The m6A writer RBM15 drives the growth of triple-negative breast cancer cells through the stimulation of serine and glycine metabolism.

N6-adenosine methylation (m6A) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how m6A methyltransferases modulate m6A levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an m6A writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes. Gene expression profiling revealed correlations between RBM15 and serine and glycine metabolic genes, including PHGDH, PSAT1, PSPH, and SHMT2. RBM15 influences m6A levels and, specifically, the m6A levels of serine and glycine metabolic genes via direct binding to target RNA. The effects of RBM15 on cell growth were largely dependent on serine and glycine metabolism. Thus, RBM15 coordinates cancer cell growth through altered serine and glycine metabolism, suggesting that RBM15 is a new therapeutic target in BC.

Incorporating Supramaximal Resection into Survival Stratification of IDH-Wildtype Glioblastoma: A Refined Multi-institutional Recursive Partitioning Analysis.

PURPOSE: To propose a novel recursive partitioning analysis (RPA) classification model in patients with IDH-wildtype glioblastomas that incorporates the recently expanded conception of the extent of resection (EOR) in terms of both supramaximal and total resections. EXPERIMENTAL DESIGN: This multicenter cohort study included a developmental cohort of 622 patients with IDH-wildtype glioblastomas from a single institution (Severance Hospital) and validation cohorts of 536 patients from three institutions (Seoul National University Hospital, Asan Medical Center, and Heidelberg University Hospital). All patients completed standard treatment including concurrent chemoradiotherapy and underwent testing to determine their IDH mutation and MGMTp methylation status. EORs were categorized into either supramaximal, total, or non-total resections. A novel RPA model was then developed and compared to a previous RTOG RPA model. RESULTS: In the developmental cohort, the RPA model included age, MGMTp methylation status, KPS, and EOR. Younger patients with MGMTp methylation and supramaximal resections showed a more favorable prognosis (class I: median overall survival [OS] 57.3 months), while low-performing patients with non-total resections and without MGMTp methylation showed the worst prognosis (class IV: median OS 14.3 months). The prognostic significance of the RPA was subsequently confirmed in the validation cohorts, which revealed a greater separation between prognostic classes for all cohorts compared to the previous RTOG RPA model. CONCLUSIONS: The proposed RPA model highlights the impact of supramaximal versus total resections and incorporates clinical and molecular factors into survival stratification. The RPA model may improve the accuracy of assessing prognostic groups.

Tailored surgical strategies for mini-access open total arch repair.

Objective: Open arch repair is perceived as a challenging, high-risk procedure, with a barrier against the use of a minimally invasive approach. We aimed to present a mini-access total arch replacement performed by stratified approaches and to evaluate perioperative outcomes to contribute to the body of evidence. Methods: We evaluated 40 consecutive patients (aged 69.5 years; interquartile range, 65.6-76.3 years) undergoing elective total arch replacement using 5- to 8-cm upper mini-sternotomy between 2018 and 2022. Surgical strategies, including arterial inflow site and methods of branching vessel reconstruction, were systematically selected at the individual level. To evaluate comparative outcomes, contemporary cases undergoing total arch replacement via sternotomy with similar eligibility criteria served as a control group, and the inverse-treatment-weighting method was used to adjust for baseline characteristics. Results: Arch-first anastomosis using trifurcate graft, distal-first anastomosis using 4-branch graft, and island anastomosis were used in 18 (45%), 12 (30.0%), and 10 (25%) patients, respectively. Lower body and cardiac ischemic times were 23.4 minutes (interquartile range, 18.0-29.0 minutes) and 66.7 minutes (interquartile range, 50.1-78.2 minutes). There was no early (30-day or in-hospital) mortality, and 2 patients experienced disabling stroke (5.0%). The contemporary control group comprised 55 patients. After an adjustment, a mini-access group showed lower risks of stroke (odds ratio, 0.88; 95% CI, 0.78-1.00; P = .049) and a composite of major complications (odds ratio, 0.79; 95% CI, 0.68-0.92; P = .003), compared with a sternotomy approach. Conclusions: Based on present results, mini-access total arch replacement may be performed with reasonable safety and efficiency.

Salvia miltiorrhiza bunge extracts: a promising source for anti-atopic dermatitis activity.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory condition characterized by the accumulation of reactive oxygen species and the expression of inflammatory factors. Regarding its anti-atopic activity, numerous traditional medicinal materials and secondary metabolic products play pivotal roles in modulating the associated mechanisms. METHODS: This study aimed to utilize Salvia miltiorrhiza Bunge (SMB) as an anti-AD source. In-vitro activity assessments and qualitative and quantitative analyses using UPLC-TQ-MS/MS and HPLC-DAD were conducted in two cultivars ('Dasan' and 'Kosan'). Statistical analysis indicated that the profiles of their secondary metabolites contribute significantly to their pharmacological properties. Consequently, bio-guided fractionation was undertaken to figure out the distinct roles of the secondary metabolites present in SMB. RESULTS: Comparative study of two cultivars indicated that 'Dasan', having higher salvianolic acid A and B, exhibited stronger antioxidant and anti-inflammatory activities. Meanwhile, 'Kosan', containing higher tanshinones, showed higher alleviating activities on anti-AD related genes in mRNA levels. Additionally, performed bio-guided fractionation re-confirmed that the hydrophilic compounds of SMB can prevent AD by inhibiting accumulation of ROS and suppressing inflammatory factors and the lipophilic components can directly inhibit AD. CONCLUSIONS: SMB was revealed as a good source for anti-AD activity. Several bioactive compounds were identified from the UPLC-TQ-MS/MS and different compounds content was linked to biological activities. Characterization of these compounds may be helpful to understand differential role of secondary metabolites from SMB on alleviation of AD.

Outcomes of Lung Transplantation in Patients With Right Ventricular Dysfunction: A Single-Center Retrospective Analysis Comparing ECMO Configurations in a Bridge-to-Transplant Setting.

This study aimed to assess the lung transplantation (LT) outcomes of patients with right ventricular dysfunction (RVD), focusing on the impact of various extracorporeal membrane oxygenation (ECMO) configurations. We included adult patients who underwent LT with ECMO as a bridge-to-transplant from 2011 to 2021 at a single center. Among patients with RVD (n = 67), veno-venous (V-V) ECMO was initially applied in 79% (53/67) and maintained until LT in 52% (35/67). Due to the worsening of RVD, the configuration was changed from V-V ECMO to veno-arterial (V-A) ECMO or a right ventricular assist device with an oxygenator (Oxy-RVAD) in 34% (18/67). They showed that lactic acid levels (2-6.1 mmol/L) and vasoactive inotropic score (6.6-22.6) increased. V-A ECMO or Oxy-RVAD was initiated and maintained until LT in 21% (14/67) of cases. There was no significant difference in the survival rates among the three configuration groups (V-V ECMO vs. configuration changed vs. V-A ECMO/Oxy-RVAD). Our findings suggest that the choice of ECMO configuration for LT candidates with RVD should be determined by the patient's current hemodynamic status. Vital sign stability supports the use of V-V ECMO, while increasing lactic acid levels and vasopressor needs may require a switch to V-A ECMO or Oxy-RVAD.

Safety and efficacy of inebilizumab for the treatment of neuromyelitis optica spectrum disorder: end-of-study results from the open-label period of the N-MOmentum trial.

BACKGROUND: Inebilizumab, an anti-CD19 B-cell-depleting antibody, demonstrated safety and efficacy in neuromyelitis optica spectrum disorder in the randomised controlled period of the N-MOmentum trial. Here, end-of-study data, including the randomised controlled period and open-label extension period, are reported. METHODS: In the double-blind, randomised, placebo-controlled, phase 2/3 N-MOmentum trial, adults aged 18 years and older with an neuromyelitis optica spectrum disorder diagnosis, Expanded Disability Status Scale score of 8·0 or less, and history of either at least one acute inflammatory attack requiring rescue therapy in the past year or two attacks requiring rescue therapy in the past 2 years, were recruited from 81 outpatient specialty clinics or hospitals in 24 countries. Eligible participants were randomly assigned (3:1), using a central interactive voice system or interactive web response system, and a permuted block randomisation scheme (block size of 4), to receive intravenous inebilizumab (300 mg) or identical placebo on days 1 and 15 of the randomised period, which lasted up to 197 days. Participants and all study staff were masked to treatment assignment. The primary endpoint of the randomised period of the trial was time to onset of adjudicated neuromyelitis optica spectrum disorder attack on or before day 197. Participants in the randomised controlled period who had an adjudicated attack, completed 197 days in the study, or were in the randomised controlled period when enrolment stopped, could voluntarily enter the open-label period. In the open-label period, participants either initiated inebilizumab if assigned placebo (receiving 300 mg on days 1 and 15 of the open-label period) or continued treatment if assigned inebilizumab (receiving 300 mg on day 1 and placebo on day 15, to maintain B-cell depletion and masking of the randomised controlled period). All participants subsequently received inebilizumab 300 mg every 6 months for a minimum of 2 years. The end-of-study analysis endpoints were time to adjudicated attack and annualised attack rate (assessed in all participants who received inebilizumab at any point during the randomised controlled period or open-label period [any inebilizumab population] and the aquaporin-4 [AQP4]-IgG seropositive subgroup [any inebilizumab-AQP4-IgG seropositive population]) and safety outcomes (in all participants who were exposed to inebilizumab, analysed as-treated). This study is registered with ClinicalTrials.gov, NCT02200770, and is now complete. FINDINGS: Between Jan 6, 2015, and Sept 24, 2018, 467 individuals were screened, 231 were randomly assigned, and 230 received at least one dose of inebilizumab (n=174) or placebo (n=56). Between May 19, 2015, and Nov 8, 2018, 165 (95%) of 174 participants in the inebilizumab group and 51 (91%) of 56 in the placebo group entered the open-label period (mean age 42·9 years [SD 12·4], 197 [91%] of 216 were female, 19 [9%] were male, 115 [53%] were White, 45 [21%] were Asian, 19 [9%] were American Indian or Alaskan Native, and 19 [9%] were Black or African American). As of data cutoff for this end of study analysis (Dec 18, 2020; median exposure 1178 days [IQR 856-1538], total exposure of 730 person-years) 225 participants formed the any inebilizumab population, and 208 (92%) participants were AQP4-IgG seropositive. Overall, 63 adjudicated neuromyelitis optica spectrum disorder attacks occurred in 47 (21%) of 225 treated participants (60 attacks occurred in 44 [21%] of 208 in the AQP4-IgG seropositive subgroup); 40 (63%) of 63 attacks occurred in 34 (15%) of 225 treated participants during the first year of treatment. Of individuals who had an adjudicated attack while receiving inebilizumab, 36 (77%) of 47 were subsequently attack-free at the end of 4 years. Annualised attack rates decreased year-on-year, with end-of-study adjusted annualised attack rates being similar in the any inebilizumab-AQP4-IgG seropositive subgroup (0·097 [95% CI 0·070-0·14]) and any inebilizumab populations (0·092 [0·067-0·13]). Overall, 208 (92%) of 225 participants who received any inebilizumab had at least one treatment-emergent adverse event, the most frequent of which were urinary tract infection (59 [26%]), nasopharyngitis (47 [21%]), and arthralgia (39 [17%]). Infection rates did not increase over 4 years. Three (1%) of 225 participants in the any inebilizumab population died during the open-label period (one each due to a CNS event of unknown cause and pneumonia, respiratory insufficiency resulting from an neuromyelitis optica spectrum disorder attack and viral pneumonia related to COVID-19), all of which were deemed to be unrelated to treatment. INTERPRETATION: Data from the end-of-study analysis of the N-MOmentum trial showed continued and sustained clinical benefits of long-term inebilizumab treatment in individuals with neuromyelitis optica spectrum disorder, which supports the role of inebilizumab as a CD19+ B-cell-depleting therapy in neuromyelitis optica spectrum disorder. FUNDING: MedImmune and Viela Bio/Horizon Therapeutics, now part of Amgen.

Comparison for the effects of different components of temperature variability on mortality: A multi-country time-series study.

BACKGROUND: Temperature variability (TV) is associated with increased mortality risk. However, it is still unknown whether intra-day or inter-day TV has different effects. OBJECTIVES: We aimed to assess the association of intra-day TV and inter-day TV with all-cause, cardiovascular, and respiratory mortality. METHODS: We collected data on total, cardiovascular, and respiratory mortality and meteorology from 758 locations in 47 countries or regions from 1972 to 2020. We defined inter-day TV as the standard deviation (SD) of daily mean temperatures across the lag interval, and intra-day TV as the average SD of minimum and maximum temperatures on each day. In the first stage, inter-day and intra-day TVs were modelled simultaneously in the quasi-Poisson time-series model for each location. In the second stage, a multi-level analysis was used to pool the location-specific estimates. RESULTS: Overall, the mortality risk due to each interquartile range [IQR] increase was higher for intra-day TV than for inter-day TV. The risk increased by 0.59% (95% confidence interval [CI]: 0.53, 0.65) for all-cause mortality, 0.64% (95% CI: 0.56, 0.73) for cardiovascular mortality, and 0.65% (95% CI: 0.49, 0.80) for respiratory mortality per IQR increase in intra-day TV0-7 (0.9 °C). An IQR increase in inter-day TV0-7 (1.6 °C) was associated with 0.22% (95% CI: 0.18, 0.26) increase in all-cause mortality, 0.44% (95% CI: 0.37, 0.50) increase in cardiovascular mortality, and 0.31% (95% CI: 0.21, 0.41) increase in respiratory mortality. The proportion of all-cause deaths attributable to intra-day TV0-7 and inter-day TV0-7 was 1.45% and 0.35%, respectively. The mortality risks varied by lag interval, climate area, season, and climate type. CONCLUSIONS: Our results indicated that intra-day TV may explain the main part of the mortality risk related to TV and suggested that comprehensive evaluations should be proposed in more countries to help protect human health.

Added value of 40 keV virtual monoenergetic images for diagnosing malignant pleural effusion on chest CT.

OBJECTIVE: This study aimed to evaluate the added value of 40 keV virtual mono-energetic images (VMIs) obtained from dual-layer detector CT (DLCT) for diagnosing malignant pleural effusion (MPE) in patients presenting with unilateral pleural effusion on chest CT. MATERIALS AND METHODS: This retrospective study included 75 patients with unilateral pleural effusion who underwent contrast-enhanced chest CT scans using DLCT. Quantitative and qualitative assessments of the visibility of pleural thickening were conducted on both conventional 120 kVp images and 40 keV VMIs. Two independent radiologists reviewed chest CT scans with or without 40 keV VMIs to detect pleural nodules or nodular thickening for the diagnosis of MPE. Diagnostic performances were compared and independent predictors of MPE were identified through multivariate logistic regression analysis using CT and clinicopathologic findings. RESULTS: Pleural thickening associated with MPE demonstrated a higher contrast-to-noise ratio value and greater visual conspicuity in 40 keV VMIs compared to benign effusions (p < 0.05). For both readers, the use of 40 keV VMIs significantly improved (p < 0.05) the diagnostic performance in terms of sensitivity and area under the curve (AUC) for diagnosing MPE through the detection of pleural nodularity. Inter-observer agreements between the two readers were substantial for both 120 kVp images alone and the combined use of 40 keV VMIs. Initial cytology results and pleural nodularity at 40 keV were identified as independent predictors of MPE. CONCLUSION: The use of 40 keV VMIs from DLCT can improve diagnostic performance of readers in detecting MPE among patients with unilateral pleural effusion.

Exploring the Role of Guanylate-Binding Protein-2 in Activated Microglia-Mediated Neuroinflammation and Neuronal Damage.

Neuron damage by microglia, which act as macrophage cells in the brain, can result in various brain diseases. However, the function of pro-inflammatory or anti-inflammatory microglia in the neurons remains controversial. Guanylate-binding protein-2 (GBP2) is expressed and activated in the microglia in the early phase of the inflammatory response and plays an important role in controlling immune responses. In this study, we evaluated whether GBP2 initially reduces the immune response induced by microglia, and whether microglia induce pro-inflammatory functions in neurons via GBP2 expression. In lipopolysaccharide (LPS)-stimulated microglia, we assessed the expression of GBP2 and how it affects neurons via activated microglia. The biological functions of microglia due to the downregulation of the GBP2 gene were examined using short hairpin RNA (shRNA)-RNA-GBP2. Downregulated GBP2 affected the function of mitochondria in the microglia and showed reduced neuronal damage when compared to the control group in the co-culture system. Furthermore, this protein was observed to be highly expressed in the brains of dementia mice. Our results are the first to report that the downregulation of GBP2 in activated microglia has an anti-inflammatory function. This study suggests that the GBP2 gene can be used as a therapeutic target biomarker for inflammation-related neurodegenerative diseases.

Automated Prediction of Proximal Middle Cerebral Artery Occlusions in Noncontrast Brain Computed Tomography.

BACKGROUND: Early identification of large vessel occlusion (LVO) in patients with ischemic stroke is crucial for timely interventions. We propose a machine learning-based algorithm (JLK-CTL) that uses handcrafted features from noncontrast computed tomography to predict LVO. METHODS: We included patients with ischemic stroke who underwent concurrent noncontrast computed tomography and computed tomography angiography in seven hospitals. Patients from 5 of these hospitals, admitted between May 2011 and March 2015, were randomly divided into training and internal validation (9:1 ratio). Those from the remaining 2 hospitals, admitted between March 2021 and September 2021, were designated for external validation. From each noncontrast computed tomography scan, we extracted differences in volume, tissue density, and Hounsfield unit distribution between bihemispheric regions (striatocapsular, insula, M1-M3, and M4-M6, modified from the Alberta Stroke Program Early Computed Tomography Score). A deep learning algorithm was used to incorporate clot signs as an additional feature. Machine learning models, including ExtraTrees, random forest, extreme gradient boosting, support vector machine, and multilayer perceptron, as well as a deep learning model, were trained and evaluated. Additionally, we assessed the models' performance after incorporating the National Institutes of Health Stroke Scale scores as an additional feature. RESULTS: Among 2919 patients, 83 were excluded. Across the training (n=2463), internal validation (n=275), and external validation (n=95) datasets, the mean ages were 68.5±12.4, 67.6±13.8, and 67.9±13.6 years, respectively. The proportions of men were 57%, 53%, and 59%, with LVO prevalences of 17.0%, 16.4%, and 26.3%, respectively. In the external validation, the ExtraTrees model achieved a robust area under the curve of 0.888 (95% CI, 0.850-0.925), with a sensitivity of 80.1% (95% CI, 72.0-88.1) and a specificity of 88.6% (95% CI, 84.7-92.5). Adding the National Institutes of Health Stroke Scale score to the ExtraTrees model increased sensitivity (from 80.1% to 92.1%) while maintaining specificity. CONCLUSIONS: Our algorithm provides reliable predictions of LVO using noncontrast computed tomography. By enabling early LVO identification, our algorithm has the potential to expedite the stroke workflow.

Overexpression of sweetpotato glutamylcysteine synthetase (IbGCS) in Arabidopsis confers tolerance to drought and salt stresses.

Various environmental stresses induce the production of reactive oxygen species (ROS), which have deleterious effects on plant cells. Glutathione (GSH) is an antioxidant used to counteract reactive oxygen species. Glutathione is produced by glutamylcysteine synthetase (GCS) and glutathione synthetase (GS). However, evidence for the GCS gene in sweetpotato remains scarce. In this study, the full-length cDNA sequence of IbGCS isolated from sweetpotato cultivar Xu18 was 1566 bp in length, which encodes 521 amino acids. The qRT-PCR analysis revealed a significantly higher expression of the IbGCS in sweetpotato flowers, and the gene was induced by salinity, abscisic acid (ABA), drought, extreme temperature and heavy metal stresses. The seed germination rate, root elongation and fresh weight were promoted in T3 Arabidopsis IbGCS-overexpressing lines (OEs) in contrast to wild type (WT) plants under mannitol and salt stresses. In addition, the soil drought and salt stress experiment results indicated that IbGCS overexpression in Arabidopsis reduced the malondialdehyde (MDA) content, enhanced the levels of GCS activity, GSH and AsA content, and antioxidant enzyme activity. In summary, overexpressing IbGCS in Arabidopsis showed improved salt and drought tolerance.

Immunosuppressive therapy in elderly patients with neuromyelitis optica spectrum disorder: a retrospective multicentre study.

BACKGROUND: The risk-benefit relationship of immunosuppressive therapies (ISTs) for elderly patients with neuromyelitis optica spectrum disorder (NMOSD) is not well established. This study aimed to investigate the safety and efficacy of IST in elderly patients with NMOSD. METHODS: This retrospective study analysed IST efficacy and safety in 101 patients with aquaporin-4 antibody-positive NMOSD aged over 65 years, treated for at least 6 months at five Korean referral centres, focusing on relapse rates, infection events and discontinuation due to adverse outcomes. RESULTS: The mean age at disease onset was 59.8 years, and female-to-male ratio was 4:1. Concomitant comorbidities at NMOSD diagnosis were found in 87 patients (86%). The median Expanded Disability Status Scale score at the initiation of IST was 3.5. The administered ISTs included azathioprine (n=61, 60%), mycophenolate mofetil (MMF) (n=48, 48%) and rituximab (n=41, 41%). Over a median of 5.8 years of IST, 58% of patients were relapse-free. The median annualised relapse rate decreased from 0.76 to 0 (p<0.001), and 81% experienced improved or stabilised disability. Patients treated with rituximab had a higher relapse-free rate than those treated with azathioprine or MMF (p=0.022). During IST, 21 patients experienced 25 severe infection events (SIEs) over the age of 65 years, and 3 died from pneumonia. 14 patients (14%) experienced 17 adverse events that led to switching or discontinuation of IST. When comparing the incidence rates of SIEs and adverse events, no differences were observed among patients receiving azathioprine, MMF and rituximab. CONCLUSION: In elderly patients with NMOSD, IST offers potential benefits in reducing relapse rates alongside a tolerable risk of adverse events.

MRI Scoring Systems for Predicting Isocitrate Dehydrogenase Mutation and Chromosome 1p/19q Codeletion in Adult-type Diffuse Glioma Lacking Contrast Enhancement.

Background According to 2021 World Health Organization criteria, adult-type diffuse gliomas include glioblastoma, isocitrate dehydrogenase (IDH)-wildtype; oligodendroglioma, IDH-mutant and 1p/19q-codeleted; and astrocytoma, IDH-mutant, even when contrast enhancement is lacking. Purpose To develop and validate simple scoring systems for predicting IDH and subsequent 1p/19q codeletion status in gliomas without contrast enhancement using standard clinical MRI sequences. Materials and Methods This retrospective study included adult-type diffuse gliomas lacking contrast at contrast-enhanced MRI from two tertiary referral hospitals between January 2012 and April 2022 with diagnoses confirmed at pathology. IDH status was predicted primarily by using T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign, followed by 1p/19q codeletion prediction. A visual rating of MRI features, apparent diffusion coefficient (ADC) ratio, and relative cerebral blood volume was measured. Scoring systems were developed through univariable and multivariable logistic regressions and underwent calibration and discrimination, including internal and external validation. Results For the internal validation cohort, 237 patients were included (mean age, 44.4 years ± 14.4 [SD]; 136 male patients; 193 patients in IDH prediction and 163 patients in 1p/19q prediction). For the external validation cohort, 35 patients were included (46.1 years ± 15.3; 20 male patients; 28 patients in IDH prediction and 24 patients in 1p/19q prediction). The T2-FLAIR mismatch sign demonstrated 100% specificity and 100% positive predictive value for IDH mutation. IDH status prediction scoring system for tumors without mismatch sign included age, ADC ratio, and morphologic characteristics, whereas 1p/19q codeletion prediction for IDH-mutant gliomas included ADC ratio, cortical involvement, and mismatch sign. For IDH status and 1p/19q codeletion prediction, bootstrap-corrected areas under the receiver operating characteristic curve were 0.86 (95% CI: 0.81, 0.90) and 0.73 (95% CI: 0.65, 0.81), respectively, whereas at external validation they were 0.99 (95% CI: 0.98, 1.0) and 0.88 (95% CI: 0.63, 1.0). Conclusion The T2-FLAIR mismatch sign and scoring systems using standard clinical MRI predicted IDH and 1p/19q codeletion status in gliomas lacking contrast enhancement. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Badve and Hodges in this issue.

Predicting leachate impact on groundwater using electrical conductivity and oxidation-reduction potential measurements: An empirical and theoretical approach.

This study developed innovative predictive models of groundwater pollution using in situ electrical conductivity (EC) and oxidation-reduction potential (ORP) measurements at livestock carcass burial sites. Combined electrode analysis (EC and ORP) and machine learning techniques efficiently and accurately distinguished between leachate and background groundwater. Two models-empirical and theoretical-were constructed based on a supervised classification framework. The empirical model constructs a classifier with high accuracy, sensitivity, and specificity, utilizing the comprehensive in situ EC and ORP measurements. The theoretical model with only two end members achieves comparable performance by simulating the leachate-groundwater interactions using a geochemical mixing model. Besides enhancing the early detection capabilities, our approach considerably reduces the reliance on extensive hydrochemical analyses, thus streamlining the monitoring process. Moreover, the use of field parameters was found to proactively identify potential pollution incidents, enhancing the efficiency of groundwater monitoring strategies. Our approach is applicable to various waste disposal sites, indicating its extensive potential for environmental monitoring and management.

Prevalences and Interrelationships of Post COVID-19 Fatigue, Sleep Disturbances, and Depression in Healthy Young and Middle-Aged Adults.

Background: An evaluation of the persistence of symptoms following COVID-19 in economically active young and middle-aged adults is crucial due to its significant socioeconomic impact resulting from compromised work performance. Methods: A prospective, multicenter study at 12 South Korean hospitals from January to December 2022 involved telephone interviews along with validated questionnaires. Results: Among 696 participants with a median age of 32 and no prior diagnoses, 30% of participants experienced persistent fatigue, while 21.4% suffered from sleep disturbance at 6 months following infection. Additionally, approximately 25% of the participants exhibited depression that endured for up to 6 months. Symptomatic individuals at 3 months exhibited a significantly higher prevalence of persistent fatigue, sleep disturbances, and depression at 6 months compared to those who remained asymptomatic. Notably, sleep disturbance and persistent fatigue at 3 months emerged as significant independent predictors of the presence of depression at 6 months. Conclusions: Even among young and middle-aged healthy adults, prolonged fatigue, sleep disturbance, and depression exhibit a significant prevalence and persisted for up to 6 months. Therefore, implementing a workplace management protocol for these symptoms is essential to mitigate the socioeconomic burden caused by the impairment of work efficiency.

Factors Influencing Wound Healing in Diabetic Foot Patients.

Background and objectives: Diabetic foot stands out as one of the most consequential and devastating complications of diabetes. Many factors, including VIPS (Vascular management, Infection management, Pressure relief, and Source of healing), influence the prognosis and treatment of diabetic foot patients. There are many studies on VIPS, but relatively few studies on "sources of healing". Nutrients that affect wound healing are known, but objective data in diabetic foot patients are insufficient. We hypothesized that "sources of healing" would have many effects on wound healing. The purpose of this study is to know the affecting factors related to the source of healing for diabetic foot patients. Materials and Methods: A retrospective review identified 46 consecutive patients who were admitted for diabetic foot management from July 2019 to April 2021 at our department. Several laboratory tests were performed for influencing factor evaluation. We checked serum levels of total protein, albumin, vitamin B, iron, zinc, magnesium, copper, Hb, HbA1c, HDL cholesterol, and LDL cholesterol. These values of diabetic foot patients were compared with normal values. Patients were divided into two groups based on wound healing rate, age, length of hospital stay, and sex, and the test values between the groups were compared. Results: Levels of albumin (37%) and Hb (89%) were low in the diabetic foot patients. As for trace elements, levels of iron (97%) and zinc (95%) were low in the patients, but levels of magnesium and copper were usually normal or high. There were no differences in demographic characteristics based on wound healing rate. However, when compared to normal adult values, diabetic foot patients in our data exhibited significantly lower levels of hemoglobin, total protein, albumin, iron, zinc, copper, and HDL cholesterol. When compared based on age and length of hospital stay, hemoglobin levels were significantly lower in both the older age group and the group with longer hospital stays. Conclusions: Serum levels of albumin, Hb, iron, and zinc were very low in most diabetic foot patients. These low values may have a negative relationship with wound healing. Nutrient replacements are necessary for wound healing in diabetic foot patients.

Using isometric log-ratio in compositional data analysis for developing a groundwater pollution index.

This study introduces a novel groundwater pollution index (GPI) formulated through compositional data analysis (CoDa) and robust principal component analysis (RPCA) to enhance groundwater quality assessment. Using groundwater quality monitoring data from sites impacted by the 2010-2011 foot-and-mouth disease outbreak in South Korea, CoDa uncovers critical hydrochemical differences between leachate-influenced and background groundwater. The GPI was developed by selecting key subcompositional parts (NH4+-N, Cl-, and NO3--N) using RPCA, performing the isometric log-ratio (ILR) transformation, and normalizing the results to environmental standards, thereby providing a more precise and accurate assessment of pollution. Validated against government criteria, the GPI has shown its potential as an alternative assessment tool, with its reliability confirmed by receiver operating characteristic curve analysis. This study highlights the essential role of CoDa, especially the ILR -transformation, in overcoming the limitations of traditional statistical methods that often neglect the relative nature of hydrochemical data. Our results emphasize the utility of the GPI in significantly advancing groundwater quality monitoring and management by addressing a methodological gap in the quantitative assessment of groundwater pollution.

Totally laparoscopic versus laparoscopy-assisted distal gastrectomy: the KLASS-07, a randomized controlled trial.

BACKGROUNDS: Strong evidence is lacking as no confirmatory randomized controlled trials (RCTs) have compared the efficacy of totally laparoscopic distal gastrectomy (TLDG) with laparoscopy-assisted distal gastrectomy (LADG). We performed an RCT to confirm if TLDG is different from LADG. METHODS: The KLASS-07 trial is a multicentre, open-label, parallel-group, phase III, RCT of 442 patients with clinical stage I gastric cancer. Patients were enrolled from 21 cancer care centers in South Korea between January 2018 and September 2020 and randomized to undergo TLDG or LADG using blocked randomization with a 1:1 allocation ratio, stratified by the participating investigators. Patients were treated through R0 resections by TLDG or LADG as the full analysis set of the KLASS-07 trial. The primary endpoint was morbidity within postoperative day 30, and the secondary endpoint was QoL for 1 year. This trial is registered at ClinicalTrials.gov (NCT NCT03393182). RESULTS: 442 patients were randomized (222 to TLDG, 220 to LADG), and 422 patients were included in the pure analysis (213 and 209, respectively). The overall complication rate did not differ between the two groups (TLDG vs. LADG: 12.2% vs. 17.2%). However, TLDG provided less postoperative ileus and pulmonary complications than LADG (0.9% vs. 5.7%, P= 0.006; and 0.5% vs. 4.3%, P= 0.035, respectively). The QoL was better after TLDG than after LADG regarding emotional functioning at 6 months, pain at 3 months, anxiety at 3 and 6 months, and body image at 3 and 6 months (all P< 0.05). However, these QoL differences were resolved at 1 year. CONCLUSIONS: The KLASS-07 trial confirmed that TLDG is not different from LADG in terms of postoperative complication but has advantages to reduce ileus and pulmonary complications. TLDG can be a good option to offer better QoL in terms of pain, body image, emotion, and anxiety at 3-6 months.

Effects of a choral program combining wind instrument performance and breathing training on respiratory function, stress, and quality of life in adolescents: A randomized controlled trial.

BACKGROUND: Choral activities are correlated with various health and wellbeing parameters. However, an intervention combining a music program using wind instruments and choral activities has not yet been investigated. Thus, this study aimed to assess the effects of a 12-week intervention combining a wind instrument performance program and a choral program on stress factors, quality of life, and respiratory function in adolescents located in a metropolitan city with exposure to air pollution. METHOD: This randomized controlled trial consisted of 50 adolescents, and the subjects were randomly assigned to a combination wind instrument and choral training group, a choral training group, and a control group. Following a 12-week intervention program, respiratory function, stress factors, and quality of life were compared between the three groups. RESULTS: Regarding respiratory function, with the exception of maximal inspiratory pressure, all measured variables exhibited an interaction to indicate a variation in the pattern of change(p<0.05). Furthermore, regarding stress factors and quality of life, all measured variables exhibited an interaction to indicate a variation in the pattern of change(p<0.05). As a result of the post-hoc analysis, significant differences were found in all variables in experimental group 1 compared to other groups (p<0.05). CONCLUSION: The results showed that the 12-week intervention combining a wind instrument performance program and a choral program had positive effects in improving the respiratory function, stress factors, and quality of life in adolescents. This study findings are expected to support future studies aimed at promoting overall health including respiratory function and psychological factors through various music-based programs.

Is replacing missing values of PM2.5 constituents with estimates using machine learning better for source apportionment than exclusion or median replacement?

East Asian countries have been conducting source apportionment of fine particulate matter (PM2.5) by applying positive matrix factorization (PMF) to hourly constituent concentrations. However, some of the constituent data from the supersites in South Korea was missing due to instrument maintenance and calibration. Conventional preprocessing of missing values, such as exclusion or median replacement, causes biases in the estimated source contributions by changing the PMF input. Machine learning (ML) can estimate the missing values by training on constituent data, meteorological data, and gaseous pollutants. Complete data from the Seoul Supersite in 2018 was taken, and a random 20% was set as missing. PMF was performed by replacing missing values with estimates. Percent errors of the source contributions were calculated compared to those estimated from complete data. Missing values were estimated using a random forest analysis. Estimation accuracy (r2) was as high as 0.874 for missing carbon species and low at 0.631 when ionic species and trace elements were missing. For the seven highest contributing sources, replacing the missing values of carbon species with estimates minimized the percent errors to 2.0% on average. However, replacing the missing values of the other chemical species with estimates increased the percent errors to more than 9.7% on average. Percent errors were maximal at 37% on average when missing values of ionic species and trace elements were replaced with estimates. Missing values, except for carbon species, need to be excluded. This approach reduced the percent errors to 7.4% on average, which was lower than those due to median replacement. Our results show that reducing the biases in source apportionment is possible by replacing the missing values of carbon species with estimates. To improve the biases due to missing values of the other chemical species, the estimation accuracy of the ML needs to be improved.