Morphological similarity of amygdala-ventral prefrontal pathways represents trait anxiety in younger and older adults.

Stronger amygdala-ventral prefrontal white matter connectivity has been associated with lower trait anxiety, possibly reflecting an increased capacity for efficient communication between the two regions. However, there are also reports arguing against this brain-anxiety association. To address these inconsistencies in the literature, we tested the possibility that idiosyncratic tract morphology may account for meaningful individual differences in trait anxiety, even among those with comparable microstructural integrity. Here, we adopted intersubject representational similarity analysis, an analytic framework that captures multivariate patterns of similarity, to analyze the morphological similarity of amygdala-ventral prefrontal pathways. Data drawn from the Leipzig Study for Mind-Body-Emotion Interactions dataset showed that younger adults (20 to 35 y of age) with low trait anxiety, in contrast to trait-anxious individuals, had consistently similar morphological configurations in their left amygdala-ventral prefrontal pathways. Additional tests on an independent sample of older adults (60 to 75 y of age) validated this finding. Our study reveals a generalizable pattern of brain-anxiety association that is embedded within the shared geometries between fiber tract morphology and trait anxiety data.

Adaptive-to-maladaptive gradient of emotion regulation tendencies are embedded in the functional-structural hybrid connectome.

BACKGROUND: Emotion regulation tendencies are well-known transdiagnostic markers of psychopathology, but their neurobiological foundations have mostly been examined within the theoretical framework of cortical-subcortical interactions. METHODS: We explored the connectome-wide neural correlates of emotion regulation tendencies using functional and diffusion magnetic resonance images of healthy young adults (N = 99; age 20-30; 28 females). We first tested the importance of considering both the functional and structural connectome through intersubject representational similarity analyses. Then, we employed a canonical correlation analysis between the functional-structural hybrid connectome and 23 emotion regulation strategies. Lastly, we sought to externally validate the results on a transdiagnostic adolescent sample (N = 93; age 11-19; 34 females). RESULTS: First, interindividual similarity of emotion regulation profiles was significantly correlated with interindividual similarity of the functional-structural hybrid connectome, more so than either the functional or structural connectome. Canonical correlation analysis revealed that an adaptive-to-maladaptive gradient of emotion regulation tendencies mapped onto a specific configuration of covariance within the functional-structural hybrid connectome, which primarily involved functional connections in the motor network and the visual networks as well as structural connections in the default mode network and the subcortical-cerebellar network. In the transdiagnostic adolescent dataset, stronger functional signatures of the found network were associated with higher general positive affect through more frequent use of adaptive coping strategies. CONCLUSIONS: Taken together, our study illustrates a gradient of emotion regulation tendencies that is best captured when simultaneously considering the functional and structural connections across the whole brain.

Risk Factors for the Mortality of Patients With Coronavirus Disease 2019 Requiring Extracorporeal Membrane Oxygenation in a Non-Centralized Setting: A Nationwide Study.

BACKGROUND: Limited data are available on the mortality rates of patients receiving extracorporeal membrane oxygenation (ECMO) support for coronavirus disease 2019 (COVID-19). We aimed to analyze the relationship between COVID-19 and clinical outcomes for patients receiving ECMO. METHODS: We retrospectively investigated patients with COVID-19 pneumonia requiring ECMO in 19 hospitals across Korea from January 1, 2020 to August 31, 2021. The primary outcome was the 90-day mortality after ECMO initiation. We performed multivariate analysis using a logistic regression model to estimate the odds ratio (OR) of 90-day mortality. Survival differences were analyzed using the Kaplan-Meier (KM) method. RESULTS: Of 127 patients with COVID-19 pneumonia who received ECMO, 70 patients (55.1%) died within 90 days of ECMO initiation. The median age was 64 years, and 63% of patients were male. The incidence of ECMO was increased with age but was decreased after 70 years of age. However, the survival rate was decreased linearly with age. In multivariate analysis, age (OR, 1.048; 95% confidence interval [CI], 1.010-1.089; P = 0.014) and receipt of continuous renal replacement therapy (CRRT) (OR, 3.069; 95% CI, 1.312-7.180; P = 0.010) were significantly associated with an increased risk of 90-day mortality. KM curves showed significant differences in survival between groups according to age (65 years) (log-rank P = 0.021) and receipt of CRRT (log-rank P = 0.004). CONCLUSION: Older age and receipt of CRRT were associated with higher mortality rates among patients with COVID-19 who received ECMO.

Cardiovascular outcomes between COVID-19 and non-COVID-19 pneumonia: a nationwide cohort study.

BACKGROUND: Previous studies that assessed the risk of cardiovascular outcomes in survivors of coronavirus disease 2019 (COVID-19) were likely limited by lack of generalizability and selection of controls nonrepresentative of a counterfactual situation regarding COVID-19-related hospitalization. This study determined whether COVID-19 hospitalization was associated with incident cardiovascular outcomes compared to non-COVID-19 pneumonia hospitalization. METHODS: Nationwide population-based study conducted using the Korean National Health Insurance Service database. A cohort of 132,784 inpatients with COVID-19 (October 8, 2020-September 30, 2021) and a cohort of 31,173 inpatients with non-COVID-19 pneumonia (January 1-December 31, 2019) were included. The primary outcome was the major adverse cardiovascular event (MACE; a composite of myocardial infarction and stroke). Hazard ratios (HRs) with 95% confidence intervals (CIs) of all outcomes of interest were estimated between inverse probability of treatment-weighted patients with COVID-19 and non-COVID-19 pneumonia. RESULTS: After weighting, the COVID-19 and non-COVID-19 pneumonia groups included 125,810 (mean [SD] age, 47.2 [17.6] years; men, 49.3%) and 28,492 patients (mean [SD] age, 48.6 [18.4] years; men, 47.2%), respectively. COVID-19 hospitalization was not associated with an increased risk of the MACE (HR, 0.84; 95% CI 0.69-1.03). However, the MACE (HR, 7.30; 95% CI 3.29-16.21), dysrhythmia (HR, 1.88; 95% CI 1.04-3.42), acute myocarditis (HR, 11.33; 95% CI 2.97-43.20), myocardial infarction (HR, 6.78; 95% CI 3.03-15.15), congestive heart failure (HR, 1.95; 95% CI 1.37-2.77), and thrombotic disease (HR, 8.26; 95% CI 4.06-16.83) risks were significantly higher in patients with COVID-19 aged 18-39 years. The findings were consistent after adjustment for preexisting cardiovascular disease. COVID-19 hospitalization conferred a higher risk of acute myocarditis (HR, 6.47; 95% CI 2.53-16.52) or deep vein thrombosis (HR, 1.97; 95% CI 1.38-2.80), regardless of vaccination status. CONCLUSIONS: Hospitalized patients with COVID-19 were not at an increased risk of cardiovascular outcomes compared to patients with non-COVID-19 pneumonia. Further studies are needed to evaluate whether the increased risk of cardiovascular outcomes is confined to younger patients.

Poly-ADP ribosylation of p21 by tankyrases promotes p21 degradation and regulates cell cycle progression.

p21WAF1/Cip1 acts as a key negative regulator of cell cycle progression, which can form complexes with cyclin-dependent kinases together with specific cyclins to induce cell cycle arrest at specific stages. p21 protein levels have been shown to be regulated primarily through phosphorylation and ubiquitination during various stages of the cell cycle. Although phosphorylation and ubiquitin-dependent proteasomal degradation of p21 have been well established, other post-translational modifications that contribute to regulation of p21 stability and function remain to be further elucidated. Here, we show that p21 degradation and its function are controlled by tankyrases, which are members of the poly(ADP-ribose) polymerase (PARP) protein family. p21 interacts with tankyrases via newly defined tankyrase-binding motifs and is PARylated by tankyrases in vitro and in vivo, suggesting that PARylation is a new post-translational modification of p21. Up-regulation of tankyrases induces ubiquitin-dependent proteasomal degradation of p21 through an E3 ligase RNF146, thus promoting cell cycle progression in the G1/S phase transition. On the contrary, inhibition of tankyrases by knockdown or inhibitor treatment stabilizes p21 protein and leads to cell cycle arrest in the G1 phase. Together, our data demonstrate that tankyrase may function as a new molecular regulator that controls the protein levels of p21 through PARylation-dependent proteasomal degradation. Hence, a novel function of the tankyrase-p21 axis may represent a new avenue for regulating cell cycle progression.

Vitamin C for ≥ 5 days is associated with decreased hospital mortality in sepsis subgroups: a nationwide cohort study.

BACKGROUND: Previous randomized trials of vitamin C, hydrocortisone, and thiamine on sepsis were limited by short-term vitamin C administration, heterogeneous populations, and the failure to evaluate each component's effect. The purpose of this study was to determine whether vitamin C alone for ≥ 5 days or in combination with corticosteroids and/or thiamine was associated with decreased mortality across the sepsis population and subpopulation. METHODS: Nationwide population-based study conducted using the Korean National Health Insurance Service database. A total of 384,282 adult patients with sepsis who were admitted to the intensive care unit were enrolled from January 2017 to December 2019. The primary outcome was hospital mortality, while the key secondary outcome was 90-day mortality. RESULTS: The mean [standard deviation] age was 69.0 [15.4] years; 57% were male; and 36,327 (9%) and 347,955 did and did not receive vitamin C, respectively. After propensity score matching, each group involved 36,327 patients. The hospital mortality was lower by - 0.9% in the treatment group (17.1% vs 18.0%; 95% confidence interval, - 1.3 to - 0.5%; p < 0.001), a significant but extremely small difference. However, mortality decreased greater in patients who received vitamin C for ≥ 5 days (vs 1-2 or 3-4 days) (15.8% vs 18.8% vs 18.3%; p < 0.001). Further, vitamin C was associated with a lower hospital mortality in patients with older age, multiple comorbidities, pneumonia, genitourinary infection, septic shock, and mechanical ventilation. Consistent findings were found for 90-day mortality. Moreover, vitamin C alone or in combination with thiamine was significantly associated with decreased hospital mortality. CONCLUSIONS: Intravenous vitamin C of ≥ 5 days was significantly associated with decreased hospital and 90-day mortality in sepsis patients. Vitamin C combined with corticosteroids and/or thiamine in specific sepsis subgroups warrants further study.

Impact of left ventricular function on tissue perfusion and renal outcomes in patients with sepsis.

AIMS: Left ventricular (LV) dysfunction is a predictor of mortality in patients with sepsis. However, it remains uncertain whether LV dysfunction aggravates tissue perfusion, leading to organ failure, or whether it has an independent impact. We investigated the association between LV dysfunction and tissue perfusion, and their impacts on renal outcomes in patients with sepsis. MATERIALS AND METHODS: We retrospectively reviewed 162 adult patients with sepsis who met the Sepsis-3 definition, including 83 (51.2%) with normal LV function, 39 (24.1%) with diastolic dysfunction (septal E/e' ratio > 15 with ejection fraction ≥ 50%), and 40 (24.7%) with systolic dysfunction (ejection fraction < 50%). Tissue perfusion was assessed using blood lactate levels. RESULTS: LV function was not associated with the initial lactate level, 24-hour lactate level, and lactate clearance (p = 0.861, 0.907, 0.363). However, acute kidney injury risk increased with blood lactate levels ≥ 2 mmol/L or systolic dysfunction in multivariate analysis (p = 0.032 and 0.090). The probability of renal replacement therapy did not depend on both blood lactate levels and LV function, conversely, the renal replacement therapy-free period was shorter in patients with LV dysfunction, independent of previous chronic kidney disease (p = 0.003). Renal function at discharge was not significantly related to lactate levels and LV function (p = 0.688 and 0.174). CONCLUSION: LV dysfunction might not influence tissue perfusion but could have unfavorable impacts on renal outcomes in patients with sepsis. Besides treatment for preserving tissue perfusion, individualized therapies tailored to LV function are needed.

Association of Renin-angiotensin-aldosterone System Inhibitors With Coronavirus Disease 2019 (COVID-19)- Related Outcomes in Korea: A Nationwide Population-based Cohort Study.

BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) inhibitors may facilitate host cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or attenuate organ injury via RAAS blockade. We aimed to assess the associations between prior use of RAAS inhibitors and clinical outcomes among Korean patients with coronavirus disease 2019 (COVID-19). METHODS: We performed a nationwide population-based cohort study using the Korean Health Insurance Review and Assessment database. Claim records were screened for 69 793 individuals who were tested for COVID-19 until 8 April 2020. Adjusted odds ratios (ORs) were used to compare the clinical outcomes between RAAS inhibitor users and nonusers. RESULTS: Among 5179 confirmed COVID-19 cases, 762 patients were RAAS inhibitor users and 4417 patients were nonusers. Relative to nonusers, RAAS inhibitor users were more likely to be older, male, and have comorbidities. Among 1954 hospitalized patients with COVID-19, 377 patients were RAAS inhibitor users, and 1577 patients were nonusers. In-hospital mortality was observed for 33 RAAS inhibitor users (9%) and 51 nonusers (3%) (P < .001). However, after adjustment for age, sex, Charlson comorbidity index, immunosuppression, and hospital type, the use of RAAS inhibitors was not associated with a higher risk of mortality (adjusted OR, 0.88; 95% confidence interval, 0.53-1.44; P = .60). No significant differences were observed between RAAS inhibitor users and nonusers in terms of vasopressor use, modes of ventilation, extracorporeal membrane oxygenation, renal replacement therapy, and acute cardiac events. CONCLUSIONS: Our findings suggest that prior use of RAAS inhibitors was not independently associated with mortality among COVID-19 patients in Korea.

Intratumorally Establishing Type 2 Innate Lymphoid Cells Blocks Tumor Growth.

A long-standing question in the field of tumor immunotherapy is how Th2 cytokines block tumor growth. Their antitumor effects are particularly prominent when they are secreted continuously in tumors, suggesting that Th2 cytokines may create a tumor microenvironment unfavorable for tumor growth independently of adaptive immunity. In this study, we show that local production of IL-33 establishes a high number of type 2 innate lymphoid cells (ILC2s) with potent antitumor activity. IL-33 promotes secretion of a massive amount of CXCR2 ligands from ILC2s but creates a tumor microenvironment where tumor cells express CXCR2 through a dysfunctional angiogenesis/hypoxia/reactive oxygen species axis. These two signaling events converge to reinforce tumor cell-specific apoptosis through CXCR2. Our results identify a previously unrecognized antitumor therapeutic pathway wherein ILC2s play a central role.

Radial probe endobronchial ultrasound using a guide sheath for peripheral lung lesions in beginners.

BACKGROUND: The diagnostic yields and safety profiles of transbronchial lung biopsy have not been evaluated in inexperienced physicians using the combined modality of radial probe endobronchial ultrasound and a guide sheath (EBUS-GS). This study assessed the utility and safety of EBUS-GS during the learning phase by referring to a database of performed EBUS-GS procedures. METHODS: From December 2015 to January 2017, all of the consecutive patients who underwent EBUS-GS were registered. During the study period, two physicians with no previous experience performed the procedure. To assess the diagnostic yields, learning curve, and safety profile of EBUS-GS performed by these inexperienced physicians, the first 100 consecutive EBUS-GS procedures were included in the evaluation. RESULTS: The overall diagnostic yield of EBUS-GS performed by two physicans in 200 patients with a peripheral lung lesion was 73.0%. Learning curve analyses showed that the diagnostic yields were stable, even when the procedure was performed by beginners. Complications related to EBUS-GS occurred in three patients (1.5%): pneumothorax developed in two patients (1%) and resolved spontaneously without chest tube drainage; another patient (0.5%) developed a pulmonary infection after EBUS-GS. There were no cases of pneumothorax requiring chest tube drainage, severe hemorrhage, respiratory failure, premature termination of the procedure, or procedure-related mortality. CONCLUSIONS: EBUS-GS is a safe and stable procedure with an acceptable diagnostic yield, even when performed by physicians with no previous experience.

Clinical Utility of Rapid Pathogen Identification for Detecting the Causative Organisms in Sepsis: A Single-Center Study in Korea.

PURPOSE: The aim of this pre- and postintervention cohort study was evaluating how effectively rapid pathogen identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) detected the causative organisms in sepsis. METHODS: All consecutive adult patients who had bacteremia within 72 h of intensive care unit admission and met ≥2 quick Sequential Organ Failure Assessment criteria at intensive care unit admission were analyzed. The patients whose microorganisms were identified via MALDI-TOF MS between March 2014 and February 2016 formed the postintervention group. The patients whose microorganisms were identified by using conventional methods between March 2011 and February 2013 formed the preintervention group. RESULTS: The postintervention group (n=58) had a shorter mean time from blood draw to receiving the antimicrobial susceptibility results than the preintervention group (n=40) (90.2 ± 32.1 vs. 108.7 ± 43.1 h; p=0.02). The postintervention group was also more likely to have received active antimicrobial therapy by the time the susceptibility report became available (77% vs. 47%; p=0.005). Its 28-day mortality was also lower (40% vs. 70%; p=0.003). Univariate analysis showed that identification via MALDI-TOF MS (odds ratio, 0.28; 95% confidence interval, 0.12-0.66; p=0.004) and active therapy (odds ratio, 0.38; 95% confidence interval, 0.16-0.95; p=0.04) were associated with lower 28-day mortality. CONCLUSION: Rapid microorganism identification via MALDI-TOF MS followed by appropriate antimicrobial therapy may improve the clinical outcomes of patients with sepsis.

Lung function in patients with lung injury due to household chemical inhalation: Post hoc analysis of a prospective nationwide cohort.

BACKGROUND AND OBJECTIVE: Inhalation exposure to household chemicals can result in serious health problems, although the long-term outcomes are unclear. We evaluated the changes in lung function after home humidifier disinfectant (HD) exposure. METHODS: This post hoc analysis of a prospective nationwide cohort involved patients with inhalation lung injury due to HD. Patients underwent spirometric measurements at onset and annually thereafter. RESULTS: Forty subjects met the eligibility criteria. Overall, mean forced vital capacity (FVC) increased significantly during the first 3 years from 2.10 ± 0.74 to 3.06 ± 1.08 L. Mean forced expiratory volume in 1 s (FEV 1 ) also rose from 1.84 ± 0.63 to 2.62 ± 0.88 L. Both variables then stabilized. However, in 19 (48%) patients, the FVCs did not normalize. Compared to subjects with an FVC at onset of <2.5 L, subjects with onset FVC ≥2.5 L exhibited significantly more improvement in percent predicted FVC over time (group × time interaction: P < 0.001). Patients with lower exposure also exhibited increasing percent predicted FVC over time, whereas more exposed patients showed a plateau starting at year 1. On multivariate analysis, onset FVC < 2.5 L associated significantly with <80% predicted FVC at year 4 (adjusted OR: 20.33; 95% CI: 1.10-376.53; P = 0.04). CONCLUSION: Half of the patients with inhalation injury exhibited stabilization of lung function within several years of onset. However, lung function was impaired in the remaining patients. This impairment associated with lung function at onset and exposure intensity.

IL-33-induced hematopoietic stem and progenitor cell mobilization depends upon CCR2.

IL-33 has been implicated in the pathogenesis of asthma, atopic allergy, anaphylaxis, and other inflammatory diseases by promoting the production of proinflammatory cytokines and chemokines or Th2 immune responses. In this study, we analyzed the in vivo effect of IL-33 administration. IL-33 markedly promoted myelopoiesis in the bone marrow and myeloid cell emigration. Concomitantly, IL-33 induced hematopoietic stem and progenitor cell (HSPC) mobilization and extramedullary hematopoiesis. HSPC mobilization was mediated mainly through increased levels of CCL7 produced by vascular endothelial cells in response to IL-33. In vivo treatment of IL-33 rapidly induced phosphorylation of ERK, JNK, and p38, and inhibition of these signaling molecules completely blocked the production of CCL7 induced by IL-33. Consistently, inhibitor of CCR2 markedly reduced IL-33-mediated HSPC mobilization in vivo and migration of HSPCs in response to CCL7 in vitro. IL-33-mobilized HSPCs were capable of homing to, and of long-term reconstitution in, the bone marrow of irradiated recipients. Immune cells derived from these recipients had normal antifungal activity. The ability of IL-33 to promote migration of HSPCs and myeloid cells into the periphery and to regulate their antifungal activity represents a previously unrecognized role of IL-33 in innate immunity. These properties of IL-33 have clinical implications in hematopoietic stem cell transplantation.

Enhanced electrical conductivity and hardness of silver-nickel composites by silver-coated multi-walled carbon nanotubes.

We investigated electrical conductivity and Vickers hardness of Ag- and Ni-based composites prepared by powder metallurgy involving spark plasma sintering. The starting composition was Ag:Ni = 61:39 vol%, which provided an electrical conductivity of 3.30 × 10(5) S cm(-1) and a hardness of 1.27 GPa. The addition of bare multi-walled carbon nanotubes (MWNTs, 1.45 vol%) increased hardness (1.31 GPa) but decreased electrical conductivity (2.99 × 10(5) S cm(-1)) and carrier mobility (11 cm(2) V(-1) s(-1)) due to the formation of Ni3C in the interface between the MWNTs and Ni during spark plasma sintering. The formation of Ni3C was prevented by coating the surface of the nanotubes with Ag (nAgMWNTs), concomitantly increasing electrical conductivity (3.43 × 10(5) S cm(-1)) and hardness (1.37 GPa) of the sintered specimen (Ag:Ni:nAgMWNTs = 59.55:39:1.45 vol%). The electrical contact switching time (133 357) was also increased by 30%, demonstrating excellent feasibility as electrical contact materials for electric power industries.

IL-33 priming regulates multiple steps of the neutrophil-mediated anti-Candida albicans response by modulating TLR and dectin-1 signals.

IL-33 is known to play an important role in Th2 immunity. In this study, we investigated the effect of IL-33 pretreatment on anti-fungal response using an acute Candida albicans peritoneal infection model. IL-33 pretreatment induced a rapid fungal clearance and markedly reduced the C. albicans infection-associated mortality. The priming effect of IL-33 occurred during multiple steps of the neutrophil-mediated anti-fungal response. First, the anti-fungal effect occurred due to the rapid and massive recruitment of neutrophils to the site of infection as a result of the release of CXCR2 chemokines by peritoneal macrophages and by reversal of the TLR-induced reduction of CXCR2 expression in neutrophils during IL-33 priming. Second, conditioning of neutrophils by IL-33 activated the TLR and dectin-1 signaling pathways, leading to the upregulation of complement receptor 3 expression induced by C. albicans. Upregulated CR3 in turn increased the phagocytosis of opsonized C. albicans and resulted in the production of high levels of reactive oxygen species and the subsequent enhanced killing activity of neutrophils. Taken together, our results suggest that IL-33 can regulate the anti-fungal activity of neutrophils by collaborative modulation of the signaling pathways of different classes of innate immune receptors.

Association between Initial Fibrinogen Levels and the Need for Massive Transfusion in Emergency Department Patients with Primary Postpartum Hemorrhage: A Retrospective Study from a Single Center in Korea.

BACKGROUND: This study aimed to evaluate the association between initial fibrinogen levels and massive transfusion (MT) in emergency department (ED) patients with primary postpartum hemorrhage (PPH). METHODS: This retrospective study was conducted in the ED of a university-affiliated, tertiary referral center from January 2004 to August 2023. Patients were divided into two groups: the MT group, which included those who received a transfusion of 10 or more units of packed red blood cells within the first 24 h, and the Non-MT group. RESULTS: Out of the 364 patients included in the study, 97 (26.6%) required MT. Fibrinogen, shock index, and lactate were independently associated with MT (odds ratio [OR] 0.987; 95% confidence interval [CI] 0.983-0.991; p < 0.001, OR 7.277; 95% CI 1.856-28.535; p = 0.004, and OR 1.261; 95% CI 1.021-1.557; p = 0.031, respectively). The area under the receiver operating characteristic curve for fibrinogen, shock index, and lactate in predicting MT was 0.871 (95% CI 0.832-0.904; p < 0.001), 0.821 (95% CI 0.778-0.859; p < 0.001), and 0.784 (95% CI 0.738-0.825; p < 0.001), respectively. When the cutoff value of fibrinogen was 400 mg/dL, both the sensitivity and negative predictive values for predicting MT were 100.0%. When the cutoff value of fibrinogen was 100 mg/dL, the specificity and positive predictive values were 91.8% and 70.7%, respectively. CONCLUSION: The initial fibrinogen levels were independently associated with the need for MT in ED patients with primary PPH.

O-GlcNAcylation of RBM14 contributes to elevated cellular O-GlcNAc through regulation of OGA protein stability.

Dysregulation of O-GlcNAcylation has emerged as a potential biomarker for several diseases, particularly cancer. The role of OGT (O-GlcNAc transferase) in maintaining O-GlcNAc homeostasis has been extensively studied; nevertheless, the regulation of OGA (O-GlcNAcase) in cancer remains elusive. Here, we demonstrated that the multifunctional protein RBM14 is a regulator of cellular O-GlcNAcylation. By investigating the correlation between elevated O-GlcNAcylation and increased RBM14 expression in lung cancer cells, we discovered that RBM14 promotes ubiquitin-dependent proteasomal degradation of OGA, ultimately mediating cellular O-GlcNAcylation levels. In addition, RBM14 itself is O-GlcNAcylated at serine 521, regulating its interaction with the E3 ligase TRIM33, consequently affecting OGA protein stability. Moreover, we demonstrated that mutation of serine 521 to alanine abrogated the oncogenic properties of RBM14. Collectively, our findings reveal a previously unknown mechanism for the regulation of OGA and suggest a potential therapeutic target for the treatment of cancers with dysregulated O-GlcNAcylation.

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.

ECMO is associated with decreased hospital mortality in COVID-19 ARDS.

This study determined whether compared to conventional mechanical ventilation (MV), extracorporeal membrane oxygenation (ECMO) is associated with decreased hospital mortality or fibrotic changes in patients with COVID-19 acute respiratory distress syndrome. A cohort of 72 patients treated with ECMO and 390 with conventional MV were analyzed (February 2020-December 2021). A target trial was emulated comparing the treatment strategies of initiating ECMO vs no ECMO within 7 days of MV in patients with a PaO2/FiO2 < 80 or a PaCO2 ≥ 60 mmHg. A total of 222 patients met the eligibility criteria for the emulated trial, among whom 42 initiated ECMO. ECMO was associated with a lower risk of hospital mortality (hazard ratio [HR], 0.56; 95% confidence interval [CI] 0.36-0.96). The risk was lower in patients who were younger (age < 70 years), had less comorbidities (Charlson comorbidity index < 2), underwent prone positioning before ECMO, and had driving pressures ≥ 15 cmH2O at inclusion. Furthermore, ECMO was associated with a lower risk of fibrotic changes (HR, 0.30; 95% CI 0.11-0.70). However, the finding was limited due to relatively small number of patients and differences in observability between the ECMO and conventional MV groups.