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Highlights a study which deals with the mechanism of polycomb (PC) group gene silencing that was presented at the 69th Cold Spring Harbor Symposia on Quantitative Biology in the U.S. in 2004. Recognition of methyl-K27 of histone 3 (H3) by PC chromodomain; Significance of H3-K27 methylation to PC repressive complex 1; Evolutionary conservation of PC gene silencing.

Background: This study aims to explore the relationship between magnesium depletion score (MDS) and periodontitis in US adults using data from the National Health and Nutritional Examination Survey (NHANES) 2009-2014., Methods: This cross-sectional study's outcome was periodontitis, defined by the CDC/AAP using clinical periodontal parameters. The exposure of this study was MDS, which was calculated according to four parameters (diuretic use, proton pump inhibitor use, renal function and alcohol consumption). Weighted univariable and multivariable logistic regression analyses were performed to explore the association between MDS intake and periodontitis. Confounding factors included in the adjusted model were age, sex, race, income, smoking status, dietary magnesium, obesity, diabetes, hypertension, education level, recreational activity, and work activity., Results: A total of 8,628 participants over the age 30 were included in our study. Individuals with high level of magnesium deficiency were more likely referred to poorer periodontal health in both crude model (OR = 2.01, 95% CI: 1.54-2.61, p < 0.0001) and fully adjusted model (OR = 1.35, 95% CI: 1.03-1.77, p = 0.03)., Conclusions: MDS is positively associated with moderate/severe periodontitis. Further longitudinal studies are needed to understand the impact of MDS on periodontitis., (© 2024. The Author(s).)

Background: Hepatic cancer is a common cancer in clinical practice. Current drug therapies for this condition include targeted therapy, chemotherapy, and immunotherapy. Tumor lysis syndrome (TLS) is the most serious complication of oncology treatment. According to the literature, several cases reported TLS occurred with targeted therapies for hepatic cancer., Methods: Reporting odds ratio and information component were used to measure the disproportionate signals for TLS associated with targeted therapies, using data from the FDA's Adverse Event Reporting System (FAERS). A stepwise sensitivity analysis was conducted to test the robustness of signals. Time-to-onset analysis was used to describe the latency of TLS events associated with targeted therapies. The Bradford Hill criteria were used to perform a global assessment of the evidence., Results: Sorafenib, lenvatinib, cabozantinib, and bevacizumab showed higher disproportionate signals for TLS than chemotherapy. The median number of days to TLS occurrence after drug therapy was 5.5, 6.5, and 6.5 days for sorafenib, lenvatinib, and bevacizumab, respectively., Conclusions: There is a significant association between tumor lysis syndrome and targeted therapies for hepatic carcinoma, with particularly strong signals for sorafenib and lenvatinib. Clinicians should be aware of the potential for tumor lysis syndrome in targeted therapies for hepatic carcinoma.

Relative fat mass (RFM) is a novel indicator for measuring body fat. This cross-section study aims to explore the association between RFM and periodontitis and to investigate possible effect modifiers in U.S. adults based on the National Health and Nutrition Examination Survey 2009-2014. The category of periodontitis was defined by the CDC/AAP. Mean clinical attachment loss and mean pocket probing depth (PPD) were calculated. The RFM formula is: 64 - (20 × height/WC) + (12 × sex), with sex coded as 1 for female and 0 for male. Natural cubic spline and weighted multivariable regression analyses were conducted to investigate the relationship between RFM and periodontal status. Subgroup and interaction analyses were also employed to assess the moderating roles of age, gender, and race. A total of 10,307 participants were included in our study. Compared to the lowest quartiles, individuals in the highest quartiles of RFM levels were more likely to have moderate/severe periodontitis (OR Q4vs1  = 1.64, 95% CI 1.30-2.06) and had a higher mean PPD (β Q4vs1  = 0.15, 95% CI 0.09-0.22). This association was particularly stronger in populations under the age of 60, with significant interactions. Taken together, RFM is positively associated with periodontitis, particularly in those under 60 years old., (© 2024. The Author(s).)

Aim: To assess the relationship between dietary antioxidant intake and periodontal health in US adults and the potential role of mitochondrial function., Materials and Methods: We performed a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Dietary antioxidant intake was evaluated using three diet-related indices: dietary oxidative balance score (DOBS), dietary total antioxidant capacity (DTAC) of antioxidant vitamins and composite dietary antioxidant index (CDAI). Periodontal parameters included attachment loss (AL) and probing pocket depth (PPD). Mitochondrial dysfunction was assessed using the methylmalonic acid (MMA) level. Weighted multivariable linear regression analyses were employed to investigate the association between dietary antioxidant intake and periodontal status. Additionally, exploratory mediation analyses were conducted to determine the mediating effect of MMA on the association., Results: Totally, 5520 participants were included in our study. Participants with higher DOBS and DTAC scores had lower mean AL/PPD and MMA values. CDAI was negatively associated with mean AL and PPD. Furthermore, MMA mediated 9.4% and 4.9% of the associations between DOBS and mean AL and mean PPD, respectively. MMA also accounted for 7.2% and 3.3% of the association between DTAC and mean AL and PPD, respectively., Conclusions: The findings support that dietary antioxidant intake helps in improving periodontal health, possibly and partially by enhancing mitochondrial function., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: To examine the relationship between the systemic immune-inflammation index (SII) and periodontitis and to investigate possible effect modifiers., Methods: Data used in the present cross-sectional study are from the National Health and Nutrition Examination Survey (NHANES) 2009-2014 (N = 10,301). The SII was calculated using the following formula: (neutrophils count × platelet count)/lymphocytes count. The category of periodontitis was defined by the Centers for Disease Control and Prevention and American Academy of Periodontology (CDC/AAP) classification. We employed natural cubic spline and multivariable logistic regression analyses to evaluate the associations of the SII with periodontitis., Results: The associations between SII and periodontal health followed a J-shape (p < 0.001). The risk of periodontitis tended to reduce with the increment of log 2 (SII) in participants with log 2 (SII) ≤ 8.66 (odds radio [OR] = 0.83; 95% CI: 0.69-0.999), especially among non-Hispanic Whites (OR = 0.70; 95% CI: 0.52-0.95), and increased with the increment of log 2 (SII) in participants with log 2 (SII) > 8.66 (OR = 1.19; 95% CI: 1.02-1.38). A similar trend was also observed between the SII and the number of sites with probing pocket depth (PPD) ≥4 mm and clinical attachment loss (CAL) ≥ 3 or 5 mm. Furthermore, we found a significantly stronger correlation between lymphocytes and either neutrophils or platelets in individuals with log 2 (SII) > 8.66, as opposed to those with log 2 (SII) ≤ 8.66., Conclusions: There is a J-shaped association between SII and periodontitis in US adults, with an inflection point of log 2 (SII) at 8.66, which may provide potential adjunctive treatment strategies for periodontitis with different immune response states. Further prospective trials are still required to confirm our findings., (© 2023 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

In this study, we studied the performance of the 2022 American College of Rheumatology (ACR)/ European Alliance of Associations for Rheumatology (EULAR) classification criteria for Takayasu's arteritis (TAK) as compared to the 1990 ACR classification criteria in a Chinese population. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and the area under the receiver operating characteristics curve (AUC) of the above two criteria were compared. The sensitivity (92.6%), positive predictive value (95.6%), negative predictive value (94.6%), accuracy (95.0%) and AUC (0.981) of the 2022 criteria were superior to those of the 1990 criteria (45.7%, 91.5%, 70.5%, 75.0% and 0.874, respectively), and the difference of AUC was statistically significant (Z = 5.362, P < 0.001). In addition, we included new imaging modalities in the 1990 criteria, whose sensitivity, positive predictive value, negative predictive value, accuracy and AUC were significantly improved, but still lower than those of the 2022 criteria, the difference in AUC was also statistically significant (Z = 2.023, P = 0.043). The 2022 criteria for TAK exhibited superior performance compared with the 1990 criteria and may be more appropriate for the Chinese population. Incorporating additional imaging modalities could enhance the classification performance of the 1990 criteria even further., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: Albumin-corrected calcium is usually calculated to reflect the real serum calcium level of the whole body by physicians. However, studies on the association between albumin-corrected calcium and 30-day in-hospital mortality in Intensive Care Unit (ICU) patients are rare. The purpose of our study was to explore the association between baseline albumin-corrected calcium and 30-day in-hospital mortality in the American ICU population., Methods: A multicenter retrospective cohort study of 102,245 ICU patients in the eICU-CRD v2.0 from the USA during 2014-2015 was performed. The average age was 63.7 ± 16.9 years, of which 55,313 (53.7%) were men and 47,758 (46.3%) were women. The association between albumin-corrected calcium and 30-day in-hospital mortality was analyzed by Cox proportional-hazards regression, smooth curve fitting, piecewise linear regression, subgroup analyses, and a series of sensitivity analyses., Results: We found that among ICU patients with calcium abnormalities, more than 95% were mild hypocalcemia or mild hypercalcemia. The risk of 30-day in-hospital mortality will increase by 10% in the ≥7.5-< 8.5 mg/dl subgroup (OR=1.1, 95% CI 1.0-1.3) or 20% in the ≥10.3-<12 mg/dl subgroup (OR=1.2, 95% CI 1.1-1.3) when the albumin-corrected calcium level increases by 1 mg/dl. Additionally, the relationship between albumin-corrected calcium and 30-day in-hospital mortality was U shaped; the inflection point was 8.9 mg/dl (log likelihood ratio test P = 0.005). Finally, after a series of sensitivity analyses, we found that the relationship between albumin-corrected calcium and 30-day in-hospital mortality remained significant., Conclusion: In a large nationally representative cohort of ICU patients, abnormalities in albumin-corrected calcium, particularly slight hypocalcemia or slight hypercalcemia, were associated with an increased 30-day in-hospital mortality risk, and yet the findings in this study need to be further confirmed by prospective studies., Competing Interests: Author XC was employed by Empower U, X&Y Solutions Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qin, Cen, Hu, Chen, Wei, Wan and Cao.)

In this research, we take a multivariate, multi-method approach to predicting the incidence of lung cancer in the United States. We obtain public health and ambient emission data from multiple sources in 2000-2013 to model lung cancer in the period 2013-2017. We compare several models using four sources of predictor variables: adult smoking, state, environmental quality index, and ambient emissions. The environmental quality index variables pertain to macro-level domains: air, land, water, socio-demographic, and built environment. The ambient emissions consist of Cyanide compounds, Carbon Monoxide, Carbon Disulfide, Diesel Exhaust, Nitrogen Dioxide, Tropospheric Ozone, Coarse Particulate Matter, Fine Particulate Matter, and Sulfur Dioxide. We compare various models and find that the best regression model has variance explained of 62 percent whereas the best machine learning model has 64 percent variance explained with 10% less error. The most hazardous ambient emissions are Coarse Particulate Matter, Fine Particulate Matter, Sulfur Dioxide, Carbon Monoxide, and Tropospheric Ozone. These ambient emissions could be curtailed to improve air quality, thus reducing the incidence of lung cancer. We interpret and discuss the implications of the model results, including the tradeoff between transparency and accuracy. We also review limitations of and directions for the current models in order to extend and refine them.

Transmembrane domain (TMD) mutations of ERBB2 have previously been reported in lung cancer patients in addition to well-studied kinase domain (KD) mutations, which may stabilize ERBB2 heterodimerization with other EGFR family members and favor a kinase active conformation. However, the frequency and clinical significance of ERBB2 TMD mutations in Chinese population is unknown. We prospectively analyzed the next-generation sequencing data of 34 368 Chinese lung cancer patients with different sample types, including tumor tissue, plasma, cerebrospinal fluid, and pleural effusion. Patients' clinical characteristics and treatment history were retrieved from the database for further evaluation. Our findings show that ERBB2 V659/G660 mutations were detected at a frequency of 0.13% (45/34 368), of which the most frequent was V659D/E (88.9%), with a trend in nonsmokers and male. Moreover, 18% of patients (8/45) showed EGFR and/or ERBB2 amplification, whereas nine patients presented EGFR L858R or exon19 deletion. Interestingly, novel ERBB3 TMD mutation I646R was found coexisting in three patients with ERBB2 V659D and one patient with ERBB2 G660D, which might influence its heterodimerization with ERBB2 and further activate ERBB2. Four ERBB2 TMD mutation-positive patients received afatinib monotherapy or combination therapy, but showed variable responses. One patient with V659E responded well to ERBB2 inhibitor lapatinib plus capecitabine as well as subsequent afatinib treatment upon progression. Our study provides valuable insights into the distribution of ERBB2 TMD mutations by employing the largest Asian lung cancer cohort thus far. Patients with ERBB2 TMD mutations who received afatinib, a pan-ERBB inhibitor, demonstrated mixed responses, posing the urgent need to develop more effective therapeutic strategy for patients who carry ERBB2 TMD mutations., (© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Fingolimod is a new immunosuppressive agent approved by Food and Drug Administration (FDA) for treating multiple sclerosis (MS). It acts as a functional antagonist to downregulate the S1P1 receptor, which is known to signal through the Akt-mTOR pathway. We investigated the mechanism of fingolimod action in the classical animal model of MS: experimental autoimmune encephalomyelitis (EAE). Fingolimod treatment significantly reduced clinical scores and histopathology in this model, even when treatment was begun after the onset of pathology. The Akt-mTOR signaling pathway was shown to be activated in the EAE model, by measuring the abundance of downstream activation markers, pAkt and ps6k. And this pathway was inhibited when EAE mice were treated with fingolimod. Mice with EAE exhibited an increased frequency of Th1 cells in the spleen, with concomitant increases in the mRNA levels of Tbet and Ifng and increased IFN-γ production by activated splenocytes; the frequency of Treg cells, as well as mRNA levels of Foxp3 and Tgfb, was reduced, as was TGF-β production by activated splenocytes. After treatment with fingolimod, these parameters were reversed, suggesting that fingolimod treatment inhibits the Akt-mTOR axis in EAE, which affects the differentiation and function of Th1 and Treg cells. These results provide an insight into the mechanism of action of fingolimod treatment and may provide new ideas for treating EAE and MS., (Copyright © 2015 Elsevier B.V. All rights reserved.)