Neural Effects of One's Own Voice on Self-Talk for Emotion Regulation.

One's own voice undergoes unique processing that distinguishes it from others' voices, and thus listening to it may have a special neural basis for self-talk as an emotion regulation strategy. This study aimed to elucidate how neural effects of one's own voice differ from those of others' voices on the implementation of emotion regulation strategies. Twenty-one healthy adults were scanned using fMRI while listening to sentences synthesized in their own or others' voices for self-affirmation and cognitive defusion, which were based on mental commitments to strengthen one's positive aspects and imagining metaphoric actions to shake off negative aspects, respectively. The interaction effect between voice identity and strategy was observed in the superior temporal sulcus, middle temporal gyrus, and parahippocampal cortex, and activity in these regions showed that the uniqueness of one's own voice is reflected more strongly for cognitive defusion than for self-affirmation. This interaction was also seen in the precuneus, suggesting intertwining of self-referential processing and episodic memory retrieval in self-affirmation with one's own voice. These results imply that unique effects of one's own voice may be expressed differently due to the degree of engagement of neural sharpening-related regions and self-referential networks depending on the type of emotion regulation.

Dendritic cells pulsed with penetratin-OLFM4 inhibit the growth and metastasis of melanoma in mice.

Cancer stem cells (CSCs) can self-renew and differentiate, contributing to tumor heterogeneity, metastasis, and recurrence. Their resistance to therapies, including immunotherapy, underscores the importance of targeting them for complete remission and relapse prevention. Olfactomedin 4 (OLFM4), a marker associated with various cancers such as colorectal cancer, is expressed on CSCs promoting immune evasion and tumorigenesis. However, its potential as a target for CSC-specific immunotherapy remains underexplored. The primary aim of this study is to evaluate the effectiveness of targeting OLFM4 with dendritic cell (DC)-based vaccines in inhibiting tumor growth and metastasis. To improve antigen delivery and immune response, OLFM4 was conjugated with a protein-transduction domain (PTD) from the antennapedia of Drosophila called penetratin, creating a fusion protein (P-OLFM4). The efficacy of DCs pulsed with P-OLFM4 (DCs [P-OLFM4]) was compared to DCs pulsed with OLFM4 (DCs [OLFM4]) and PBS (DCs [PBS]). DCs [P-OLFM4] inhibited tumor growth by 91.2 % and significantly reduced lung metastasis of OLFM4+ melanoma cells by 97 %, compared to the DCs [PBS]. DCs [OLFM4] also demonstrated a reduction in lung metastasis by 59.7 % compared to DCs [PBS]. Immunization with DCs [P-OLFM4] enhanced OLFM4-specific T-cell proliferation, interferon-γ production, and cytotoxic T cell activity in mice. The results indicate that OLFM4 is a viable target for CSC-focused immunotherapy. DC [P-OLFM4] vaccines can elicit robust immune responses, significantly inhibiting tumor growth and metastasis. This strategy holds promise for developing more effective cancer treatments that specifically target CSCs, potentially leading to better patient outcomes by reducing the likelihood of tumor relapse and metastasis.

Severe Fever with Thrombocytopenia Syndrome in South Korea, 2016-2021: Clinical Features of Severe Progression and Complications.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infection with a high case fatality rate. The serious clinical features need to be further defined. We performed a retrospective analysis among SFTS patients in South Korea during 2016-2021 to update the current status. The basic epidemiology of all reported cases was analyzed, and the detailed clinical data of the subjects were further collected from study hospitals selected in terms of their geographic location and capability of SFTS care. Cases of SFTS were reported across the country and were greatly increased since the initial endemic phase, even under the passive surveillance system. The case fatality rate remained at approximately 16.8%. Coinfections at admission were present in 7.8% of the patients. Major complications included bleeding (15.2%), hemophagocytic lymphohistiocytosis (6.7%), bacteremia or candidemia (4.0%), and invasive pulmonary aspergillosis (1.7%). It took a median 4 days from the onset of illness to hospital admission. Rapid clinical deterioration was observed with a median 1 day for intensive care unit admission, 3 days for mechanical ventilation, 4 days for renal replacement therapy, and 5 days for death, all after the hospitalization. Multivariate analysis showed that the fatality was associated with older age, bacteremia, or candidemia during hospitalization, and the presence of several variables at admission such as fever, altered mentality, aspartate aminotransferase >200 IU/L, serum creatinine level >1.2 mg/dL, and prolonged prothrombin time and activated partial thromboplastin time. Treatment options to improve clinical outcomes are limited, despite best supportive care. Specific treatment is urgently needed to change the fatal course.

Cross-sectional associations of gender identity and sexual orientation, with co-occurrence and clustering of health-related behaviours among British adolescents: Millennium cohort study.

PURPOSE: We examined whether gender identity and sexual orientation were associated with seven health-related behaviours, and with co-occurrence and clustering of these behaviours among British adolescents. METHODS: Millennium Cohort Study (age 17 wave) provided data on the exposures, gender identity (male, female, genderqueer) and sexual orientation (heterosexual, bisexual, gay or lesbian, or other), and seven self-reported health-related behaviours (binge drinking, drug use, no consumption of breakfast, no consumption of fruits or vegetables, physical inactivity, poor sleep, and smoking or vaping). Poisson regressions examined associations between the exposures and single behaviours (reporting prevalence ratios (PRs)); and multinomial logistic regressions were used for behavioural cumulative co-occurrence score (reporting PRs). Cluster patterns were identified using Ward's agglomerative hierarchical cluster analysis while associations with cluster membership were performed using logistic regressions (reporting odds ratios (ORs)). RESULTS: Our sample included 6022 adolescents (55.4% female, 1.5% genderqueer, 11.6% non-heterosexual). Adolescents who identified as genderqueer had the highest prevalence of not eating breakfast (PR: 60.5% [95%CI 48.4-71.4]) and poor sleep (68.7% [95%CI 55.6-79.3]). Those who identified as bisexual had a higher PR of co-occurring behaviours (2.46 [95%CI 1.39-4.27]). Among the three clusters identified (1: Multiple risk behaviours; 2: Physical inactivity and binge drinking; 3: Poor diet and physical inactivity), adolescents who identified as genderqueer or other sexual orientation showed the highest prevalence in cluster 3. CONCLUSION: Gender and sexual minority British adolescents showed a higher prevalence of risky health-related behaviours, and higher risk of co-occurring behaviours. Physical inactivity and poor diet behaviours commonly clustered together for these groups.

Remdesivir is Associated with Reduced Mortality in Patients Hospitalized for COVID-19 Not Requiring Supplemental Oxygen.

Background: Remdesivir has demonstrated benefit in some hospitalized patients with coronavirus disease 2019 (COVID-19) on supplemental oxygen and in nonhospitalized patients breathing room air. The durability of this benefit across time periods with different circulating severe acute respiratory syndrome coronavirus 2 variants of concern (VOC) is unknown. This comparative effectiveness study in patients hospitalized for COVID-19 and not receiving supplemental oxygen at admission compared those starting remdesivir treatment in the first 2 days of admission with those receiving no remdesivir during their hospitalization across different VOC periods. Method: Using a large, multicenter US hospital database, in-hospital mortality rates were compared among patients hospitalized for COVID-19 but not requiring supplemental oxygen at admission between December 2020 and April 2022. Patients receiving remdesivir at hospital admission were matched 1:1 to those not receiving remdesivir during hospitalization, using propensity score matching. Cox proportional hazards models were used to assess 14- and 28-day in-hospital mortality rates or discharge to hospice. Results: Among the 121 336 eligible patients, 58 188 remdesivir-treated patients were matched to 17 574 unique patients not receiving remdesivir. Overall, 5.4% of remdesivir-treated and 7.3% in the non-remdesivir group died within 14 days, and 8.0% and 9.8%, respectively, died within 28 days. Remdesivir treatment was associated with a statistically significant reduction in the in-hospital mortality rate compared with non-remdesivir treatment (14-day and 28-day adjusted hazard ratios [95% confidence interval], 0.75 [0.68-0.83] and 0.83 [0.76-0.90], respectively). This significant mortality benefit endured across the different VOC periods. Conclusions: Remdesivir initiation in patients hospitalized for COVID-19 and not requiring supplemental oxygen at admission was associated with a significantly reduced in-hospital mortality rate. These findings highlight a potential survival benefit when clinicians initiated remdesivir on admission across the dominant variant eras of the evolving pandemic.

Outcomes of Bypass Surgery in Adult Moyamoya Disease by Onset Type.

Importance: Moyamoya disease (MMD) is a rare chronic cerebrovascular disease, and the outcomes of bypass management in adult patients remain controversial. Objective: To categorize adult MMD based on asymptomatic, ischemic, and hemorrhagic onset and compare the outcomes (death, hemorrhagic stroke [HS], and ischemic stroke [IS]) of bypass surgery (direct or indirect) with those of conservative management. Design, Setting, and Participants: This retrospective, nationwide, population-based longitudinal cohort study used Korean National Health Insurance Research data to identify adults (aged ≥15 years) with MMD who were diagnosed between January 1, 2008, and December 31, 2020, and followed up until December 31, 2021 (median follow-up, 5.74 [IQR, 2.95-9.42] years). A total of 19 700 participants (3194 with hemorrhagic, 517 with ischemic, and 15 989 with asymptomatic MMD) were included. Data were analyzed from January 2 to April 1, 2023. Exposures: Bypass surgery and conservative management. Main Outcomes and Measures: Death constituted the primary outcome; secondary outcomes consisted of HS or IS. Kaplan-Meier survival curve and Cox proportional hazards regression analysis were applied. The propensity score-matching and stratified analyses were performed to control covariate effects. Results: A total of 19 700 patients (mean [SD] age, 45.43 [14.98] years; 12 766 [64.8%] female) were included. Compared with conservative management, bypass was associated with a reduced risk of death (adjusted hazard ratio [AHR], 0.50 [95% CI, 0.41-0.61]; P < .001) and HS (AHR, 0.36 [0.30-0.40]; P < .001) in hemorrhagic MMD; reduced risk of IS (AHR, 0.55 [95% CI, 0.37-0.81]; P = .002) in ischemic MMD; and reduced risk of death (AHR, 0.74 [95% CI, 0.66-0.84]; P < .001) in asymptomatic MMD. However, bypass was associated with an increased risk of HS (AHR, 1.76 [95% CI, 1.56-2.00]; P < .001) in asymptomatic MMD. Both direct and indirect bypass demonstrated similar effects in hemorrhagic and asymptomatic MMD, except only direct bypass was associated with a reduced risk of IS (AHR, 0.52 [95% CI, 0.33- 0.83]; P = .01) in ischemic MMD. After stratification, bypass was associated with a reduced risk of death in patients younger than 55 years with ischemic (AHR, 0.34 [95% CI, 0.13- 0.88]; P = .03) and asymptomatic (AHR, 0.69 [95% CI, 0.60-0.79]; P < .001) MMD, but an increased risk of HS in patients 55 years or older with ischemic MMD (AHR, 2.13 [95% CI, 1.1-4.16]; P = .03). Conclusions and Relevance: The findings of this cohort study of bypass outcomes for patients with MMD emphasize the importance of tailoring management strategies in adult patients based on onset types.

THP-1 Monocytic Cells Are Polarized to More Antitumorigenic Macrophages by Serial Treatment with Phorbol-12-Myristate-13-Acetate and PD98059.

Background and Objectives: As modulators of the tumor microenvironment, macrophages have been extensively studied for their potential in developing anticancer strategies, particularly in regulating macrophage polarization towards an antitumorigenic (M1) phenotype rather than a protumorigenic (M2) one in various experimental models. Here, we evaluated the effect of PD98059, a mitogen-activated protein kinase kinase MAPKK MEK1-linked pathway inhibitor, on the differentiation and polarization of THP-1 monocytes in response to phorbol-12-myristate-13-acetate (PMA) under various culture conditions for tumor microenvironmental application. Materials and Methods: Differentiation and polarization of THP-1 were analyzed by flow cytometry and RT-PCR. Polarized THP-1 subsets with different treatment were compared by motility, phagocytosis, and so on. Results: Clearly, PMA induced THP-1 differentiation occurs in adherent culture conditions more than nonadherent culture conditions by increasing CD11b expression up to 90%, which was not affected by PD98059 when cells were exposed to PMA first (post-PD) but inhibited when PD98059 was treated prior to PMA treatment (pre-PD). CD11bhigh THP-1 cells treated with PMA and PMA-post-PD were categorized into M0 (HLA-DRlow and CD206low), M1 (HLA-DRhigh and CD206low), and M2 (HLA-DRlow and CD206high), resulting in an increased population of M1 macrophages. The transcription levels of markers of macrophage differentiation and polarization confirmed the increased M1 polarization of THP-1 cells with post-PD treatment rather than with PMA-only treatment. The motility and cytotoxicity of THP-1 cells with post-PD treatment were higher than THP-1 cells with PMA, suggesting that post-PD treatment enhanced the anti-tumorigenicity of THP-1 cells. Confocal microscopy and flow cytometry showed the effect of post-PD treatment on phagocytosis by THP-1 cells. Conclusions: We have developed an experimental model of macrophage polarization with THP-1 cells which will be useful for further studies related to the tumor microenvironment.

U-Shape Pillar Strip for 3D Cell-Lumped Organoid Model (3D-COM) Mimicking Lung Cancer Hypoxia Conditions in High-Throughput Screening (HTS).

Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients. Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a U-shape pillar strip for a 3D cell-lumped organoid model (3D-COM) to study the effects of hypoxia on lung cancer in a high-throughput manner. We developed a U-pillar strip that facilitates the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the U-shape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.

Limited impact of bacterial virulence on early mortality risk factors in Acinetobacter baumannii bacteremia observed in a Galleria mellonella model.

Acinetobacter baumannii (AB) has emerged as a major pathogen in vulnerable and severely ill patients. It remains unclear whether early mortality (EM) due to AB bacteremia is because of worse clinical characteristics of the infected patients or the virulence of the pathogen. In this study, we aimed to investigate the effect of AB virulence on EM due to bacteremia. This retrospective study included 138 patients with AB bacteremia (age: ≥ 18 years) who were admitted to a tertiary care teaching hospital in South Korea between 2015 and 2019. EM was defined as death occurring within 7 days of bacteremia onset. The AB clinical isolates obtained from the patients' blood cultures were injected into 15 Galleria mellonella larvae each, which were incubated for 5 days. Clinical isolates were classified into high- and low-virulence groups based on the number of dead larvae. Patients' clinical data were combined and subjected to multivariate Cox regression analyses to identify the risk factors for EM. In total, 48/138 (34.8%) patients died within 7 days of bacteremia onset. The Pitt bacteremia score was the only risk factor associated with EM. In conclusion, AB virulence had no independent effect on EM in patients with AB bacteremia.

Linking microbial population dynamics in anaerobic bioreactors to food waste type and decomposition stage.

A key question in anaerobic microbial ecology is how microbial communities develop over different stages of waste decomposition and whether these changes are specific to waste types. We destructively sampled over time 26 replicate bioreactors cultivated on fruit/vegetable waste (FVW) and meat waste (MW) based on pre-defined waste components and composition. To characterize community shifts, we examined 16S rRNA genes from both the leachate and solid fractions of the waste. Waste decomposition occurred faster in FVW than MW, as accumulation of ammonia in MW reactors led to inhibition of methanogenesis. We identified population succession during different stages of waste decomposition and linked specific populations to different waste types. Community analyses revealed underrepresentation of methanogens in the leachate fractions, emphasizing the importance of consistent and representative sampling when characterizing microbial communities in solid waste.

Association between mukbang and cookbang viewing and body image perception and BMI in adolescents.

BACKGROUND: Adolescence is a critical period for establishing healthy eating habits and weight management, essential for preventing obesity and promoting overall health. This study investigates the impact of mukbang and cookbang-popular online broadcasts in Korea that feature excessive consumption of food-on the dietary habits and body image perception of Korean adolescents. With digital media, especially platforms like YouTube, becoming an integral part of daily life, these broadcasts have the potential to significantly influence adolescent health behaviors. METHODS: Employing data from the 18th Korea Youth Risk Behavior Web-based Survey (2022), this descriptive survey research explores the relationship between watching mukbang and cookbang and various health-related factors among adolescents. The survey's comprehensive dataset provided a unique opportunity to examine this association in a population that is increasingly exposed to digital media content. The analysis focused on the frequency of watching mukbang and cookbang, their impact on eating habits, body mass index (BMI), body shape perception, and body image distortion among adolescents. RESULTS: The results revealed a significant engagement with mukbang and cookbang among adolescents, with notable gender differences in viewing habits and effects. Increased frequency of viewing was associated with negative impacts on eating habits and body image perception. Furthermore, psychological factors such as stress levels and sleep quality emerged as significant predictors of the frequency of watching these broadcasts. CONCLUSIONS: This study highlights the need for further investigation into the causal relationships between mukbang and cookbang viewership and adolescent health outcomes. The findings suggest the importance of developing targeted interventions to mitigate the negative influences of such content on adolescents' eating habits and body perceptions. Given the widespread popularity of these broadcasts, it is crucial to address their potential health implications through public health strategies, educational content, and policy development aimed at promoting healthier lifestyles among adolescents.

Cost-benefit analysis of human adenovirus vaccine development in a Korean military setting.

BACKGROUND: Human adenovirus (HAdV) is a prevalent causative agent of acute respiratory disease (ARD) and is frequently responsible for outbreaks, particularly in military environments. Current vaccines do not effectively cover HAdV subtypes commonly found among Korean military personnel, highlighting the need for a new targeted vaccine. This study presents a cost-benefit analysis to evaluate the economic viability of developing and implementing such a vaccine within a military context. METHODS: We adopted a societal perspective for this cost-benefit analysis, which included estimating costs associated with vaccine development, production, and distribution over a projected timeline. We assumed a development period of five years, after which vaccine production and administration were initiated in the sixth year. The cost associated with vaccine development, production, and dispensation was considered. The benefits were calculated based on both direct and indirect cost savings from preventing HAdV infections through vaccination. All financial figures were expressed in 2023 US dollars. A sensitivity analysis was conducted to explore the impact of varying factors such as vaccination rate, incidence of infection, vaccine efficacy, and discount rate. RESULTS: For the base case scenario, we assumed a vaccination rate of 100 %, an incidence rate of 0.02, and a vaccine efficacy of 95 %, applying a 3 % discount rate. Initially, in the sixth year, the benefit-cost ratio stood at 0.71, suggesting a cost disadvantage at the onset of vaccination. However, this ratio improved to 1.32 in the following years, indicating a cost benefit from the seventh year onward. The cumulative benefit-cost ratio over a decade reached 2.72. The outcomes from the sensitivity analysis were consistent with these findings. CONCLUSION: Our cost-benefit analysis demonstrates that the introduction of an HAdV vaccine for the Korean military is economically advantageous, with substantial cost benefits accruing from the seventh year after the commencement of vaccination.

Design, Synthesis, and Biological Evaluation of New 2,6,7-Substituted Purine Derivatives as Toll-like Receptor 7 Agonists for Intranasal Vaccine Adjuvants.

TLR7/8 agonists are versatile immune stimulators capable of treating various diseases such as viral infections, autoimmune, and cancer. Despite the structural similarity of TLR7/8, their immune stimulation mechanisms and time-course responses significantly differ. In this study, a new series of TLR7-selective agonists was synthesized utilizing the economical building block 2,6-dichloropurine. Compound 27b showed the most potent activity on hTLR7 with an EC50 of 17.53 nM and demonstrated high hTLR7 selectivity (224 folds against TLR8). 27b effectively stimulated the secretion of proinflammatory cytokines in mouse macrophages and enhanced intranasal vaccine efficacy against influenza A virus in vivo. Assessment of humoral and mucosal antibody titers confirmed that 27b elevates IgG and IgA levels, protecting against both homologous and heterologous influenza viral infections. These findings suggest that 27b is a promising candidate as a vaccine adjuvant to prevent viral infections or as a robust immunomodulator with prolonged activity for treating immune-suppressed diseases.

Comparative diagnostic performance of rapid urease test with the sweeping method versus tissue sampling method after Helicobacter pylori eradication (with video).

BACKGROUND AND AIMS: The rapid urease test (RUT) is widely used to detect Helicobacter pylori infection; however, it is not preferred as a monitoring strategy after eradication owing to its low sensitivity. In this study, we evaluated the diagnostic performance of RUT using the sweeping method, which overcomes the limitations of conventional tissue sampling methods after eradication. METHODS: Patients who received H pylori eradication treatment were enrolled. Each of the sweeping and conventional methods was performed on the same patients to compare diagnostic performance. Urea breath test (UBT), histology, and polymerase chain reaction were performed to determine true infection. Logistic regression analysis was conducted to investigate reasons for discrepancies between the results of the 2 methods. RESULTS: In 216 patients, the eradication success rate was 68.1%, and the sensitivity and specificity of the sweeping method were 0.812 and 0.912, respectively, whereas those of the conventional method were 0.391 and 0.993, respectively (P < .05 for all). The area under the receiver operating characteristic curve for the sweeping method was higher than that for the conventional method (0.862 vs 0.692, P < .001). The mean time to H pylori detection for the sweeping method was 4.7 ± 4.4 minutes and 12.3 ± 16.1 minutes for the conventional method (P < .001). The risk for inconsistent results between the 2 methods was the highest for UBT values of 1.4‰ to 2.4‰ (odds ratio, 3.8; P = .016). CONCLUSIONS: The RUT with the sweeping method could potentially replace the tissue sampling method as a test to confirm H pylori eradication and be an alternative option to UBT for patients requiring endoscopy.

Physical Fitness Surveillance and Monitoring Systems Inventory for Children and Adolescents: A Scoping Review with a Global Perspective.

Surveillance of health-related physical fitness can improve decision-making and intervention strategies promoting health for children and adolescents. However, no study has comprehensively analyzed surveillance/monitoring systems for physical fitness globally. This review sought to address this gap by identifying: (1) national-level surveillance/monitoring systems for physical fitness among children and adolescents globally, (2) the main barriers and challenges to implementing surveillance/monitoring systems, and (3) governmental actions related to existing surveillance/monitoring systems. We used a scoping review to search, obtain, group, summarize, and analyze available evidence. Our review involved three stages: (1) identification of surveillance systems through a systematic literature review, with complementary search of the grey literature (e.g., reference lists, Google Scholar, webpages, recommendations), (2) systematic consultation with relevant experts using a Delphi method to confirm/add systems and to gather and analyze information on the barriers and challenges to implementing systems, and (3) Web searches for public documents on government sites and surveillance/monitoring system pages, and direct internet searches to identify relevant governmental actions related to surveillance systems. A total of 15 fitness surveillance/monitoring systems met our inclusion criteria. Experts identified a lack of government support and funding, and the low priority of fitness on the public health agenda as the main barriers/challenges to implementation. Several governmental actions related to surveillance systems were identified, including policies, strategies, programs, and guidelines. We propose a Global Observatory of Physical Fitness to help address these issues.

The effect of inhaler prescription on the development of lung cancer in COPD: a nationwide population-based study.

BACKGROUND: COPD is associated with the development of lung cancer. A protective effect of inhaled corticosteroids (ICS) on lung cancer is still controversial. Hence, this study investigated the development of lung cancer according to inhaler prescription and comorbidties in COPD. METHODS: A retrospective cohort study was conducted based on the Korean Health Insurance Review and Assessment Service database. The development of lung cancer was investigated from the index date to December 31, 2020. This cohort included COPD patients (≥ 40 years) with new prescription of inhalers. Patients with a previous history of any cancer during screening period or a switch of inhaler after the index date were excluded. RESULTS: Of the 63,442 eligible patients, 39,588 patients (62.4%) were in the long-acting muscarinic antagonist (LAMA) and long-acting ß2-agonist (LABA) group, 22,718 (35.8%) in the ICS/LABA group, and 1,136 (1.8%) in the LABA group. Multivariate analysis showed no significant difference in the development of lung cancer according to inhaler prescription. Multivariate analysis, adjusted for age, sex, and significant factors in the univariate analysis, demonstrated that diffuse interstitial lung disease (DILD) (HR = 2.68; 95%CI = 1.86-3.85), a higher Charlson Comorbidity Index score (HR = 1.05; 95%CI = 1.01-1.08), and two or more hospitalizations during screening period (HR = 1.19; 95%CI = 1.01-1.39), along with older age and male sex, were independently associated with the development of lung cancer. CONCLUSION: Our data suggest that the development of lung cancer is not independently associated with inhaler prescription, but with coexisting DILD, a higher Charlson Comorbidity Index score, and frequent hospitalization.

Prediction of TKI response in EGFR-mutant lung cancer patients-derived organoids using malignant pleural effusion.

Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform.

Real-world evidence of survival benefit of remdesivir: study of 419 propensity score-matched patients hospitalized over the alpha and delta waves of COVID-19 in New Orleans, LA.

Background: The direct acting antiviral remdesivir (RDV) has shown promising results in randomized clinical trials. This study is a unique report of real clinical practice RDV administration for COVID-19 from alpha through delta variant circulation in New Orleans, Louisiana (NOLA). Patients in NOLA have among US worst pre-COVID health outcomes, and the region was an early epicenter for severe COVID. Methods: Data were directly extracted from electronic medical records through REACHnet. Of 9,106 adults with COVID, 1,928 were admitted to inpatient care within 7 days of diagnosis. The propensity score is based upon 22 selected covariates, related to both RDV assignment and outcome of interest. RDV and non-RDV patients were matched 1:1 with replacement, by location and calendar period of admission. Primary and secondary endpoints were, death from any cause and inpatient discharge, within 28 and 14 days after inpatient admission. Results: Of 448 patients treated with RDV, 419 (94%) were successfully matched to a non-RDV patient. 145 (35%) patients received RDV for < 5 days, 235 (56%) for 5 days, and 39 (9%) for > 5 days. 96% of those on RDV received it within 2 days of admission. RDV was more frequently prescribed in patients with pneumonia (standardized difference: 0.75), respiratory failure, hypoxemia, or dependence on supplemental oxygen (0.69), and obesity (0.35) within 5 days prior to RDV initiation or corresponding day in non-RDV patients (index day). RDV patients were numerically more likely to be on steroids within 5 days prior to index day (86 vs. 82%) and within 7 days after inpatient admission (96 vs. 87%). RDV was significantly associated with lower risk of death within 14 days after admission (hazard ratio [HR]: 0.37, 95% CI: 0.19 to 0.69, p = 0.002) but not within 28 days (HR: 0.62, 95% CI: 0.36 to 1.07, p = 0.08). Discharge within 14 days of admission was significantly more likely for RDV patients (p < 0.001) and numerically more likely within 28 days after admission (p = 0.06). Conclusion: Overall, our findings support recommendation of RDV administration for COVID-19 in a highly comorbid, highly impoverished population representative of both Black and White subjects in the US Gulf South.

The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation.

Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/ß-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/ß-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.

Traumatic spinal cord injury in South Korea for 13 years (2008-2020).

Traumatic spinal cord injury (TSCI) has significant physical, psychological, and socioeconomic impacts. However, the epidemiological characteristics and treatment patterns of TSCI in South Korea remain unclear. This study aimed to investigate TSCI incidence and treatment behaviors in South Korea from 2008 to 2020. We included data from 30,979 newly diagnosed TSCI patients obtained from the Health Insurance Review and Assessment Service (HIRA). Treatment trends, location of surgery, surgical method, comorbidities, factors affecting hospital stay, and risk factors affecting readmission were analyzed. Patients were divided into the surgery group [n = 7719; (25%)] and the non-surgery group [n = 23,260; (75%)]. Surgical cases involved cervical (64%), thoracic (17%), and lumbar/sacral (19%) lesions. Anterior fusion (38%), posterior fusion (54%), and corpectomy (8%) were the surgical methods. Surgical treatments increased annually. Factors influencing hospital stay included male sex, older age, and higher Charlson comorbidity index (CCI). Female sex and higher CCI scores were associated with readmission. In conclusion, a quarter of all TSCI patients underwent surgery, with an upward trend. Risk factors for longer hospital stays were thoracic spine injury, older age, higher CCI, and male sex. Risk factors for readmission included age range of 40-59 years, lumbar/sacral spine injuries, CCI score of 2, and female sex.