Reporting quality of heart failure randomized controlled trials 2000-2020: Temporal trends in adherence to CONSORT criteria.

AIM: Heart failure (HF) is a major cause of morbidity and mortality in older adults. Randomized controlled trials (RCTs) inform HF policy and practice, but the accurate interpretation of results is contingent on clear and transparent reporting. The CONsolidated Standards Of Reporting Trials (CONSORT) statement serves as a guide to RCT reporting. We evaluated the quality of reporting in HF RCTs in high-impact journals by assessing their adherence to CONSORT. METHODS AND RESULTS: We searched MEDLINE, EMBASE and CINAHL for HF RCTs published in high-impact journals 2000-2020. We assessed the proportion of CONSORT criteria that individual HF RCTs adhered to, and used the Jonckheere-Terpstra test to examine temporal trends in adherence. Multivariable linear regression explored the association between trial characteristics and adherence to CONSORT. Primary analysis assessed adherence to CONSORT 2010 update. A sensitivity analysis assessed adherence to the original (1996) CONSORT criteria. Among 221 RCTs analysed, the mean (standard deviation [SD]) adherence was suboptimal overall (mean [SD] adherence 69.7 [11.5]%) (5513/7913 criteria), with a temporal increase in adherence over the 20-year period (p < 0.001). Factors associated with adherence included publication after versus during/before 2010 (ß = 10.17, 95% confidence interval [CI] 7.64-12.70; p < 0.001); two-group parallel individual-level randomization versus other (including multi-group or cluster randomization) (ß = 5.81, 95% CI 2.88-8.73; p < 0.001); and multicentre versus single-centre trials (ß = 7.26, 95% CI 3.25-11.27; p < 0.001). There was no difference in trial adherence to the updated CONSORT (2010) versus the original (1996) CONSORT criteria, and temporal trends in adherence to both sets of criteria were similar, likely due to overlap between the two sets of criteria. Trials with greater adherence to CONSORT were published in higher impact factor journals, with a positive correlation (r = 0.312; p < 0.001). CONCLUSION: The quality of reporting in HF RCTs, as measured by CONSORT adherence, has improved over time but remains suboptimal.

Structural and Electronic Chirality in Inorganic Crystals: from Construction to Application.

Chirality represents a fundamental characteristic inherent in nature, playing a pivotal role in the emergence of homochirality and the origin of life. While the principles of chirality in organic chemistry are well-documented, the exploration of chirality within inorganic crystal structures continues to evolve. This ongoing development is primarily due to the diverse nature of crystal/amorphous structures in inorganic materials, along with the intricate symmetrical and asymmetrical relationships in the geometry of their constituent atoms. In this review, we commence with a summary of the foundational concept of chirality in molecules and solid states matters. This is followed by an introduction of structural chirality and electronic chirality in three-dimensional and two-dimensional inorganic materials. The construction of chirality in inorganic materials is classified into physical photolithography, wet-chemistry method, self-assembly, and chiral imprinting. Highlighting the significance of this field, we also summarize the research progress of chiral inorganic materials for applications in optical activity, enantiomeric recognition and chiral sensing, selective adsorption and enantioselective separation, asymmetric synthesis and catalysis, and chirality-induced spin polarization. This review aims to provide a reference for ongoing research in chiral inorganic materials and potentially stimulate innovative strategies and novel applications in the realm of chirality.

Stevioside Ameliorates Palmitic Acid-Induced Abnormal Glucose Uptake via the PDK4/AMPK/TBC1D1 Pathway in C2C12 Myotubes.

BACKGROUND: Stevioside (SV) with minimal calories is widely used as a natural sweetener in beverages due to its high sweetness and safety. However, the effects of SV on glucose uptake and the pyruvate dehydrogenase kinase isoenzyme (PDK4) as an important protein in the regulation of glucose metabolism, remain largely unexplored. In this study, we used C2C12 skeletal muscle cells that was induced by palmitic acid (PA) to assess the effects and mechanisms of SV on glucose uptake and PDK4. METHODS: The glucose uptake of C2C12 cells was determined by 2-NBDG; expression of the Pdk4 gene was measured by quantitative real-time PCR; and expression of the proteins PDK4, p-AMPK, TBC1D1 and GLUT4 was assessed by Western blotting. RESULTS: In PA-induced C2C12 myotubes, SV could significantly promote cellular glucose uptake by decreasing PDK4 levels and increasing p-AMPK and TBC1D1 levels. SV could promote the translocation of GLUT4 from the cytoplasm to the cell membrane in cells. Moreover, in Pdk4-overexpressing C2C12 myotubes, SV decreased the level of PDK4 and increased the levels of p-AMPK and TBC1D1. CONCLUSION: SV was found to ameliorate PA-induced abnormal glucose uptake via the PDK4/AMPK/TBC1D1 pathway in C2C12 myotubes. Although these results warranted further investigation for validation, they may provide some evidence of SV as a safe natural sweetener for its use in sugar-free beverages to prevent and control T2DM.

A population-based cohort of drug exposures and adverse pregnancy outcomes in China (DEEP): rationale, design, and baseline characteristics.

The DEEP cohort is the first population-based cohort of pregnant population in China that longitudinally documented drug uses throughout the pregnancy life course and adverse pregnancy outcomes. The main goal of the study aims to monitor and evaluate the safety of drug use through the pregnancy life course in the Chinese setting. The DEEP cohort is developed primarily based on the population-based data platforms in Xiamen, a municipal city of 5 million population in southeast China. Based on these data platforms, we developed a pregnancy database that documented health care services and outcomes in the maternal and other departments. For identifying drug uses, we developed a drug prescription database using electronic healthcare records documented in the platforms across the primary, secondary and tertiary hospitals. By linking these two databases, we developed the DEEP cohort. All the pregnant women and their offspring in Xiamen are provided with health care and followed up according to standard protocols, and the primary adverse outcomes - congenital malformations - are collected using a standardized Case Report Form. From January 2013 to December 2021, the DEEP cohort included 564,740 pregnancies among 470,137 mothers, and documented 526,276 live births, 14,090 miscarriages and 6,058 fetal deaths/stillbirths and 25,723 continuing pregnancies. In total, 13,284,982 prescriptions were documented, in which 2,096 chemicals drugs, 163 biological products, 847 Chinese patent medicines and 655 herbal medicines were prescribed. The overall incidence rate of congenital malformations was 2.0% (10,444/526,276), while there were 25,526 (4.9%) preterm births and 25,605 (4.9%) live births with low birth weight.

Standardized ileal digestibility of amino acids in Chinese fermented soybean meal from different sources fed to mid and late-gestating sows.

We determined apparent ileal digestibility (AID) and standardized ileal digestibility (SID) values of crude protein (CP) and amino acids (AA) in fermented soybean meal from five different sources (FSBM 1 to 5) in China when fed to mid and late-gestating sows. Twenty-four parity four sows (12 at 30 d in gestation and 12 at 80 d in gestation) were fitted with a T-cannula in the distal ileum and used in this experiment. Sows were randomly assigned to a replicated 6 × 3 Youden square design including six diets and three periods. Six diets were provided for sows in mid and late gestation, including a nitrogen-free diet and five test diets containing 26% FSBM from different sources. Results showed that there were differences in AID and SID of CP among the different FSBM samples, but no differences between sow physiological stages were observed. Specifically, when mid-gestating sows were fed FSBM 2, the AID of CP was the lowest, whereas FSBM 3 exhibited a greater AID of CP when compared to the other FSBM samples (P < 0.01). Furthermore, during late gestation, FSBM 3 consistently had greater SID of CP when compared to other FSBM samples (P < 0.01). The ileal digestibility of most AA varied with different FSBM samples. In both mid and late gestation, differences (P < 0.05) were observed for AID of lysine, tryptophan, histidine, and arginine across different FSBM samples. Similarly, the AID of dispensable AA (cysteine, glutamine, and serine) also exhibited differences (P < 0.05) across different FSBM samples in both mid and late-gestating sows. For mid-gestating sows, SID differences relating to lysine, phenylalanine, tryptophan, threonine, and arginine were observed among different diets (P < 0.05). In late-gestating sows, SID values for lysine, tryptophan, leucine, and arginine differed across diets (P < 0.05). Furthermore, the ileal digestibility of some dispensable AA was influenced by physiological stage, as evidenced by greater AID and SID values for glycine, glutamine, cysteine, and serine in late-gestating sows when compared to mid-gestating sows (P < 0.01). In summary, our study determined AA ileal digestibility of different FSBM fed to mid and late-gestating sows. We observed that the AA ileal digestibility differed among five FSBM samples, but the physiological stage of sows did not affect the ileal digestibility of CP and most AA. Additionally, when formulating diets for sows, it is crucial to consider the nutritional value differences of FSBM.

Fermented soybean meal (FSBM) is obtained from the microbial fermentation of soybean meal, which reduces anti-nutritional factor levels and enhances other nutrient content. Substituting soybean meal with FSBM in piglet and growing pig diets improves nutrient digestibility. However, its nutritional value for sows remains unclear. Therefore, five sources of FSBM were fed to sows in mid and late gestation to evaluate apparent ileal digestibility (AID) and standardized ileal digestibility (SID) values of amino acids (AA). We found that different FSBM samples impacted the SID value of AA when fed to gestating sows. Additionally, sow physiological stage influenced the SID of some dispensable AA. These findings provide valuable insights into the incorporation of FSBM into sow diets.

Ratiometric fluorescence platform for the ultrasensitive detection of kanamycin based on split aptamer co-recognition triggers Mg2+-DNAzyme-driven DNA walker systems.

In this work, a novel 3D-DNA walker signal amplification strategy was designed to construct a fluorescent aptasensor for the detection of kanamycin (KAN). The aptasensor utilizes split aptamers for the synergistic recognition of KAN. The presence of KAN induces the split aptamers recombination to form the Mg2+-DNAzyme structure, which is activated by Mg2+ to drive the 3D-DNA walker process for cascading signal amplification. Employing gold nanoflowers (AuNFs) as walking substrate material increases the local DNA concentration to enhance the walker efficiency. The prepared fluorescent aptasensor achieved efficient and sensitive detection of KAN with satisfactory results in the concentration range of 1 × 10-8 - 1 × 10-3 µg/kg and the detection limit of 5.63 fg/kg. Meanwhile, the designed fluorescent aptasensor exhibited favorable specificity, anti-interference, storage stability and reproducibility, and verified the feasibility of its application in milk samples. The present work provides an effective tool for the regulation of KAN contamination in animal-derived foods with promising prospects.

Peanut LEAFY COTYLEDON1-type genes participate in regulating the embryo development and the accumulation of storage lipids.

KEY MESSAGE: Two peanut LEC1-type genes exhibit partial functional redundancy. AhNFYB10 could complement almost all the defective phenotypes of lec1-2 in terms of embryonic morphology, while AhNF-YB1 could partially affect these phenotypes. LEAFY COTYLEDON1 (LEC1) is a member of the nuclear factor Y (NF-Y) family of transcription factors and has been identified as a key regulator of embryonic development. In the present study, two LEC1-type genes from Arachis hypogeae were identified and designated as AhNF-YB1 and AhNF-YB10; these genes belong to subgenome A and subgenome B, respectively. The functions of AhNF-YB1 and AhNF-YB10 were investigated by complementation analysis of their defective phenotypes of the Arabidopsis lec1-2 mutant and by ectopic expression in wild-type Arabidopsis. The results indicated that both AhNF-YB1 and AhNF-YB10 participate in regulating embryogenesis, embryo development, and reserve deposition in cotyledons and that they have partial functional redundancy. In contrast, AhNF-YB10 complemented almost all the defective phenotypes of lec1-2 in terms of embryonic morphology and hypocotyl length, while AhNF-YB1 had only a partial effect. In addition, 30-40% of the seeds of the AhNF-YB1 transformants exhibited a decreasing germination ratio and longevity. Therefore, appropriate spatiotemporal expression of these genes is necessary for embryo morphogenesis at the early development stage and is responsible for seed maturation at the mid-late development stage. On the other hand, overexpression of AhNF-YB1 or AhNF-YB10 at the middle to late stages of Arabidopsis seed development improved the weight, oil content, and fatty acid composition of the transgenic seeds. Moreover, the expression levels of several genes associated with fatty acid synthesis and embryogenesis were significantly greater in developing AhNF-YB10-overexpressing seeds than in control seeds. This study provides a theoretical basis for breeding oilseed crops with high yields and high oil content.

From Charge to Spin: An In-Depth Exploration of Electron Transfer in Energy Electrocatalysis.

Catalytic materials play crucial roles in various energy-related processes, ranging from large-scale chemical production to advancements in renewable energy technologies. Despite a century of dedicated research, major enduring challenges associated with enhancing catalyst efficiency and durability, particularly in green energy-related electrochemical reactions, remain. Focusing only on either the crystal structure or electronic structure of a catalyst is deemed insufficient to break the linear scaling relationship (LSR), which is the golden rule for the design of advanced catalysts. The discourse in this review intricately outlines the essence of heterogenous catalysis reactions by highlighting the vital roles played by electron properties. The physical and electrochemical properties of electron charge and spin that govern catalysis efficiencies are analyzed. Emphasis is placed on the pronounced influence of external fields in perturbing the LSR, underscoring the vital role that electron spin plays in advancing high-performance catalyst design. The review culminates by proffering insights into the potential applications of spin catalysis, concluding with a discussion of extant challenges and inherent limitations. This article is protected by copyright. All rights reserved.

Handling time-varying treatments in observational studies: A scoping review and recommendations.

OBJECTIVE: Time-varying treatments are common in observational studies. However, when assessing treatment effects, the methodological framework has not been systematically established for handling time-varying treatments. This study aimed to examine the current methods for dealing with time-varying treatments in observational studies and developed practical recommendations. METHODS: We searched PubMed from 2000 to 2021 for methodological articles about time-varying treatments, and qualitatively summarized the current methods for handling time-varying treatments. Subsequently, we developed practical recommendations through interactive internal group discussions and consensus by a panel of external experts. RESULTS: Of the 36 eligible reports (22 methodological reviews, 10 original studies, 2 tutorials and 2 commentaries), most examined statistical methods for time-varying treatments, and only a few discussed the overarching methodological process. Generally, there were three methodological components to handle time-varying treatments. These included the specification of treatment which may be categorized as three scenarios (i.e., time-independent treatment, static treatment regime, or dynamic treatment regime); definition of treatment status which could involve three approaches (i.e., intention-to-treat, per-protocol, or as-treated approach); and selection of analytic methods. Based on the review results, a methodological workflow and a set of practical recommendations were proposed through two consensus meetings. CONCLUSIONS: There is no consensus process for assessing treatment effects in observational studies with time-varying treatments. Previous efforts were dedicated to developing statistical methods. Our study proposed a stepwise workflow with practical recommendations to assist the practice.

Sarcopenic obesity is part of obesity paradox in dementia development: evidence from a population-based cohort study.

BACKGROUND: Sarcopenic obesity, a clinical and functional condition characterized by the coexistence of obesity and sarcopenia, has not been investigated in relation to dementia risk and its onset. METHODS: We included 208,867 participants from UK biobank, who aged 60 to 69 years at baseline. Dementia diagnoses were identified using hospital records and death register data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models to evaluate the associations of obesity, sarcopenia, and sarcopenic obesity with dementia risk, stratified by sex. Stratified analyses were performed across dementia-related polygenic risk score (PRS). Restricted mean survival time models were established to estimate the difference and 95%CIs of dementia onset across different status. Additionally, linear regression models were employed to estimate associations of different status with brain imaging parameters. The mediation effects of chronic diseases were also examined. RESULTS: Obese women with high PRS had a decreased risk (HR = 0.855 [0.761-0.961]), but obese men with low PRS had an increased risk (HR = 1.223 [1.045-1.431]). Additionally, sarcopenia was associated with elevated dementia risk (HRwomen = 1.323 [1.064-1.644]; HRmen = 2.144 [1.753-2.621]) in those with low PRS. Among those with high PRS, however, the association was only significant in early-life (HRwomen = 1.679 [1.355-2.081]; HRmen = 2.069 [1.656-2.585]). Of note, sarcopenic obesity was associated with higher dementia risk (HRwomen = 1.424 [1.227-1.653]; HRmen = 1.989 [1.702-2.323]), and results remained similar stratified by PRS. Considering dementia onset, obesity was associated with dementia by 1.114 years delayed in women, however, 0.170 years advanced in men. Sarcopenia (women: 0.080 years; men: 0.192 years) and sarcopenic obesity (women: 0.109 years; men: 0.511 years) respectively advanced dementia onset. Obesity, sarcopenia, and sarcopenic obesity were respectively related to alterations in different brain regions. Association between sarcopenic obesity and dementia was mediated by chronic diseases. CONCLUSIONS: Sarcopenic obesity and sarcopenia were respectively associated with increased dementia risk and advanced dementia onset to vary degree. The role of obesity in dementia may differ by sex and genetic background.

Effect of steviol glycosides as natural sweeteners on glucose metabolism in adult participants.

Steviol glycosides (SGs) are recognized as safe natural sweeteners; however, evidence from randomized controlled trials (RCTs) showed an inconclusive effect of SGs on glucose metabolism in adult participants. We aimed to conduct a systematic review and meta-analysis of RCTs to assess the effect of SGs on glucose metabolism. We systematically searched PubMed, Web of Science and EMBASE to include eligible RCTs. Our primary outcomes were differences between SGs and the control group with respect to changes in blood glucose from the baseline to the end of intervention (including fasting blood glucose [FBG], and HbA1c measurements). A random-effects meta-analysis was conducted for data synthesis to calculate the pooled mean difference (MD). There were twelve RCTs included for analyses with a total of 871 participants (48% females). A significant effect of SGs on FBG (MD = -4.10 mg dl-1, 95% CI -6.55 to -1.65) was found, while no significant difference in HbA1c (MD = 0.01%, 95% CI -0.12% to 0.13%) was observed between SGs and controls. The whole quality of evidence was rated as low. Subgroup analyses demonstrated favorable effects of SGs on FBG in participants aged ≤50 years, those without diabetes mellitus (DM) or hypertension at the baseline, and overweight and obese adults. Sensitivity analyses yielded results largely similar to the main findings. To conclude, SGs are found to produce significant improvement in glucose metabolism in adult participants when compared with the control. More evidence is required to further clarify and support the benefit of SGs as a sugar substitute for glucose metabolism.

ITGB2 fosters the cancerous characteristics of ovarian cancer cells through its role in mitochondrial glycolysis transformation.

Related studies have shown that ITGB2 mediates mitochondrial glycolytic transformation in cancer-associated fibroblasts and participates in tumor occurrence, metastasis and invasion of cancer cells. Based on these studies, we tried to construct a mitochondrial glycolysis regulatory network and explored its effect on mitochondrial homeostasis and ovarian cancer cells' cancerous characteristics. Our research revealed a distinct increase in the expression of ITGB2 and associated signaling pathway elements (PI3K-AKT-mTOR) in cases of ovarian cancer. ITGB2 might control mTOR expression via the PI3K-AKT pathway, thus promote mitochondrial glycolysis transformation and cell energy supply in ovarian cancer. This pathway could also inhibit mitophagy, maintain mitochondrial stability, and enhance the cancerous characteristics in case of ovarian cancer cells by mediating mitochondrial glycolytic transformation. Thus, we concluded that ITGB2-associated signaling route (PI3K-AKT-mTOR) may contribute to the progression of cancerous traits in ovarian cancer via mediating mitochondrial glycolytic transformation.

Compromised very-low density lipoprotein induced polyunsaturated triglyceride accumulation in N-nitrosodiethylamine-induced hepatic steatosis.

N-Nitrosodiethylamine (NDEA), a carcinogen in some foods and medications, is linked to liver damage similar to non-alcoholic fatty liver disease (NAFLD). This study explores how NDEA disrupts liver lipid metabolism. Sprague-Dawley rats were given two doses of NDEA (100 mg/kg) orally, 24 h apart. Liver response was assessed through tissue staining, blood tests, and biochemical markers, including fatty acids, lipid peroxidation, and serum very-low density lipoprotein (VLDL) levels. Additionally, lipidomic analysis of liver tissues and serum was performed. The results indicated significant hepatic steatosis (fat accumulation in the liver) following NDEA exposure. Blood analysis showed signs of inflammation and liver damage. Biochemical tests revealed decreased liver protein synthesis and specific enzyme alterations, suggesting liver cell injury but maintaining mitochondrial function. Increased fatty acid levels without a rise in lipid peroxidation were observed, indicating fat accumulation. Lipidomic analysis showed increased polyunsaturated triglycerides in the liver and decreased serum VLDL, implicating impaired VLDL transport in liver dysfunction. In conclusion, NDEA exposure disrupts liver lipid metabolism, primarily through the accumulation of polyunsaturated triglycerides and impaired fat transport. These findings provide insight into the mechanisms of NDEA-induced liver injury and its progression to hepatic steatosis.

Relationship between trajectories of dietary iron intake and risk of type 2 diabetes mellitus: evidence from a prospective cohort study.

BACKGROUND: The association between dietary iron intake and the risk of type 2 diabetes mellitus (T2DM) remains inconsistent. In this study, we aimed to investigate the relationship between trajectories of dietary iron intake and risk of T2DM. METHODS: This study comprised a total of 61,115 participants without a prior T2DM from the UK Biobank database. We used the group-based trajectory model (GBTM) to identify different dietary iron intake trajectories. Cox proportional hazards models were used to evaluate the relationship between trajectories of dietary iron intake and risk of T2DM. RESULTS: During a mean follow-up of 4.8 years, a total of 677 T2DM events were observed. Four trajectory groups of dietary iron intake were characterized by the GBTM: trajectory group 1 (with a mean dietary iron intake of 10.9 mg/day), 2 (12.3 mg/day), 3 (14.1 mg/day) and 4 (17.6 mg/day). Trajectory group 3 was significantly associated with a 38% decreased risk of T2DM when compared with trajectory group 1 (hazard ratio [HR] = 0.62, 95% confidence interval [CI]: 0.49-0.79), while group 4 was significantly related with a 30% risk reduction (HR = 0.70, 95% CI: 0.54-0.91). Significant effect modifications by obesity (p = 0.04) and history of cardiovascular disease (p < 0.01) were found to the relationship between trajectories of dietary iron intake and the risk of T2DM. CONCLUSIONS: We found that trajectories of dietary iron intake were significantly associated with the risk of T2DM, where the lowest T2DM risk was observed in trajectory group 3 with a mean iron intake of 14.1 mg/day. These findings may highlight the importance of adequate dietary iron intake to the T2DM prevention from a public health perspective. Further studies to assess the relationship between dietary iron intake and risk of T2DM are needed, as well as intervention studies to mitigate the risks of T2DM associated with dietary iron changes.

Missing Outcome Data in Recent Perinatal and Neonatal Clinical Trials.

Missing outcome data in clinical trials may jeopardize the validity of the trial results and inferences for clinical practice. Although sick and preterm newborns are treated as a captive patient population during their stay in the NICUs, their long-term outcomes are often ascertained after discharge. This greatly increases the risk of attrition. We surveyed recently published perinatal and neonatal randomized trials in 7 high-impact general medical and pediatric journals to review the handling of missing primary outcome data and any choice of imputation methods. Of 87 eligible trials in this survey, 77 (89%) had incomplete primary outcome data. The missing outcome data were not discussed at all in 9 reports (12%). Most study teams restricted their main analysis to participants with complete information for the primary outcome (61 trials; 79%). Only 38 of the 77 teams (49%) performed sensitivity analyses using a variety of imputation methods. We conclude that the handling of missing primary outcome data was frequently inadequate in recent randomized perinatal and neonatal trials. To improve future approaches to missing outcome data, we discuss the strengths and limitations of different imputation methods, the appropriate estimation of sample size, and how to deal with data withdrawal. However, the best strategy to reduce bias from missing outcome data in perinatal and neonatal trials remains prevention. Investigators should anticipate and preempt missing data through careful study design, and closely monitor all incoming primary outcome data for completeness during the conduct of the trial.

Numerical study on atomization characteristics of biomimetic evaporation tube in micro turbine engine.

A micro turbine engine's thrust relies on combustion chamber efficiency, closely tied to the design of its evaporation tube. This study thoroughly investigates evaporation and atomization processes within the tube, introducing a pioneering bionic-inspired structure. Integrating a honeycomb sheet into the traditional tube, both configurations undergo a comparative analysis. Results show a direct correlation between elevated air temperatures and reduced fuel droplet diameters, leading to increased fuel evaporation rates. The bionic tube, with a 1mm-thick honeycomb sheet, 0.6 mm aperture diameter, and 3 sheets, significantly improves fuel droplet atomization and evaporation compared to the conventional design. This research holds broader significance in understanding and enhancing micro turbine engine performance.

Relationship between metabolic status, physical activity and cardiovascular disease in participants with obesity.

OBJECTIVE: We aimed to investigate the independent and joint associations between metabolic status, PA (physical activity) and risk of CVD (cardiovascular disease) in participants with obesity. METHODS: We included 109,301 adults with obesity free of baseline CVD enrolled from 2006 to 2010 in the UK Biobank cohort (aged 56 ± 7.9 years). Based on metabolic status, obesity was grouped into metabolically healthy obesity (MHO; free of hypertension, hypercholesterolemia and diabetes; n = 26,989; BMI 33 ± 3.3 kg/m2) and metabolically unhealthy obesity (MUO; n = 82,312; BMI 34 ± 4.0 kg/m2). PA was categorized into four groups according to moderate-to-vigorous PA (MVPA): none, low, medium, and high. Multivariable Cox regression models were used for the main analyses adjusting for sociodemographic factors, lifestyles and comorbidities. RESULTS: There were 8,059 CVD events during a median follow-up of 8.1 years. MHO was associated with a 42% reduced risk of CVD compared with MUO (HR = 0.58, 95% CI: 0.53-0.63). A significant interaction effect between PA and metabolic status on CVD risk was found. Among MUO participants, individuals with PA had significantly decreased CVD risk when compared with no MVPA (HR = 0.87, 95% CI: 0.81-0.94 for low PA; HR = 0.85, 95% CI: 0.78-0.93 for medium PA; and HR = 0.86, 95% CI: 0.80-0.92 for high PA). The lowest CVD risk was observed in MHO & medium PA group when compared with MUO & no MVPA (HR = 0.45, 95% CI: 0.37-0.56). CONCLUSIONS: Both MHO and any MVPA were associated with reduced risk of CVD in adults with obesity, while PA could modify the relationship between metabolic status and CVD risk.

PINN Model of Diffusion Coefficient Identification Problem in Fick's Laws.

This study tackles the complex task of determining diffusion coefficients in inverse problems, addressing the challenges of instability and computational demands. The primary objective is to introduce an efficient model for estimating diffusion coefficients under specific conditions. Through a unique fusion of Fick's laws and a Neural Network framework, a physics-informed neural network (PINN) is developed for the diffusion coefficient identification problem. The model accommodates scenarios where both diffusion flux and concentration gradient are known, where diffusion flux is known while the concentration gradient is unknown, and where diffusion flux is unknown while the concentration gradient is known. Results demonstrate the model's efficiency, obtaining diffusion coefficients in less than 1000, 2000, and 3000 iterations for the respective scenarios. Sensitivity analysis underscores the model's validity across conditions, highlighting the positive impact of a higher proportion of effective data on convergence and alignment with general diffusion coefficient patterns. In conclusion, the PINN model stands out as a powerful tool for accurately estimating diffusion coefficients under varying conditions.

Relationship Between Lipoprotein(a), Renal Function Indicators, and Chronic Kidney Disease: Evidence From a Large Prospective Cohort Study.

BACKGROUND: Chronic kidney disease (CKD) poses a significant global public health challenge. While lipoprotein(a) (Lp[a]) has been established as a significant factor in cardiovascular disease, its connection to CKD risk remains a topic of debate. Existing evidence indicates diverse risks of kidney disease among individuals with various renal function indicators, even when within the normal range. OBJECTIVE: This study aims to investigate the joint associations between different renal function indicators and Lp(a) regarding the risks of incident CKD in the general population. METHODS: The analysis involved a cohort of 329,415 participants without prior CKD who were enrolled in the UK Biobank between 2006 and 2010. The participants, with an average age of 56 (SD 8.1) years, included 154,298/329,415 (46.84%) males. At baseline, Lp(a) levels were measured using an immunoturbidimetric assay and classified into 2 groups: low (<75 nmol/L) and high (≥75 nmol/L). To assess participants' baseline renal function, we used the baseline urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). The relationship between Lp(a), renal function indicators, and the risk of CKD was evaluated using multivariable Cox regression models. These models were adjusted for various factors, including sociodemographic variables, lifestyle factors, comorbidities, and laboratory measures. RESULTS: A total of 6003 incident CKD events were documented over a median follow-up period of 12.5 years. The association between elevated Lp(a) levels and CKD risk did not achieve statistical significance among all participants, with a hazard ratio (HR) of 1.05 and a 95% CI ranging from 0.98 to 1.13 (P=.16). However, a notable interaction was identified between Lp(a) and UACR in relation to CKD risk (P for interaction=.04), whereas no significant interaction was observed between Lp(a) and eGFR (P for interaction=.96). When compared with the reference group with low Lp(a) and low-normal UACR (<10 mg/g), the group with high Lp(a) and low-normal UACR exhibited a nonsignificant association with CKD risk (HR 0.98, 95% CI 0.90-1.08; P=.74). By contrast, both the low Lp(a) and high-normal UACR (≥10 mg/g) group (HR 1.16, 95% CI 1.08-1.24; P<.001) and the high Lp(a) and high-normal UACR group (HR 1.32, 95% CI 1.19-1.46; P<.001) demonstrated significant associations with increased CKD risks. In individuals with high-normal UACR, elevated Lp(a) was linked to a significant increase in CKD risk, with an HR of 1.14 and a 95% CI ranging from 1.03 to 1.26 (P=.01). Subgroup analyses and sensitivity analyses consistently produced results that were largely in line with the main findings. CONCLUSIONS: The analysis revealed a significant interaction between Lp(a) and UACR in relation to CKD risk. This implies that Lp(a) may act as a risk factor for CKD even when considering UACR. Our findings have the potential to provide valuable insights into the assessment and prevention of CKD, emphasizing the combined impact of Lp(a) and UACR from a public health perspective within the general population. This could contribute to enhancing public awareness regarding the management of Lp(a) for the prevention of CKD.

PCV-VG combined individualized PEEP determination in one-lung ventilated patients with PEEP step change direction: A randomized controlled trial.

INTRODUCTION: The efficacy of pressure-controlled volume-guaranteed ventilation (PCV-VG) combined with a gradient-directional change in positive end-expiratory pressure (PEEP) during one-lung ventilation (OLV) in patients who underwent thoracoscopic surgery was investigated. METHODS: Ninety patients were randomly divided into the PC (PCV-VG + 5 cm H2 O fixed PEEP), PI (PCV-VG + incremental PEEP titration), and PD (PCV-VG + decremental PEEP titration) groups. Hemodynamic (heart rate [HR] and mean arterial pressure [MAP]), respiratory mechanics (Ppeak , Pmean, and Cdyn), and arterial blood gas (pH, PaCO2 , PaO2 , and PaO2 /FiO2 ) indices were evaluated at T1 (10 min of two-lung ventilation [TLV]), T2 (10 min of OLV), and T3 (10 min of recovery, TLV). Enzyme-linked immunosorbent assay was performed to detect neutrophil elastase (NE), clara cell secretory protein (CC16), and interleukin-8 (IL-8) levels at T1 and T3. RESULTS: At T2 and T3 , Ppeak was lower in the PI and PD groups than in the PC group, while Pmean and Cdyn were higher than in the PC group. Ppeak in the PD group was lower than that in the PI group; however, Pmean was higher at T2 and T3 (P < 0.05). At T2 , PaO2 and PaO2 /FiO2 were higher, but PaO2 /FiO2 and VD /VT were lower in the PD and PI groups than in the PC group (P < 0.05). NE, CC16, IL-6, and IL-8 levels were elevated in all three groups at T3 , but the PI and PD groups had lower levels than the PC group (P < 0.05). The incidences of postoperative pulmonary complications (PPCs) and surgical intensive care unit hospitalizations in the PD and PI groups were much lower. CONCLUSION: Gradient-directed altered PEEP titration could improve respiratory mechanics, arterial blood gases, and inflammatory responses and reduce the incidence of PPCs in patients undergoing thoracoscopic surgery.