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Summary: Binary data subject to one type of misclassification exist in various fields. It is collected in a double‐sampling scheme that includes a gold standard test and a fallible test. The main parameter of interest for this type of data is the positive probability p$$ p $$ of the gold standard test. Existing intervals are unreliable because the given nominal level 1−α$$ 1-\alpha $$ is not achieved. In this paper, we construct an exact interval by inverting the E+M score tests and improve it by the general h$$ h $$‐function method. We find that the total length of the improved interval is shorter than the exact intervals that are also the improved intervals when we apply the h$$ h $$‐function to several existing approximate intervals, including the score and Bayesian intervals. Therefore, it is recommended for practice. We are also interested in two other parameters: p∗$$ {p}^{\ast } $$—the difference between the two positive rates for the fallible and gold standard tests—and ξ$$ \xi $$—the false positive rate for the fallible test. To the best of our knowledge, the research on these two parameters is limited. For p∗$$ {p}^{\ast } $$, we find that any interval for p$$ p $$ can be converted to an interval for p∗$$ {p}^{\ast } $$. So, the interval converted from the aforementioned recommended interval for p$$ p $$ is recommended for inferring p∗$$ {p}^{\ast } $$. For ξ$$ \xi $$, the improved interval by the h$$ h $$‐function method over the E+M score interval is derived. We use an example to illustrate how the intervals are computed and provide a real data analysis. [ABSTRACT FROM AUTHOR]

The 2×2$$ 2\times 2 $$ table with a structural zero represents a common scenario in clinical trials and epidemiology, characterized by a specific empty cell. In such cases, the risk ratio serves as a vital parameter for statistical inference. However, existing confidence intervals, such as those constructed through the score test and Bayesian methods, fail to achieve the prescribed nominal level. Our focus is on numerically constructing exact confidence intervals for the risk ratio. We achieve this by optimally combining the modified inferential model method and the h$$ h $$‐function method. The resulting interval is then compared with intervals generated by four existing methods: the score method, the exact score method, the Bayesian tailed‐based method and the inferential model method. This comparison is conducted based on the infimum coverage probability, average interval length and non‐coverage probability criteria. Remarkably, our proposed interval outperforms other exact intervals, being notably shorter. To illustrate the effectiveness of our approach, we discuss two examples in detail. [ABSTRACT FROM AUTHOR]

The weighted sum of binomial proportions and the interaction effect are two important cases of the linear combination of binomial proportions. Existing confidence intervals for these two parameters are approximate. We apply the h -function method to a given approximate interval and obtain an exact interval. The process is repeated multiple times until the final-improved interval (exact) cannot be shortened. In particular, for the weighted sum of two proportions, we derive two final-improved intervals based on the (approximate) adjusted score and fiducial intervals. After comparing several currently used intervals, we recommend these two final-improved intervals for practice. For the weighted sum of three proportions and the interaction effect, the final-improved interval based on the adjusted score interval should be used. Three real datasets are used to detail how the approximate intervals are improved. [ABSTRACT FROM AUTHOR]

The relative risk and odds ratio are widely used in many fields, including biomedical research, to compare two treatments. Extensive research has been done to infer the two parameters through approximate or exact confidence intervals. However, these intervals may be liberal or conservative. A natural question is whether the intervals can be further improved in maintaining the correct confidence coefficient of an approximate interval or shortening an exact but conservative interval. In this article, when two independent binomials are observed we offer an effort to improve any of the existing intervals by applying the h$$ h $$‐function method. In particular, if the given interval is approximate, then the improved interval is exact; if the given interval is exact, then the improved interval is a subset of the given interval. This method is also applied multiple times to the improved intervals until the final resultant interval cannot be shortened any further. To demonstrate the effectiveness of the method, we use three real datasets to illustrate in detail how several good intervals in practice are improved. Two exact intervals are then recommended for estimating each of the two parameters in different scenarios. [ABSTRACT FROM AUTHOR]

Mechanical interactions between cells have been shown to play critical roles in regulating cell signaling and communications. However, the precise measurement of intercellular forces is still quite challenging, especially considering the complex environment at cell–cell junctions. In this study, we report a fluorescence lifetime‐based approach to image and quantify intercellular molecular tensions. Using this method, tensile forces among multiple ligand–receptor pairs can be measured simultaneously. We first validated our approach and developed lifetime measurement‐based DNA tension probes to image E‐cadherin‐mediated tension on epithelial cells. These probes were then further applied to quantify the correlations between E‐cadherin and N‐cadherin tensions during an epithelial–mesenchymal transition process. The modular design of these probes can potentially be used to study the mechanical features of various physiological and pathological processes. [ABSTRACT FROM AUTHOR]

M-estimation is a widely used technique for robust statistical inference. In this paper, we study model selection and model averaging for M-estimation to simultaneously improve the coverage probability of confidence intervals of the parameters of interest and reduce the impact of heavy-tailed errors or outliers in the response. Under general conditions, we develop robust versions of the focused information criterion and a frequentist model average estimator for M-estimation, and we examine their theoretical properties. In addition, we carry out extensive simulation studies as well as two real examples to assess the performance of our new procedure, and find that the proposed method produces satisfactory results. [ABSTRACT FROM AUTHOR]

Recently, researchers have been attempting to control pluripotent stem cell fate or generate self-organized tissues from stem cells. Advances in bioengineering enable generation of organotypic structures, which capture the cellular components, spatial cell organization and even some functions of tissues or organs in development. However, only a few engineering tools have been utilized to regulate the formation and organization of spatially complex tissues derived from stem cells. Here, we provide a review of recent progress in the culture of organotypic structures in vitro, focusing on how microengineering approaches including geometric confinement, extracellular matrix (ECM) property modulation, spatially controlled biochemical factors, and external forces, can be utilized to generate organotypic structures. Moreover, we will discuss potential technologies that can be applied to further control both soluble and insoluble factors spatiotemporally in vitro. In summary, advanced engineered approaches have a great promise in generating miniaturized tissues and organs in a reproducible fashion, facilitating the cellular and molecular understanding of embryogenesis and morphogenesis processes. [ABSTRACT FROM AUTHOR]

In this article, we study model selection and model averaging in quantile regression. Under general conditions, we develop a focused information criterion and a frequentist model average estimator for the parameters in quantile regression model, and examine their theoretical properties. The new procedures provide a robust alternative to the least squares method or likelihood method, and a major advantage of the proposed procedures is that when the variance of random error is infinite, the proposed procedure works beautifully while the least squares method breaks down. A simulation study and a real data example are presented to show that the proposed method performs well with a finite sample and is easy to use in practice. [ABSTRACT FROM AUTHOR]

In this paper, we discuss the model checking problem for a partial linear model when some covariates are missing at random. A weighted model-adjustment method is applied to estimate the regression coefficients and the nonparametric function for the null hypothetical partial linear model. A testing procedure based on a residual-marked empirical process is developed to check the adequacy of the partial linear model. It is shown that the proposed test is consistent and can detect the local alternatives converging to the null hypothetical model at the rate n −1/2. Since the asymptotic null distribution of the testing statistics is case-dependent, an adjusted wild bootstrap method is used to decide the critical value, which is proved to be consistent. A simulation study and a real data analysis are conducted to show that the proposed procedure works well. [ABSTRACT FROM AUTHOR]

Spatial cluster analyses of health events are useful for enabling targeted interventions. Spatial scan statistic is the stateof- the-art method for this kind of analysis and the Poisson Generalized Linear Model (GLM) approach to the spatial scan statistic can be used for count data for spatial cluster detection with covariate adjustment. However, its use for modelling is limited due to data over-dispersion. A Generalized Linear Mixed Model (GLMM) has recently been proposed for modelling this kind of over-dispersion by incorporating random effects to model area-specific intrinsic variation not explained by other covariates in the model. However, these random effects may exhibit a geographical correlation, which may lead to a potential spatial cluster being undetected. To handle the over-dispersion in the count data, this study aimed to evaluate the performance of a negative binomial- GLM in spatial scan statistic on real-world data of low birth weights in Khyber-Pakhtunkhwa Province, Pakistan, 2019. The results were compared with the Poisson-GLM and GLMM, showing that the negative binomial-GLM is an ideal choice for spatial scan statistic in the presence of over-dispersed data. With a covariate (maternal anaemia) adjustment, the negative binomial-GLMbased spatial scan statistic detected one significant cluster covering Dir lower district. Without the covariate adjustment, it detected two clusters, each covering one district. The district of Peshawar was seen as the most likely cluster and Battagram as the secondary cluster. However, none of the clusters were detected by GLMM spatial scan statistic, which might be due to the spatial correlation of the random effects in GLMM.

Cells continuously experience and respond to different physical forces that are used to regulate their physiology and functions. Our ability to measure these mechanical cues is essential for understanding the bases of various mechanosensing and mechanotransduction processes. While multiple strategies have been developed to study mechanical forces within two-dimensional (2D) cell culture monolayers, the force measurement at cell-cell junctions in real three-dimensional (3D) cell models is still pretty rare. Considering that in real biological systems, cells are exposed to forces from 3D directions, measuring these molecular forces in their native environment is thus highly critical for the better understanding of different development and disease processes. We have recently developed a type of DNA-based molecular probe for measuring intercellular tensile forces in 2D cell models. Herein, we will report the further development and first-time usage of these molecular tension probes to visualize and detect mechanical forces within 3D spheroids and embryoid bodies (EBs). These probes can spontaneously anchor onto live cell membranes via the attached lipid moieties. By varying the concentrations of these DNA probes and their incubation time, we have first characterized the kinetics and efficiency of probe penetration and loading onto tumor spheroids and stem cell EBs of different sizes. After optimization, we have further imaged and measured E-cadherin-mediated forces in these 3D spheroids and EBs for the first time. Our results indicated that these DNA-based molecular tension probes can be used to study the spatiotemporal distributions of target mechanotransduction processes. These powerful imaging tools may be potentially applied to fill the gap between ongoing research of biomechanics in 2D systems and that in real 3D cell complexes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tian, Yang, Jiang, Bhattacharyya, Xie, Ali, Sun and You.)

A monolayer of highly motile cells can establish long-range orientational order, which can be explained by hydrodynamic theory of active gels and fluids. However, it is less clear how cell shape changes and rearrangement are governed when the monolayer is in mechanical equilibrium states when cell motility diminishes. In this work, we report that rat embryonic fibroblasts (REF), when confined in circular mesoscale patterns on rigid substrates, can transition from the spindle shapes to more compact morphologies. Cells align radially only at the pattern boundary when they are in the mechanical equilibrium. This radial alignment disappears when cell contractility or cell-cell adhesion is reduced. Unlike monolayers of spindle-like cells such as NIH-3T3 fibroblasts with minimal intercellular interactions or epithelial cells like Madin-Darby canine kidney (MDCK) with strong cortical actin network, confined REF monolayers present an actin gradient with isotropic meshwork, suggesting the existence of a stiffness gradient. In addition, the REF cells tend to condense on soft substrates, a collective cell behavior we refer to as the 'condensation tendency'. This condensation tendency, together with geometrical confinement, induces tensile prestretch (i.e. an isotropic stretch that causes tissue to contract when released) to the confined monolayer. By developing a Voronoi-cell model, we demonstrate that the combined global tissue prestretch and cell stiffness differential between the inner and boundary cells can sufficiently define the cell radial alignment at the pattern boundary., Competing Interests: TX, SS, NO, LB, MW, YS No competing interests declared, (© 2021, Xie et al.)

Mechanical interactions between cells have been shown to play critical roles in regulating cell signaling and communications. However, the precise measurement of intercellular forces is still quite challenging, especially considering the complex environment at cell-cell junctions. In this study, we report a fluorescence lifetime-based approach to image and quantify intercellular molecular tensions. Using this method, tensile forces among multiple ligand-receptor pairs can be measured simultaneously. We first validated our approach and developed lifetime measurement-based DNA tension probes to image E-cadherin-mediated tension on epithelial cells. These probes were then further applied to quantify the correlations between E-cadherin and N-cadherin tensions during an epithelial-mesenchymal transition process. The modular design of these probes can potentially be used to study the mechanical features of various physiological and pathological processes., (© 2021 Wiley-VCH GmbH.)

Recent findings suggest that mechanical forces strongly influence wound repair and fibrosis across multiple organ systems. Traction force is vital to the characterization of cellular responses to mechanical stimuli. Using hydrogel-based traction force microscopy, a FRET-based tension sensor, or microengineered cantilevers, the magnitude of traction forces can be measured. Here, we describe a traction force measurement methodology using a dense array of elastomeric microposts. This platform can be used to measure the traction force of a single cell or a colony of cells with or without geometric confinement.