Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage.

Cerebrospinal fluid (CSF) in the subarachnoid space around the brain has long been known to drain through the lymphatics to cervical lymph nodes1-17, but the connections and regulation have been challenging to identify. Here, using fluorescent CSF tracers in Prox1-GFP lymphatic reporter mice18, we found that the nasopharyngeal lymphatic plexus is a major hub for CSF outflow to deep cervical lymph nodes. This plexus had unusual valves and short lymphangions but no smooth-muscle coverage, whereas downstream deep cervical lymphatics had typical semilunar valves, long lymphangions and smooth muscle coverage that transported CSF to the deep cervical lymph nodes. α-Adrenergic and nitric oxide signalling in the smooth muscle cells regulated CSF drainage through the transport properties of deep cervical lymphatics. During ageing, the nasopharyngeal lymphatic plexus atrophied, but deep cervical lymphatics were not similarly altered, and CSF outflow could still be increased by adrenergic or nitric oxide signalling. Single-cell analysis of gene expression in lymphatic endothelial cells of the nasopharyngeal plexus of aged mice revealed increased type I interferon signalling and other inflammatory cytokines. The importance of evidence for the nasopharyngeal lymphatic plexus functioning as a CSF outflow hub is highlighted by its regression during ageing. Yet, the ageing-resistant pharmacological activation of deep cervical lymphatic transport towards lymph nodes can still increase CSF outflow, offering an approach for augmenting CSF clearance in age-related neurological conditions in which greater efflux would be beneficial.

Electrocatalysis in Solid Oxide Fuel Cells and Electrolyzers.

Interest in energy-to-X and X-to-energy (where X represents green hydrogen, carbon-based fuels, or ammonia) technologies has expanded the field of electrochemical conversion and storage. Solid oxide electrochemical cells (SOCs) are among the most promising technologies for these processes. Their unmatched conversion efficiencies result from favorable thermodynamics and kinetics at elevated operating temperatures (400-900 °C). These solid-state electrochemical systems exhibit flexibility in reversible operation between fuel cell and electrolysis modes and can efficiently utilize a variety of fuels. However, electrocatalytic materials at SOC electrodes remain nonoptimal for facilitating reversible operation and fuel flexibility. In this Review, we explore the diverse range of electrocatalytic materials utilized in oxygen-ion-conducting SOCs (O-SOCs) and proton-conducting SOCs (H-SOCs). We examine their electrochemical activity as a function of composition and structure across different electrochemical reactions to highlight characteristics that lead to optimal catalytic performance. Catalyst deactivation mechanisms under different operating conditions are discussed to assess the bottlenecks in performance. We conclude by providing guidelines for evaluating the electrochemical performance of electrode catalysts in SOCs and for designing effective catalysts to achieve flexibility in fuel usage and mode of operation.

Liver Cancer Risk Across Metabolic Dysfunction-Associated Steatotic Liver Disease and/or Alcohol: A Nationwide Study.

INTRODUCTION: New terminologies of metabolic dysfunction-associated steatotic liver disease (MASLD) have been developed. We assessed hepatocellular carcinoma (HCC) risk across MASLD and/or alcohol intake. METHODS: We included participants aged 40-79 years receiving a national health checkup from 2009 to 2010 in the Republic of Korea, classified as follows: non-MASLD, MASLD, MASLD with increased alcohol intake (MetALD; weekly alcohol 210-420 g for male and 140-350 g for female individuals), and alcohol-associated liver disease (ALD; excessive alcohol intake with weekly alcohol ≥420 g for male or ≥350 g for female individuals). The primary outcome was HCC incidence. HCC risk was estimated using multivariable Cox proportional hazard models. RESULTS: Among 6,412,209 participants, proportions of non-MASLD, MASLD, MetALD, and ALD cases were 59.5%, 32.4%, 4.8%, and 3.4%, respectively. During follow-up (median 13.3 years), 27,118 had newly developed HCC. Compared with non-MASLD, the HCC risk increased from MASLD (adjusted hazard ratio [aHR] 1.66, 95% confidence interval [CI] 1.62-1.71) and MetALD (aHR 2.17, 95% CI 2.08-2.27) to ALD (aHR 2.34, 95% CI 2.24-2.45) in a stepwise manner. Furthermore, the older and non-cirrhosis subgroups were more vulnerable to detrimental effects of MASLD and/or alcohol intake, concerning HCC risk. Among the older, female, and cirrhosis subgroups, MetALD poses similar HCC risks as ALD. DISCUSSION: HCC risk increased from MASLD and MetALD to ALD in a stepwise manner, compared with non-MASLD. For an effective primary prevention of HCC, a comprehensive approach should be required to modify both metabolic dysfunction and alcohol intake habit.

Mechano-Responsive Polymers and Nanocomposites: Recent Advances for Self-Adaptive Structural Applications.

Polymer nanocomposites exhibiting remarkable mechanical properties are a focus of research for decades in structural applications. However, their practical application faces challenges due to poor interfacial load transfer, nanofiller dispersion, and processing limitations. These issues are critical in achieving stiff, strong, lightweight, and structurally integrated materials. Additionally, they often suffer from predetermined properties, which may not be effective under specific loading conditions. Addressing these challenges, the development of design strategies for mechano-responsive materials has advanced, enabling self-adaptive properties that respond to various mechanical stimuli. Drawing inspiration from natural systems, these approaches have been implemented in synthetic material systems, leveraging the design flexibility of nanocomposites as needed. Key focus areas include exploring mechanoradical reactions for dynamic mechano-responsiveness, as well as utilizing biomimetic mineralization and mechanical training for self-strengthening. This work also examines multistability, enabling on-demand deformation of materials and structures. Recent advancements in viscoelastic damping and nonreciprocal materials are discussed, highlighting their potential for directional energy absorption, transmission, and vibration control. Despite the need for significant improvements for real-world applications, mechano-responsive polymers and nanocomposites are expected to offer enormous opportunities not only in structural applications but also in other fields such as biomedical engineering, energy harvesting, and soft robotics.

miR-29a-3p orchestrates key signaling pathways for enhanced migration of human mesenchymal stem cells.

BACKGROUND: The homing of human mesenchymal stem cells (hMSCs) is crucial for their therapeutic efficacy and is characterized by the orchestrated regulation of multiple signaling modules. However, the principal upstream regulators that synchronize these signaling pathways and their mechanisms during cellular migration remain largely unexplored. METHODS: miR-29a-3p was exogenously expressed in either wild-type or DiGeorge syndrome critical region 8 (DGCR8) knockdown hMSCs. Multiple pathway components were analyzed using Western blotting, immunohistochemistry, and real-time quantitative PCR. hMSC migration was assessed both in vitro and in vivo through wound healing, Transwell, contraction, and in vivo migration assays. Extensive bioinformatic analyses using gene set enrichment analysis and Ingenuity pathway analysis identified enriched pathways, upstream regulators, and downstream targets. RESULTS: The global depletion of microRNAs (miRNAs) due to DGCR8 gene silencing, a critical component of miRNA biogenesis, significantly impaired hMSC migration. The bioinformatics analysis identified miR-29a-3p as a pivotal upstream regulator. Its overexpression in DGCR8-knockdown hMSCs markedly improved their migration capabilities. Our data demonstrate that miR-29a-3p enhances cell migration by directly inhibiting two key phosphatases: protein tyrosine phosphatase receptor type kappa (PTPRK) and phosphatase and tensin homolog (PTEN). The ectopic expression of miR-29a-3p stabilized the polarization of the Golgi apparatus and actin cytoskeleton during wound healing. It also altered actomyosin contractility and cellular traction forces by changing the distribution and phosphorylation of myosin light chain 2. Additionally, it regulated focal adhesions by modulating the levels of PTPRK and paxillin. In immunocompromised mice, the migration of hMSCs overexpressing miR-29a-3p toward a chemoattractant significantly increased. CONCLUSIONS: Our findings identify miR-29a-3p as a key upstream regulator that governs hMSC migration. Specifically, it was found to modulate principal signaling pathways, including polarization, actin cytoskeleton, contractility, and adhesion, both in vitro and in vivo, thereby reinforcing migration regulatory circuits.

Improving radiomics reproducibility using deep learning-based image conversion of CT reconstruction algorithms in hepatocellular carcinoma patients.

OBJECTIVES: CT reconstruction algorithms affect radiomics reproducibility. In this study, we evaluate the effect of deep learning-based image conversion on CT reconstruction algorithms. METHODS: This study included 78 hepatocellular carcinoma (HCC) patients who underwent four-phase liver CTs comprising non-contrast, late arterial (LAP), portal venous (PVP), and delayed phase (DP), reconstructed using both filtered back projection (FBP) and advanced modeled iterative reconstruction (ADMIRE). PVP images were used to train a convolutional neural network (CNN) model to convert images from FBP to ADMIRE and vice versa. LAP, PVP, and DP images were used for validation and testing. Radiomic features were extracted for each patient with a semi-automatic segmentation tool. We used concordance correlation coefficients (CCCs) to evaluate the radiomics reproducibility for original FBP (oFBP) vs. original ADMIRE (oADMIRE), oFBP vs. converted FBP (cFBP), and oADMIRE vs. converted ADMIRE (cADMIRE). RESULTS: In the test group including 30 patients, the CCC and proportion of reproducible features (CCC ≥ 0.85) for oFBP vs. oADMIRE were 0.65 and 32.9% (524/1595) for LAP, 0.65 and 35.9% (573/1595) for PVP, and 0.69 and 43.8% (699/1595) for DP. For oFBP vs. cFBP, the values increased to 0.92 and 83.9% (1339/1595) for LAP, 0.89 and 71.0% (1133/1595) for PVP, and 0.90 and 79.7% (1271/1595) for DP. Similarly, for oADMIRE vs. cADMIRE, the values increased to 0.87 and 68.1% (1086/1595) for LAP, 0.91 and 82.1% (1309/1595) for PVP, and 0.89 and 76.2% (1216/1595) for DP. CONCLUSIONS: CNN-based image conversion between CT reconstruction algorithms improved the radiomics reproducibility of HCCs. CLINICAL RELEVANCE STATEMENT: This study demonstrates that using a CNN-based image conversion technique significantly improves the reproducibility of radiomic features in HCCs, highlighting its potential for enhancing radiomics research in HCC patients. KEY POINTS: Radiomics reproducibility of HCC was improved via CNN-based image conversion between two different CT reconstruction algorithms. This is the first clinical study to demonstrate improvements across a range of radiomic features in HCC patients. This study promotes the reproducibility and generalizability of different CT reconstruction algorithms in radiomics research.

Assessing hypercoagulability and VTE risk using thromboelastography and Khorana score in women with cancers receiving chemotherapy.

Venous thromboembolism (VTE) is a common occurrence in cancer and chemotherapy increases thrombosis risk. Current risk assessment models such as the Khorana score (KS) and its modifications have limitations in female cancers. We assessed the coagulation profile of a group of women cancer patients under chemotherapy using thromboelastography (TEG) to determine if this can inform VTE risk assessment. Cancer patients who planned to receive chemotherapy were recruited. Baseline demographics, cancer data, BMI, Khorana Score (KS), and VTE risk factors were recorded and patients were followed for 6 months, for any thrombotic events. A total of 36 patients aged 35-85 (18 breast, 11 endometrial, 7 ovarian cancer) were evaluated. Hypercoagulability was detected in 63% of patients post-chemo cycle 1 and 75% post-cycle 2, with a significant increase in MA (maximum amplitude) and CI (clotting index), reduction in R (reaction time), K (clot kinetics), and LY30 (lysis time after 30 min of MA). KS showed only 7% of patients were high risk, 23% were low, and 70% were intermediate risk. MA and CI significantly increased in patients with intermediate and high-risk KS when compared with the low-risk patients and MA was positively correlated with KS. Five patients developed actual VTE; 100% of the tested ones were hypercoagulable either post-cycle 1 or 2 and 80% were KS intermediate risk. TEG is a hypercoagulability marker and TEG-MA and CI can potentially assess VTE risk. Larger studies are needed to assess the utility of TEG as an adjuvant to KS to better predict VTE in specific female cancers.

Effect of long working hours on psychological distress among young workers in different types of occupation.

BACKGROUND: We investigated how the association between long working hours and psychological distress varies across different employment and occupation types in young workers. METHODS: Examining a nationally representative sample of 7246 Korean workers (3621 women) aged 15 to 40, we analyzed 23,492 observations spanning from 2016 to 2020. Psychological distress was measured using the Brief Encounter Psychosocial Instrument. We employed a generalized estimating equation to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of the total observations, 5.2% worked <35 h/week, 52.9% worked 35-40 h/week, 23.5% worked 41-48 h/week, 10.3% worked 49-54 h/week, and 8.2% worked ≥55 h/week. The OR (95% CI) of the association between long working hours and psychological distress was 1.38 (1.11-1.72) for <35 h/week, 1.47 (1.32-1.65) for 41-48 h/week, 1.74 (1.49-2.04) for 49-54 h/week, and 2.11 (1.75-2.55) for ≥55 h/week compared to 35-40 h/week. The OR (95% CI) of the association between working ≥55 h/week and psychological distress was significantly higher among wage workers (OR [95% CI]: 2.37 [1.94-2.89]) compared to self-employed workers (OR [95% CI]: 0.84 [0.52-1.36]). Additionally, the OR (95% CI) of the association between working ≥55 h/week and psychological distress was significantly higher among white-collar workers (OR [95% CI]: 3.24 [2.54-4.13]) compared to service/sales workers (OR [95% CI]: 1.22 [0.86-1.72]) or blue-collar workers (OR [95% CI]: 1.71 [1.10-2.67]). No clear gender differences were observed. CONCLUSION: Psychological distress caused by long working hours can be pronounced among white-collar and wage workers.

Association between long working hours and engagement in preventive healthcare services in Korean workers: Findings from the Korean National Health and Nutrition Examination Survey.

BACKGROUND: Engagement in preventive healthcare services is crucial for preventing diseases. We explored how working hours are associated with engagement in preventive healthcare services, with a focus on gender differences. METHODS: This cross-sectional study used data from the 2007-2012 Korean National Health and Nutrition Examination Survey. The dependent variable was engagement in each of the five preventive healthcare services (health check-ups, influenza vaccination, and stomach, breast, and cervical cancer screenings). We estimated the prevalence ratios (PRs) and 95% confidence intervals (CIs) using robust Poisson regression. RESULTS: The study analyzed 19,819 workers (9119 women). The adjusted PRs (95% CI) of the association between working ≥55 h per week and engagement in preventive healthcare services among men were 0.95 (0.90-1.00) for health check-ups, 0.86 (0.77-0.96) for influenza vaccination, and 0.95 (0.87-1.03) for stomach cancer screening compared to working 35-40 h per week. Among women, the adjusted PRs (95% CI) of the association between working ≥55 h per week and engagement in preventive healthcare services were 0.84 (0.78-0.91) for health check-ups, 0.82 (0.73-0.92) for influenza vaccination, and 0.88 (0.80-0.97) for stomach, 0.85 (0.78-0.94) for breast, and 0.82 (0.74-0.91) for cervical cancer screenings. CONCLUSION: Long working hours were negatively associated with engagement in preventive healthcare services, and the association was pronounced among female workers. Efforts to promote preventive healthcare participation among individuals with long working hours are necessary, and it is essential to consider the unique vulnerabilities of women when developing such policies.

Association between long working hours and diet quality and patterns: A latent profile analysis of a nationally representative sample of Korean workers.

BACKGROUND: Long working hours are associated with cardiovascular and metabolic diseases. This study investigated the relationship between the working hours and dietary qualities and patterns in Korean workers. METHODS: Data from 24,523 workers were extracted from the Korea National Health and Nutrition Examination Survey, 2013-2021. The Korean Healthy Eating Index (KHEI), which ranges from 0 to 100, with a higher score indicating greater adherence to Korean dietary guidelines and superior dietary quality, was used for dietary assessment. We identified dietary patterns and classified workers using latent profile analysis. Logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Five distinct dietary patterns emerged: healthy diet (24.8%), low-vegetable diet (14.0%), average diet (7.8%), low-fruit diet (31.4%), and poor diet (22.0%). The mean KHEI score was 60.8, with the highest score observed in the healthy diet pattern (71.3) and the lowest, in the poor diet pattern (50.0). Compared with working 35-40 h/week, working ≥55 h/week was negatively associated with KHEI scores (ß: -1.08; 95% CI: -1.67, -0.49). Those working ≥55 h/week were less likely to have a healthy diet pattern (OR: 0.81; 95% CI: 0.72, 0.91) and more likely to have a low-fruit diet (OR: 1.36; 95% CI: 1.20, 1.55) or poor diet pattern (OR: 1.23; 95% CI: 1.05, 1.43) compared with those working 35-40 h/week. CONCLUSION: Long working hours are associated with undesirable dietary quality and patterns. Policy interventions aimed at enhancing dietary quality are needed to alleviate the health burdens associated with long working hours.

Improvement in functional motor scores in patients with non-ambulatory spinal muscle atrophy during Nusinersen treatment in South Korea: a single center study.

We analyzed the changes in various motor function scores over a four-year period in patients with non-ambulatory spinal muscular atrophy (SMA) during Nusinersen treatment. Patients underwent Hammersmith Infant Neurological Examination (HINE) or Hammersmith Functional Motor Scale Expanded (HFMSE) before treatment, and approximately every 4 months thereafter. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) or Children's Hospital of Philadelphia - Adult Test of Neuromuscular Disorders (CHOP ATEND), Revised Upper Limb Module (RULM), and Motor Function Measure (MFM) were performed based on baseline functional status. Narrative interviews were conducted to explore post-treatment physical improvement regarding activities of daily living (ADLs) and fatigue after ADLs. Based on HFMSE results, 9 patients achieved minimum clinically important differences. Average rates of change (slopes) with corresponding 95% confidence intervals for all assessment tools were in a positive direction. CHOP-INTEND showed the most prominent improvement in children and adolescents followed by HFMSE. Improvements in CHOP-ATEND were most noticeable in adults. Improvements were accompanied by changes in ADLs as observed in the narrative interviews. It is necessary to consider various functional aspects to determine the effectiveness of Nusinersen therapy. The objective assessment of the therapeutic effect of Nusinersen in non-ambulatory SMA requires consideration of functional aspects and the related ADLs.

Sex-dependent different clinicopathological characterization of Epstein-Barr virus-associated gastric carcinoma: a large-scale study.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) has been reported to account for approximately 5-16% of all GCs with good prognosis compared to EBV-negative GC. We evaluated the clinicopathological characteristics of EBVaGC including survival rate in South Korea. METHODS: A total of 4,587 patients with GC who underwent EBV in situ hybridization (EBV-ISH) were prospectively enrolled at the Seoul National University Bundang Hospital from 2003 to 2021. Age, sex, smoking status, cancer type and stage, tumor size and location, histological type, molecular features and survival information were analyzed. RESULTS: A total of 456 patients with GC (9.9%) were positive for EBV. The EBVaGC group displayed a higher proportion of males (P < 0.001), a predominant presence in the proximal stomach (P < 0.001), a higher proportion of undifferentiated cancer (P < 0.001), and a lower cancer stage (P = 0.004) than the EBV-negative group. Cox multivariate analyses revealed age (hazard ratio [HR] = 1.025, P < 0.001), tumor size (HR = 1.109, P < 0.001), and cancer stage (stage2 HR = 4.761, P < 0.001; stage3 HR = 13.286, P < 0.001; stage4 HR = 42.528, P < 0.001) as significant risk factors for GC-specific mortality, whereas EBV positivity was inversely correlated (HR = 0.620, P = 0.022). Furthermore, the EBVaGC group displayed statistically significant survival advantages over the EBV-negative cancer group in terms of both overall (P = 0.021) and GC-specific survival (P = 0.007) on the Kaplan-Meier survival curve. However, this effect was evident only in males. CONCLUSIONS: EBVaGC patients showed better prognoses despite their association with proximal location and poorly differentiated histology in male, probably due to the difference in immunity between males and females.

Interaction between old age and precarious employment on poor mental well-being in workers: Evidence from a nationally representative sample in Korea.

OBJECTIVE: This study examined the relationship between precarious employment (PE) and mental well-being, focusing on age-specific interactions. METHODS: Nationally representative Korean workers (N = 29,961) were surveyed between 2020 and 2021 to collect data on multidimensional PE (categorized as low, moderate, or high) and the WHO-5 well-being index. Workers' ages were classified as young (<35 years), middle-aged (35-54 years), and older (≥55 years). Logistic regression was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). The interaction between PE and age on well-being was examined by including interaction terms in the regression models. RESULTS: The prevalence of poor well-being was 25%, 29%, and 39% for low, moderate, and high precariousness, respectively, whereas it was 26%, 30%, and 39% for young, middle-aged, and older workers, respectively. In the overall sample, the OR (95% CI) of the association between PE and poor well-being was 1.24 (1.17-1.32) for moderate and 1.54 (1.43-1.65) for high precariousness, compared with low precariousness. There was a significant interaction between old age and PE on the odds of poor well-being. Compared with young workers with low PE, middle-aged workers with high PE (OR: 1.85, 95% CI: 1.62-2.10) and older workers with high PE (OR: 2.10, 95% CI: 1.83-2.40) exhibited increased odds of having poor mental well-being. CONCLUSION: PE serves as a social determinant of older workers' psychological well-being. Policy interventions are required to protect older workers' psychological well-being.

Long working hours, work-life imbalance, and poor mental health: a cross-sectional mediation analysis based on the sixth Korean Working Conditions Survey, 2020-2021.

Background There has been growing concern about the negative mental health impact of long working hours and overwork. Our study examined how work-life imbalance (WLI) could be a mediator between working hours and poor mental well-being.Methods We included 34,968 individuals from a nationwide cross-sectional survey in Korea. Self-reported working hours per week was collected, and mental health was assessed by the WHO-5 Well-Being Index. Counterfactual-based mediation models were employed to disentangle the total effects into a direct effect (work hour - poor mental health) and an indirect effect (work hour - WLI - poor mental health).Results Out of 34,968 participants, 52.6% worked 35-40 h/week, 20.0% worked 41-48 h/week, 11.7% worked 49-54 h/week, and 15.6% worked ≥55 h/week. The odds ratios (ORs) of the total impact of working hours on poor mental health were 1.08 (95% CI: 1.01-1.16) for 41-48 h/week, 1.28 (1.17-1.39) for 49-54 h/week, and 1.60 (1.48-1.74) for ≥55 h/week in comparison to 35-40 h/week. The ORs of the indirect effects were 1.04 (1.03-1.05) for 41-48 h/week, 1.08 (1.07-1.09) for 49-54 h/week, and 1.14 (1.12-1.16) for ≥55 h/week, accounting for 51%, 31%, and 28% of the total effects.Conclusion: Our findings suggest that WLI can partially mediate the association of long working hours with mental health deterioration. Policy efforts are required to mitigate the adverse mental health effects of overwork.

Association between temporary employment and current smoking and change in smoking behaviors: A prospective cohort study from South Korea (2009-2018).

Background Previous studies have suggested that employment insecurity is associated with adverse health outcomes. We explored the association between temporary employment and smoking behaviors.Methods We analyzed 11,795 workers (51,867 observations) from the Korea Health Panel Study (2009-2018). Employment types were categorized as regular, fixed-term, or daily, based on the duration of labor contract. The outcomes were current smoking status and changes in smoking behavior (initiation or cessation) in the following year. Generalized estimating equations were used to estimate odds ratio (OR) and 95% confidence interval (CI).Results The proportions of fixed-term and daily workers were 41.2% and 16.4% for women and 23.6% and 12.4% for men, respectively. Temporary employment was associated with increased odds of current smoking, while also demonstrating prospective associations with changes in smoking behaviors. For instance, in prospective analyses, male workers with fixed-term and daily employments were associated with a decreased likelihood of smoking cessation (OR:0.77; 95% CI:0.65-0.91 for fixed-term employment and OR:0.66; 95% CI:0.52-0.83 for daily employment) in the following year compared to those with regular employment. Moreover, those experiencing consecutive temporary employment was most inversely associated with smoking cessation in both men (OR:0.56; 95% CI:0.44-0.71) and women (OR:0.37; 95% CI:0.16-0.85) compared to those experiencing consecutive regular employment. However, no clear association between temporary employment and smoking initiation was observed in both men and women.Conclusions Temporary employment is directly associated with current smoking and inversely associated with smoking cessation. Policies are needed to improve job insecurity among temporary employees.

Income dynamics and risk of colorectal cancer in individuals with type 2 diabetes: a nationwide population-based cohort study.

BACKGROUND: Individuals with type 2 diabetes (T2D) have increased colorectal cancer (CRC) risk, but it is unknown whether income dynamics are associated with CRC risk in these individuals. We examined whether persistent low- or high-income and income changes are associated with CRC risk in non-elderly adults with T2D. METHODS: Using nationally representative data from the Korean Health Insurance Service database, 1,909,492 adults aged 30 to 64 years with T2D and no history of cancer were included between 2009 and 2012 (median follow-up of 7.8 years). We determined income levels based on health insurance premiums and assessed annual income quartiles for the baseline year and the four preceding years. Hazard ratios(HRs) and 95% confidence intervals(CIs) were estimated after adjusting for sociodemographic factors, CRC risk factors, and diabetes duration and treatment. RESULTS: Persistent low income (i.e., lowest income quartile) was associated with increased CRC risk (HRn=5years vs. n=0years 1.11, 95% CI 1.04-1.18; P for trend=0.004). Income declines (i.e., a decrease≥25% in income quantile) were also associated with increased CRC risk (HR≥2 vs. 0 declines 1.10, 95% CI 1.05-1.16; p for trend=0.001). In contrast, persistent high income (i.e., highest income quartile) was associated with decreased CRC risk (HRn=5years vs. n=0years 0.81, 95% CI 0.73-0.89; p for trend<0.0001), which was more pronounced for rectal cancer (HR 0.64, 95% CI 0.53-0.78) and distal colon cancer (HR 0.70, 95% CI 0.57-0.86). CONCLUSIONS: Our findings underscore the need for increased public policy awareness of the association between income dynamics and CRC risk in adults with T2D.

Interest in and Willingness to Use PrEP: A Cross-Sectional Study of Individuals with Problematic Substance Use Residing in a High HIV Prevalence Jurisdiction.

Although it is an effective HIV prevention method, pre-exposure prophylaxis (PrEP) is underutilized in the Southern US. Many people who use drugs (PWUD) have increased susceptibility to HIV which could be lessened by using PrEP. Potential barriers to PrEP use include lack of awareness of PrEP, low knowledge about HIV prevention, low self-efficacy for HIV prevention, inaccurate risk perceptions, and anticipated stigma. The current study examined predisposing, enabling, and reinforcing factors that may predict interest in PrEP. The purpose of the current study was to explore factors associated with interest in and willingness to use daily oral and long acting injectable PrEP among sexually active adult PWUD. The data were collected from adult participants (n = 270) residing in Harris County, TX, who self-reported problematic substance use and who reported oral, anal, or vaginal sex in the six months prior to completing the survey. The survey was distributed and completed online via Qualtrics Panels in March of 2022 and included measures of PrEP and HIV knowledge, PrEP stigma, sexual health self-efficacy, experiences of discrimination, health literacy, and medical mistrust. The majority of participants reported circumstances or behaviors that increased their susceptibility to HIV. Findings indicated that PrEP user stereotypes and PrEP anticipated disapproval by others were associated with interest in using daily oral PrEP and willingness to use long acting injectable PrEP. These results provide insight into reasons for low PrEP uptake among PWUD who live in a high HIV prevalence jurisdiction. Implications for HIV prevention intervention are discussed.

Genome-wide identification of the plant homeodomain-finger family in rye and ScPHD5 functions in cold tolerance and flowering time.

KEY MESSAGE: 111 PHD genes were newly identified in rye genome and ScPHD5's role in regulating cold tolerance and flowering time was suggested. Plant homeodomain (PHD)-finger proteins regulate the physical properties of chromatin and control plant development and stress tolerance. Although rye (Secale cereale L.) is a major winter crop, PHD-finger proteins in rye have not been studied. Here, we identified 111 PHD genes in the rye genome that exhibited diverse gene and protein sequence structures. Phylogenetic tree analysis revealed that PHDs were genetically close in monocots and diverged from those in dicots. Duplication and synteny analyses demonstrated that ScPHDs have undergone several duplications during evolution and that high synteny is conserved among the Triticeae species. Tissue-specific and abiotic stress-responsive gene expression analyses indicated that ScPHDs were highly expressed in spikelets and developing seeds and were responsive to cold and drought stress. One of these genes, ScPHD5, was selected for further functional characterization. ScPHD5 was highly expressed in the spike tissues and was localized in the nuclei of rye protoplasts and tobacco leaves. ScPHD5-overexpressing Brachypodium was more tolerant to freezing stress than wild-type (WT), with increased CBF and COR gene expression. Additionally, these transgenic plants displayed an extremely early flowering phenotype that flowered more than two weeks earlier than the WT, and vernalization genes, rather than photoperiod genes, were increased in the WT. RNA-seq analysis revealed that diverse stress response genes, including HSPs, HSFs, LEAs, and MADS-box genes, were also upregulated in transgenic plants. Our study will help elucidate the roles of PHD genes in plant development and abiotic stress tolerance in rye.

Therapeutic effect of selective interleukin-2-inducible tyrosine kinase inhibitor in orbital fibroblasts from patients with Graves' orbitopathy.

Interleukin-2-inducible tyrosine kinase (ITK) is a crucial cytoplasmic protein in the T-cell signaling pathway. Here, we aimed to demonstrate the anti-inflammatory effect of the selective IL-2-induced tyrosine kinase inhibitor BMS-509744 (BMS) on Graves' orbitopathy (GO) in an in vitro model. ITK mRNA expression in orbital tissues from GO and normal controls was compared using real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Primary cultured orbital fibroblasts from each group were pretreated with BMS and stimulated with interleukin (IL)-1ß to induce inflammatory reaction. ITK mRNA expression was evaluated using western blotting, and inflammatory cytokine production and downstream transcription factor expression were analyzed after pretreatment with BMS. ITK mRNA expression in GO tissues was significantly higher than that in normal control tissues. After stimulation with IL-1ß, ITK phosphorylation significantly increased in both GO orbital and normal control tissues. BMS inhibited IL-1ß-induced IL-8 expression in the GO orbital fibroblasts. BMS pretreatment significantly suppressed NF-κB phosphorylation in both GO and normal controls. The selective ITK inhibitor attenuates proinflammatory cytokine production and proinflammatory transcription factor phosphorylation in in vitro model of GO.

Job dissatisfaction as a risk factor of depressive symptoms and suicidal ideation among female workers: evidence from a nationwide longitudinal study in South Korea.

This study aimed to investigate the relationship between job dissatisfaction (JD) and depressive symptoms and suicidal ideation among female workers. Additionally, it examined how the cumulative exposure to JD over multiple years can exacerbate the effect. We conducted our analyses on a nationwide sample of 6111 female workers from the Korean Longitudinal Survey of Women and Family (Waves 5-7). Depressive symptoms were measured using the 10-item version of the Centre for Epidemiologic Studies Depression Scale. JD was classified into quartiles (Q1-Q4), and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using generalised estimating equations. The overall prevalence of depressive symptoms and suicidal ideation among study participants was 13.9% and 2.4%, respectively. Our findings revealed that female workers with the highest level of JD (Q4) had a significantly greater risk of depressive symptoms (OR [95% CI]: 1.61 [1.37-1.89]) and suicidal ideation (OR [95% CI]: 2.08 [1.37-3.17]) after 2-year follow-up compared to those with the lowest level of JD (Q1). Consecutive exposure to JD over multiple years was also associated with depressive symptoms and suicidal ideation after a 2-year follow-up. For instance, women exposed to JD for three consecutive waves exhibited a high risk of depressive symptoms (OR [95% CI]: 1.61 [1.33-1.95]) and suicidal ideation (OR [95% CI]: 1.67 [1.04-2.70]). JD was positively associated with depressive symptoms and suicidal ideation. Our study suggests that JD is a risk factor for mental health problems in female workers.