SARS-CoV2 mRNA vaccine intravenous administration induces myocarditis in chronic inflammation.

The current COVID-19 mRNA vaccines were developed and applied for pandemic-emergent conditions. These vaccines use a small piece of the virus's genetic material (mRNA) to stimulate an immune response against COVID-19. However, their potential effects on individuals with chronic inflammatory conditions and vaccination routes remain questionable. Therefore, we investigated the effects of mRNA vaccines in a mouse model of chronic inflammation, focusing on their cardiac toxicity and immunogenicity dependent on the injection route. mRNA vaccine intravenous administration with or without chronic inflammation exacerbated cardiac pericarditis and myocarditis; immunization induced mild inflammation and inflammatory cytokine IL-1beta and IL-6 production in the heart. Further, IV mRNA vaccination induced cardiac damage in LPS chronic inflammation, particularly serum troponin I (TnI), which dramatically increased. IV vaccine administration may induce more cardiotoxicity in chronic inflammation. These findings highlight the need for further research to understand the underlying mechanisms of mRNA vaccines with chronic inflammatory conditions dependent on injection routes.

Excess Deaths in Korea During the COVID-19 Pandemic: 2020-2022.

OBJECTIVES: Excess deaths, an indicator that compares total mortality rates before and during a pandemic, offer a comprehensive view of the pandemic's impact. However, discrepancies may arise from variations in estimating expected deaths. This study aims to compare excess deaths in Korea during the coronavirus disease 2019 pandemic using 3 methods and to analyze patterns using the most appropriate method. METHODS: Expected deaths from 2020 to 2022 were estimated using mortality data from 2015-2019 as reference years. This estimation employed 3 approaches: (1) simple average, (2) age-adjusted average, and (3) age-adjusted linear regression. Excess deaths by age, gender, and cause of death were also presented. RESULTS: The number of excess deaths varied depending on the estimation method used, reaching its highest point with the simple average and its lowest with the age-adjusted average. Age-adjusted linear regression, which accounts for both the aging population and declining mortality rates, was considered most appropriate. Using this model, excess deaths were estimated at 0.3% for 2020, 4.0% for 2021, and 20.7% for 2022. Excess deaths surged among individuals in their 20s throughout the pandemic, largely attributed to a rise in self-harm and suicide. Additionally, the results indicated sharp increases in deaths associated with "endocrine, nutritional, and metabolic diseases" and "symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified." CONCLUSIONS: Substantial variations in excess deaths were evident based on estimation method, with a notable increase in 2022. The heightened excess deaths among young adults and specific causes underscore key considerations for future pandemic responses.

TAS-102 (trifluridine/tipiracil) plus bevacizumab versus TAS-102 alone as salvage treatment options for metastatic colorectal cancer in routine clinical practice.

Introduction: Both regimens of TAS-102 (trifluridine/tipiracil) with and without bevacizumab are considered standard options for salvage treatment in patients with refractory metastatic colorectal cancer. Materials and methods: This analysis included patients with metastatic colorectal cancer who received either TAS-102 plus bevacizumab or TAS-102 alone between July 2022 and November 2023 at Samsung Medical Center. We evaluated the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety profile of both regimens. Results: In total, 139 patients were included in this analysis. Median age was 60.8 years, and median number of previous lines of therapy was four (range: 2.45-6.55). More than half of the subjects (56.8%) had RAS mutations and 92.9% received previous anti-VEGF therapy. 83 (59.7%) patients received the combination of TAS-102 and bevacizumab and 56 (40.3%) received TAS-102 alone. The number of patients with prior regorafenib treatment was 14 in the TAS-102 with bevacizumab group and 5 in the TAS-102 alone group. The disease control rate was 51.8% in the combination group and 32.1% in the TAS-102 alone group. The median PFS was 3.3 months (95% CI, 2.7-6.6) in the combination group and 2.5 months (95% CI, 2.0-3.8) in the TAS-102 alone group (HR, 0.56; 95% CI, 0.38-0.82; p=0.003). The median OS in these two groups was 10.8 months (95% CI, 8.4-NA) and 6.0 months (95% CI, 4.8-9.8), respectively (HR, 0.62; 95% CI, 0.40-0.97, p=0.033). In the exploratory analysis of TAS-102 + Bev group, patients with the KRAS G12 mutation had inferior OS compared to those without the mutation (HR, 2.01, 95% CI, 1.04-3.90, p=0.035). Commonly observed adverse events were hematologic-related, including neutropenia, anemia, and thrombocytopenia, as well as nausea. While any grade neutropenia was observed at similar frequencies in the two groups (57.8% and 57.1%), grade 3 or higher neutropenia was more frequent in the combination group than the TAS-102 alone group (31.3% vs. 17.9%). Among patients who received subsequent anticancer therapy after treatment failure, 74.1% received regorafenib. Conclusions: The combination of TAS-102 and bevacizumab resulted in a better survival outcome than TAS-102 monotherapy, consistent with previous studies. This analysis supports the use of the combination of TAS-102 and bevacizumab as the best therapeutic option for patients with refractory metastatic colorectal cancer in clinical practice.

The safety and efficacy of through-and-through wire technique for ureteral Double-J stent placement.

Objective: To evaluate the efficacy and safety of the through-and-through wire (TTW) technique for antegrade ureteral Double-J stent placement after failure of either antegrade or retrograde ureteral stent placement. Method: This retrospective study analyzed the medical records of consecutive patients who underwent Double-J stent placement with the TTW technique at Asan Medical Center and Gil Medical Center between January 2016 and February 2023. Patient histories, reasons for employing the TTW technique, TTW pathways, and complications were reviewed. Eight patients were included in the study. The reasons for using the TTW technique were failure to advance a larger-diameter catheter, balloon catheter, or Double-J stent passing over the guidewire beyond the stricture (6/8, 75.0%); failure to negotiate the stricture with a guidewire (1/8, 12.5%); and guidewire passing through a ureteropelvic junction defect (1/8, 12.5%). Results: TTW was applied either between a percutaneous nephrostomy (PCN) and the urethral orifice (n=4), between a PCN and an ileostomy pouch (n=3), or between a left and right PCN (n = 1). Urologic assistance was required for retrograde ureteral cannulation in one male patient (12.5%). Subsequently, balloon dilation and/or Double-J stent placement were performed in all eight patients, resulting in 100% technical success. No major or minor complications occurred. Conclusions: The TTW technique was safe and effective in the undertaking of PCN and antegrade Double-J stent placement in patients for whom either antegrade or retrograde access had failed.

Suicide Rates and Subgroups With Elevated Suicide Risk Among Patients With Psychiatric Disorders: A Nationwide Cohort Study in Korea.

BACKGROUND: Despite the distinctly high risk of suicide among patients with psychiatric disorders, little is known regarding the nationwide rates and risk factors for suicide among individual subgroups of patients with psychiatric disorders. This study aimed to assess differences in suicide rates and identify risk factors for suicide across multiple psychiatric diseases using data from a nationally representative cohort in Korea. METHODS: Six groups of incident patients with psychiatric disorders, namely those with drug use disorder (DUD), alcohol use disorder (AUD), schizophrenia (SCZ), bipolar disorder (BD), depressive disorder (DD), or other affective disorders (OADs), were extracted from the National Health Information Database and followed up. Suicide rates and risk factors were then determined for each disease group. RESULTS: Patients with psychiatric disorders had higher suicide rates than did the general population, with standardized mortality ratios (SMRs) ranging from 2.5 to 16.6. In particular, patients with DUD showed markedly higher suicide rate (584.0 per 100,000 person-years [PYs]; SMR, 16.6) than did patients with affective disorders, including DD (119.8 per 100,000 PYs; SMR, 3.1). AUD, DUD, SCZ, and BD showed lower male/female suicide rate ratios (1.1-1.4) than did depressive and OADs (2.2-2.4). Old age increased the risk for suicide among those with DUD and OADs, while medical aid recipients exhibited the lowest suicide risk among those with the AUD and SCZ. Male sex and the presence of multiple psychiatric comorbidities were consistently identified as suicide risk factors across mental illness subgroups. CONCLUSION: The current study observed substantial variations in suicide rates and risk factors across psychiatric disorders and patient characteristics, which have significant implications for suicide prevention strategies.

Single-Center Experience With Dynamic Contrast-Enhanced Magnetic Resonance Lymphangiography for Diagnosing Lymphatic Disorders and Guiding Percutaneous Embolization.

BACKGROUND: The pragmatic role of dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) needs to be evaluated and compared across distinct lymphatic disorders. We aimed to evaluate the performance of DCMRL for identifying the underlying causes of lymphatic disorders and to define the potential benefit of DCMRL for planning lymphatic interventions. METHODS: Patients who underwent DCMRL between August 2017 and July 2022 were included in this retrospective analysis. DCMRL was performed with intranodal injection of a gadolinium-based contrast medium through inguinal lymph nodes under local anesthesia. Technical success of DCMRL and feasibility of percutaneous embolization were assessed based on the lymphatic anatomy visualized by DCMRL. Based on the underlying causes, clinical outcomes were evaluated and compared. RESULTS: Seventy consecutive patients were included. The indications were traumatic chylothorax (n = 42), traumatic chylous ascites (n = 11), and nontraumatic lymphatic leak (n = 17). The technical success rate of DCMRL was the highest in association with nontraumatic lymphatic disorders (94.1% [16/17]), followed by traumatic chylothorax (92.9% [39/42]) and traumatic chylous ascites (81.8% [9/11]). Thirty-one (47.7%) patients among 65 patients who underwent technically successful DCMRL had feasible anatomy for intervention. Clinical success was achieved in 90.3% (28/31) of patients with feasible anatomy for radiologic intervention, while 62.5% (10/16) of patients with anatomical challenges showed improvement. Most patients with traumatic chylothorax showed improvement (92.9% [39/42]), whereas only 23.5% (4/17) of patients with nontraumatic lymphatic disorders showed clinical improvement. CONCLUSION: DCMRL can help identify the underlying causes of lymphatic disorders. The performance of DCMRL and clinical outcomes vary based on the underlying cause. The feasibility of lymphatic intervention can be determined using DCMRL, which can help in predicting clinical outcomes.

Liver-specific Coxsackievirus and adenovirus receptor deletion develop metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver disease associated with obesity and is caused by the accumulation of ectopic fat without alcohol consumption. Coxsackievirus and adenovirus receptor (CAR) are vital for cardiac myocyte-intercalated discs and endothelial cell-to-cell tight junctions. CAR has also been reported to be associated with obesity and high blood pressure. However, its function in the liver is still not well understood. The liver of obese mice exhibit elevated CAR mRNA and protein levels. Furthermore, in the liver of patients with non-alcoholic steatohepatitis, CAR is reduced in hepatocyte cell-cell junctions compared to normal levels. We generated liver-specific CAR knockout (KO) mice to investigate the role of CAR in the liver. Body and liver weights were not different between wild-type (WT) and KO mice fed a paired or high-fat diet (HFD). However, HFD induced significant liver damage and lipid accumulation in CAR KO mice compared with WT mice. Additionally, inflammatory cytokines transcription, hepatic permeability, and macrophage recruitment considerably increased in CAR KO mice. We identified a new interaction partner of CAR using a protein pull-down assay and mass spectrometry. Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3C) demonstrated a complex relationship with CAR, and hepatic CAR expression tightly regulated its level. Moreover, Apolipoprotein B (ApoB) and Low-density lipoprotein receptor (LDLR) levels correlated with APOBEC3C expression in the liver of CAR KO mice, suggesting that CAR may regulate lipid accumulation by controlling APOBEC3C activity. In this study, we showed that hepatic CAR deficiency increased cell-to-cell permeability. In addition, CAR deletion significantly increased hepatic lipid accumulation by inducing ApoB and LDLR expression. Although the underlying mechanism is unclear, CARs may be a target for the development of novel therapies for MAFLD.

Association of Polymorphisms in FSHR, ESR1, and BMP15 with Primary Ovarian Insufficiency and Meta-Analysis.

Primary ovarian insufficiency (POI) can lead to menstrual disturbance, resulting in ovarian dysfunction before age 40. Prevalence of POI is usually less than 1%; however, ethnicity or population characteristics may affect prevalence. POI is a heterogeneous disease that results from abnormalities in immunological and hormonal factors. Genetic factors can also contribute to POI. Here, we examine FSHR, ESR1, and BMP15 polymorphisms in patients with POI, and controls. We examined a hormonal gene that is important for pregnancy, follicle-stimulating hormone receptor (FSHR), as well as estrogen receptor 1 (ESR1), and associated it with FSHR expression, ovulation rate, and bone morphogenetic protein 15 (BMP15). We examined 139 Korean patients under age 40 with POI, and 350 Korean control participants without POI. Genotyping was performed by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and TaqMan assays. Each identified genotype was subjected to statistical analysis to determine the odds ratios (ORs) and 95% confidence intervals (CIs). In combination genotype analyses, FSHR rs6165 A > G combined with ESR1 rs9340799 A > G, AG/GG (OR: 5.693; 95% CI: 1.088-29.792), as well as FSHR rs6166 A > G combined with ESR1 rs9340799 C > T, AG/GG (OR: 5.940; 95% CI: 1.134-31.131), were significantly associated with POI prevalence. Furthermore, an FSHR rs6165 A > G and BMP rs17003221 C > T, AG/CC combination was associated with POI prevalence (OR: 1.874; 95% CI: (1.059-3.316; p-value: 0.031)). In meta-analysis, FSHR rs6165 AA vs. AG + GG is associated with POI (p = 0.0013), and ESR1 rs2234693 AA vs. AG + GG is also associated with POI (p = 0.0101). Here, we compared the genotypes of FSHR, ESR1, and BMP15 in patients with POI, and controls. We found significant differences in genotype combinations between polymorphisms in FSHR and other genes. Through meta-analysis, we found that ESR1 rs9340799 and rs2234693 are associated with POI prevalence, and that BMP15 rs17003221 increases POI risk. These findings help to improve POI diagnosis in Korean women.

High-Efficiency, Prevascularization-Free Macroencapsulation System for Subcutaneous Transplantation of Pancreatic Islets for Enhanced Diabetes Treatment.

Pancreatic islet macroencapsulation systems for subcutaneous transplantation have garnered significant attention as a therapy for Type I diabetes due to their minimal invasiveness and low complication rates. However, the low vascular density of subcutaneous tissue threatens the long-term survival of islets. To address this issue, prevascularized systems are introduced but various challenges remain, including system complexity and vascular-cell immunogenicity. Here, a novel prevasculature-free macroencapsulation system designed as a multilayer sheet, which ensures sufficient mass transport even in regions with sparse vasculature, is presented. Islets are localized in top/bottom micro-shell layers (≈300 µm thick) to maximize proximity to the surrounding host vasculature. These sheets, fabricated via bioprinting using rat islets and alginate-based bio-ink, double islet viability and optimize islet density, improving insulin secretion function by 240%. The subcutaneous transplantation of small islet masses (≈250 islet equivalent) into diabetic nude mice enable rapid (<1 day) recovery of blood glucose, which remain stable for >120 days. Additionally, antifibrotic drug-loaded multilayer sheets facilitate blood glucose regulation by rat islets at the subcutaneous sites of diabetic immunocompetent mice for >35 days. Thus, this macroencapsulation system can advance the treatment of Type I diabetes and is also effective for islet xenotransplantation in subcutaneous tissue.

Common Cancer-Related Factors and the Risk of Developing Kaposi Sarcoma in Individuals without AIDS: Korea National Health Insurance Services Claims Database.

Backgrounds: Kaposi sarcoma (KS) is a unique form of cancer with epidemiological characteristics distinct from those of other solid cancers. While common risk factors including alcohol consumption, smoking, and metabolic disorders have been well studied in various cancers, their relationship with KS remains unclear. Methods: This study used a cohort approach with adults without AIDS, utilizing data from the National Health Insurance Service in South Korea. This study examined various conventional cancer-related risk factors related to the incidence of KS, including psoriasis. Results: Alcohol consumption, smoking, body mass index, diabetes mellitus, hypertension, hypercholesterolemia, and regular exercise were not significantly associated with the incidence of KS. Additionally, older age and male sex were associated with a higher incidence of KS. KS risk was increased in pathological conditions such as psoriasis and proteinuria, which require immunosuppressive medication. Conclusions: Our study suggests that traditional cancer-related risk factors may not play a significant role in the pathogenesis of KS, unlike other cancers. This, in turn, emphasizes the importance of immunosuppression and HHV-8 infection in the development of KS.

Effectiveness of electrocardiogram interpretation education program using mixed learning methods and webpage.

AIM: This study was conducted to develop an electrocardiogram education program that incorporates an HTML webpage and blended learning methods to enhance electrocardiogram interpretation skills. Through continual and efficient education, the program aims to assist nurses in providing appropriate care and treatment to patients. DESIGN: Pre-post design study. METHODS: We developed an electrocardiogram interpretation HTML webpage based on an electrocardiogram interpretation algorithm and implemented an 18-week (2023.5.15 ~ 2023.9.22) electrocardiogram education program, which included daily 5-minute training sessions. Twenty-seven ward nurses were provided with the URL ( https://ecgweb.github.io/ECGwebEN ) to the electrocardiogram interpretation HTML webpage and shared one electrocardiogram case daily for self-interpretation. Electrocardiogram interpretation performance and confidence were evaluated through questionnaires at three phases: before the program, after 6 weeks of basic electrocardiogram and arrhythmia education, and after 12 weeks of application of the electrocardiogram interpretation HTML webpage and case-based lecture education. The statistical tests used were repeated-measures ANOVA or the Wilcoxon signed-rank test. RESULTS: The average score for electrocardiogram interpretation performance before the electrocardiogram education program was 11.89(SD = 3.50), after 6 weeks of basic electrocardiogram and arrhythmia education it was 14.15(SD = 3.68), and after 12 weeks of application of the electrocardiogram interpretation HTML webpage and case-based lecture education, it was 15.56(SD = 3.04). This shows that electrocardiogram interpretation performance significantly improved over time (p < .001). Additionally, post-hoc analysis revealed significant differences in electrocardiogram interpretation performance at each stage, i.e., before, during, and after the application of an electrocardiogram education program. Furthermore, the electrocardiogram interpretation confidence questionnaire score (pre-Median 18, IQR = 5; post-Median 23, IQR = 3) was improved significantly after the completion of the 18-week education program (p < .001). CONCLUSIONS: Based on the results of this study, we believe that an electrocardiogram education program using HTML webpage, and a blended teaching method would be very beneficial for maintaining and improving electrocardiogram interpretation skills of clinical nurses. Such a program can help nurses interpret electrocardiograms more effectively and assist them in making important decisions in patient care.

Association between TGF-ß/BMP signaling pathway polymorphisms and the risk of primary ovarian insufficiency in Korean women.

BACKGROUND: Primary ovarian insufficiency (POI) is one of the leading female infertility diseases in which ovarian function stops before the age of 40. Reports that POI is associated with transforming growth factor (TGF)-ß/bone morphogenetic protein (BMP) signaling pathway-associated genes (e.g., TGF-ß, and BMP15) have been continuous since publication that the TGF-ß superfamily acts as important regulators for ovary and placenta function in humans. Mechanistically, the secretion of follicle-stimulating hormone, progesterone, and estrogen is affected by the TGF-ß superfamily in granulosa cells, which are involved in the development of theca cells, oocytes, and granulosa cells. OBJECTIVE: This study aimed to identify the association between genes related to the TGF-ß/BMP signaling pathway and the risk of POI pathogenesis. METHODS: Possible associations between six gene polymorphisms and POI susceptibility were examined in 139 patients with POI and 345 control subjects. RESULTS: Allele combination of TGFBR1 rs334348 G > A and TGFBR3 rs1805110G > A exhibited association with decreased POI risk (adjusted odds ratio [AOR] = 0.165; 95% confidence interval [CI] 0.032-0.847; P = 0.031). Also, TGFBR1 rs1590 G > T and rs334348 G > A and TGFBR3 rs1805110 G > A allele combination exhibited association with decreased POI risk (OR = 0.553; 95% CI 0.374-0.816; P = 0.003). CONCLUSION: This study suggests that polymorphisms in the TGF-ß signaling pathway genes can be useful biomarkers for POI diagnosis and treatment.

Angiogenic factor-driven improvement of refractory thin endometrium with autologous platelet-rich plasma intrauterine infusion in frozen embryo transfer cycles.

Objective: A beneficial effect on endometrial thickness (EMT) and improvement of pregnancy outcome after intrauterine infusion of platelet-rich plasma (PRP) has been suggested. This study assessed the effect of intrauterine PRP infusion on live birth rate and obstetrical outcomes and analyzed cytokines that can potentially improve pregnancy outcomes through PRP. Method: This study was a prospective cohort study conducted in a university hospital fertility center. The study included ninety-one patients who had a history of two or more failed in vitro fertilization (IVF) attempts and refractory thin endometrium that remained unresponsive after at least two conventional treatments for thin endometrium. Patients were treated with an intrauterine infusion of autologous PRP between days 7 and 14 of their hormone replacement therapy-frozen embryo transfer (HRT-FET) cycle. PRP was administered at 3-day intervals until their EMT reached 7mm. After a maximum of three PRP administrations, embryo transfer (ET) was performed. The primary outcome was the live birth rate. Secondary outcomes included the implantation rate and increase in EMT compared to the previous cycle. We compared the cytokines related to angiogenesis in a patient's whole blood (WB) and PRP by utilizing a commercial screening kit. Results: The live birth rate in the PRP treatment cycle was 20.9% (19 of 91 patients), significantly superior to the previous cycle without PRP infusion (p < 0.001). The implantation rate was also significantly higher during the PRP treatment cycle (16.4%) compared to the previous cycle (3.1%) (p < 0.001). The mean EMT post-PRP treatment was 6.1 mm, showing a significant increase of 0.8 mm (p < 0.001). Nonetheless, an increase in EMT was also observed in the non-pregnancy group. No adverse effects were reported by patients treated with autologous PRP. Cytokine array analysis confirmed marked increases in well-known pro-angiogenic factors such as Ang-1, EGF, LAP (TGF-b1), MMP-8, PDGF-AA, and PDGF-AB/PDGF-BB. Conclusion: Intrauterine PRP infusion offers a safe and effective treatment for patients with refractory thin endometrium and implantation failures. The angiogenic cytokines present in PRP are the primary drivers of this improvement.

Challenges in endoscopic third ventriculostomy for patients with achondroplasia: a focus on third ventricle floor anatomy.

OBJECTIVE: Hydrocephalus is one of the neurological risks occurring in patients with achondroplasia. Ventriculoperitoneal shunt (VPS) insertion is the most common treatment. However, reports of successful endoscopic third ventriculostomy (ETV) suggest that ETV may be a good alternative to VPS insertion in achondroplasia. However, it has been stated that ETV in achondroplasia patients is technically demanding to perform. The current study examined the anatomical variations of the third ventricle and the brainstem in achondroplasia patients and correlated the findings with the difficulty of performing ETV. METHODS: A retrospective analysis of 51 patients with achondroplasia and 138 hydrocephalus patients without achondroplasia (48 patients had tumor-related hydrocephalus and 90 patients had hydrocephalus of nontumorous origin) who have visited the authors' institution since 2012 was performed. Preoperative T2-weighted sagittal MR images were used to measure α (steepness of the third ventricle floor), ß (endoscopic angle of incidence), d1 (vertical distance between the dorsum sellae and basilar bifurcation), and d2 (horizontal distance between the dorsum sellae and basilar artery). Each value was compared using the Tukey multicomparison test. RESULTS: Achondroplasia patients showed significantly smaller α (p < 0.001) and ß (p < 0.001) angles, while there were no significant differences between the control groups (p = 0.947 for α, p = 0.836 for ß). The d1 value was significantly larger in achondroplasia patients (p < 0.001), and d2 was smaller (p < 0.001). The control groups showed similar d1 and d2 values (p = 0.415 for d1, p = 0.154 for d2). Smaller α and ß values meant that in achondroplasia patients the third ventricle floor stood more vertically than in other patients with hydrocephalus, and the endoscopic contact angles were small, increasing the risk of ventriculostomy devices slipping down into the infundibular recess. Additionally, a large d1 meant that the basilar artery was shifted upward and a small d2 indicated that the basilar artery was located closer to the dorsum sellae, potentially increasing the risk of basilar artery damage. CONCLUSIONS: Achondroplasia patients' skull and brain anatomies were significantly different from those of other hydrocephalus patients, with steeper third ventricle floors and basilar arteries closer to the dorsum sellae. Because these anatomical differences lead to difficulties in performing ETVs in achondroplasia patients, such differences should be considered when ETV is planned for the patients.

Multipartite network analysis to identify environmental and genetic associations of metabolic syndrome in the Korean population.

Network analysis has become a crucial tool in genetic research, enabling the exploration of associations between genes and diseases. Its utility extends beyond genetics to include the assessment of environmental factors. Unipartite network analysis is commonly used in genomics to visualize initial insights and relationships among variables. Syndromic diseases, such as metabolic syndrome, are characterized by the simultaneous occurrence of various signs, symptoms, and clinicopathological features. Metabolic syndrome encompasses hypertension, diabetes, obesity, and dyslipidemia, and both genetic and environmental factors contribute to its development. Given that relevant data often consist of distinct sets of variables, a more intuitive visualization method is needed. This study applied multipartite network analysis as an effective method to understand the associations among genetic, environmental, and disease components in syndromic diseases. We considered three distinct variable sets: genetic factors, environmental factors, and disease components. The process involved projecting a tripartite network onto a two-mode bipartite network and then simplifying it into a one-mode network. This approach facilitated the visualization of relationships among factors across different sets and within individual sets. To transition from multipartite to unipartite networks, we suggest both sequential and concurrent projection methods. Data from the Korean Association Resource (KARE) project were utilized, including 352,228 SNPs from 8840 individuals, alongside information on environmental factors such as lifestyle, dietary, and socioeconomic factors. The single-SNP analysis step filtered SNPs, supplemented by reference SNPs reported in a genome-wide association study catalog. The resulting network patterns differed significantly by sex: demographic factors and fat intake were crucial for women, while alcohol consumption was central for men. Indirect relationships were identified through projected bipartite networks, revealing that SNPs such as rs4244457, rs2156552, and rs10899345 had lifestyle interactions on metabolic components. Our approach offers several advantages: it simplifies the visualization of complex relationships among different datasets, identifies environmental interactions, and provides insights into SNP clusters sharing common environmental factors and metabolic components. This framework provides a comprehensive approach to elucidate the mechanisms underlying complex diseases like metabolic syndrome.

Optimization of Sodium Iodide-Based Root Filling Material for Clinical Applications: Enhancing Physicochemical Properties.

Premature loss of root canal-treated primary teeth has long been a concern in dentistry. To address this, researchers developed a sodium iodide-based root canal-filling material as an alternative to traditional iodoform-based materials. The goal of this study was to improve the physicochemical properties of the sodium iodide-based material to meet clinical use standards. To resolve high solubility issues in the initial formulation, researchers adjusted component ratios and added new ingredients, resulting in a new paste called L5. This study compared L5 with L0 (identical composition minus lanolin) and Vitapex as controls, conducting physicochemical and antibacterial tests. Results showed that L5 met all ISO 6876 standards, demonstrated easier injection and irrigation properties than Vitapex, and exhibited comparable antibacterial efficacy to Vitapex, which is currently used clinically. The researchers conclude that if biological stability is further verified, L5 could potentially be presented as a new option for root canal-filling materials in primary teeth.

A winged-helix DNA-binding protein is essential for self-fertility during sexual development of the homothallic fungus Fusarium graminearum.

Sexual reproduction is crucial for increasing the genetic diversity of populations and providing overwintering structures, such as perithecia and associated tissue, in the destructive plant pathogenic fungus Fusarium graminearum. While mating-type genes serve as master regulators in fungal sexual reproduction, the molecular mechanisms underlying this process remain elusive. Winged-helix DNA-binding proteins are key regulators of embryogenesis and cell differentiation in higher eukaryotes. These proteins are implicated in the morphogenesis and development of several fungal species. However, their involvement in sexual reproduction remains largely unexplored in F. graminearum. Here, we investigated the function of winged-helix DNA-binding proteins in vegetative growth, conidiation, and sexual reproduction, with a specific focus on the FgWING27, which is highly conserved among Fusarium species. Deletion of FgWING27 resulted in an abnormal pattern characterized by a gradual increase in the expression of mating-type genes during sexual development, indicating its crucial role in the stage-specific genetic regulation of MAT genes in the late stages of sexual development. Furthermore, using chromatin immunoprecipitation followed by sequencing analysis, we identified Fg17056 as a downstream gene of Fgwing27, which is essential for sexual reproduction. These findings underscore the significance of winged-helix DNA-binding proteins in fungal development and reproduction in F. graminearum, and highlight the pivotal role of Fgwing27 as a core genetic factor in the intricate genetic regulatory network governing sexual reproduction.IMPORTANCEFusarium graminearum is a devastating plant pathogenic fungus causing significant economic losses due to reduced crop yields. In Fusarium Head Blight epidemics, spores produced through sexual and asexual reproduction serve as inoculum, making it essential to understand the fungal reproduction process. Here, we focus on winged-helix DNA-binding proteins, which have been reported to play crucial roles in cell cycle regulation and differentiation, and address their requirement in the sexual reproduction of F. graminearum. Furthermore, we identified a highly conserved protein in Fusarium as a key factor in self-fertility, along with the discovery of its direct downstream genes. This provides crucial information for constructing the complex genetic regulatory network of sexual reproduction and significantly contribute to further research on sexual reproduction in Fusarium species.

The connection between aging, cellular senescence and gut microbiome alterations: A comprehensive review.

The intricate interplay between cellular senescence and alterations in the gut microbiome emerges as a pivotal axis in the aging process, increasingly recognized for its contribution to systemic inflammation, physiological decline, and predisposition to age-associated diseases. Cellular senescence, characterized by a cessation of cell division in response to various stressors, induces morphological and functional changes within tissues. The complexity and heterogeneity of senescent cells, alongside the secretion of senescence-associated secretory phenotype, exacerbate the aging process through pro-inflammatory pathways and influence the microenvironment and immune system. Concurrently, aging-associated changes in gut microbiome diversity and composition contribute to dysbiosis, further exacerbating systemic inflammation and undermining the integrity of various bodily functions. This review encapsulates the burgeoning research on the reciprocal relationship between cellular senescence and gut dysbiosis, highlighting their collective impact on age-related musculoskeletal diseases, including osteoporosis, sarcopenia, and osteoarthritis. It also explores the potential of modulating the gut microbiome and targeting cellular senescence as innovative strategies for healthy aging and mitigating the progression of aging-related conditions. By exploring targeted interventions, including the development of senotherapeutic drugs and probiotic therapies, this review aims to shed light on novel therapeutic avenues. These strategies leverage the connection between cellular senescence and gut microbiome alterations to advance aging research and development of interventions aimed at extending health span and improving the quality of life in the older population.

A comprehensive multi-task deep learning approach for predicting metabolic syndrome with genetic, nutritional, and clinical data.

Metabolic syndrome (MetS) is a complex disorder characterized by a cluster of metabolic abnormalities, including abdominal obesity, hypertension, elevated triglycerides, reduced high-density lipoprotein cholesterol, and impaired glucose tolerance. It poses a significant public health concern, as individuals with MetS are at an increased risk of developing cardiovascular diseases and type 2 diabetes. Early and accurate identification of individuals at risk for MetS is essential. Various machine learning approaches have been employed to predict MetS, such as logistic regression, support vector machines, and several boosting techniques. However, these methods use MetS as a binary status and do not consider that MetS comprises five components. Therefore, a method that focuses on these characteristics of MetS is needed. In this study, we propose a multi-task deep learning model designed to predict MetS and its five components simultaneously. The benefit of multi-task learning is that it can manage multiple tasks with a single model, and learning related tasks may enhance the model's predictive performance. To assess the efficacy of our proposed method, we compared its performance with that of several single-task approaches, including logistic regression, support vector machine, CatBoost, LightGBM, XGBoost and one-dimensional convolutional neural network. For the construction of our multi-task deep learning model, we utilized data from the Korean Association Resource (KARE) project, which includes 352,228 single nucleotide polymorphisms (SNPs) from 7729 individuals. We also considered lifestyle, dietary, and socio-economic factors that affect chronic diseases, in addition to genomic data. By evaluating metrics such as accuracy, precision, F1-score, and the area under the receiver operating characteristic curve, we demonstrate that our multi-task learning model surpasses traditional single-task machine learning models in predicting MetS.

Exposure to ambient air pollution mixture and senescence-associated secretory phenotype proteins among middle-aged and older women.

Our study aimed to investigate the impact of environmental exposures, such as ambient air pollutants, on systemic inflammation and cellular senescence in middle-aged and older women. We utilized epidemiological data linked with exposure data of six air pollutants (particulate matters [PM10, PM2.5], sulphur dioxide [SO2], nitrogen dioxide [NO2], carbon monoxide [CO], and ozone [O3]) and blood samples of 380 peri- and postmenopausal women participants of the Korean Genome and Epidemiology Study. We measured blood high-sensitivity C-reactive protein (hsCRP) and age-related 27 circulatory senescence-associated secretory phenotypes (SASP) produced by senescent cells. We employed single exposure models to explore the general pattern of association between air pollution exposure and proteomic markers. Using quantile g-computation models, we assessed the association of six air pollutant mixtures with hsCRP and SASP proteins. In single-exposure, single-period models, nine out of the 27 SASP proteins including IFN-γ (ß = 0.04, 95% CI: 0.01, 0.07 per interquartile range-increase), IL-8 (0.15, 95% CI: 0.09, 0.20), and MIP1α (0.11, 95% CI: 0.04, 0.18) were positively associated with the average level of O3 over one week. Among the age-related SASP proteins, IFN-γ (0.11, 95% CI: 0.03, 0.20) and IL-8 (0.22, 95% CI: 0.05, 0.39) were positively associated with exposure to air pollutant mixture over one week. The MIP1ß was higher with an increasing one-month average concentration of the air pollutant mixture (0.11, 95% CI: 0.00, 0.21). The IL-8 showed consistently positive association with the ambient air pollutant mixture for the exposure periods ranging from one week to one year. O3 predominantly showed positive weights in the associations between air pollutant mixtures and IL-8. These findings underscore the potential of proteomic indicators as markers for biological aging attributed to short-term air pollution exposure.