Exploring the Link between Head and Neck Cancer and the Elevated Risk of Acute Myocardial Infarction: A National Population-Based Cohort Study.

Enhanced screening protocols for cancer detection have increased survival in patients with head and neck cancer (HNC), which highlights the need to address the sequelae of therapy-induced cardiovascular complications. This study was conducted to assess the incidence and risk of acute myocardial infarction (AMI) in patients with HNC who have not undergone radiation or chemotherapy using a comprehensive, population-based cohort dataset. A total of 2976 individuals without cancer and 744 individuals with HNC were matched using the propensity score method. The findings indicated that the occurrence rates of AMI were comparable between the HNC (2.19) and non-cancer groups (2.39). Cox regression analysis did not demonstrate a significant increase in the risk of AMI in patients with HNC (hazard ratio: 0.93, 95% confidence interval: 0.50-1.73). No increased risk of AMI was observed in the HNC group compared to the non-cancer group, regardless of the time since the HNC diagnosis. Subgroup analyses showed no notable differences in the AMI risk between the groups when considering sex, age, comorbidities, and cancer type. This study showed that patients with HNC who have not been treated with radiation or chemotherapy did not exhibit an increased incidence or risk of AMI compared to individuals without cancer.

Virtual Golf, "Exergaming", Using Virtual Reality for Healthcare in Older Adults: Focusing on Leisure Constraints, Participation Benefits, and Continuous Participation Intention.

Exergaming, a new type of sport, combined with virtual reality, has provided new opportunities for the aging population. This study analyzed the differences in leisure constraints, participation benefits, and continuous participation intention in virtual golf (represented as an exergame) depending on the participants' ages. Data collection was conducted from August 2023 to November 2023. A quantitative research design and a convenience sampling method were employed, targeting 310 regular virtual golf participants aged 20 years or older in the Republic of Korea. For comparative analysis, the survey participants were segmented into three groups: Group 1, young adults (18-35 years); Group 2, middle-aged adults (36-55 years); and Group 3, older adults (56-69 years). To compare and analyze participation behaviors in virtual golf, the dependent variables were identified: (a) leisure constraints (four factors) to limit formation and participation in leisure; (b) participation benefits (four factors) to encourage participation in leisure; and (c) continuous participation intention (single factor) to show likelihood to participate in leisure in the future. The results revealed that the young adult group showed statistically high results for costs under leisure constraints (F = 14.949, p < 0.001, ηp2 = 0.089), and the older adult group reported statistically high results in physical (F = 9.346, p < 0.001, ηp2 = 0.057) and mental (F = 7.249, p < 0.001, ηp2 = 0.045) participation benefits and continuous participation intention (F = 6.486, p < 0.01, ηp2 = 0.041). This study confirmed that virtual golf using advanced technology brings physical and mental benefits to older people based on reasonable cost and enables continuous participation in physical activity.

Microstructure-Based Modeling of Deformation and Damage Behavior of Extruded and Additively Manufactured 316L Stainless Steels.

In this study, we investigated the micromechanical deformation and damage behavior of commercially extruded and additively manufactured 316L stainless steels (AMed SS316L) by combining experimental examinations and crystal plasticity modeling. The AMed alloy was fabricated using the laser powder bed fusion (LPBF) technique with an orthogonal scanning strategy to control the directionality of the as-fabricated material. Optical microscopy and electron backscatter diffraction measurements revealed distinct grain morphologies and crystallographic textures in the two alloys. Uniaxial tensile test results suggested that the LPBFed alloy exhibited an increased yield strength, reduced elongation, and comparable ultimate tensile strength in comparison to those of the extruded alloy. A microstructure-based crystal plasticity model was developed to simulate the micromechanical deformation behavior of the alloys using representative volume elements based on realistic microstructures. A ductile fracture criterion based on the microscopically dissipated plastic energy on a slip system was adopted to predict the microscopic damage accumulation of the alloys during plastic deformation. The developed model could accurately predict the stress-strain behavior and evolution of the crystallographic textures in both the alloys. We reveal that the increased yield strength in the LPBFed alloy, compared to that in the extruded alloy, is attributed to the higher as-manufactured dislocation density and the cellular subgrain structure, resulting in a reduced elongation. The presence of annealing twins and favorable texture in the extruded alloy contributed to its excellent elongation, along with a higher hardening rate owing to twin-dislocation interactions during plastic deformation. Moreover, the grain morphology and defect state (e.g., dislocations and twins) in the initial state can significantly affect strain localization and damage accumulation in alloys.

Association between Head and Neck Cancer and Increased Risk of Ischemic Heart Disease: A Retrospective Cohort Study Using National Population Data.

Although cancer and ischemic heart disease (IHD) frequently manifest in the same individual, the risk of IHD events in cancer, especially head and neck cancer (HNC), remains unclear. We aimed to examine the incidence and risk of IHD events in patients with HNC using a population-based cohort dataset in South Korea (2002-2013). Through rigorous propensity score matching, we compared data from 2816 individuals without HNC and 704 individuals with HNC. Key independent variables were matched between groups, and the Charlson Comorbidity Index was used to match comorbidities. The Kaplan-Meier method depicted the cumulative probability of IHD throughout the follow-up period for both the study and control groups. The overall IHD incidence was significantly higher (19.93) in patients with HNC than in those without HNC (14.81), signifying an augmented IHD risk in the HNC cohort. Subsequent temporal analysis revealed a significant surge in IHD risk commencing 4 years after HNC diagnosis and persisting throughout the follow-up period. Subgroup analysis revealed an increased IHD risk in men with HNC and patients with cancers affecting the oral and sinonasal regions. This retrospective cohort study provides valuable scientific insights into the nuanced relationship between HNC and IHD, underscoring the need for tailored monitoring protocols and specialized care for susceptible individuals.

Retinoic Acid Treatment Mitigates PM2.5-Induced Type 2 Inflammation: Insights into Modulation of Innate Immune Responses.

Some studies have demonstrated the effects of particulate matter (PM) on chronic rhinosinusitis with nasal polyps (CRSwNP) development, as well as the therapeutic role of retinoic acid (RA) in nasal polypogenesis. However, the immunologic effect of PM in innate lymphoid cells (ILCs) and the exact mechanism of the therapeutic effect of RA remain unclear. Therefore, the present study investigated the effects of fine-dust-induced inflammation in CRSwNP and the mechanisms of the therapeutic effect of RA. PM2.5 exposure exacerbated pathological damage in the nasal mucosa of mice with nasal polyps (NP) via upregulation of type 2 inflammation. Additionally, PM2.5 exposure increased the expression of type 2 cytokines and epithelial-cell-derived cytokines (IL-33 and IL-25) significantly, as well as the ILC populations in human-NP-derived epithelial cells (HNECs). Moreover, RA supplementation significantly increased the expression of ILCreg in Lin-CD45+CD127+ cells, which in turn increased the levels of the anti-inflammatory cytokine IL-10. The findings suggest that PM2.5 exposures could aggravate the CRSwNP type 2 inflammation, and RA treatment may ameliorate fine-dust-induced inflammation by modulating the innate immune response.

The association of job training duration and risk of depression among wage workers: an analysis of the mediating factors.

Background: Research on job training and job satisfaction has been conducted from various perspectives. Job training is thought to be associated with job satisfaction, which is known as an important factor for depression among workers. We hypothesized that job training duration could influence depression through potential mediators (job satisfaction, motivation to work, and work engagement). Methods: This study encompassed participants from the sixth Korean Working Conditions Survey (KWCS), conducted between 2020 and 2021. To show the relationships between demographic or occupational characteristics and risk of depression, a χ2 test was conducted. The association between job training duration, potential mediators, and risk of depression was analyzed by constructing multiple logistic regression models. The mediating effects of potential mediators on job training duration and risk of depression was evaluated with flexible mediation analysis with weighting-based methods. Results: The final study population consisted of 25,294 participants. Longer job training duration significantly decreased risk of depression after adjusting for confounders. In the group that received the longest job training duration (≥ 10 days), compared with the group without job training, the odds ratio (OR) for high risk of depression was 0.46 (95% confidence interval [CI], 0.39-0.54). Each three potential mediators showed statistically significant indirect effects and direct effect. Although indirect effects were not strong compared to direct effect, motivation to work had the strongest mediating effect in this study, with an OR of 0.94 (95% CI, 0.92-0.95). Conclusions: Job training duration was found to have a statistically significant negative association on the risk of depression, and three mediators partially mediating this effect. Although the mechanism was unknown, our findings suggest that job training has a positive influence on workers' mental health. Furthermore, by suggesting the possibility of other pathways existing between job training and depression, we provide directions for future research.

Type-I-interferon-responsive microglia shape cortical development and behavior.

Microglia are brain-resident macrophages that shape neural circuit development and are implicated in neurodevelopmental diseases. Multiple microglial transcriptional states have been defined, but their functional significance is unclear. Here, we identify a type I interferon (IFN-I)-responsive microglial state in the developing somatosensory cortex (postnatal day 5) that is actively engulfing whole neurons. This population expands during cortical remodeling induced by partial whisker deprivation. Global or microglial-specific loss of the IFN-I receptor resulted in microglia with phagolysosomal dysfunction and an accumulation of neurons with nuclear DNA damage. IFN-I gain of function increased neuronal engulfment by microglia in both mouse and zebrafish and restricted the accumulation of DNA-damaged neurons. Finally, IFN-I deficiency resulted in excess cortical excitatory neurons and tactile hypersensitivity. These data define a role for neuron-engulfing microglia during a critical window of brain development and reveal homeostatic functions of a canonical antiviral signaling pathway in the brain.

Exploring the Link between Head and Neck Cancer and Elevated Risk of Rheumatoid Arthritis: A National Population-Based Cohort Study.

An increased risk of cancer among patients with rheumatoid arthritis (RA) has been reported. However, the risk of RA events among patients with head and neck cancer (HNC) is unknown. Therefore, we investigated the incidence and risk of RA among patients with HNC. This study was based on a cohort dataset. Overall, 2824 individuals without HNC and 706 patients with HNC were selected using propensity score matching. The overall RA event rate was 12.19 for patients with HNC and 7.60 for those without HNC. A significantly increased risk of developing RA was also observed among patients with HNC. The risk of developing RA over time was relatively high within the first year after HNC diagnosis; further, it increased significantly during the follow-up period. Moreover, middle-aged male patients with HNC exhibited an increased risk of developing RA compared with the controls; however, no significant difference was noted among female patients or other age groups. Notably, subgroup analysis according to cancer subtype revealed that only oral cancer survivors had an increased risk of developing RA. These results underscore the importance of vigilant monitoring by clinicians to promptly identify the onset of RA in patients with HNC.

Characterization of hyperpolarization-activated cyclic nucleotide-gated channels in oligodendrocytes.

Mature oligodendrocytes (OLG) are the myelin-forming cells of the central nervous system. Recent work has shown a dynamic role for these cells in the plasticity of neural circuits, leading to a renewed interest in voltage-sensitive currents in OLG. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and their respective current (Ih) were recently identified in mature OLG and shown to play a role in regulating myelin length. Here we provide a biochemical and electrophysiological characterization of HCN channels in cells of the oligodendrocyte lineage. We observed that mice with a nonsense mutation in the Hcn2 gene (Hcn2ap/ap) have less white matter than their wild type counterparts with fewer OLG and fewer oligodendrocyte progenitor cells (OPCs). Hcn2ap/ap mice have severe motor impairments, although these deficits were not observed in mice with HCN2 conditionally eliminated only in oligodendrocytes (Cnpcre/+; Hcn2F/F). However, Cnpcre/+; Hcn2F/F mice develop motor impairments more rapidly in response to experimental autoimmune encephalomyelitis (EAE). We conclude that HCN2 channels in OLG may play a role in regulating metabolism.

Detection Rate of Small Pancreas Cysts and Intrareader Reliability of the Cysts Size Measurements on Transabdominal Ultrasonography.

ABSTRACT: This study aimed to assess the detection rate of small (<10 mm) pancreas cyst and intrareader reliability for cyst size measurements on transabdominal ultrasonography (US). From 2020 to 2022, 194 pancreas cysts in 173 patients, incidentally detected on computed tomography or magnetic resonance imaging, were evaluated on US by 1 of 2 radiologists (readers 1 and 2). Intrareader agreements of cyst size measurements on US were assessed by intraclass correlation coefficient (ICC). Bland-Altman plot was used to visualize the differences between the first and second size measurements in each reader. In this study, readers 1 and 2 evaluated 86 cysts in 76 patients and 108 cysts in 97 patients, respectively. Most of the cysts (191 of 194) were located in the nontail portion of the pancreas. Overall detection rate of pancreas cysts by US was 92.3% (179 of 194). The mean size of measured 179 pancreas cysts was 4.7 ± 1.5 mm. The readers showed excellent intrareader agreements (ICC = 0.925 and 0.960) for cyst size measurements, except for the cysts with size ≤5 mm, where both readers showed good intrareader agreements (ICC = 0.848 and 0.873). The 95% limits of agreement of readers 1 and 2 were 13.8% and 14.9% of the mean, respectively. Therefore, transabdominal US could be a reliable follow-up imaging modality for small (<10 mm) nontail pancreas cysts incidentally detected on computed tomography or magnetic resonance imaging, especially for the cysts with size between 5 and 10 mm. Size changes of the pancreas cysts approximately less than 15% may be within the measurement error.

Brain hypothyroidism silences the immune response of microglia in Alzheimer's disease animal model.

Thyroid hormone (TH) imbalance is linked to the pathophysiology of reversible dementia and Alzheimer's disease (AD). It is unclear whether tissue hypothyroidism occurs in the AD brain and how it affects on AD pathology. We find that decreased iodothyronine deiodinase 2 is correlated with hippocampal hypothyroidism in early AD model mice before TH alterations in the blood. TH deficiency leads to spontaneous activation of microglia in wild-type mice under nonstimulated conditions, resulting in lowered innate immune responses of microglia in response to inflammatory stimuli or amyloid-ß. In AD model mice, TH deficiency aggravates AD pathology by reducing the disease-associated microglia population and microglial phagocytosis. We find that TH deficiency reduces microglial ecto-5'-nucleotidase (CD73) and inhibition of CD73 leads to impaired innate immune responses in microglia. Our findings reveal that TH shapes microglial responses to inflammatory stimuli including amyloid-ß, and brain hypothyroidism in early AD model mice aggravates AD pathology by microglial dysfunction.

Artificial intelligence-driven drug repositioning uncovers efavirenz as a modulator of α-synuclein propagation: Implications in Parkinson's disease.

Parkinson's disease (PD) is a complex neurodegenerative disorder with an unclear etiology. Despite significant research efforts, developing disease-modifying treatments for PD remains a major unmet medical need. Notably, drug repositioning is becoming an increasingly attractive direction in drug discovery, and computational approaches offer a relatively quick and resource-saving method for identifying testable hypotheses that promote drug repositioning. We used an artificial intelligence (AI)-based drug repositioning strategy to screen an extensive compound library and identify potential therapeutic agents for PD. Our AI-driven analysis revealed that efavirenz and nevirapine, approved for treating human immunodeficiency virus infection, had distinct profiles, suggesting their potential effects on PD pathophysiology. Among these, efavirenz attenuated α-synuclein (α-syn) propagation and associated neuroinflammation in the brain of preformed α-syn fibrils-injected A53T α-syn Tg mice and α-syn propagation and associated behavioral changes in the C. elegans BiFC model. Through in-depth molecular investigations, we found that efavirenz can modulate cholesterol metabolism and mitigate α-syn propagation, a key pathological feature implicated in PD progression by regulating CYP46A1. This study opens new avenues for further investigation into the mechanisms underlying PD pathology and the exploration of additional drug candidates using advanced computational methodologies.

Integration of National Health Insurance claims data and animal models reveals fexofenadine as a promising repurposed drug for Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a common and costly progressive neurodegenerative disease of unclear etiology. A disease-modifying approach that can directly stop or slow its progression remains a major unmet need in the treatment of PD. A clinical pharmacology-based drug repositioning strategy is a useful approach for identifying new drugs for PD. METHODS: We analyzed claims data obtained from the National Health Insurance Service (NHIS), which covers a significant portion of the South Korean population, to investigate the association between antihistamines, a class of drugs commonly used to treat allergic symptoms by blocking H1 receptor, and PD in a real-world setting. Additionally, we validated this model using various animal models of PD such as the 6-hydroxydopmaine (6-OHDA), α-synuclein preformed fibrils (PFF) injection, and Caenorhabditis elegans (C. elegans) models. Finally, whole transcriptome data and Ingenuity Pathway Analysis (IPA) were used to elucidate drug mechanism pathways. RESULTS: We identified fexofenadine as the most promising candidate using National Health Insurance claims data in the real world. In several animal models, including the 6-OHDA, PFF injection, and C. elegans models, fexofenadine ameliorated PD-related pathologies. RNA-seq analysis and the subsequent experiments suggested that fexofenadine is effective in PD via inhibition of peripheral immune cell infiltration into the brain. CONCLUSION: Fexofenadine shows promise for the treatment of PD, identified through clinical data and validated in diverse animal models. This combined clinical and preclinical approach offers valuable insights for developing novel PD therapeutics.

Clinical course of patients with hepatocellular carcinoma who experienced radiologic complete response after radioembolization.

Purpose: The purpose of this study is to elucidate the patterns of recurrence of hepatocellular carcinoma and to analyze factors that can predict recurrence after complete response to radioembolization. Materials and methods: A total of 289 consecutive patients who underwent radioembolization for the treatment of hepatocellular carcinoma at a single tertiary center were retrospectively reviewed. Baseline characteristics were collected and compared between the group showing complete response and the group showing noncomplete response. Data on recurrence status, time to recurrence, and the patterns of recurrence among the patients who showed radiologic complete response were collected. The group that maintained complete response and the group that experienced recurrence were compared, and the risk factors affecting recurrence were evaluated by logistic regression analysis. Results: The complete response rate was 24.9% (73/289). Age, sex, tumor markers, maximum tumor diameter, multiplicity, presence of vascular invasion, and target radiation dose were significantly different between the complete response and noncomplete response groups. The recurrence rate after complete response was 38.4% (28/73), and 67.9% (19/28) of recurrences occurred by 8 months after complete response. Eight patients who underwent resection/transplantation after complete response experienced no recurrence. Multiple tumors and a lower target radiation dose were independent risk factors of recurrence after complete response in the multivariate logistic regression. Conclusion: Hepatocellular carcinoma recurrence following complete response after radioembolization is not uncommon and frequently occurs within 1 year after complete response. Multiple tumors and a lower target radiation dose may be risk factors for recurrence.

Medial Patellar Plica Thickness as a Morphologic Predictor of the Medial Patellar Plica Syndrome.

OBJECTIVE: The aim of this study was to evaluate the association between medial patellar plica (MPP) syndrome and the morphological features of the MPP, including length, width, and thickness, on knee magnetic resonance imaging (MRI). MATERIALS AND METHODS: From 2018 to 2022, 167 patients diagnosed with isolated MPP syndrome based on both MRI and arthroscopic findings were included in the "study group" and 226 patients without knee pathology on both MRI and physical examination were included in the "control group." Finally, 393 patients (mean age, 38.9 ± 5.7 years) with 405 knee MRI examinations were included. Morphological MR features of MPP were assessed, including width, length, and thickness. Multivariate regression and receiver operating characteristic analyses were performed to identify the factors associated with MPP syndrome. RESULTS: The mean thickness of MPP was significantly higher in the study group than control group (2.3 ± 0.5 mm vs 1.0 ± 0.8 mm, P < 0.001). Moreover, on multivariate analysis, MPP thickness was the only significant factor associated with MPP syndrome (odds ratio, 6.452; 95% confidence interval, 0.816-15.073; P = 0.002). On receiver operating characteristic analysis, thickness ≥1.8 mm was estimated as the optimal cutoff for predicting MPP syndrome with sensitivity of 75.9%, specificity of 65.4%, and area under the curve of 0.727 (95% confidence interval, 0.667-0.788; P < 0.001). CONCLUSIONS: Measurement of MPP thickness on MRI could be a morphological predictor of MPP syndrome.

Microvilli regulate the release modes of alpha-tectorin to organize the domain-specific matrix architecture of the tectorial membrane.

The tectorial membrane (TM) is an apical extracellular matrix (ECM) in the cochlea essential for auditory transduction. The TM exhibits highly ordered domain-specific architecture. Alpha-tectorin/TECTA is a glycosylphosphatidylinositol (GPI)-anchored ECM protein essential for TM organization. Here, we identified that TECTA is released by distinct modes: proteolytic shedding by TMPRSS2 and GPI-anchor-dependent release from the microvillus tip. In the medial/limbal domain, proteolytically shed TECTA forms dense fibers. In the lateral/body domain produced by the supporting cells displaying dense microvilli, the proteolytic shedding restricts TECTA to the microvillus tip and compartmentalizes the collagen-binding site. The tip-localized TECTA, in turn, is released in a GPI-anchor-dependent manner to form collagen-crosslinking fibers, required for maintaining the spacing and parallel organization of collagen fibrils. Overall, we showed that distinct release modes of TECTA determine the domain-specific organization pattern, and the microvillus coordinates the release modes along its membrane to organize the higher-order ECM architecture.

Increased Risk of Alzheimer's Disease in Patients with Head and Neck Cancer.

Patients with head and neck cancer (HNC) often experience cognitive impairment. However, the relationship between cancer and Alzheimer's disease (AD) remains unclear. We aimed to elucidate the relationship between patients with HNC and their subsequent AD development. This retrospective study used data from a nationwide representative cohort sample, the Korean National Health Insurance Service Cohort. The cancer group was defined based on the presence of diagnostic codes for HNC (C00-C14 and C30-C32). After matching the independent variables with a propensity score of 4:1, a total of 2304 people without HNC and 576 with HNC were enrolled in this study. Hazard ratios (HRs) of AD incidence (per 1000 person-years) and 95% confidence intervals (CIs) in HNC patients were calculated. The incidence of AD was 14.92 in HNC patients and 9.77 in non-cancer patients. Additionally, the HNC group was found to have a higher risk of developing AD compared with the non-cancer group. Female and middle-aged HNC patients had a higher risk of developing AD events compared with other subgroups. Surprisingly, during the observation period, the risk of developing AD was relatively high within the first year after HNC diagnosis. In conclusion, our study suggests that HNC and AD are positively correlated.

Incidence Rates and Risk Ratios of Normal Tension Glaucoma in Patients with Chronic Rhinosinusitis: A Population-Based Longitudinal Follow-Up Study.

Several studies have investigated the association between chronic rhinosinusitis (CRS) and ophthalmological complications. However, it remains uncertain whether CRS is independently associated with the development of normal tension glaucoma (NTG). Therefore, this retrospective cohort study aimed to investigate the prospective association between CRS and the increased incidence and risk of NTG using a representative population-based dataset. The selection of both the CRS and comparison groups was meticulously conducted through the propensity scoring method. The incidence and risk ratios of NTG were measured using person-years at risk and a weighted Cox proportional hazards model. We enrolled 30,284 individuals without CRS (comparison group) and 15,142 individuals with CRS. The NTG incidence rates were 1.19 and 0.81 in the CRS and comparison groups, respectively. The CRS group showed a significantly increased risk of subsequent development for NTG (adjusted hazard ratio = 1.41, 95% confidence interval = 1.16-1.72), regardless of the CRS subtype. Additionally, the risk of developing NTG was relatively higher in the first 2 years after CRS diagnosis. Moreover, a subgroup analysis revealed a higher risk of NTG in elderly female individuals with CRS. The present findings underscore the importance of monitoring and managing NTG risk in individuals with CRS, especially in elderly female patients.