Robust High-dimensional Tuning Free Multiple Testing

A stylized feature of high-dimensional data is that many variables have heavy tails, and robust statistical inference is critical for valid large-scale statistical inference. Yet, the existing developments such as Winsorization, Huberization and median of means require the bounded second moments and involve variable-dependent tuning parameters, which hamper their fidelity in applications to large-scale problems. To liberate these constraints, this paper revisits the celebrated Hodges-Lehmann (HL) estimator for estimating location parameters in both the one- and two-sample problems, from a non-asymptotic perspective. Our study develops Berry-Esseen inequality and Cram\'{e}r type moderate deviation for the HL estimator based on newly developed non-asymptotic Bahadur representation, and builds data-driven confidence intervals via a weighted bootstrap approach. These results allow us to extend the HL estimator to large-scale studies and propose \emph{tuning-free} and \emph{moment-free} high-dimensional inference procedures for testing global null and for large-scale multiple testing with false discovery proportion control. It is convincingly shown that the resulting tuning-free and moment-free methods control false discovery proportion at a prescribed level. The simulation studies lend further support to our developed theory.Comment: In this paper, we develop tuning-free and moment-free high dimensional inference procedures

Spectral Ranking Inferences based on General Multiway Comparisons

This paper studies the performance of the spectral method in the estimation and uncertainty quantification of the unobserved preference scores of compared entities in a very general and more realistic setup in which the comparison graph consists of hyper-edges of possible heterogeneous sizes and the number of comparisons can be as low as one for a given hyper-edge. Such a setting is pervasive in real applications, circumventing the need to specify the graph randomness and the restrictive homogeneous sampling assumption imposed in the commonly-used Bradley-Terry-Luce (BTL) or Plackett-Luce (PL) models. Furthermore, in the scenarios when the BTL or PL models are appropriate, we unravel the relationship between the spectral estimator and the Maximum Likelihood Estimator (MLE). We discover that a two-step spectral method, where we apply the optimal weighting estimated from the equal weighting vanilla spectral method, can achieve the same asymptotic efficiency as the MLE. Given the asymptotic distributions of the estimated preference scores, we also introduce a comprehensive framework to carry out both one-sample and two-sample ranking inferences, applicable to both fixed and random graph settings. It is noteworthy that it is the first time effective two-sample rank testing methods are proposed. Finally, we substantiate our findings via comprehensive numerical simulations and subsequently apply our developed methodologies to perform statistical inferences on statistics journals and movie rankings

Perioperative immunotherapy for stage II-III non-small cell lung cancer: a meta-analysis base on randomized controlled trials

BackgroundIn recent years, we have observed the pivotal role of immunotherapy in improving survival for patients with non-small cell lung cancer (NSCLC). However, the effectiveness of immunotherapy in the perioperative (neoadjuvant + adjuvant) treatment of resectable NSCLC remains uncertain. We conducted a comprehensive analysis of its antitumor efficacy and adverse effects (AEs) by pooling data from the KEYNOTE-671, NADIM II, and AEGEAN clinical trials.MethodsFor eligible studies, we searched seven databases. The randomized controlled trials (RCTs) pertaining to the comparative analysis of combination neoadjuvant platinum-based chemotherapy plus perioperative immunotherapy (PIO) versus perioperative placebo (PP) were included. Primary endpoints were overall survival (OS) and event-free survival (EFS). Secondary endpoints encompassed drug responses, AEs, and surgical outcomes.ResultsThree RCTs (KEYNOTE-671, NADIM II, and AEGEAN) were included in the final analysis. PIO group (neoadjuvant platinum-based chemotherapy plus perioperative immunotherapy) exhibited superior efficacy in OS (hazard ratio [HR]: 0.63 [0.49-0.81]), EFS (HR: 0.61 [0.52, 0.72]), objective response rate (risk ratio [RR]: 2.21 [1.91, 2.54]), pathological complete response (RR: 4.36 [3.04, 6.25]), major pathological response (RR: 2.79 [2.25, 3.46]), R0 resection rate (RR: 1.13 [1.00, 1.26]) and rate of adjuvant treatment (RR: 1.08 [1.01, 1.15]) compared with PP group (neoadjuvant platinum-based chemotherapy plus perioperative placebo). In the subgroup analysis, EFS tended to favor the PIO group in almost all subgroups. BMI (>25), T stage (IV), N stage (N1-N2) and pathological response (with pathological complete response) were favorable factors in the PIO group. In the safety assessment, the PIO group exhibited higher rates of serious AEs (28.96% vs. 23.51%) and AEs leading to treatment discontinuation (12.84% vs. 5.81%). Meanwhile, although total adverse events, grade 3-5 adverse events, and fatal adverse events tended to favor the PP group, the differences were not statistically significant.ConclusionPIO appears to be superior to PP for resectable stage II-III NSCLC, demonstrating enhanced survival and pathological responses. However, its elevated adverse event (AE) rate warrants careful consideration.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023487475

ELM of ELM-WD: An extremely low mass hot donor star discovered in LAMOST survey

The Extremely Low Mass White Dwarfs (ELM WDs) and pre-ELM WDs are helium core white dwarfs with mass $<\sim 0.3M_{\odot}$. They are formed in close binaries and have lost over half of their initial masses via Common Envelope (CE) ejection or stable Roche Lobe Over Flow (RLOF). Both evolution simulations and observations show that a lower mass limit for ELM WDs exists at $\approx0.14M_{\odot}$. Here we report the discovery of an extremely low mass ELM WD, ID70904216 in LAMOST survey, that may be lower than the ELM WD mass limit. Based on LAMOST and P200 spectroscopic observations, ID70904216 shows orbital period $P_{orb} =$ 0.219658 days and radial velocity semi-amplitude $K1=317.33km/s$, which gives the mass function of 0.73$M_{\odot}$, indicating the companion is a compact star. The low resolution spectra shows a F type star with $T_{\rm eff} \sim 7361K$ without emission features. The temperature is consistent with that derived from SED fitting($7440K$) and multi-color light curve solution($7400K$). The optical light curves, in ZTF g, r and i bands and Catalina V band, show ellipsoidal variability with amplitudes $\approx30\%$, suggesting that the visible companion is heavily tidal distorted. Combining with the distance from Gaia survey, the WD code modeling estimates that the mass of the visible star is $M1=0.08^{+0.06}_{-0.03}M_{\odot}$, and the mass of the invisible star is $M2=0.94^{+0.45}_{-0.10}M_{\odot}$. The radius of the visible donor is $R=0.29\pm0.01R_{\odot}$. The inclination angle is constrained between 60$^{\circ}$ and 90$^{\circ}$. The observations indicate the system is a pre-ELM WD + WD/NS binary system with an extremely low mass hot donor below the $0.14M_{\odot}$ theoretical limit.Comment: 16 pages, 10 figure

Effect of natural polymer materials on skin healing based on internal wound microenvironment: a review

The concept of wound microenvironment has been discussed for a long time. However, the mechanism of the internal microenvironment is relatively little studied. Here, we present a systematic discussion on the mechanism of natural polymer materials such as chitosan, cellulose, collagen and hyaluronic acid through their effects on the internal wound microenvironment and regulation of wound healing, in order to more comprehensively explain the concept of wound microenvironment and provide a reference for further innovative clinical for the preparation and application of wound healing agents

Chloride Ion Penetration Resistance of Reactive Powder Concrete with Mineral Admixtures

This study employed the rapid chloride ion penetration test and the salt spray erosion method to examine electric flux changes in mineral-admixed reactive powder concrete (RPC). Variations in the chloride ion content and diffusion coefficient under different erosion durations and depths were also investigated. The impact of mineral admixtures on the chloride penetration resistance was explored. Notably, after mixing fly ash (FA) and granulated blast furnace slag (GGBS), the electric flux values of RPC of each group were significantly reduced, and the electric flux values of RPC of the mixed group were significantly lower than those of the single mixed group and the reference group, in which the electric flux of FA10G10 was reduced by 85.2% compared to the control group; at the same erosion cycle and depth, the chloride ion content and diffusion coefficient of the mixed group were significantly lower than the control group. It shows that the reasonable compounding of mineral admixtures can better exert the "superposition effect", improve the compactness inside the matrix, and effectively reduce the chloride ion penetration rate. Considering comprehensively, the FA10G10 group has the best chloride penetration ion resistance effect

Identification of key genes and pathways in human clear cell renal cell carcinoma (ccRCC) by co-expression analysis

Human clear cell renal cell carcinoma (ccRCC) is the most common solid lesion within kidney, and its prognostic is influenced by the progression covering a complex network of gene interactions. In our study, we screened differential expressed genes, and constructed protein-protein interaction (PPI) network and a weighted gene co-expression network to identify key genes and pathways associated with the progression of ccRCC (n = 56). Functional and pathway enrichment analysis demonstrated that upregulated differentially expressed genes (DEGs) were significantly enriched in response to wounding, positive regulation of immune system process, leukocyte activation, immune response and cell activation. Downregulated DEGs were significantly enriched in oxidation reduction, monovalent inorganic cation transport, ion transport, excretion and anion transport. In the PPI network, top 10 hub genes were identified (TOP2A, MYC, ALB, CDK1, VEGFA, MMP9, PTPRC, CASR, EGFR and PTGS2). In co-expression network, 6 ccRCC-related modules were identified. They were associated with immune response, metabolic process, cell cycle regulation, angiogenesis and ion transport. In conclusion, our study illustrated the hub genes and pathways involved in the progress of ccRCC, and further molecular biological experiments are needed to confirm the function of the candidate biomarkers in human ccRCC

DNA oxidation after exercise: a systematic review and meta-analysis

Purpose: 8-Hydroxy-2′-deoxyguanosine (8-OHdG) is a byproduct of DNA oxidation resulting from free radical attacks. Paradoxically, treatment with 8-OHdG accelerates tissue healing. The aim of this study is to quantify the 8-OHdG response after a single session of exercise in both trained and untrained adults.Methods: A systematic review and meta-analysis of exercise intervention studies measuring changes in blood 8-OHdG following resistance exercise and aerobic exercise were conducted. The literature search included Web of Science, PubMed, BASE, and Scopus, with publications up to February 2023 included. Subgroup analysis of training status was also conducted.Results: Sixteen studies involving 431 participants met the eligibility criteria. Resistance exercise showed a medium effect on increasing circulating 8-OHdG levels (SMD = 0.66, p &lt; 0.001), which was similar for both trained and untrained participants. However, studies on aerobic exercise presented mixed results. For trained participants, a small effect of aerobic exercise on increasing circulating 8-OHdG levels was observed (SMD = 0.42; p &lt; 0.001). In contrast, for untrained participants, a large effect of decreasing circulating 8-OHdG levels was observed, mostly after long-duration aerobic exercise (SMD = −1.16; p &lt; 0.05). Similar to resistance exercise, high-intensity aerobic exercise (5–45 min, ≥75% VO2max) significantly increased circulating 8-OHdG levels, primarily in trained participants.Conclusion: Pooled results from the studies confirm an increase in circulating 8-OHdG levels after resistance exercise. However, further studies are needed to fully confirm the circulating 8-OHdG response to aerobic exercise. Increases in 8-OHdG after high-intensity aerobic exercise are observed only in trained individuals, implicating its role in training adaptation.Systematic Review Registration: [https://Systematicreview.gov/], identifier [CRD42022324180

CIRBP is a novel oncogene in human bladder cancer inducing expression of HIF-1 alpha

Cold-inducible RNA binding protein (CIRBP) has been reported to be associated with distinct tumorigenesis. In this study, we investigated the role of CIRBP in human bladder cancer (BCa), indicating that CIRBP is overexpressed in BCa tissues and cell lines to promote proliferation and migration. Moreover, CIRBP could induce expression of HIF-1 alpha via binding to the 3'-UTR of its mRNA to increase the mRNA stability in BCa cells. Furthermore, we demonstrated that PTGIS is a HIF-1 alpha targeted gene, a major regulator in hypoxic cancer progression by activating transcription of various oncogenes. Our results also suggested that overexpression of HIF-1 alpha may suppress the expression of PTGIS in BCa cells, by binding to HRE sequence at the promoter region of PTGIS. In addition, we found a strongly downregulation of PTGIS in BCa tissue and transcriptionally inhibited by HIF-1 alpha in BCa cells, which could be triggered by its DNA methylation. Further result suggested that knockdown of CIRBP could promote the expression of PTGIS, meanwhile knockdown of PTGIS could partially rescue CIRBP-deficiency induced inhibition of migration and proliferation in BCa cells. Taken together, our study indicated that CIRBP could be a novel oncogene in human bladder cancer inducing transcription of HIF-1 alpha, which could inhibit expression of methylated PTGIS