American Cancer Society's report on the status of cancer disparities in the United States, 2023.

In 2021, the American Cancer Society published its first biennial report on the status of cancer disparities in the United States. In this second report, the authors provide updated data on racial, ethnic, socioeconomic (educational attainment as a marker), and geographic (metropolitan status) disparities in cancer occurrence and outcomes and contributing factors to these disparities in the country. The authors also review programs that have reduced cancer disparities and provide policy recommendations to further mitigate these inequalities. There are substantial variations in risk factors, stage at diagnosis, receipt of care, survival, and mortality for many cancers by race/ethnicity, educational attainment, and metropolitan status. During 2016 through 2020, Black and American Indian/Alaska Native people continued to bear a disproportionately higher burden of cancer deaths, both overall and from major cancers. By educational attainment, overall cancer mortality rates were about 1.6-2.8 times higher in individuals with ≤12 years of education than in those with ≥16 years of education among Black and White men and women. These disparities by educational attainment within each race were considerably larger than the Black-White disparities in overall cancer mortality within each educational attainment, ranging from 1.03 to 1.5 times higher among Black people, suggesting a major role for socioeconomic status disparities in racial disparities in cancer mortality given the disproportionally larger representation of Black people in lower socioeconomic status groups. Of note, the largest Black-White disparities in overall cancer mortality were among those who had ≥16 years of education. By area of residence, mortality from all cancer and from leading causes of cancer death were substantially higher in nonmetropolitan areas than in large metropolitan areas. For colorectal cancer, for example, mortality rates in nonmetropolitan areas versus large metropolitan areas were 23% higher among males and 21% higher among females. By age group, the racial and geographic disparities in cancer mortality were greater among individuals younger than 65 years than among those aged 65 years and older. Many of the observed racial, socioeconomic, and geographic disparities in cancer mortality align with disparities in exposure to risk factors and access to cancer prevention, early detection, and treatment, which are largely rooted in fundamental inequities in social determinants of health. Equitable policies at all levels of government, broad interdisciplinary engagement to address these inequities, and equitable implementation of evidence-based interventions, such as increasing health insurance coverage, are needed to reduce cancer disparities.

Assessing the reliability of point mutation as data augmentation for deep learning with genomic data.

BACKGROUND: Deep neural networks (DNNs) have the potential to revolutionize our understanding and treatment of genetic diseases. An inherent limitation of deep neural networks, however, is their high demand for data during training. To overcome this challenge, other fields, such as computer vision, use various data augmentation techniques to artificially increase the available training data for DNNs. Unfortunately, most data augmentation techniques used in other domains do not transfer well to genomic data. RESULTS: Most genomic data possesses peculiar properties and data augmentations may significantly alter the intrinsic properties of the data. In this work, we propose a novel data augmentation technique for genomic data inspired by biology: point mutations. By employing point mutations as substitutes for codons, we demonstrate that our newly proposed data augmentation technique enhances the performance of DNNs across various genomic tasks that involve coding regions, such as translation initiation and splice site detection. CONCLUSION: Silent and missense mutations are found to positively influence effectiveness, while nonsense mutations and random mutations in non-coding regions generally lead to degradation. Overall, point mutation-based augmentations in genomic datasets present valuable opportunities for improving the accuracy and reliability of predictive models for DNA sequences.

Living alone and cancer mortality by race/ethnicity and socioeconomic status among US working-age adults.

BACKGROUND: Previous studies have shown an association between living alone and cancer mortality; however, findings by sex and race/ethnicity have generally been inconsistent, and data by socioeconomic status are sparse. The association between living alone and cancer mortality by sex, race/ethnicity, and socioeconomic status in a nationally representative US cohort was examined. METHODS: Pooled 1998-2019 data for adults aged 18-64 years at enrollment from the National Health Interview Survey linked to the National Death Index (N = 473,648) with up to 22 years of follow-up were used to calculate hazard ratios (HRs) for the association between living alone and cancer mortality. RESULTS: Compared to adults living with others, adults living alone were at a higher risk of cancer death in the age-adjusted model (HR, 1.32; 95% CI, 1.25-1.39) and after additional adjustments for multiple sociodemographic characteristics and cancer risk factors (HR, 1.10; 95% CI, 1.04-1.16). Age-adjusted models stratified by sex, poverty level, and educational attainment showed similar associations between living alone and cancer mortality, but the association was stronger among non-Hispanic White adults (HR, 1.33; 95% CI, 1.25-1.42) than non-Hispanic Black adults (HR, 1.18; 95% CI, 1.05-1.32; p value for difference < .05) and did not exist in other racial/ethnic groups. These associations were attenuated but persisted in fully adjusted models among men (HR, 1.13; 95% CI, 1.05-1.23), women (HR, 1.09; 95% CI, 1.01-1.18), non-Hispanic White adults (HR, 1.13; 95% CI, 1.05-1.20), and adults with a college degree (HR, 1.22; 95% CI, 1.07-1.39). CONCLUSIONS: In this nationally representative study in the United States, adults living alone were at a higher risk of cancer death in several sociodemographic groups.

Factors contributing to differences in cervical cancer screening in rural and urban community health centers.

INTRODUCTION: Community health centers (CHCs) provide historically marginalized populations with primary care, including cancer screening. Previous studies have reported that women living in rural areas are less likely to be up to date with cervical cancer screening than women living in urban areas. However, little is known about rural-urban differences in cervical cancer screening in CHCs and the contributing factors, and whether such differences changed during the COVID-19 pandemic. METHODS: Using 8-year pooled Uniform Data System (2014-2021) data and Oaxaca-Blinder decomposition, the extent to which CHC- and catchment area-level characteristics explained rural-urban differences in up-to-date cervical cancer screening was estimated. RESULTS: Up-to-date cervical cancer screening was lower in rural CHCs than urban CHCs (38.2% vs 43.0% during 2014-2019), and this difference increased during the pandemic (43.5% vs 49.0%). The rural-urban difference in cervical cancer screening in 2014-2019 was mostly explained by differences in CHC-level proportions of patients with limited English proficiency (55.9%) or income below the poverty level (12.3%) and females aged 21 to 64 years (9.8%), and catchment area-level's unemployment (3.4%) and primary care physician density (3.2%). However, Medicaid (-48.5%) or no insurance (-19.6%) counterbalanced the differences between rural-urban CHCs. The contribution of these factors to rural-urban differences in cervical cancer screening generally increased in 2020-2021. CONCLUSIONS: Rural-urban differences in cervical cancer screening were mostly explained by multiple CHC-level and catchment area-level characteristics. The findings call for tailored interventions, such as providing resources and language services, to improve cancer screening utilization among uninsured, Medicaid, and patients with limited English proficiency in rural CHCs.

Novel Assessment of the Impact of Irritability on Physiological and Psychological Frustration Responses in Adolescents.

OBJECTIVE: Irritability, typically defined as a proneness to anger, particularly in response to frustration, falls at the intersection of emotion and disruptive behavior. Despite well-defined translational models, there are few convergent findings regarding the pathophysiology of irritability. Most studies utilize computer-based tasks to examine neural responses to frustration, with little work examining stress-related responding to frustration in social contexts. The present study is the first to utilize the novel Frustration Social Stressor for Adolescents (FSS-A) to examine associations between adolescent irritability and psychological and physiological responses to frustration. METHOD: The FSS-A was completed by a predominantly male, racially, ethnically, and socioeconomically diverse sample of 64 12- to 17-year-olds, who were originally recruited as children with varying levels of irritability. Current irritability was assessed using the Multidimensional Assessment Profiles-Temper Loss scale (MAP-TL-Youth). Adolescents rated state anger and anxiety before and after the FSS-A, and usable salivary cortisol data were collected from 43 participants. RESULTS: Higher MAP-TL-Youth scores were associated with greater increases in anger during the FSS-A, but not increases in anxiety, or alterations in cortisol. Pre-task state anger negatively predicted the slope of the rise in cortisol observed in anticipation of the FSS-A. CONCLUSIONS: Results provide support for unique associations between adolescent irritability and anger during, and in anticipation of, frustrating social interactions. Such findings lay a foundation for future work aimed at informing physiological models and intervention targets.

Mildly Reduced Renal Function Is Associated With Increased Heart Failure Admissions in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: The association between renal dysfunction and cardiovascular outcomes has yet to be determined in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate whether mildly reduced renal function is associated with the prognosis in patients with HCM. METHODS: Patients with HCM were enrolled at two tertiary HCM centers. Patients who were on dialysis, or had a previous history of heart failure (HF) or stroke were excluded. Patients were categorized into 3 groups by estimated glomerular filtration rate (eGFR): stage I (eGFR ≥ 90 mL/min/1.73 m², n = 538), stage II (eGFR 60-89 mL/min/1.73 m², n = 953), and stage III-V (eGFR < 60 mL/min/1.73 m², n = 265). Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, hospitalization for HF (HHF), or stroke during median 4.0-year follow-up. Multivariable Cox regression model was used to adjust for covariates. RESULTS: Among 1,756 HCM patients (mean 61.0 ± 13.4 years; 68.1% men), patients with stage III-V renal function had a significantly higher risk of MACEs (adjusted hazard ratio [aHR], 2.71; 95% confidence interval [CI], 1.39-5.27; P = 0.003), which was largely driven by increased incidence of cardiovascular death and HHF compared to those with stage I renal function. Even in patients with stage II renal function, the risk of MACE (vs. stage I: aHR, 2.21' 95% CI, 1.23-3.96; P = 0.008) and HHF (vs. stage I: aHR, 2.62; 95% CI, 1.23-5.58; P = 0.012) was significantly increased. CONCLUSION: This real-world observation showed that even mildly reduced renal function (i.e., eGFR 60-89 mL/min/1.73 m²) in patients with HCM was associated with an increased risk of MACEs, especially for HHF.

Systemic proinflammatory-profibrotic response in aortic stenosis patients with diabetes and its relationship with myocardial remodeling and clinical outcome.

BACKGROUND: Previous studies have mainly focused more on how diabetes affects the valve than the myocardium in aortic stenosis (AS). In the pressure-overloaded heart, myocardial fibrosis is an important driver of the progression from compensated hypertrophy to heart failure. Using comprehensive noninvasive imaging and plasma proteomics, we investigated whether and how diabetes aggravates the remodeling of the myocardium and its relation with prognosis in AS patients. METHODS: Severe AS patients were enrolled in two prospective cohorts for imaging and biomarker analysis. The imaging cohort (n = 253) underwent echocardiography and cardiac magnetic resonance, and the biomarker cohort (n = 100) blood sampling with multiplex proximity extension assay for 92 proteomic biomarkers. The composite outcome of hospitalization for heart failure admissions and death was assessed in the imaging cohort. RESULTS: Diabetic patients were older (70.4 ± 6.8 versus 66.7 ± 10.1 years) with more advanced ventricular diastolic dysfunction and increased replacement and diffuse interstitial fibrosis (late gadolinium enhancement % 0.3 [0.0-1.6] versus 0.0 [0.0-0.5], p = 0.009; extracellular volume fraction % 27.9 [25.7-30.1] versus 26.7 [24.9-28.5], p = 0.025) in the imaging cohort. Plasma proteomics analysis of the biomarker cohort revealed that 9 proteins (E-selectin, interleukin-1 receptor type 1, interleukin-1 receptor type 2, galectin-4, intercellular adhesion molecule 2, integrin beta-2, galectin-3, growth differentiation factor 15, and cathepsin D) were significantly elevated and that pathways related to inflammatory response and extracellular matrix components were enriched in diabetic AS patients. During follow-up (median 6.3 years), there were 53 unexpected heart failure admissions or death in the imaging cohort. Diabetes was a significant predictor of heart failure and death, independent of clinical covariates and aortic valve replacement (HR 1.88, 95% CI 1.06-3.31, p = 0.030). CONCLUSIONS: Plasma proteomic analyses indicate that diabetes potentiates the systemic proinflammatory-profibrotic milieu in AS patients. These systemic biological changes underlie the increase of myocardial fibrosis, diastolic dysfunction, and worse clinical outcomes in severe AS patients with concomitant diabetes.

Comparative cardiovascular outcomes in type 2 diabetes patients taking dapagliflozin versus empagliflozin: a nationwide population-based cohort study.

BACKGROUND: Sodium-glucose co-transporter-2 inhibitors displayed cardiovascular benefits in type 2 diabetes mellitus in previous studies; however, there were some heterogeneities regarding respective cardiovascular outcomes within the class. Furthermore, their efficacies in Asians, females, and those with low cardiovascular risks were under-represented. Thus, we compared the cardiovascular outcomes between new users of dapagliflozin and empagliflozin in a broad range of patients with type 2 diabetes mellitus using a nationwide population-based real-world cohort from Korea. METHODS: Korean National Health Insurance registry data between May 2016 and December 2018 were extracted, and an active-comparator new-user design was applied. The primary outcome was a composite of heart failure (HF)-related events (i.e., hospitalization for HF and HF-related death), myocardial infarction, ischemic stroke, and cardiovascular death. The secondary outcomes were individual components of the primary outcome. RESULTS: A total of 366,031 new users of dapagliflozin or empagliflozin were identified. After 1:1 nearest-neighbor propensity score matching, 72,752 individuals (mean age approximately 56 years, 42% women) from each group were included in the final analysis, with a follow-up of 150,000 ~ person-years. Approximately 40% of the patients included in the study had type 2 diabetes mellitus as their sole cardiovascular risk factor, with no other risk factors. The risk of the primary outcome was not different significantly between dapagliflozin and empagliflozin users (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.855-1.006). The risks of secondary outcomes were also similar, with the exception of the risks of HF-related events (HR 0.84, 95% CI 0.714-0.989) and cardiovascular death (HR 0.76, 95% CI 0.618-0.921), which were significantly lower in the dapagliflozin users. CONCLUSIONS: This large-scale nationwide population-based real-world cohort study revealed no significant difference in composite cardiovascular outcomes between new users of dapagliflozin and empagliflozin. However, dapagliflozin might be associated with lower risks of hospitalization or death due to HF and cardiovascular death than empagliflozin in Asian patients with type 2 diabetes mellitus.

Racial and ethnic disparities in monthly trends in alcohol-induced mortality among US adults from January 2018 through December 2021.

Background: Historically, American Indians/Alaska Natives (AIANs), Blacks, and Hispanics have experienced higher alcohol-induced mortality rates. Given a disproportionate surge in unemployment rate and financial strain among racial and ethnic minorities and limited access to alcohol use disorder treatment during the COVID-19 pandemic, it is essential to examine monthly trends in alcohol-induced mortality in the United States during the pandemic.Objectives: This study estimates changes in monthly alcohol-induced mortality among US adults by age, sex, and race/ethnicity.Methods: Using monthly deaths from 2018-2021 national mortality files (N = 178,201 deaths, 71.5% male, 28.5% female) and census-based monthly population estimates, we calculated age-specific monthly alcohol-induced death rates and performed log-linear regression to derive monthly percent increases in mortality rates.Results: Alcohol-induced deaths among adults aged ≥25 years increased by 25.7% between 2019 (38,868 deaths) and 2020 (48,872 deaths). During 2018-2021, the estimated monthly percent change was higher for females (1.1% per month) than males (1.0%), and highest for AIANs (1.4%), followed by Blacks (1.2%), Hispanics (1.0%), non-Hispanic Whites (1.0%), and Asians (0.8%). In particular, between February 2020 and January 2021, alcohol-induced mortality increased by 43% for males, 53% for females, 107% for AIANs, the largest increase, followed by Blacks (58%), Hispanics (56%), Asians (44%), and non-Hispanic Whites (39%).Conclusions: During the peak months of the pandemic, the rising trends in alcohol-induced mortality differed substantially by race and ethnicity. Our findings indicate that behavioral and policy interventions and future investigation on underlying mechanisms should be considered to reduce alcohol-induced mortality among Blacks and AIANs.

Quercetin 3-O-Galactoside Isolated from Limonium tetragonum Inhibits Melanogenesis by Regulating PKA/MITF Signaling and ERK Activation.

Quercetin 3-O-galactoside (Q3G) is a common dietary flavanol that has been shown to possess several bioactivities, including anti-melanogenesis. However, how Q3G exerts its anti-melanogenic effect has not been studied. The current study, therefore aimed to investigate the anti-melanogenesis potential of Q3G and elucidate the underlying action mechanism in α-melanocyte-stimulating hormone (α-MSH)-induced hyperpigmentation model of B16F10 murine melanoma cells. Results showed that α-MSH stimulation significantly increased tyrosinase (TYR) and melanin production, which were significantly downregulated by Q3G treatment. The treatment with Q3G suppressed the transcriptional and protein expressions of melanogenesis-related enzymes TYR, tyrosinase related protein-1 (TRP-1), and TRP-2, along with the melanogenic transcription factor microphthalmia-associated transcription factor (MITF) in B16F10 cells. It was shown that Q3G downregulated MITF expression and suppressed its transcriptional activity by inhibiting the cAMP-dependent protein kinase A (PKA)-mediated activation of CREB and GSK3ß. In addition, MAPK-regulated MITF activation signaling was also involved in the inhibition of melanin production by Q3G. The results suggest that the anti-melanogenic properties of Q3G rationalize further studies in vivo to confirm its action mechanism and consequent utilization as a cosmetic ingredient against hyperpigmentation.

Targeting the Sequences of Circulating Tumor DNA of Cholangiocarcinomas and Its Applications and Limitations in Clinical Practice.

Cholangiocarcinoma is a malignant epithelial tumor arising from bile ducts that is frequently fatal. Diagnosis is difficult due to tumor location in the biliary tract. Earlier diagnosis requires less invasive methods of identifying effective biomarkers for cholangiocarcinoma. The present study investigated the genomic profiles of cell-free DNA (cfDNA) and DNA from corresponding primary cholangiocarcinomas using a targeted sequencing panel. Somatic mutations in primary tumor DNA and circulating tumor DNA (ctDNA) were compared and clinical applications of ctDNA validated in patients with cholangiocarcinoma. A comparison of primary tumor DNA and ctDNA identified somatic mutations in patients with early cholangiocarcinomas that showed clinical feasibility for early screening. The predictive value of single-nucleotide variants (SNVs) of preoperative plasma cfDNA positive for somatic mutations of the primary tumor was 42%. The sensitivity and specificity of postoperative plasma SNVs in detecting clinical recurrence were 44% and 45%, respectively. Targetable fibroblast growth factor receptor 2 (FGFR2) and Kirsten rat sarcoma virus (KRAS) mutations were detected in 5% of ctDNA samples from patients with cholangiocarcinoma. These findings showed that genomic profiling of cfDNA was useful in clinical evaluation, although ctDNA had limited ability to detect mutations in cholangiocarcinoma patients. Serial monitoring of ctDNA is important clinically and in assessing real-time molecular aberrations in cholangiocarcinoma patients.

The Impact of Telemedicine Parity Requirements on Telehealth Utilization in the United States During the COVID-19 Pandemic.

BACKGROUND: Research has shown a dramatic increase in telehealth utilization during the COVID-19 pandemic and marked socioeconomic disparities in telehealth utilization. However, previous studies have shown discrepant findings on the association between the state's telehealth payment parity laws and telehealth utilization, and dearth of differential impact studies by subgroups. METHODS: Using a nationally representative Household Pulse Survey from April 2021 to August 2022 and the logistic regression modeling, we estimated the impact of parity payment laws on overall, video, and phone telehealth utilization and related disparities by race and ethncity during the pandemic. RESULTS: We found that adults in parity states had 23% higher odds of telehealth utilization (odds ratio [OR] = 1.23; 95% confidence interval [CI], 1.14-1.33) and 124% higher odds of video telehealth utilization (OR = 2.24; 95% CI, 1.95-2.57) than their counterparts in nonparity states. In parity states, non-Hispanic White adults had 24% higher odds of telehealth utilization (OR = 1.24; 95% CI: 1.14, 1.35) and non-Hispanic Black adults had 31% higher odds of telehealth utilization (OR = 1.31; 95% CI: 1.03, 1.65), compared with those in nonparity states. For Hispanics, non-Hispanic Asians, and non-Hispanic other races, there was not a statistically significant effect of parity act on overall telehealth utilization. CONCLUSIONS: Given inequalities in telehealth utilization, increased state policy efforts are needed to reduce access disparities during the ongoing pandemic and beyond.

The Differential Impact of the COVID-19 Pandemic on Prenatal Care Utilization Among US Women by Medicaid Expansion and Race and Ethnicity.

BACKGROUND: The 2014 Medicaid expansion improved racial and ethnic equity in insurance coverage and access to maternal care among women of reproductive age. This study examines differential effects of the COVID-19 pandemic on prenatal care utilization by Medicaid expansion and by race and ethnicity. METHODS: Using the pooled 2019-2020 National Natality file (N = 7 361 190), logistic regression was used to estimate the effect of COVID-19 on prenatal care utilization among US women aged 10 to 54 years after controlling for maternal age, race, ethnicity, marital status, parity, nativity/immigrant status, education, payment type, and smoking during pregnancy. Outcome measures were having no care and delayed prenatal care (third trimester or no care). Stratified models by race/ethnicity and Medicaid expansion status yielded the differential effects of COVID-19 on prenatal care utilization. RESULTS: During the COVID-19 pandemic, the adjusted odds of having no prenatal care decreased by 4% (adjusted odds ratio [AOR] = 0.96; 95% confidence interval [CI], 0.94-0.97) in expansion states but increased by 13% (AOR = 1.13; 95% CI, 1.11-1.15) in nonexpansion states. While most racial and ethnic groups in expansion states experienced a decrease in having no prenatal care, the adjusted odds of having no prenatal care increased by 15% for non-Hispanic Whites, 9% for non-Hispanic Blacks, 33% for American Indians/Alaska Natives, 25% for Asian/Pacific Islanders, and 13% for Hispanics in nonexpansion states. Women in expansion states experienced no change in delayed prenatal care during the pandemic, but women in nonexpansion states experienced an increase in delayed care. CONCLUSIONS: Prenatal care utilization decreased during the pandemic among women in nonexpansion states, particularly for American Indians/Alaska Natives and Asian/Pacific Islanders, compared with expansion states.

Continuity and Stability of Child and Adolescent Depressive Symptoms in South Korea: A Meta-analysis of Longitudinal Studies.

Many adolescents in South Korea experience risk-level depressive symptoms due to stress caused by personal and environmental changes. Prior studies investigated various characteristics of depressive symptoms. However, it is unclear when the mean level of depression changes with the development of children and adolescents and whether it is stable relative to one another over time. Thus, it is necessary to closely understand the continuity and stability of depressive symptoms across developmental stages in children and adolescents. In this study, continuity refers to the consistency in a group's mean level of depressive symptoms over time; however, stability refers to the consistency in the relative placement of the levels of depressive symptoms of individuals within a group over time. To comprehensively understand previous studies, this meta-analysis compiled data from 95 South Korean longitudinal studies (N = 200,338; 49.7% females) published between 2000 and 2021. Data were analyzed using a three-level random effects model with a 1-year interval for each age group to integrate effect sizes, followed by a generalized additive mixed model integrating age as a continuous variable. The results indicate that the mean-level continuity of depressive symptoms was relatively high and the rank-order stability was low for the children in elementary school (including both upper and lower grades). Additionally, as the adolescents aged, the mean-level continuity of depressive symptoms slightly decreased while stability increased. When entering early adulthood, the continuity and stability of depressive symptoms converged without significant change. As a result of moderating effect, the female-only group indicated a high level of continuity and stability than the male-only or mixed group. The findings highlight that South Korean childhood is a period of relatively high continuity and low stability. Moreover, female students' depressive symptoms fluctuate more than those of males, suggesting the need for providing effective and appropriate help.

Metagenomic characterization of bacterial community and antibiotic resistance genes found in the mass transit system in Seoul, South Korea.

Mass transit systems, including subways and buses, are useful environments for studying the urban microbiome, as the vast majority of populations in urban areas use public transportation. Microbial communities in urban environments include both human- and environment-associated bacteria that play roles in health and pathogen transmission. In this study, we used shotgun metagenomic sequencing to profile microbial communities sampled from various surfaces found in subway stations and bus stops within the Seoul mass transit system. The metagenomic approach and network analysis were used to investigate broad-spectrum antibiotic resistance genes (ARGs) and their co-occurrence patterns. We uncovered 598 bacterial species in 76 samples collected from various surfaces within the Seoul mass transit system. All samples were dominated by the potential human pathogen Salmonella enterica (40 %) and the human skin bacterium Cutibacterium acnes (19 %). Significantly abundant biomarkers detected in subway station samples were associated with bacteria typically found in the human oral cavity and respiratory tract, whereas biomarkers detected in bus stop samples were associated with bacteria commonly found in soil, water, and plants. Temperature and location had significant effects on microbial community structure and diversity. In total, 41 unique ARG subtypes were identified, associated with single-drug or multidrug resistance to clinically important and extensively used antibiotics, including aminoglycosides, carbapenem, glycopeptide, and sulfonamides. We revealed that Seoul subway stations and bus stops possess unique microbiomes containing potential human pathogens and ARGs. These findings provide insights for refining location-specific responses to reduce exposure to potentially causative agents of infectious diseases, improving public health.

A simple technique for the traditional method to estimate mean radiant temperature.

The mean radiant temperature (Tmrt) is the most important meteorological factor influencing human thermal comfort in urban areas. Numerous methods have been implemented for estimating Tmrt using measured radiometer or thermometer data, and exhibit different levels of accuracy. This study presents a simple technique based on the traditional method (Tmrt_TM) to estimate Tmrt by utilizing measured radiation data from the radiometers. The estimated Tmrt values from the six-directional method (Tmrt_SM) and two black globe thermometer methods (Tmrt_BG and Tmrt_BGv) at two stations (sky view factor 0.69 and 0.94) in Jeju, Republic of Korea, for 8 days (5 sunny days, 3 (semi-) cloudy days) in spring and summer were used to validate the Tmrt_TM. The results showed that the mean differences between Tmrt_TM and Tmrt_SM were within the required accuracy for comfort in ISO 7726 (± 2 ℃) on sunny days and were reduced to 0.1-0.3 ℃ in high Tmrt conditions such as clear summer days. The Tmrt_BG in most sunny and semi-cloudy days and Tmrt_BGv on all days resulted in large mean differences from the Tmrt_TM that exceeded the required accuracy for thermal stress in ISO 7726 (± 5 ℃). Therefore, both black globe thermometer methods should be used carefully when estimating Tmrt, especially during sunny days. The correlations between Tmrt_TM and Tmrt_SM were highly significant, 0.93 on all days (p = 0.01). The newly developed regression equations between Tmrt_TM and Tmrt_SM could reduce mean differences within 0.5 ℃ for all days, and their r2 values exceeded 0.87. Therefore, the simple Tmrt_TM technique can be used for Tmrt estimation in human thermal comfort studies.

Dracunculin Inhibits Adipogenesis in Human Bone Marrow-Derived Mesenchymal Stromal Cells by Activating AMPK and Wnt/ß-Catenin Signaling.

Increased bone marrow adiposity is widely observed in patients with obesity and osteoporosis and reported to have deleterious effects on bone formation. Dracunculin (DCC) is a coumarin isolated from Artemisia spp. but, until now, has not been studied for its bioactive potential except antitrypanosomal activity. In this context, current study has reported the anti-adipogenic effect of DCC in human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). DCC dose-dependently inhibited the lipid accumulation and expression of adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) in hBM-MSCs induced to undergo adipogenesis. To elucidate its action mechanism, the effect of DCC on Wnt/ß-catenin and AMPK pathways was examined. Results showed that DCC treatment activated Wnt/ß-catenin signaling pathway via AMPK evidenced by increased levels of AMPK phosphorylation and Wnt10b expression after DCC treatment. In addition, DCC treated adipo-induced hBM-MSCs exhibited significantly increased nuclear levels of ß-catenin compared with diminished nuclear PPARγ levels. In conclusion, DCC was shown to be able to hinder adipogenesis by activating the ß-catenin via AMPK, providing potential utilization of DCC as a nutraceutical against bone marrow adiposity.

The ThiL enzyme is a valid antibacterial target essential for both thiamine biosynthesis and salvage pathways in Pseudomonas aeruginosa.

Thiamine pyrophosphate (TPP) is an essential cofactor for various pivotal cellular processes in all living organisms, including bacteria. Thiamine biosynthesis occurs in bacteria but not in humans; therefore, the enzymes in this pathway are attractive targets for antibiotic development. Among these enzymes, thiamine monophosphate kinase (ThiL) catalyzes the final step of this pathway, phosphorylating thiamine monophosphate to produce TPP. Here, we extensively investigated ThiL in Pseudomonas aeruginosa, a major pathogen responsible for hospital-acquired infections. We demonstrate that thiL deletion abolishes not only thiamine biosynthesis but also thiamine salvage capability and results in growth defects of the ΔthiL strain even in the presence of thiamine derivatives, except for TPP. Most importantly, the pathogenesis of the ΔthiL strain was markedly attenuated, compared with that of WT cells, with lower inflammatory cytokine induction and 103-104-fold decreased bacterial loads in an in vivo infection model in which the intracellular TPP level was in the submicromolar range. To validate P. aeruginosa ThiL (PaThiL) as a drug target, we further characterized its biochemical properties, determining a Vmax of 4.0 ± 0.2 nmol·min-1 and Km values of 111 ± 8 and 8.0 ± 3.5 µm for ATP and thiamine monophosphate, respectively. An in vitro small-molecule screening assay identified PaThiL inhibitors including WAY213613, a noncompetitive inhibitor with a Ki value of 13.4 ± 2.3 µm and potential antibacterial activity against P. aeruginosa These comprehensive biological and biochemical results indicate that PaThiL represents a potential drug target for the development of an augmented repertoire of antibiotics against P. aeruginosa.

Overexpression of dopamine receptor D2 promotes colorectal cancer progression by activating the ß-catenin/ZEB1 axis.

Colorectal cancer (CRC) is a recurring cancer that is often resistant to conventional therapies and therefore requires the development of molecular-based therapeutic approaches. Dopamine receptor D2 (DRD2) is associated with the growth of many types of tumors, but its oncogenic role in CRC is unclear. Here, we observed that elevated DRD2 expression was associated with a poor survival rate among patients with CRC. Depletion of DRD2 suppressed CRC cell growth and motility by downregulating ß-catenin/ZEB signaling in vitro and in vivo, whereas overexpression of DRD2 promoted CRC cell progression. Inhibition of DRD2 by the antagonist pimozide inhibited tumor growth and lymph node metastasis in vivo and enhanced the cytotoxic effects of conventional agents in vitro. Taken together, our findings indicate that targeting the DRD2/ß-catenin/ZEB1 signaling axis is a potentially promising therapeutic strategy for patients with CRC.

Force-history dependence and cyclic mechanical reinforcement of actin filaments at the single molecular level.

The actin cytoskeleton is subjected to dynamic mechanical forces over time and the history of force loading may serve as mechanical preconditioning. While the actin cytoskeleton is known to be mechanosensitive, the mechanisms underlying force regulation of actin dynamics still need to be elucidated. Here, we investigated actin depolymerization under a range of dynamic tensile forces using atomic force microscopy. Mechanical loading by cyclic tensile forces induced significantly enhanced bond lifetimes and different force-loading histories resulted in different dissociation kinetics in G-actin-G-actin and G-actin-F-actin interactions. Actin subunits at the two ends of filaments formed bonds with distinct kinetics under dynamic force, with cyclic mechanical reinforcement more effective at the pointed end compared to that at the barbed end. Our data demonstrate force-history dependent reinforcement in actin-actin bonds and polarity of the actin depolymerization kinetics under cyclic tensile forces. These properties of actin may be important clues to understanding regulatory mechanisms underlying actin-dependent mechanotransduction and mechanosensitive cytoskeletal dynamics.This article has an associated First Person interview with the first author of the paper.