respectively. The methanol spike recovery study gave overall recoveries ranging from 89 to 91%, demonstrating acceptable method accuracy. Conclusions: The results of this study demonstrate the previously validated HS-GCMS method for ethanol determination in kombucha can also be used to quantify ethanol in water kefir samples. The method is also suitable for the determination of methanol within water kefir samples. Highlights: A straightforward method has been adapted to include the the quantification of ethanol and methanol in fermented beverages such as Water Kefir samples. [ABSTRACT FROM AUTHOR]

Background: Kombucha is a fermented beverage made with tea, sugar, and a symbiotic colony of bacteria and yeast that is usually marketed as a non-alcoholic beverage. Products must contain <0.5% and <1.1% alcohol by volume in the United States and Canada respectively to be classified as non-alcoholic products. Prior studies have found that Kombucha beverages can become very acidic and may contain levels of alcohol above 1% which can be a potential health risk to children and the developing fetus during pregnancy. Objective: Given the public safety concerns and legal requirements associated with the level of alcohol within Kombucha beverages, there is a need for accurate and reliable methods. Herein we describe the validation of a sensitive, rapid, and simple Headspace Gas Chromatographic method with mass spectrometric detection for determining ethanol in Kombucha. Methods: Method performance characteristics measured included linearity, accuracy, precision, limit of detection (LOD), and limit of quantification (LOQ) as per AOAC International guideline Appendix K Part 1. Performance was evaluated against the AOAC Standard Method Performance Requirements 2016.001 for determination of ethanol in Kombucha. Results: The linear dynamic range for this method was confirmed over the range of 0.025 to 2.47% ABV. The LOD and LOQ were determined to be 0.0002% and 0.002% ABV, respectively. With a spike recovery of 102% for accuracy and precision of RSDr ≤ 4% the method met the SMPR requirements within the analytical range. Conclusions: The results of this validation study demonstrated the method is fit for the purpose of quantifying ethanol in Kombucha and is suitable for rapid and easy integration by laboratories to ensure that regulatory requirements are met. [ABSTRACT FROM AUTHOR]

The HIV epidemic in Vietnam is concentrated, with high prevalence estimates among injection drug users and commercial sex workers. Socio-demographics, substance use and clinical correlates of antiretroviral therapy non-adherence were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy for at least 6 months in Hanoi, Vietnam. All study participants were men with a mean age of 29.9 ± 4.9 years. The median duration on antiretroviral therapy was 16.2 ± 12.7 months; 83% reported ‘very good’ or ‘perfect’ adherence in the past 30 days on a subjective one-item Likert scale at time of study enrollment; 48% of participants reported drug use within the previous 6 months, with 22% reporting current drug use. Injection drug use with or without non-injection drug use in the past 6 months (95% C.I. 2.19, 1.30–3.69) and years on antiretroviral therapy (95% C.I. 1.43, 1.14–1.78) were correlated with suboptimal adherence. These findings support Vietnam's ongoing scale-up of harm reduction programmes for injection drug users and their integration with antiretroviral therapy delivery. Moreover, results highlight the need to identify and implement new ways to support high levels of antiretroviral therapy adherence as duration on antiretroviral therapy increases. [ABSTRACT FROM PUBLISHER]

Background: Little is known about why surrogate decision makers for patients with advanced illness often have overly optimistic expectations about prognosis.Objective: To determine how surrogates interpret prognostic statements and to explore factors influencing surrogates' interpretations of grim prognostic information.Design: Multicenter, mixed-methods study.Setting: Intensive care units of 3 hospitals in San Francisco, California.Participants: 80 surrogates of critically ill patients.Measurements: Participants recorded their interpretation of 16 prognostic statements using a standard probability scale. Generalized estimating equations were used to determine whether participants interpreted statements more optimistically as the expressed probability of survival decreased. Fifteen surrogates whose responses exhibited this trend participated in a semistructured interview.Results: Participants' interpretations of prognostic statements expressing a low risk for death were relatively accurate, but interpretations of statements conveying a high risk for death were more optimistic than the actual meaning (P < 0.001; generalized estimating equation model). Interpretations of the statement "90% chance of surviving" did not differ from the actual meaning, but interpretations of "5% chance of surviving" were more optimistic and showed substantial variability (median, 90% [interquartile range, 90% to 95%; P = 0.11] vs. 15% [interquartile range, 5% to 40%; P < 0.001], respectively). Two main themes from the interviews explained this trend: surrogates' need to register optimism in the face of a poor prognosis and surrogates' belief that patient attributes unknown to the physician would lead to better-than-predicted outcomes.Limitation: Surrogates' interpretations were elicited in an experimental setting rather than during actual clinician-surrogate conversations.Conclusion: Inaccurate interpretations of physicians' prognostications by surrogates arise partly from optimistic biases rather than simply from misunderstandings.Primary Funding Source: National Heart, Lung, and Blood Institute. [ABSTRACT FROM AUTHOR]

Background: Kombucha is a nonalcoholic, fermented tea beverage that has recently received negative attention because of documented concentrations of ethanol in excess of allowable limits of ≥0.5% alcohol by volume (ABV). Objective: Our previously reported headspace GC with flame-ionization detection (GC-FID) method was adopted by the AOAC Expert Review Panel as First Action Official Method SM 2016.12 in September 2016 based on published single-laboratory validation study results. This paper describes the corresponding multilaboratory study using this method to further validate its performance parameters. Methods: Four laboratories participated in the study and received practice samples, test samples, reference standards, and detailed protocols. Eight kombucha samples sent out to laboratories were randomly assigned sample numbers and were blinded in terms of content and identity. Each laboratory analyzed all samples using the GC-FID method and reported their results. Results: Cochran’s C-test and single and double Grubbs’ tests were used to identify and remove outliers. Horwitz ratio values for all samples were between 0.5 and 1.7. As per the Standard Method Performance Requirements (SMPRs®), all samples within the analytical range of 0.1–2.0 ABV% had RSDR values <6%. Conclusions: The results from this study demonstrate the evaluated GC-FID method meets the SMPR requirements and is fit for purpose for detecting ethanol in kombucha products. Highlights: Kombucha, a nonalcoholic, fermented beverage, has been found to contain ≥0.5% ABV. First Action Official Method 2016.12, a headspace GC-FID method for determining ethanol in kombucha, is supported by a multilaboratory study. [ABSTRACT FROM AUTHOR]

Background: Japanese encephalitis (JE) has been predominantly controlled through vaccination. However, the isolation of JE virus (JEV) genotype V (GV) in China in 2009, and the subsequent alarming increase in JE cases in the Republic of Korea since 2010, present a new challenge., Methods: Serum samples from individuals vaccinated with genotype III (GIII)-based JE vaccines were analyzed for neutralizing seroresponse to GV isolates., Results: Serum from immunocompromised pediatric patients vaccinated with an inactivated JE vaccine showed higher 50% plaque reduction neutralization test (PRNT50) geometric mean titer (GMT) against GIII Nakayama (11,358; 95% CI = 1,790, 29,658), but lower GMTs against GV isolates: GV Muar (499; 95% CI = 0, 2,437), GV 43279 (308; 95% CI = 159, 582), and GV 43413 (231; 95% CI = 108, 738). Similarly, 32 healthy volunteers receiving a live attenuated JE vaccine achieved 100% seroprotection against GIII Nakayama with GMT of 338 (95% CI = 304, 651) at 1 month post-vaccination. However, GMTs against GV isolates were 123 (95% CI = 102, 446) for GV Muar, 81 (95% CI = 63, 168) for GV 43279, and 107 (95% CI = 100, 322) for GV 43413, not achieving 100% seroprotection against these isolates. At 6 months post-vaccination, GMT against Nakayama increased to 696 (95% CI = 409, 2,353), while remaining similar for GV isolates., Conclusions: Our study underscores that current GIII-based vaccines do not provide comparable protection against GV JEVs, impacting individuals in both current and potential endemic regions, as well as travelers to these regions., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Urolithiasis is a prevalent urological ailment characterized by increasing prevalence and recurrence rates, resulting in substantial social and economic burden. While men exhibit an incidence rate nearly twice that of women, this gender disparity is gradually diminishing. Nevertheless, the mechanisms underlying this condition remain incompletely elucidated. The identification of the urinary microbiome (urobiome) has provided a fresh perspective on urolithiasis. This study aimed to analyze the urobiome of unilateral stone formers in the renal pelvis and evaluate the variations in microbial diversity and community composition between males and females., Methods: Renal pelvis urine samples were obtained from a cohort of 21 male and 9 female patients and subsequently subjected to taxonomic and functional analysis using 2bRAD sequencing for Microbiome (2bRAD-M). The collected samples were categorized into four distinct groups, namely the stone side of males (SM), stone side of females (SF), non-stone side of males (NSM), and non-stone side of females (NSF)., Results: Through the application of beta diversity analysis, dissimilarity was observed between NSM and NSF. Additionally, NSF exhibited a higher abundance of microbial populations, and a total of 29 distinct species were identified as differentially present between NSM and NSF using LEfSe. Lactobacillus iners, Atopobium deltae, Lawsonella clevelandensis, and Meyerozyma guilliermondii exhibited enrichment in the SF group compared to the SM group. Furthermore, we identified distinct species that differed between the SM and NSM groups, as well as the SF and NSF groups. Besides, we conducted COG annotation and KEGG pathway predictions, revealing significant differences in urobiome function across the different groups., Conclusion: Variations in microbial community composition and predicted functions were observed among the various groups. Future research could potentially leverage the urobiome to personalize urolithiasis treatment based on individual microbial characteristics, taking into account gender-specific differences., (© 2024. The Author(s).)

The inverted inorganic CsPbI 3 perovskite solar cells (PSCs) are prospective candidates for next-generation photovoltaics owing to inherent robust thermal/photo-stability and compatibility for tandems. However, the performance and stability of the inverted CsPbI 3 PSCs fall behind the n-i-p counterparts due to poor energetic alignment and abundant interfacial defect states. Here, an inorganic 0D Cs 4 PbBr 6 with a good lattice strain arrangement is implemented as the surface anchoring capping layer on CsPbI 3 . The Cs 4 PbBr 6 perovskite induces enhanced electron-selective junction and thus facilitates efficient charge extraction and effectively inhibits non-radiative recombination. Consequently, the CsPbI 3 PSCs with Cs 4 PbBr 6 demonstrate the highest power conversion efficiency (PCE) of CsPbI 3 -based inverted PSCs, reaching 21.03% PCE from a unit cell and 17.39% PCE from a module with a 64 cm 2 aperture area. Furthermore, the resulting devices retain 92.48% after 1000 h under simultaneous 1-sun and damp heat (85 °C / 85% relative humidity) environment., (© 2024 Wiley‐VCH GmbH.)

Background: There are few studies that have examined clinical and radiological outcomes at 5 years after isolated medial patellofemoral ligament (MPFL) reconstruction. To date, midterm outcomes after isolated double-bundle (DB) MPFL reconstruction are not well known., Hypothesis: Isolated DB MPFL reconstruction using a patellar suture anchor technique would lead to improved functional scores and radiological findings, and these improvements would remain stable over the 5-year postoperative period., Study Design: Case series; Level of evidence, 4., Methods: Isolated MPFL reconstruction was performed in patients with recurrent patellar instability between March 2013 and February 2017. Clinical and functional evaluations were performed via an interview using the Kujala, Lysholm, and Tegner scores preoperatively and at 6, 12, 24, and 60 months postoperatively. Radiographs were taken preoperatively, immediately postoperatively, and at 24 and 60 months after surgery. Radiographic assessments included measuring the modified Insall-Salvati ratio, congruence angle, and lateral patellofemoral angle., Results: A total of 31 patients (31 knees) underwent isolated MPFL reconstruction; 4 patients did not complete 5-year follow-up, and thus, 27 patients (27 knees) were enrolled in the study. The mean age at the time of surgery was 22.0 ± 6.4 years (range, 14-32 years). All clinical and functional scores significantly improved in the first 2 years ( P < .001), with the mean Kujala, Lysholm, and Tegner scores improving from 52.7 to 90.7, 49.6 to 92.7, and 2.9 to 5.1, respectively. There was no significant difference in scores between 2- and 5-year follow-up. All radiographic parameters significantly improved between preoperatively and immediately postoperatively ( P < .001), with mean values for the modified Insall-Salvati ratio, congruence angle, and lateral patellofemoral angle improving from 1.7° to 1.6°, 5.7° to -6.6°, and 3.0° to 5.9°, respectively. No significant differences were observed in radiographic measurements between the postoperative time points. No patients experienced a patellar redislocation or fracture., Conclusion: The prospective analysis of isolated DB MPFL reconstruction at 5-year follow-up showed that clinical and radiological outcomes significantly improved postoperatively and were maintained to 5 years. These midterm results suggest that isolated DB MPFL reconstruction is an effective treatment option for patients with patellar instability., Competing Interests: The authors have declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Introduction: The factors contributing to blood loss during hemodialysis (HD) procedures remain underexplored. This study aimed to quantify blood loss during HD and identify the potential factors associated with it., Methods: The study included 70 ESRD patients undergoing HD. After dialysis, the extracorporeal blood circuits were rinsed with 1,000 mL of 0.05% NH3 solution in distilled water, and hemoglobin levels were measured. Univariate regression was used to assess the linear relationship between residual red blood cell (RBC) volume and various parameters, including HD mode, dialyzer surface area, ultrafiltration goal, hypotension during HD, blood flow rate, activated partial thromboplastin time, and C-reactive protein. Multivariate regression was also conducted to explore the relationships among these parameters., Results: The mean RBC volume remaining in the extracorporeal blood circuit after HD was 1.6 ± 0.9 mL (mode: 1.0, range: 0.3-6.5 mL). When converted to whole blood volume per patient, the mean blood volume was 5.3 ± 3.0 mL (median: 4.1 mL, mode: 4.0 mL, range: 1.0-19.0 mL). Multivariate analysis identified the dialyzer surface area as the only significant determinant of residual RBC volume., Conclusion: After HD, the remaining RBC volume in the extracorporeal blood circuit varies from 1.6 to 6.5 mL. When the RBC volume was converted to whole blood volume for each case, the blood loss ranged from 1.0 to 19.0 mL. Dialyzer surface area was the only significant determinant of residual RBC volume., (© 2024 S. Karger AG, Basel.)

Our study aimed to apply a proteomic approach to investigate the molecular mechanisms underlying the effects of oxalate on rat renal tubular epithelial cells. NRK-52E cells were treated with or without oxalate and subjected to quantitative proteomics to identify key proteins and key pathological changes under high oxalate stimulation. A total of 268 differentially expressed proteins (DEPs) between oxalate-treated and control groups were identified, with 132 up-regulated and 136 down-regulated proteins. Functional enrichment analysis revealed that DEPs are associated with oxidative stress, apoptosis, ferroptosis, pro-inflammatory cytokines, vitamin D, and biomineralization. SPP1, MFGE8, ANKS1A, and NAP1L1 were up-regulated in the oxalate-treated cells and the hyperoxaluric stone-forming rats, while SUB1, RNPS1, and DGLUCY were down-regulated in both cases. This altered proteomic landscape sheds light on the pathological processes involved in oxalate-induced renal damage and identifies potential biomarkers and therapeutic targets to mitigate the effects of hyperoxaluria and reduce the risk of CaOx stone formation.

Purpose: Although leukemic retinopathy accounts for 80% of ocular complications in acute leukemia, its pathogenesis remains unclear. To evaluate changes in retinal and choroicapillaris and structural parameters in patients with acute leukemia, we analyzed the correlation between vascular perfusion metrics and laboratory parameters and assessed the changes after hematopoietic stem cell transplantation (HSCT)., Methods: Herein, 104 eyes of 52 patients aged 18 and above with acute leukemia were enrolled. 80 eyes of 40 healthy patients were recruited as control participants. All participants underwent optical coherence tomography (OCT) and OCT angiography (OCTA) at baseline., Results: Patients with acute leukemia had a significantly thicker ganglion cell-inner plexiform layer (GCIPL) and lower circularity index than the control participants. Post-HSCT perfusion metrics did not differ significantly, but parafoveal thickness decreased significantly. During the active phase of acute leukemia, lower platelet levels were associated with significant GCIPL thickening and increased foveal avascular zone and perimeter. D-dimer levels positively correlated with GCIPL thickness., Conclusion: Patients with acute leukemia had subclinical retinal microvascular deficits on OCTA and GCIPL thickening on OCT, possibly associated with bone marrow function. GCIPL thickness may indicate acute ischemia in such patients. Further studies must elucidate their clinical and prognostic significance., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Our study aimed to elucidate the mechanisms behind the interaction between calcium oxalate (CaOx) crystals and renal tubular epithelial cells through transcriptome sequencing analysis. HK-2 cells were stimulated with or without CaOx monohydrate crystals and subjected to RNA-seq to assess the effects of CaOx crystals on gene expression changes, key pathways, and molecular players during this interaction. A total of 629 differentially expressed genes (DEGs) were identified between the control group and experimental group, with 491 genes up-regulated and 138 down-regulated. Functional enrichment analysis indicated that the DEGs were significantly associated with endoplasmic reticulum stress (ERS) and unfolded protein response. To validate our findings, we compared our results with the public dataset GSE73680 and confirmed the increased expression of two ERS-related DEGs, CHAC1 and FGF21, in renal papillary tissues from patients with CaOx stones. Collectively, these findings suggest that ERS plays a crucial role in the crystal-cell interaction and highlight the potential for developing therapeutic strategies aimed at reducing CaOx stone formation by targeting ERS-related molecules and pathways.

Background: This study addresses the gap in knowledge regarding the long-term mortality implications of postoperative acute kidney injury (PO-AKI) utilizing advanced machine learning techniques to predict outcomes more accurately than traditional statistical models., Methods: A retrospective cohort study was conducted using data from seven institutions between March 2009 and December 2019. Machine learning models were developed to predict all-cause mortality of PO-AKI patients using 23 preoperative variables and one postoperative variable. Model performance was compared to a traditional statistical approach with Cox regression analysis. The concordance index was used as a predictive performance metric to compare prediction capabilities among different models., Results: Among 199,403 patients, 2,105 developed PO-AKI. During a median follow-up of 144 months (interquartile range, 99.61-170.71 months), 472 in-hospital deaths occurred. Subjects with PO-AKI had a significantly lower survival rate than those without PO-AKI (p < 0.001). For predicting mortality, the XGBoost with an accelerated failure time model had the highest concordance index (0.7521), followed by random survival forest (0.7371), multivariable Cox regression model (0.7318), survival support vector machine (0.7304), and gradient boosting (0.7277)., Conclusion: XGBoost with an accelerated failure time model was developed in this study to predict long-term mortality associated with PO-AKI. Its performance was superior to conventional models. The application of machine learning techniques may offer a promising approach to predict mortality following PO-AKI more accurately, providing a basis for developing targeted interventions and clinical guidelines to improve patient outcomes.

This review discusses recent advances in robotic surgery for urologic tumors, focusing on three key areas: robotic systems, assistive technologies, and artificial intelligence. The Da Vinci SP system has enhanced the minimally invasive nature of robotic surgeries, while the Senhance system offers advantages such as tactile feedback and eye-tracking capabilities. Technologies like 3D reconstruction combined with augmented reality and fluorescence imaging aid surgeons in precisely identifying the anatomical relationships between tumors and surrounding structures, improving surgical efficiency and outcomes. Additionally, the development of artificial intelligence lays the groundwork for automated robotics. As these technologies continue to evolve, we are entering an era of minimally invasive, precise, and intelligent robotic surgery.

Background and Objective: Exosomes have been confirmed to be implicated in the pathogenesis of calcium oxalate (CaOx) stones. tRNA-derived small RNAs (tsRNAs) are among the oldest small RNAs involved in exosome-mediated intercellular communication, yet their role in kidney stones remains unexplored. This pilot study aimed to identify differentially expressed tsRNAs (DEtsRNAs) in urine exosomes between CaOx stone patients and healthy controls and explore their potential roles in nephrolithiasis., Method: First-morning urine samples were collected from three CaOx stone patients and three healthy controls. Urinary exosomes were isolated and analyzed by high-throughput sequencing to generate the expression profiles of tsRNAs and detect DEtsRNAs. Predicted target genes of DEtsRNAs were subjected to functional enrichment analysis. The authors also combined the public dataset GSE73680 to investigate how DEtsRNAs were related to stone formation., Results: Four DEtsRNAs were significantly upregulated in CaOx stone patients compared to healthy controls. tRF-Lys-TTT-5005c was the most elevated, followed by tRF-Lys-CTT-5006c, tRF-Ala-AGC-5017b, and tRF-Gly-CCC-5004b. Bioinformatics analysis indicated that these four types of DEtsRNAs might serve distinct biological functions. Combined with data mining from the public dataset GSE73680, the authors assumed that exosomes carrying tRF-Lys-TTT-5005c and tRF-Lys-CTT-5006c could inhibit the expression of SMAD6, FBN1, and FZD1, thereby activating the BMP signaling pathway, which might induce an osteogenic-like transformation in target cells, resulting in the formation of Randall's plaques and CaOx stones., Conclusion: The authors' findings shed light on the potential roles of tsRNAs in the pathogenesis of CaOx stone disease, highlighting exosomal DEtsRNAs as promising diagnostic biomarkers and therapeutic targets in nephrolithiasis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: This study has a purpose to investigate the side effects of three EGFR-TKIs targeted therapeutic agents (gefitinib, erlotinib, and afatinib) and all-cause mortality in patients with metastatic lung cancer., Methods: We performed a prospective cohort study. We selected all patients with newly diagnosed metastatic lung cancer between January and November 2019. Main exposure was daytime versus nighttime use of targeted EGFR TKIs. The study outcome was a symptom change using the mobile application, and all-cause mortality between January 2019 and March 2023., Results: Among the 87 study participants, 35 (40%) took their medication at night. Among the 87 study participants, 35 (40%) took their medication at night. At 6 weeks of treatment, acne (1.36; 95% confidence interval [CI] 1.09, 1.64; p for interaction = 0.04) and dry skin (1.35; 95% CI 1.09, 1.61, p for interaction = 0.01) in the day group showed a much increase from baseline compared to the night group. In contrast, the night group reported greater reductions in lung cancer-related symptoms from baseline compared to the day. During follow-up (median 43 months), the night group had a lower risk of all-cause death than the day group, especially in younger patients (adjusted hazard ratio = 0.34; 95% CI 0.13, 0.87)., Conclusions: The group taking EGFR-TKIs at night experienced fewer side effects and had longer overall survival compared to the day group. Clinicians should consider recommending that lung cancer patients take their once-daily oral anticancer drugs in the evening rather than the morning to improve treatment outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Immunological factors play a pivotal role in the outcomes of solid organ transplantation. We aimed to elucidate the effects of donor-specific antibodies (DSAs) and ABO compatibility on living donor liver transplantation (LDLT) outcomes., Methods: A retrospective analysis was conducted on 584 LDLT recipients from 2015 to 2020. The recipients were stratified into 3 groups: ABO-compatible recipients without DSAs (group 1), ABO-compatible recipients with DSAs (group 2), and ABO-incompatible recipients without DSAs (group 3). Propensity score matching was used for balanced comparisons., Results: In the matched comparisons, group 2 exhibited a higher incidence of T cell-mediated rejection compared with group 1 (22.7% versus 4.5%, P  = 0.030). Despite this, the 5-y survival rates were similar between groups 1 and 2 (81.6% versus 95.5%, P  = 0.085). Group 3, in comparison with group 1, showed elevated rates of cytomegalovirus infection (23.2% versus 7.3%, P  = 0.008), T cell-mediated rejection (28.0% versus 7.3%, P  = 0.001), and antibody-mediated rejection (13.4% versus 0%, P  = 0.001). However, the survival rates were comparable between group 3 and group 1 (82.0% versus 86.5%, P  = 0.220, respectively). Comparisons between group 2 and group 3 did not reveal significant differences in postoperative outcomes or survival rates ( P  > 0.05)., Conclusions: DSA positivity and ABO incompatibility contribute to distinct posttransplant complications in LDLT. The integrated consideration of both factors in pretransplant assessment may enhance risk stratification and inform tailored interventions. Further research is required to corroborate these findings and provide mechanistic insights., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Vertical mixing within the planetary boundary layer (PBL) is crucial for determining surface-level pollutant concentrations. However, standard PBL schemes in chemical transport models (CTMs) often fail to adequately define the upper bounds of vertical mixing, particularly at night. This limitation frequently results in overestimated nocturnal concentrations of pollutants near the surface. To address this issue, we propose a parameterization of mixed layer height (MLH) derived from the Yonsei University (YSU) PBL scheme and thoroughly evaluate it by comparing simulations with various observations. We utilized the Weather Research and Forecasting model coupled with GEOS-Chem (WRF-GC) to simulate gas and aerosol distributions over South Korea during the Satellite Integrated Joint Monitoring of Air Quality (SIJAQ) campaign in 2021. The WRF-GC simulations incorporating the MLH parameterization improved the excessive titration of O 3 and the overproduction of HNO 3 and NO 3 - in the model. Consequently, the model performances in gaseous and aerosol simulations showed a better agreement with observations, with changes in normalized mean biases (NMBs) of NO X (from 50 % to -27 %), O 3 (from -49 % to -28 %), NO 3 - (from 126 % to 91 %), NH 4 + (from 113 % to 85 %), BC (from 322 % to 135 %), and PM 2.5 (from 58 % to 28 %)., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Japanese encephalitis (JE), caused by the Japanese encephalitis virus (JEV) infection, continues to pose significant public health challenges worldwide despite efficient vaccines. The virus is classified into five genotypes, among which genotype V (GV) was not detected for a long period after its initial isolation in 1952, until reports emerged from China and the Republic of Korea (ROK) since 2009. The characteristics of the virus are crucial in estimating its potential epidemiological impact. However, characterization of GV JEVs has so far been limited to two strains: Muar, the original isolate, and XZ0934, isolated in China. Two additional ROK GV JEV isolates, NCCP 43279 and NCCP 43413, are currently available, but their characteristics have not been explored. Our phylogenetic analysis revealed that GV virus sequences from the ROK segregate into two clades. NCCP 43279 and NCCP 43413 belong to different clades and exhibit distinct in vitro phenotypes. NCCP 43279 forms larger plaques but demonstrates inefficient propagation in cell culture compared to NCCP 43413. In vivo , NCCP 43279 induces higher morbidity and mortality in mice than NCCP 43413. Notably, NCCP 43279 shows more severe blood-brain barrier damage, suggesting superior brain invasion capabilities. Consistent with its higher virulence, NCCP 43279 displays more pronounced histopathological and immunopathological outcomes. In conclusion, our study confirms that the two ROK isolates are not only classified into different clades but also exhibit distinct in vitro and in vivo characteristics.

Japanese encephalitis (JE), caused by the Japanese encephalitis virus (JEV), is a highly threatening disease with no specific treatment. Fortunately, the development of vaccines has enabled effective defense against JE. However, re-emerging genotype V (GV) JEV poses a challenge as current vaccines are genotype III (GIII)-based and provide suboptimal protection. Given the isolation of GV JEVs from Malaysia, China, and the Republic of Korea, there is a concern about the potential for a broader outbreak. Under the hypothesis that a GV-based vaccine is necessary for effective defense against GV JEV, we developed a pentameric recombinant antigen using cholera toxin B as a scaffold and mucosal adjuvant, which was conjugated with the E protein domain III of GV by genetic fusion. This GV-based vaccine antigen induced a more effective immune response in mice against GV JEV isolates compared to GIII-based antigen and efficiently protected animals from lethal challenges. Furthermore, a bivalent vaccine approach, inoculating simultaneously with GIII- and GV-based antigens, showed protective efficacy against both GIII and GV JEVs. This strategy presents a promising avenue for comprehensive protection in regions facing the threat of diverse JEV genotypes, including both prevalent GIII and GI as well as emerging GV strains.

Backgrounds/aims: Challenges arise when translating pure laparoscopic donor right hepatectomy (PLDRH) results from Asian to Western donors, due to differences in body mass index (BMI). This study compares the outcomes of PLDRH and conventional open donor right hepatectomy (CDRH) in donors with BMI over 30., Methods: Medical records of live liver donors (BMI > 30) undergoing right hepatectomy (2010-2021) were compared: 25 PLDRH cases vs. 19 CDRH cases. Donor and recipient demographics, operative details, and outcomes were analyzed., Results: PLDRH and CDRH had similar donor and recipient characteristics. PLDRH had longer liver removal and warm ischemic times, but a shorter post-liver removal duration than CDRH. Donor complication rates were comparable, with the highest complication being grade IIIa in PLDRH, necessitating needle aspiration for biloma on postoperative day 11. Fortunately, this donor fully recovered without additional treatment. No complications exceeding Clavien-Dindo grade IIIa occurred in either group. Recipient outcomes between the groups were similar., Conclusions: This study supports PLDRH as a viable option for donors with BMI over 30, challenging the notion that high BMI should deter considering PLDRH. The findings provide valuable insights into the safety and feasibility of PLDRH, encouraging further exploration of this technique in diverse donor populations.

Titrating tacrolimus concentration in liver transplantation recipients remains a challenge in the early post-transplant period. This multicenter retrospective cohort study aimed to develop and validate a machine-learning algorithm to predict tacrolimus concentration. Data from 443 patients undergoing liver transplantation between 2017 and 2020 at an academic hospital in South Korea were collected to train machine-learning models. Long short-term memory (LSTM) and gradient-boosted regression tree (GBRT) models were developed using time-series doses and concentrations of tacrolimus with covariates of age, sex, weight, height, liver enzymes, total bilirubin, international normalized ratio, albumin, serum creatinine, and hematocrit. We conducted performance comparisons with linear regression and populational pharmacokinetic models, followed by external validation using the eICU Collaborative Research Database collected in the United States between 2014 and 2015. In the external validation, the LSTM outperformed the GBRT, linear regression, and populational pharmacokinetic models with median performance error (8.8%, 25.3%, 13.9%, and - 11.4%, respectively; P < 0.001) and median absolute performance error (22.3%, 33.1%, 26.8%, and 23.4%, respectively; P < 0.001). Dosing based on the LSTM model's suggestions achieved therapeutic concentrations more frequently on the chi-square test (P < 0.001). Patients who received doses outside the suggested range were associated with longer ICU stays by an average of 2.5 days (P = 0.042). In conclusion, machine learning models showed excellent performance in predicting tacrolimus concentration in liver transplantation recipients and can be useful for concentration titration in these patients., (© 2024. The Author(s).)

Genotype V (GV) Japanese encephalitis virus (JEV) has been predominantly reported in the Republic of Korea (ROK) since 2010. GV JEV exhibits higher virulence and distinct antigenicity compared to other genotypes, which results in reduced efficacy of existing vaccines. Research on GV JEV is essential to minimize its clinical impact, but the only available clinical strain in the ROK is K15P38, isolated from the cerebrospinal fluid of a patient in 2015. We obtained this virus from National Culture Collection for Pathogens (NCCP) and isolated a variant forming small plaques during our research. We identified that this variant has one amino acid substitution each in the PrM and NS5 proteins compared to the reported K15P38. Additionally, we confirmed that this virus exhibits delayed propagation in vitro and an attenuated phenotype in mice. The isolation of this variant is a critical reference for researchers intending to study K15P38 obtained from NCCP, and the mutations in the small plaque-forming virus are expected to be useful for studying the pathology of GV JEV.