Likelihood Ratio Test Research Articles

Heart failure risk assessment using biomarkers in patients with atrial fibrillation: analysis of 32,041 patients from the COMBINE-AF study

Abstract Introduction Heart failure (HF) is one of the most common comorbidities in patients with AF, resulting in a clinical need for robust risk assessment. Purpose To investigate the incremental value of adding NTproBNP, high-sensitivity cardiac troponin T (hs-cTnT), and growth-differentiation factor-15 (GDF-15) to clinical predictors for HF risk stratification in patients with AF, and the individual contribution of each biomarker accounting for inter-biomarker correlation. Methods We used pooled individual patient data from 3 large RCTs investigating DOACs versus VKAs (ARISTOTLE, ENGAGE AF-TIMI 48, RE-LY) from the COMBINE-AF cohort and included all patients with available biomarkers at baseline. The composite primary endpoint was hospitalization for HF (HHF) or CV death (CVD), with HHF as secondary endpoint. We employed analyses of absolute risk and Cox-regression adjusting for clinical factors to assess the association of the individual biomarkers with both endpoints, testing incremental discrimination with the likelihood ratio test from nested models. To address the inter-biomarker correlation, weighted quantile sum (WQS) regression analysis summarizing the adjusted risk of all biomarkers (per quartile) in one index was applied, thereby exploring the individual and additive contribution of each biomarker to risk assessment. Results Data were available in 32,041 patients (median age 71 [IQR 64-77] years, 36.7% female, 23.0% with paroxysmal AF, 41.6% with established HF). Higher biomarker values were associated with a graded increase in absolute risk for HHF/CVD and HHF (Figure 1). In a model adjusting for clinical variables and all biomarkers, hs-cTnT (HR per 1-SD 1.39 [95% CI 1.33-1.44]), NT-proBNP (HR 1.67 [95% CI 1.58-1.76]), and GDF-15 (HR 1.20 [95% CI 1.15-1.25]) were associated with HHF/CVD. The c-index increased with addition of biomarkers (0.70 [0.69, 0.70] to 0.77 [0.76, 0.78]; Likelihood ratio test p<0.001). Results were similar for HHF alone. NTproBNP was significantly correlated with hs-cTnT (r=0.40, p<0.0001) and GDF-15 (r=0.36, p<0.001). To address this correlation, WQS regression analysis was conducted (Figure 2). NTproBNP and hs-cTnT contributed nearly equally to the risk assessment for HHF/CVD and HHF, with GDF-15 providing statistically significant but less contribution to risk assessment (Figure 2). Conclusion Hs-cTnT, NT-proBNP and GDF-15 contribute individually and additively to the risk assessment for HHF/CVD and HHF in patients with AF. Our analysis suggests that hs-cTnT is as important as NTproBNP for HF risk assessment, with significant but less contribution of GDF-15. Our findings support the possible future routine use of biomarkers to distinguish patients with AF at low or high risk for HF and could guide the introduction of therapies to mitigate the risk of HF events in this growing population.Event incidence by biomarker quartilesWeighted quantil sum regression analysis

Treatment of kidney disease: an analytical decision model at a Swiss university hospital

Abstract Background An observational hospital-based cohort study, where the kidney disease staging is identified as a digital marker, and the association between the standardised staging of Kidney Disease (KD) and the outcomes is assessed along the treatment process. Methods The clinical and administrative data for all patients are stored in the Clinical Data Warehouse. A specific digital marker for an exact KD staging is applied. Three retrospective patient cohorts for exact and imprecise staging and missing diagnosis are defined and compared regarding the in-hospital mortality, all-cause mortality and disease progression. Results In total, 83146 hospitalisations of 40421 patients with KD, treated in 2014-2023 (2016-2023 will be updated) were identified; the number of the first hospitalisations with exact staging was 847 (2%), unprecise 29934 (72%) and missing diagnosis (26%). The demographic and baseline factors distribution between groups was tested with no association (chi-squared test statistic). The median survival time with a 95% CI was 7.94 (7.66, 8.81) years for the exact and 7.47 (7.42, 7.53) for the imprecise staging group. A log-rank and loglikelihood tests indicated a significant difference in survival between the groups, p < 0.0001. The Cox regression model shows a statistically significant difference in Hazard Ratio; KD staging, age, Elixhauser van Walraven index, treatment, nephrotoxic medication, contrast agent application, and AKI were identified as the significant covariates, C-statistic 0.730, Likelihood ratio test, Wald test, log-rank score on 42 df, p < 2e-16. ANOVA analysis confirmed a significant difference in cost distribution between the groups. An economic decision model proposal integrates the findings, combining a profile-level Markov cohort with a Discreet Time-To-Event Simulation DICE. Conclusions The study demonstrates a better outcome regarding all-cause mortality, in-hospital mortality, and costs if a standardised KD staging was applied. Key messages • Intuition (clinical judgement) and standardised kidney disease staging perform differently regarding clinical outcomes and costs. • The study demonstrates a better outcome regarding all-cause mortality, in-hospital mortality, and costs if a standardised KD staging was applied.

The importance of heart rate on left ventricular global longitudinal strain in echocardiography: novel insights facilitated by automated deep learning methods

Abstract Background Heart rate (HR) is assumed to influence echocardiographic measurements. Consequently, HR needs to be considered for accurate assessment of cardiac function. Despite left ventricular global longitudinal strain (LV GLS) being recognised as a valuable measure of cardiac function, its normal reference ranges remain confined to patients within a limited range of resting HR. So far, time-consuming manual analyses and high measurement variability have precluded comprehensive assessment of the interplay between HR and LV GLS. Using fully automated GLS measurements provided by novel deep learning (DL) methods, it is now possible to evaluate changes in LV GLS across a wide range of HR. Purpose To improve echocardiographic assessments across a wide range of HR intervals, we aimed to study the influence of controlled HR variations on LV GLS using programmable pacemakers and fully automated DL measurements. Methods Participants with sinus node dysfunction and implanted programmable pacemakers were enrolled. Echocardiographic acquisitions were obtained at baseline HR and during stepwise increments by 10 beats/min, targeting a range from 50 to 140 beats/min. Recordings of cine-loops including 10 cardiac cycles were obtained for the four-chamber, two-chamber, and apical long axis view. LV GLS was measured for all cycles using a fully automated DL method developed by our group, and presented as mean of the three standard apical views for all patients at each HR level. A linear mixed model was used for construction of an overall trendline based on the estimated fixed effects across all 50 patients, stating patient number as the random effect. The correlation between HR and LV GLS was evaluated by a likelihood ratio test. Results Fifty patients were included, 52% females, mean age 68 years (27 to 88 years). All patients had preserved atrioventricular conduction. Resting HR ranged from 50 to 87 beats/min (mean 64 beats/min). At baseline echocardiographic acquisition, most participants were within normal ranges for LV volumes, systolic and diastolic function. A total of about 13,000 cardiac cycles were automatically analysed by the DL method. The overall trend demonstrated a linear relation between increasing HR and decreasing absolute LV GLS (Figure 1). Across HR increments from 50 to 140 beats/min, there was a 32% (22%–42%) reduction in absolute LV GLS, declining from -17.1% to -11.7%. The strong correlation between changes in HR and LV GLS was further supported by a highly significant likelihood ratio test (p-value <0.001). Conclusions There was a reduction of absolute LV GLS with increasing HR. These findings emphasize the importance of integrating HR considerations into clinical echocardiography practice. Moreover, the results highlight that DL methods can unlock substantially richer insights from individual patient data, offering a new pathway towards more personalized and precise cardiac diagnostics.Figure 1

Nomogram for the Pathological Complete Response After Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer Patients.

No validated instrument currently exists to predict neoadjuvant chemotherapy (NAC) response in muscle-invasive bladder cancer (MIBC) patients. We aim to develop and validate a nomogram based on clinicopathological factors for predicting who would benefit most from NAC. Between January 2016 and April 2023, 361 consecutive MIBC patients treated with NAC were enrolled in the study. Two hundred sixty patients at the Hu Nan institution comprised the development cohort. The validation cohort (91 patients) was from the Xiang Hua center. Patient clinicopathologic information was documented. Using regression coefficients, a predictive model was constructed using multivariate logistic regression. The likelihood ratio test with Akaike's information criterion was then used as the ending rule for backward stepwise selection. This predictive model's efficacy was evaluated for discrimination, calibration, and clinical utility. Predictors of this model included the origin of MIBC, pathological tumor type, clinical tumor stage, and tumor size. In the validation cohort, the model demonstrated good discrimination with an AUROC of 0.7221 (P < 0.001) and calibration (Unreliability test, P = 0.580). In addition, decision curve analysis revealed that the model was clinically beneficial. This study indicated that primary MIBC, pure UC pathological type, lower clinical tumor stage, and maximum tumor diameter <3 cm were significant predictors of ypCR in MIBC patients after NAC. This nomogram may contribute to the preciousadministration of NAC and the avoidance of chemotherapy toxicity and delayed RC.

“Friendships fizzled out”: Trajectories and risk factors of youth loneliness following COVID-19

Abstract Background Social distancing and isolation during the COVID-19 pandemic left a mark on the social, emotional and cognitive development of youth. We aimed to identify the course of Dutch youth loneliness and its predictors since the Omicron lockdown in December 2021. Methods Data were obtained from a repeated cross-sectional panel study between March 2022 and September 2023, in which loneliness was assessed using the 6-item De Jong Gierveld Loneliness Scale. Youth (12-25 years) participating in at least three timepoints were included. A latent class growth analysis (LCGA) was performed to identify trajectories of loneliness. Themes identified in qualitative data (open-ended questions halfway 2022) were recoded into binary quantitative variables to be included in regression analyses. Two-step multivariable multinomial logistic regression was used to determine risk factors per trajectory class. Goodness of fit was assessed using the likelihood-ratio test. Results Identified trajectories were: 1) very lonely (n = 140), 2) moderate lonely (n = 373), 3) recovering (n = 511), and 4) not lonely (n = 384; reference). Compared to the other trajectories, youngsters following a moderate or very lonely trajectory had more often little to no trust in the future and more often experienced non-specific symptoms and stress due to various causes. Including perceptions showed that youth in these trajectories experienced a greater impact of the pandemic on their social relationships. The inclusion of perception also improved the model’s goodness of fit (p &amp;lt; 0.001). Conclusions Up to 18 months after the COVID-19 pandemic, youngsters that reported loneliness continue to endure its consequences on their social lives. Despite the apparent association between the Omicron lockdown and continuing loneliness, claims about causality should be made with caution. However, findings implicate the importance of political and social recognition of the pandemic’s ongoing impact on vulnerable youth. Key messages • Lonely youth experienced a greater impact of the COVID-19 pandemic on their social lives. • Political and social recognition of the pandemic’s ongoing impact on vulnerable youth is wanted.

Impact of aortic valve calcium score on conductive disturbances after transcatheter aortic valve implantation: a monocentre retrospective study

Abstract Introduction Conductive disorders requiring permanent pacemaker implantation (PPI) remain an important issue after transcatheter aortic valve implantation (TAVI). Aims To assess the impact of aortic valve calcium score (AVCS) on conductive disorders requiring PPI after TAVI. Methods All patients who underwent TAVI with an available AVCS from the pre-procedural CT-scan report from 2016 to 2022 were included in this retrospective single-centre study. The primary endpoint was the occurrence of a conductive disorder requiring PPI at 30 days. The association between PPI and AVCS was analyzed using multivariable logistic regression and receiver operating characteristics (ROC) curves analyses. Results Seven hundred and sixty-one patients were included, of whom 125 (16%) patients required a PPI at 30 days. AVCS score was significantly higher in patients requiring PPI (3788 (2487-5218) vs. 3050 (2043-4367) AU, p&amp;lt;0.001). Using multivariable analysis, pre-procedural right bundle branch block (OR=6.61, 95%CI=3.82-11.5, p&amp;lt;0.001), first atrioventricular block (OR=1.71, 95%CI=1.03-2.83, p=0.037), the use of a self-expanding valve (OR=3.25, 95%CI=1.17-9.09, p=0.025), and AVCS &amp;gt;4510 AU (OR=1.83, 95%CI=1.04-3.20, p=0.035) were independently associated with PPI. The area under the curve for ACVS to predict PPI was 60.3% (95%CI=54.7%-65.9%), indicating moderate discrimination. Of note, AVCS had an incremental discriminative value (C-index 0.79 vs 0.77, LR test p=0.036) over and above traditional PPI risk factors. Conclusion The results of our study suggest that a high AVCS is associated with an increased risk of PPI after TAVI.Central illustration

Prognostic value of left atrial strain for outcome of catheter ablation in patients with atrial fibrillation and moderately enlarged left atrium

Abstract Background Atrial fibrillation catheter ablation (AFCA) is an effective rhythm control method for patients with AF, but AF recurrence is higher in patients with a large left atrium (LA). We explored whether pre-procedural LA strain has incremental prognostic value for the long-term rhythm outcomes of AFCA in patients with AF and moderately enlarged LA size (45≤LA diameter&amp;lt;50mm). Methods We included 2,269 patients who underwent de novo AF catheter ablation (men 72.2%, 59.1[±10.7] years, paroxysmal AF 64.0%). We divided grouped into 5 mm increments and determined the appropriate cut-off of LA diameter (45mm) predicting the difference in long-term rhythm outcome by the log-likelihood values of multivariate Cox proportional hazard models. Patients with moderately enlarged LA size (45≤LA diameter&amp;lt;50mm, n=413) with borderline rhythm outcomes were used for analysis. Results In the cohort of 413 patients who underwent AFCA with moderately enlarged LA size, AF was recurred in 208 patients (43.7%) after AFCA. We determined the appropriate cut-off of LA strain (12.5) predicting the difference in long-term rhythm outcome by the log-likelihood values of multivariate Cox proportional hazard models. During 24 months [10-50] follow-up, patients with low LA strain (&amp;lt;12.5) were showed worsen rhythm outcome than high LA strain (Log-rank p&amp;lt;0.001). Patients with AF recurrence after AFCA were independently associated with low LA strain (HR 1.539 [1.130-2.094], p=0.006), and paroxysmal AF (OR 0.651 [0.469-0.905], p=0.011). Furthermore, the likelihood ratio test demonstrated a significant influence of adding LA strain by TTE (χ2 = 13.90 [P &amp;lt; 0.001]). Conclusions LA strain using baseline echocardiography has a predictive power for AF recurrence after AFCA in patients with moderately enlarged LA size (45≤LA diameter&amp;lt;50mm).

Association between hs-CRP/HDL-C ratio and three-month unfavorable outcomes in patients with acute ischemic stroke: a second analysis based on a prospective cohort study

ObjectiveThe associations between the ratio of blood high-sensitivity C-reactive protein (hs-CRP) to high-density lipoprotein cholesterol (HDL-C) (hs-CRP/HDL-C ratio) and outcomes in patients with acute ischemic stroke (AIS) have yet to be established. This study is the first to examine the relationship between the hs-CRP/HDL-C ratio and three-month unfavorable outcomes in patients with AIS.MethodsThis secondary analysis utilized data from a prospective cohort study involving 1559 AIS patients recruited at a South Korean hospital between January 2010 and December 2016. We constructed a binary logistic regression model to explore the association between the hs-CRP/HDL-C ratio and unfavorable outcomes in patients with AIS. An attempt was made to use a generalized additive model (GAM) with smooth curve fitting to elucidate potential nonlinear interactions. Furthermore, inflection points were identified via a recursive method, and binary logistic regression models were developed for each side of these inflection points. Ultimately, a log-likelihood ratio test was used to identify the most appropriate model for explaining the connection between the hs-CRP/HDL-C ratio and unfavorable outcomes in patients with AIS.ResultsThe incidence of unfavorable outcomes was 24.5%, with a median hs-CRP/HDL-C ratio of 3.64. After accounting for other factors, the binary logistic regression model revealed a statistically significant positive association between the hs-CRP/HDL-C ratio and the likelihood of poor outcomes in AIS patients (OR = 1.013, 95% CI: 1.005–1.022; P = 0.002). A nonlinear relationship was observed, with the first inflection point of the hs-CRP/HDL-C ratio at 42.74. Each 1-unit increase in the hs-CRP/HDL-C ratio was associated with a 2.4% greater risk of unfavorable outcomes (OR = 1.024, 95% CI: 1.011–1.038, P < 0.001).ConclusionThis study provides evidence of a positive and nonlinear correlation between the hs-CRP/HDL-C ratio and poor three-month functional outcomes in AIS patients. When the hs-CRP/HDL-C ratio was less than 42.74, a positive association was observed with the risk of unfavorable outcomes. This finding offers a reference for optimizing early individualized therapy and aids in clinical counseling for patients with AIS.

Estimates of genetic parameters and genetic trends for growth traits in Menz sheep under community-based breeding programs

The main objectives of this study were to estimate genetic and phenotypic parameters for growth traits in Menz sheep under community-based breeding programs (CBBPs). Data used in the study were collected from five Menz CBBPs villages during 15-year period (2009–2023). Studied growth traits were birth weight (BW), weaning weight (WW), six-month weight (6 MW), yearling weight (YW), Average daily gain from birth to weaning (ADG1), average daily gain from weaning to six months (ADG2) and average daily gain from six months to yearling (ADG3). Fixed effects were estimated using the GLM procedure of SAS 9.4. Genetic parameters were estimated fitting different univariate animal models using Average Information Restricted Maximum Likelihood (AI-REML) procedure with WOMBAT software. The most appropriate model for each trait was determined applying likelihood ratio tests. Model including only direct additive genetic effect was the most appropriate model for BW, YW, ADG2 and ADG3, whereas model including direct additive and maternal additive genetic effect without taking into account covariance between them was the most appropriate for WW, 6 MW and ADG1. Based on the most appropriate models, direct heritability of BW, WW, 6 MW, YW, ADG1, ADG2 and ADG3 were 0.29 ± 0.01, 0.45 ± 0.01, 0.46 ± 0.02, 0.42 ± 0.02, 0.44 ± 0.01, 0.75 ± 0.02 and 0.21 ± 0.02, respectively. The estimated maternal heritability were 0.04 ± 0.01, 0.02 ± 0.01 and 0.02 ± 0.01 for WW, 6 MW and ADG1, respectively. Additive coefficient of variance were ranged from 9.53 % for BW to 33.02 % for ADG2. Moderate to higher estimates of direct heritability and additive coefficient of variation (CVA) in the current study indicates higher potential for genetic improvement of studied traits through direct selection. The genetic trend for the Menz sheep's six-month weight in Molale CBBPs village reveals a promising annual growth rate of 0.20 kg. Optimizing the ongoing breeding program into specializing-sire producer groups and applying intensive selection on the sub-nucleus flock could improve the efficiency of the breeding program. Genetic correlations among the studied traits were ranged from −0.50 for ADG-ADG2 to 0.98 for WW-ADG1. Genetic correlation between 6 MW and other studied traits was positive and moderate in magnitude. To achieve optimum genetic gain, the implemented selection criteria for Menz sheep (6 MW) should be continued.

Subspace‐based distributed target detection method with small training data samples

AbstractDetecting distributed targets precisely in homogeneous environments has been a hot topic in radar signal processing. Generally, distributed targets are often modelled with subspace models of unknown coordinates, and clutter is modelled as the complex Gaussian distribution with zero mean and unknown covariance matrix, while covariance matrix is estimated with a set of training data without the target signal. However, in practice, the complexity of the external environment makes the training data that satisfy the condition of independent homogeneous distribution less available. Therefore, it is assumed that the covariance matrix of the clutter is persymmetric structure and the approach of dimensionality reduction using subspace transformations is introduced, two detectors based upon generalised likelihood ratio test criterion and Wald test criterion in homogeneous environments are proposed. Theoretical analyses indicate the constant false alarm rate characteristics of the two proposed detectors for unknown clutter covariance matrices. Simulation analyses indicate that the proposed detector works well even with fewer training data samples, and its detection performance outperforms that of existing contrast detectors.

Determinants of micronutrient supplementation during pregnancy among women in three sub-Saharan African countries: a multilevel logistic regression model.

Poor maternal nutrition during pregnancy is a common cause of poor maternal and infant outcomes. Micronutrient deficiencies are common among pregnant women in low- and middle-income countries, including sub-Saharan Africa. Pregnant women are recommended to take micronutrients like iron or folic acid and deworming medication during pregnancy. Therefore, this study was conducted to assess micronutrient intake and its associated factors among pregnant women in three countries using the most recent demographic and health survey. We used data from the most recent demographic and health surveys, which were carried out between 2019 and 2022 in three sub-Saharan African countries. The study included a weighted sample of 13,568 reproductive-age women who had given birth within the five years prior to the survey. Utilizing multilevel logistic regression, the factors associated with the dependent variable were identified. Model comparison and fitness were assessed using the deviance (-2LLR), likelihood ratio test, median odds ratio, and intra-class correlation coefficient. Ultimately, factors were deemed statistically significant if they had a p-value less than 0.05. The pooled prevalence of micronutrient intake among pregnant women during pregnancy of last birth was 77.56% (95% CI: 76.85%-78.25%). Factors like age [AOR = 1.78; 95% CI (1.14, 2.77)], educational status [AOR = 1.49; 95% CI (1.23, 1.79)], marital status [AOR = 0.66; 95% CI (0.58, 0.75)], working status [AOR = 1.17; 95% CI (1.01, 1.34)], media exposure [AOR = 1.20; 95% CI (1.05, 1.38)], preceding birth interval [AOR = 1.17; 95% CI (1.01, 1.34)], number of ANC visits [AOR = 1.65; 95% CI (1.29, 2.10)], and residence [AOR = 1.19; 95% CI (1.03, 1.37)] were significantly associated with micronutrient intake among pregnant women. More than three-fourths of the study subjects were micronutrient supplemented during their pregnancy. Improving women's education, disseminating nutrition information through media, providing more attention to young pregnant women who live in rural areas, increasing the number of ANC visits, and women's empowerment are strongly recommended.

What is the optimal range of fasting stress hyperglycemia ratio for all-cause mortality in American adults: An observational study.

To date, no studies have been conducted to assess the impact of fasting stress hyperglycemia ratio (SHR) on all-cause mortality. Therefore, the objective of our study is to investigate the association between SHR and all-cause mortality in a population of American adults. The study population was derived from NHANES data spanning from 2005 to 2018. The exposure variable SHR was derived from fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c%), and the specific calculation formula was as follows: (FBG (mmol/L))/(1.59 × HbA1c (%) - 2.59). The outcome variable was all-cause mortality. A total of 18,457 participants were enrolled in this prospective cohort study. Following a median follow-up period of 90 months, all-cause mortality was observed in 10.32% of the subjects. Cox proportional hazards regression model indicates that there is no significant difference between SHR and all-cause mortality in the fully adjusted model, whether analyzed as a continuous or categorical variable (P for trend > 0.05). Through the 2-piecewise Cox proportional hazards regression model, we have determined that the inflection point of SHR in relation to all-cause mortality is 0.88. It has also been observed that when the value of SHR is on the left side of the inflection point (SHR ≤ 0.88), there is a significant 77% (HR: 0.23; 95% CI: 0.10-0.50) reduction in all-cause mortality for each additional unit increase in SHR. Conversely, when the value of SHR exceeds 0.88, there is a substantial 2.40-fold (HR: 2.40; 95% CI: 1.61-3.58) increase in the risk of all-cause mortality (P for log likelihood ratio test < .001). The subgroup analysis results demonstrate that sex has the potential to modify the association between SHR and all-cause mortality within the population exhibiting SHR ≤ 0.88. The relationship between SHR and all-cause mortality follows a U-shaped pattern, where in the lowest risk of death for the average American adult is observed at an SHR value of 0.88. Furthermore, in men with SHR ≤ 0.88, there is a significant inverse relationship between the increase in SHR and the risk of all-cause mortality.

Subclassification of obesity for precision prediction of cardiometabolic diseases.

Obesity and cardiometabolic disease often, but not always, coincide. Distinguishing subpopulations within which cardiometabolic risk diverges from the risk expected for a given body mass index (BMI) may facilitate precision prevention of cardiometabolic diseases. Accordingly, we performed unsupervised clustering in four European population-based cohorts (N ≈ 173,000). We detected five discordant profiles consisting of individuals with cardiometabolic biomarkers higher or lower than expected given their BMI, which generally increases disease risk, in total representing ~20% of the total population. Persons with discordant profiles differed from concordant individuals in prevalence and future risk of major adverse cardiovascular events (MACE) and type 2 diabetes. Subtle BMI-discordances in biomarkers affected disease risk. For instance, a 10% higher probability of having a discordant lipid profile was associated with a 5% higher risk of MACE (hazard ratio in women 1.05, 95% confidence interval 1.03, 1.06, P = 4.19 × 10-10; hazard ratio in men 1.05, 95% confidence interval 1.04, 1.06, P = 9.33 × 10-14). Multivariate prediction models for MACE and type 2 diabetes performed better when incorporating discordant profile information (likelihood ratio test P < 0.001). This enhancement represents an additional net benefit of 4-15 additional correct interventions and 37-135 additional unnecessary interventions correctly avoided for every 10,000 individuals tested.

Moderate Deviation Principle for the Determinant of Sample Correlation Matrix

ABSTRACTLet be a sequence of independence random vectors from with population correlation matrix , and its sample correlation matrix is denoted as , where the matrix element represents the Pearson correlation coefficient between the and columns of the data matrix . is an interesting part in multivariate analysis, and the likelihood ratio test (LRT) statistic used to test the complete independence of all components of can be expressed as a function of . On this basis, under the condition that the sample size and the dimension satisfy as , we derive the moderate deviation principle (MDP) of the LRT statistic for the hypothesis testing problem vs .

Evaluating the role of pericoronary adipose tissue on coronary artery disease: insights from CCTA on risk assessment, vascular stenosis, and plaque characteristics.

Pericoronary adipose tissue (PCAT) plays a significant role in the occurrence and progression of coronary artery disease (CAD). This study investigates the relationship between PCAT and CAD, focusing on the occurrence of the disease, the severity of vascular narrowing, and the characteristics of arterial plaques. We analyzed a cohort of 152 individuals with CAD and 55 individuals with non-coronary artery disease (N-CAD). Participants underwent both coronary computed tomography angiography (CCTA) and digital subtraction angiography (DSA). Utilizing United Imaging software for artificial intelligence delineation, we measured the fat attenuation index (FAI) and volume of PCAT in the left anterior descending (LAD), left circumflex (LCX), and right coronary arteries (RCA). Our findings demonstrate that while CCTA is effective in diagnosing CAD compared to DSA, its diagnostic power for individual coronary arteries remains limited. Further analysis revealed that the FAI of the RCA and the overall PCAT volume independently influenced CAD (OR: 1.057, 95% CI: 1.002 to 1.116; OR: 0.967, 95% CI: 0.936 to 0.999). FAI showed a significant independent effect on RCA stenosis (OR: 1.041, 95% CI: 1.003 to 1.081), while the fat volume of the LAD had a significant independent effect on LAD stenosis (OR: 0.884, 95% CI: 0.809 to 0.965). A higher FAI and a lower fat volume were significantly correlated with more severe vascular stenosis percentages in all three arteries (p < 0.05), except for the fat volume and stenosis of the LCX. Moreover, we found the significant differences in the fat volume of the LCX between different plaque types (H = 8.869, p = 0.012), with calcified plaques consistently exhibiting the lowest fat volume across all three arteries. Finally, the likelihood ratio test confirmed that incorporating the PCAT fat volume parameter of LAD significantly improved the diagnostic ability of CCTA for both CAD (p = 0.01543) and LAD stenosis (p = 0.001585). The quantification of PCAT has potential application value in the comprehensive assessment of CAD. It is recommended that cardiology and radiology departments consider incorporating PCAT into the assessment criteria for patients suspected of having CAD.

Generative adversarial networks for whispered to voiced speech conversion: a comparative study

AbstractGenerative Adversarial Networks (GANs) have demonstrated promising results as end-to-end models for whispered to voiced speech conversion. Leveraging non-autoregressive systems like GANs capable of performing conditional waveform generation eliminates the need for separate models to estimate voiced speech features, and leads to faster inference compared to autoregressive methods. This study aims to identify the optimal GAN architecture for the whispered to voiced speech conversion task by comparing six state-of-the-art models. Furthermore, we present a method for evaluating the preservation of speaker identity and local accent, using embeddings obtained from speaker- and language identification systems. Our experimental results show that building the speech conversion system based on the HiFi-GAN architecture yields the best objective evaluation scores, outperforming the baseline by $$\sim$$ ∼ 9% relative using frequency-weighted Signal-to-Noise Ratio and Log Likelihood Ratio, as well as by $$\sim$$ ∼ 29% relative using Root Mean Squared Error. In subjective tests, HiFi-GAN yielded a mean opinion score of 2.9, significantly outperforming the baseline with a score of 1.4. Furthermore, HiFi-GAN enhanced ASR performance and preserved speaker identity and accent, with correct language detection rates of up to $$\sim$$ ∼ 98%.

The association between triglyceride-glucose index and gallstones: NHANES 2017-2020.

It remains unclear whether the triglyceride-glucose (TyG) index has correlations with gallstones. This study aimed to investigate the association between TyG index and gallstones. Data was obtained from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). Participants who provided complete data about TyG index and gallstones were included in the analysis. Multivariable regression analysis and subgroup analysis were preformed to estimate the relationship between TyG index and gallstones. Restricted cubic splines (RSC) was employed to calculate the cut off value. The TyG index was independently associated with gallstones and demonstrates a clear positive correlation (OR = 1.10; 95% CI: 1.01-1.21; p = 0.033). The threshold value is 8.98, showing a positive correlation between TyG index and gallstones when the TyG index is less than 8.98 (Log likelihood ratio P < 0.001). Subgroup analysis indicates that the correlation between TyG and gallstones is mainly observed in individuals with obesity, females, younger individuals, and those with normal blood sugar levels, with these subgroups all acting as mediators between TyG and gallstones. Higher TyG index was linked to a higher chance of developing gallstones. Managing insulin resistance (IR) could help reduce the risk of gallstones since the TyG index is an indicator of IR.

Comparison of progression risk of monoclonal gammopathy of undetermined significance by method of detection

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic pre-malignant disorder. The current standard of care is not to screen for MGUS, so it is often incidentally diagnosed in the clinic. It is unknown whether the outcomes of screened versus clinically detected MGUS differ. We compared the progression risk between screened versus clinical MGUS cohorts and assessed whether the MGUS detection method impacted risk prediction of established clinical factors (score). We included 379 screened MGUS from the Olmsted County population based study and 1384 MGUS patients diagnosed during routine clinical evaluation at Mayo Clinic. Median follow-up time for the screened versus clinical cohort was 26.6 and 40.1 years, respectively. Accounting for death as a competing risk, the cumulative incidence of progression at 25 years was similar in the screened (11.1% [95% CI 8.3-14.8]) versus clinical (10.1% [95% CI 8.6-11.8%]) MGUS cohorts, even when stratified by sex, age, or the baseline MGUS risk score. Overall, 0.9 (95% CI 0.6-1.2) screened versus 1.0 (95% CI 0.9-1.2) clinically detected MGUS patients experienced disease progression for every 100 person years of follow-up. MGUS detection method did not modify the association between MGUS risk score and progression risk (pinteraction=0.217) and did not add to known risk factors for progression (likelihood ratio test, p=0.839). Here we show that progression risk among patients with screened versus clinically detected heavy-chain MGUS was similar. Future studies are needed to assess if tailored follow-up of screened MGUS patients affects clinical outcomes.

A method for determining potential parental contamination: linkage disequilibrium-based log-likelihood ratio analysis for IVF-PGT

BackgroundAt present, embryologists are attempting to use conventional in vitro fertilization (cIVF) as an alternative to intracytoplasmic sperm injection (ICSI) for preimplantation genetic testing (PGT). However, the potential parental contamination origin of sperm cells and cumulus cells is considered the main limiting factor in the inability of cIVF embryos to undergo PGT.MethodsIn this study, we established an IVF-PGTA assay for parental contamination tests with a contamination prediction model based on allele frequencies and linkage disequilibrium (LD) to compute the log-likelihood ratio (LLR) under competing ploidy hypotheses, and then verified its sensitivity and accuracy. Finally, comparisons of the effectiveness of SNP-based analysis and LLR-based IVF-PGTA among 40 cIVF embryos was performed, based on both statistical analysis of the parental contamination rate and chromosomal ploidy concordance rate between TE biopsy and ICM isolations.ResultsWith IVF-PGTA assay, biopsies with 10% maternal contamination could be detected accurately, and contamination caused by sperm cells could be eliminated completely. Utilizing LLR-based or single Nucleotide Polymorphism (SNP) -based analyses, our comprehensive examination of 40 clinically discarded fresh cIVF embryos revealed an absence of paternal contamination. Strikingly, the LLR-based analysis uniquely revealed a mere instance of 24% maternal contamination within the trophectoderm cell (TE) biopsy of 5* embryo. Furthermore, it was solely through this analysis that embryo (9-F) was identified as a triploid of paternal origin.ConclusionsIn this study, we developed a new bioinformatics analysis method for identifying parental contamination during IVF-PGT, especially for couples with nonmale factor infertility.

U-shaped association between dietary niacin intake and chronic kidney disease among US elderly: a nationwide cross-sectional study.

In addition to hypertension or diabetes, elderly people are also considered one of the high-risk groups for chronic kidney disease (CKD). Although niacin is recognized for its renal protective properties, the link between dietary niacin intake and CKD remains uncertain. This study investigated this relationship in the elderly. We included participants aged 60 and older from the National Health and Nutrition Examination Survey (NHANES) for the years 2003-2018. Dietary niacin intake was assessed through two non-consecutive 24-hour dietary recalls. CKD was diagnosed in individuals with a urine albumin-to-creatinine ratio exceeding 30 mg/g or an estimated glomerular filtration rate below 60 mL/min per 1.73 m^2. The study cohort comprised 4,649 participants, 1,632 of whom had CKD. Propensity score matching (PSM) was utilized to adjust for baseline differences between the groups. Our analysis, using smooth curve fitting and generalized additive models both before and after PSM, found a U-shaped curve depicting the relationship between dietary niacin intake and CKD risk, confirmed by a log-likelihood ratio test (P < 0.05). Threshold effect analysis (after PSM) indicated a reduced risk of CKD in older adults with a niacin intake below 38.83 mg per day [odds ratio (OR)= 0.99, 95% confidence interval (CI) 0.97-1.00]. In contrast, higher intake levels significantly increased the risk (OR = 1.03, 95% CI 1.00-1.06). Subgroup analysis indicated that these associations were consistent across different stratification variables (P for interaction > 0.05). Our findings suggested a U-shaped association between dietary niacin intake and CKD risk among older Americans. However, further prospective cohort studies are needed to confirm this finding.