Pointwise convergence of some continuous-time polynomial ergodic averages

In this paper, we study the pointwise convergence of some continuous-time polynomial ergodic averages. Our method is based on the topological models of measurable flows. One of main results of the paper is as follow. Let $(X,\mathcal{X},\mu, (T^{t})_{t\in \mathbb{R}})$ and $(X,\mathcal{X},\mu, (S^{t})_{t\in \mathbb{R}})$ be two measurable flows, $a\in \mathbb{Q}$, and $Q\in \mathbb{R}[t]$ with $\text{deg}\ Q\ge 2$. Then for any $f_1, f_2, g\in L^{\infty}(\mu)$, the limit \begin{equation*} \lim\limits_{M\to\infty}\frac{1}{M}\int_{0}^{M}f_1(T^{t}x)f_2(T^{at}x)g(S^{Q(t)}x)dt \end{equation*} exists for $\mu$-a.e. $x\in X$.Comment: 46 page

T-Helper Cell Cytokine Expression Profiling in Rheumatoid Arthritis Patients by Flow Cytometric Bead Array Analysis

Background: Rheumatoid arthritis (RA) is the most common chronic autoimmune disease affecting multiple joints. A chronic imbalance in cytokine production by T-helper (Th) cells is likely a key factor in RA development. Our objective was to profile the serum cytokine expression from three key Th cell types (Th1, Th2, and Th17) in RA patients in order to correlate the resulting cytokine expression profiles with RA activity. Material and Methods: From a population of RA patients (n = 71) and healthy controls (n = 18), the serum concentrations of seven cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and TNF-α) were analyzed by flow cytometric bead array (CBA). Results: The serum concentrations of all seven cytokines were significantly higher in RA patients than in healthy controls. Interestingly, the serum concentration profiles varied with the 28-joint Disease Activity Score (DAS28), a measure of RA activity derived from joint indices (tender joints and swollen joints count) and the erythrocyte sedimentation rate. In the high RA activity group (DAS28 > 5.1), all seven cytokines were significantly elevated. In the moderate RA activity group (DAS28 between 3.2 and 5.1), only IL-2, IL-6, IL-10, and IL-17A were significantly increased. In the low RA activity group (DAS28 ≤ 3.2), only IL-2, IL-4, and TNF-α were significantly elevated. Conclusions: The Th cell-derived cytokine expression profile significantly changes across varying levels of RA activity. Th1/Th17 cell-derived TNF-α and Th2 cell-derived IL-4 appear to play more important roles in the early stages of RA, while all seven cytokines derived from Th1, Th2, and Th17 cells (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and TNF-α) are overtly involved in the advanced stages of RA

Safety and efficacy of ETC-1002 in hypercholesterolaemic patients: a meta-analysis of randomised controlled trials

Background: Due to the myopathic adverse events of statins, safer alternatives are being studied. Bempedoic acid (ETC-1002) is a novel low-density lipoprotein cholesterol (LDL-C)-lowering agent, currently under trial in hypercholesterolaemic patients. Aims: To investigate the tolerability and efficacy of ETC-1002 in hypercholesterolaemic patients through a systematic review of published randomised controlled trials (RCTs). Methods: Five databases were searched for RCTs that investigated the safety and efficacy of ETC-1002 in hypercholesterol­aemic patients. The retrieved search results were screened, and then data were extracted and analysed (as mean difference [MD] or odds ratio [OR]) using the RevMan software. Results: Five RCTs (625 hypercholesterolaemic patients) were identified. ETC-1002 was superior to placebo in terms of percent­age changes from baseline in serum levels of LDL-C (MD –26.58, 95% confidence interval [CI] –35.50 to –17.66, p < 0.0001), non–high-density lipoprotein cholesterol (MD –21.54, 95% CI –28.48 to –14.6, p < 0.00001), and apolipoprotein-B (MD –15.97, 95% CI –19.36 to –12.57, p < 0.0001). When compared to ezetimibe, ETC-1002 was superior in reducing LDL-C (–30.1 ± 1.3 vs. –21.1 ± 1.3). Regarding safety, ETC-1002 did not increase the risk of all adverse events (OR 0.58, 95% CI 0.37–0.91, p = 0.02) and arthralgia (OR 0.32, 95% CI 0.13–0.81, p = 0.02) compared to placebo. All other adverse events including myalgia, headache, and urinary tract infections were similar between ETC-1002 and placebo groups. The evidence certainty in the assessed outcomes was moderate to high except for lipoprotein(a), free fatty acids, and very low-density lipoprotein particle number (very low certainty). Conclusions: ETC-1002 is a safe and effective lipid-lowering agent and may be a suitable alternative in statin-intolerant pa­tients. Well-designed studies are needed to explore the long-term safety and efficacy of ETC-1002 in these patients

Comparative Diagnostic Accuracy of Contrast-Enhanced Ultrasound and Shear Wave Elastography in Differentiating Benign and Malignant Lesions: A Network Meta-Analysis

Background: We performed a network meta-analysis to compare the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) and shear wave elastography (SWE) in differentiating benign and malignant lesions in different body sites.Methods: A computerized literature search of Medline, Embase, SCOPUS, and Web of Science was performed using relevant keywords. Following data extraction, we calculated sensitivity, specificity, positive likelihood ratio (LR), negative LR, and diagnostic odds ratio (DOR) for CEUS, and SWE compared to histopathology as a reference standard. Statistical analyses were conducted by MetaDiSc (version 1.4) and R software (version 3.4.3).Results: One hundred and fourteen studies (15,926 patients) were pooled in the final analyses. Network meta-analysis showed that CEUS had significantly higher DOR than SWE (DOR = 27.14, 95%CI [2.30, 51.97]) in breast cancer detection. However, there were no significant differences between CEUS and SWE in hepatic (DOR = −6.67, 95%CI [−15.08, 1.74]) and thyroid cancer detection (DOR = 3.79, 95%CI [−3.10, 10.68]). Interestingly, ranking analysis showed that CEUS achieved higher DOR in detecting breast and thyroid cancer, while SWE achieved higher DOR in detecting hepatic cancer. The overall DOR for CEUS in detecting renal cancer was 53.44, 95%CI [29.89, 95.56] with an AUROC of 0.95, while the overall DOR for SWE in detecting prostate cancer was 25.35, 95%CI [7.15, 89.89] with an AUROC of 0.89.Conclusion: Both diagnostic tests showed relatively high sensitivity and specificity in detecting malignant tumors in different organs. Network meta-analysis showed that CEUS had higher diagnostic accuracy than SWE in detecting breast and thyroid cancer, while SWE had higher accuracy in detecting hepatic cancer. However, the results were not statistically significant in hepatic and thyroid malignancies. Further head-to-head comparisons are needed to confirm the optimal imaging technique to differentiate each cancer type

High-throughput, combinatorial synthesis of multimetallic nanoclusters

Multimetallic nanoclusters (MMNCs) offer unique and tailorable surface chemistries that hold great potential for numerous catalytic applications. The efficient exploration of this vast chemical space necessitates an accelerated discovery pipeline that supersedes traditional “trial-and-error” experimentation while guaranteeing uniform microstructures despite compositional complexity. Herein, we report the high-throughput synthesis of an extensive series of ultrafine and homogeneous alloy MMNCs, achieved by 1) a flexible compositional design by formulation in the precursor solution phase and 2) the ultrafast synthesis of alloy MMNCs using thermal shock heating (i.e., ∼1,650 K, ∼500 ms). This approach is remarkably facile and easily accessible compared to conventional vapor-phase deposition, and the particle size and structural uniformity enable comparative studies across compositionally different MMNCs. Rapid electrochemical screening is demonstrated by using a scanning droplet cell, enabling us to discover two promising electrocatalysts, which we subsequently validated using a rotating disk setup. This demonstrated high-throughput material discovery pipeline presents a paradigm for facile and accelerated exploration of MMNCs for a broad range of applications

Urine output for predicting in-hospital mortality of intensive care patients with cardiogenic shock

Background: The role of urine output (UO) in the first 24 h of admission in the clinical management of cardiogenic shock (CS) patients has not been elucidated. Methods: This study retrospectively analyzed intensive care CS patients in the MIMIC-IV database. Binomial logistic regression analysis was conducted to evaluate whether UO was an independent risk factor for in-hospital mortality in CS patients. The performance of UO in predicting mortality was evaluated by the receiver operating characteristic (ROC) curve and compared with the Oxford Acute Severity of Illness Score (OASIS). The clinical net benefit of UO in predicting mortality was determined using the decision curve analysis (DCA). Survival analysis was performed with Kaplan-Meier curves. Results: After adjusting for confounding factors including diuretic use and acute kidney injury (AKI), UO remained an independent risk factor for in-hospital mortality in CS patients. The areas under the ROC curves (AUCs) of UO for predicting in-hospital mortality were 0.712 (UO, ml/day) and 0.701 (UO, ml/kg/h), which were comparable to OASIS (AUC = 0.695). In terms of clinical net benefit, UO was comparable to OASIS, with different degrees of benefit at different threshold probabilities. Survival analysis showed that the risk of in-hospital death in the low-UO (≤857 ml/day) group was 3.0143 times that of the high-UO (>857 ml/day) group. Conclusions: UO in the first 24 h of admission is an independent risk factor for in-hospital mortality in intensive care CS patients and has moderate predictive value in predicting in-hospital mortality