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Biological Trace Element Research Jul 2024This study aimed to examine the relationship between serum cholesterol levels and the ratio of zinc (Zn) and copper (Cu) in the blood serum and the incidence of...
This study aimed to examine the relationship between serum cholesterol levels and the ratio of zinc (Zn) and copper (Cu) in the blood serum and the incidence of cardiovascular disease (CVD). In Phase I of the study, 9704 individuals between the age of 35 and 65 years were recruited. Phase II of the cohort study comprised 7561 participants who completed the 10-year follow-up. The variables which were measured at the baseline of the study included gender, age, systolic blood pressure (SBP), diastolic blood pressure (DBP); biochemical parameters including serum Cu, Zn, copper-zinc ratio (Cu/Zn), zinc-copper ratio (Zn/Cu); fasted lipid profile consisting of triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) as well as fasting serum glucose, and triglycerides-glucose (TyG) index. Decision tree (DT) and logical regression (LR) models were applied to examine the relationship between the aforementioned factors and CVD. CVD was diagnosed in 837 individuals (378 males and 459 females) out of 7561 participants. According to the LR models, SBP, TC, HDL, age, Zn/Cu, and TyG index for males and SBP, age, TyG index, HDL, TC, Cu/Zn, and Cu for females had the highest correlation with CVD (p-value ≤ 0.033). Based on the DT algorithm, 88% of males with SPB < 129.66 mmHg, younger age (age < 53 years), TyG index < 9.53, 173 ≤ TC < 187 mg/dL, and HDL ≥ 32 mg/dL had the lowest risk of CVD. Also, 98% of females with SBP < 128 mmHg, TyG index < 9.68, age < 44, TC < 222 mg/dL, and HDL ≥ 63.7 mg/dL had the lowest risk of CVD. It can be concluded that the Zn/Cu for men and Cu/Zn for women, along with dyslipidemia and SBP, could significantly predict the risk of CVD in this cohort from northeastern Iran.
PubMed: 38956010
DOI: 10.1007/s12011-024-04288-0 -
Natural Products and Bioprospecting Jul 2024In this study, the effects of sea buckthorn oil (SBO), fish oil (FO) and an enzymatically synthesized structured lipid (SL) on serum, short-chain fatty acids (SCFAs) and...
Revealing the effect of sea buckthorn oil, fish oil and structured lipid on intestinal microbiota, colonic short chain fatty acid composition and serum lipid profiles in vivo.
In this study, the effects of sea buckthorn oil (SBO), fish oil (FO) and an enzymatically synthesized structured lipid (SL) on serum, short-chain fatty acids (SCFAs) and intestinal microbiota in Sprague-Dawley (SD) rats were investigated. The results demonstrated that FO, SBO, and SL effectively reduced the levels of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in the serum of SD rats. SBO increased serum triglyceride levels, while FO elevated total cholesterol levels. Furthermore, all three dietary lipids decreased short-chain fatty acid production and enhanced intestinal microbiota diversity. FO increased the abundance of intestinal microbiota including Romboutsia, Lactobacillus, Escherichia-Shigella, and Lachnospiraceae_NK4A136_group. Conversely, all three dietary lipids reduced the abundance of Klebsiella and Blautia. These findings provide a foundation for understanding the functionality of SBO and FO as well as their potential application in synthesizing novel SLs to regulate intestinal microbiota.
PubMed: 38955923
DOI: 10.1007/s13659-024-00461-z -
International Ophthalmology Jul 2024To review long-term outcomes of circumscribed choroidal hemangioma (CCH).
PURPOSE
To review long-term outcomes of circumscribed choroidal hemangioma (CCH).
METHODS
Hospital charts of all CCH cases diagnosed from 2008 to 2019 were retrospectively reviewed.
RESULTS
All 172 patients were managed with either observation, transpupillary thermotherapy, argon laser photocoagulation, photodynamic therapy, plaque brachytherapy or stereotactic radiosurgery. The most common 3 modes of management were clinical observation (30.2%), transpupillary thermotherapy (52.9%) and argon laser photocoagulation (8.7%). Median follow-up time was 10 months (range: 3, 160). Anatomical outcomes were stable in 87.1% of observation group and improved in 60.5% of thermotherapy group. Quantified optical coherence tomography angiography findings showed statistical differences in vascular and perfusion densities in fellow eyes of hemangioma patients.
CONCLUSION
Circumscribed choroidal hemangioma can be treated in various ways. Transpupillary thermotherapy is an anatomically effective treatment in selected cases. The diagnosis of CCH may have vascular implications in fellow eyes of the patients.
Topics: Humans; Choroid Neoplasms; Female; Male; Retrospective Studies; Middle Aged; Tomography, Optical Coherence; Fluorescein Angiography; Adult; Tertiary Care Centers; Hemangioma; Visual Acuity; Aged; Follow-Up Studies; Photochemotherapy; Hyperthermia, Induced; Fundus Oculi; Young Adult; Choroid
PubMed: 38955894
DOI: 10.1007/s10792-024-03238-y -
European Spine Journal : Official... Jul 2024This study aimed to develop and validate a predictive model for osteoporotic vertebral fractures (OVFs) risk by integrating demographic, bone mineral density (BMD), CT...
OBJECTIVE
This study aimed to develop and validate a predictive model for osteoporotic vertebral fractures (OVFs) risk by integrating demographic, bone mineral density (BMD), CT imaging, and deep learning radiomics features from CT images.
METHODS
A total of 169 osteoporosis-diagnosed patients from three hospitals were randomly split into OVFs (n = 77) and Non-OVFs (n = 92) groups for training (n = 135) and test (n = 34). Demographic data, BMD, and CT imaging details were collected. Deep transfer learning (DTL) using ResNet-50 and radiomics features were fused, with the best model chosen via logistic regression. Cox proportional hazards models identified clinical factors. Three models were constructed: clinical, radiomics-DTL, and fusion (clinical-radiomics-DTL). Performance was assessed using AUC, C-index, Kaplan-Meier, and calibration curves. The best model was depicted as a nomogram, and clinical utility was evaluated using decision curve analysis (DCA).
RESULTS
BMD, CT values of paravertebral muscles (PVM), and paravertebral muscles' cross-sectional area (CSA) significantly differed between OVFs and Non-OVFs groups (P < 0.05). No significant differences were found between training and test cohort. Multivariate Cox models identified BMD, CT values of PVM, and CSA reduction as independent OVFs risk factors (P < 0.05). The fusion model exhibited the highest predictive performance (C-index: 0.839 in training, 0.795 in test). DCA confirmed the nomogram's utility in OVFs risk prediction.
CONCLUSION
This study presents a robust predictive model for OVFs risk, integrating BMD, CT data, and radiomics-DTL features, offering high sensitivity and specificity. The model's visualizations can inform OVFs prevention and treatment strategies.
PubMed: 38955868
DOI: 10.1007/s00586-024-08235-4 -
European Journal of Internal Medicine Jul 2024Metabolic disorders exhibit strong inflammatory underpinnings and vice versa. This study aimed to investigate the association between metabolic health status, genetic...
BACKGROUND
Metabolic disorders exhibit strong inflammatory underpinnings and vice versa. This study aimed to investigate the association between metabolic health status, genetic predisposition, and the risk of inflammatory bowel disease (IBD), and to explore the potential benefits of maintaining ideal metabolic status for individuals with a predetermined genetic risk of IBD.
METHOD
This population-based prospective study included 385,820 unrelated European descent participants from the UK Biobank. Using multivariable Cox regression, we assessed the relationship of metabolic phenotypes with risk of IBD and its subtypes. We also developed a polygenic risk score to examine how metabolic health status interacted with genetic risk in relation to IBD risk.
RESULTS
During the follow-up period of 4,328,895 person-years, 2,044 newly-diagnosed IBD cases were identified. Higher genetic risk and an increasing number of abnormal metabolic phenotypes were associated with elevated IBD risk (p-trend <0.001). Individuals with high genetic risk and poor metabolic health had a significantly higher risk of IBD (HR=4.56, 95 % CI=3.27-6.36) compared to those with low genetic risk and ideal metabolic health. These results remained consistent for IBD subtypes. Maintaining ideal metabolic status reduced IBD risk within each genetic risk category and jointly decreased subsequent risk by 40 % in high genetic risk individuals.
CONCLUSION
Our study reveals a combined impact of poor metabolic health and genetic risk on IBD incidence. Those with low genetic risk and optimal metabolic health exhibit the lowest IBD risk, offering insights into potential management strategies for individuals at predefined genetic risk.
PubMed: 38955589
DOI: 10.1016/j.ejim.2024.06.020 -
Journal of Epidemiology and Community... Jul 2024Excess mortality during the COVID-19 pandemic provides a comprehensive measure of disease burden, and its local variation highlights regional health inequalities. We...
BACKGROUND
Excess mortality during the COVID-19 pandemic provides a comprehensive measure of disease burden, and its local variation highlights regional health inequalities. We investigated local excess mortality in 2020 and its determinants at the community level.
METHODS
We collected data from 250 districts in South Korea, including monthly all-cause mortality for 2015-2020 and community characteristics from 2019. Excess mortality rate was defined as the difference between observed and expected mortality rates. A Seasonal Autoregressive Integrated Moving Average model was applied to predict the expected rates for each district. Penalized regression methods were used to derive relevant community predictors of excess mortality based on the elastic net.
RESULTS
In 2020, South Korea exhibited significant variation in excess mortality rates across 250 districts, ranging from no excess deaths in 46 districts to more than 100 excess deaths per 100 000 residents in 30 districts. Economic status or the number of medical centres in the community did not correlate with excess mortality rates. The risk was higher in ageing, remote communities with limited cultural and sports infrastructure, a higher density of welfare facilities, and a higher prevalence of hypertension. Physical distancing policies and active social engagement in voluntary activities protected from excess mortality.
CONCLUSION
Substantial regional disparities in excess mortality existed within South Korea during the early stages of COVID-19 pandemic. Weaker segments of the community were more vulnerable. Local governments should refine their preparedness for future novel infectious disease outbreaks, considering community circumstances.
PubMed: 38955462
DOI: 10.1136/jech-2023-221763 -
The Journal of Organic Chemistry Jul 2024The chemistry of dicationic and tricationic 2-norbornyl cations has been studied. A series of -heterocyclic functionalized norborneol substrates were prepared and...
The chemistry of dicationic and tricationic 2-norbornyl cations has been studied. A series of -heterocyclic functionalized norborneol substrates were prepared and ionization of these compounds in superacid provided superelectrophilic species. These highly charged 2-norbornyl cations were found to react with arene nucleophiles in high yields and stereoselectivity. Density functional theory computational studies suggest that increasing positive charge on the structures tends to enhance the degree of nonclassical (or 3-center-2-electron) bonding through separation of the cationic charges.
PubMed: 38955424
DOI: 10.1021/acs.joc.3c02870 -
Journal For Immunotherapy of Cancer Jul 2024Small-cell lung cancer (SCLC) is an aggressive disease with a dismal prognosis. The addition of immune checkpoints inhibitors to standard platinum-based chemotherapy in...
Extensive-stage small-cell lung cancer in patients receiving atezolizumab plus carboplatin-etoposide: stratification of outcome based on a composite score that combines gene expression profiling and immune characterization of microenvironment.
PURPOSE
Small-cell lung cancer (SCLC) is an aggressive disease with a dismal prognosis. The addition of immune checkpoints inhibitors to standard platinum-based chemotherapy in first-line setting achieves a durable benefit only in a patient subgroup. Thus, the identification of predictive biomarkers is an urgent unmet medical need.
EXPERIMENTAL DESIGN
Tumor samples from naive extensive-stage (ES) SCLC patients receiving atezolizumab plus carboplatin-etoposide were analyzed by gene expression profiling and two 9-color multiplex immunofluorescence panels, to characterize the immune infiltrate and SCLC subtypes. Associations of tissue biomarkers with time-to-treatment failure (TTF), progression-free survival (PFS) and overall survival (OS), were assessed.
RESULTS
42 patients were included. Higher expression of exhausted CD8-related genes was independently associated with a longer TTF and PFS while increased density of B lymphocytes correlated with longer TTF and OS. Higher percentage of M2-like macrophages close to tumor cells and of CD8+T cells close to CD4+T lymphocytes correlated with increased risk of TF and longer survival, respectively. A lower risk of TF, disease progression and death was associated with a higher density of ASCL1+tumor cells while the expression of POU2F3 correlated with a shorter survival. A composite score combining the expression of exhausted CD8-related genes, B lymphocyte density, ASCL1 tumor expression and quantification of CD163+macrophages close to tumor cells, was able to stratify patients into high-risk and low-risk groups.
CONCLUSIONS
In conclusion, we identified tissue biomarkers and a combined score that can predict a higher benefit from chemoimmunotherapy in ES-SCLC patients.
Topics: Humans; Carboplatin; Lung Neoplasms; Male; Antibodies, Monoclonal, Humanized; Female; Small Cell Lung Carcinoma; Tumor Microenvironment; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Aged; Middle Aged; Gene Expression Profiling; Adult; Neoplasm Staging
PubMed: 38955418
DOI: 10.1136/jitc-2024-008974 -
Bone & Joint Research Jul 2024The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule...
AIMS
The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.
METHODS
Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.
RESULTS
The expression of all fibrosis-related genes was higher in Db met(-) than in WT met(-) and was suppressed by metformin. Increased levels of fibrosis-related genes, posterior capsule thickness, and collagen density were observed in the capsules of db/db mice compared with those in WT mice; these effects were suppressed by metformin. Glucose addition increased fibrosis-related gene expression in both groups of mice in vitro. When glucose was added, metformin inhibited the expression of fibrosis-related genes other than cellular communication network factor 2 () in WT mouse cells.
CONCLUSION
Hyperglycaemia promotes fibrosis in the mouse knee joint capsule, which is inhibited by metformin. These findings can help inform the development of novel strategies for treating knee joint capsule fibrosis.
PubMed: 38955349
DOI: 10.1302/2046-3758.137.BJR-2023-0384.R1 -
Journal of Physics. Condensed Matter :... Jul 2024Ab-initio crystal structure searches have played a pivotal role in recent discovery of high-Tc hydride superconductors under high pressure. Using evolutionary crystal...
Ab-initio crystal structure searches have played a pivotal role in recent discovery of high-Tc hydride superconductors under high pressure. Using evolutionary crystal searches, we predict novel ground state structures of N-doped LuH3 at ambient conditions. We find an insulating ground state structure for LuN0.125H2.875 (~1.0 wt.% N), contrary to earlier studies where assumed structures were all metallic. This insulating behavior of ground state was found to persist up to ~45 GPa. However our crystal structure search revealed a metallic state for an H-deficient variant of LuN0.125H2.875. We study bonding characteristics of important structures by calculating electronic density of states, electronic-localization functions and Bader charges. Our Bader charge analysis shows that insulators have both H+ and H- ions whereas metals have only H- ions. We find that H+ ions are bonded to N atoms via a very short covalent bond. Thus we identify a clear relationship between formation of N-H bonds and insulating behavior of materials. Besides this, we perform crystal structure searches for three more compositions with higher N-content (> 1.0 wt.%). Analysis of electronic properties shows that the ground states of these compositions are insulator.
PubMed: 38955341
DOI: 10.1088/1361-648X/ad5e52