Estimation and inference for high-dimensional nonparametric additive instrumental-variables regression

The method of instrumental variables provides a fundamental and practical tool for causal inference in many empirical studies where unmeasured confounding between the treatments and the outcome is present. Modern data such as the genetical genomics data from these studies are often high-dimensional. The high-dimensional linear instrumental-variables regression has been considered in the literature due to its simplicity albeit a true nonlinear relationship may exist. We propose a more data-driven approach by considering the nonparametric additive models between the instruments and the treatments while keeping a linear model between the treatments and the outcome so that the coefficients therein can directly bear causal interpretation. We provide a two-stage framework for estimation and inference under this more general setup. The group lasso regularization is first employed to select optimal instruments from the high-dimensional additive models, and the outcome variable is then regressed on the fitted values from the additive models to identify and estimate important treatment effects. We provide non-asymptotic analysis of the estimation error of the proposed estimator. A debiasing procedure is further employed to yield valid inference. Extensive numerical experiments show that our method can rival or outperform existing approaches in the literature. We finally analyze the mouse obesity data and discuss new findings from our method.Comment: Submitted versio

Remineralization of demineralized dentin using a dual analog system.

ObjectiveImproved methods are needed to remineralize dentin caries in order to promote conservation of dentin tissue and minimize the surgical interventions that are currently required for clinical treatment. Here, we test the hypothesis that bulk substrates can be effectively mineralized via a dual analog system proposed by others, using a tripolyphosphate (TPP) "templating analog" and a poly(acrylic acid) (PAA) or poly(aspartic acid) (pAsp) "sequestration analog," the latter of which generates the polymer-induced liquid-precursor (PILP) mineralization process studied in our laboratory.Material & methodsDemineralized human dentin slices were remineralized with and without pre-treatment with TPP, using either PAA or pAsp as the PILP process-directing agent. A control experiment with no polymer present was used for comparison.ResultsNo mineralization was observed in any of the PAA groups. In both the pAsp and no polymer groups, TPP inhibited mineralization on the surfaces of the specimens but promoted mineralization within the interiors. Pre-treatment with TPP enhanced overall mineralization of the pAsp group. However, when analysed via TEM, regions with little mineral were still present.ConclusionPoly(acrylic acid) was unable to remineralize demineralized dentin slices under the conditions employed, even when pre-treated with TPP. However, pre-treatment with TPP enhanced overall mineralization of specimens that were PILP-remineralized using pAsp

Ultralong nitrogen/sulfur Co‐doped carbon nano‐hollow‐sphere chains with encapsulated cobalt nanoparticles for highly efficient oxygen electrocatalysis

The development of simple and effective strategies to prepare electrocatalysts, which possess unique and stable structures comprised of metal/nonmetallic atoms for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), is currently an urgent issue. Herein, an efficient bifunctional electrocatalyst featured by ultralong N, S-doped carbon nano-hollow-sphere chains about 1300 nm with encapsulated Co nanoparticles (Co-CNHSCs) is developed. The multifunctional catalytic properties of Co together with the heteroatom-induced charge redistribution (i.e., modulating the electronic structure of the active site) result in superior catalytic activities toward OER and ORR in alkaline media. The optimized catalyst Co-CNHSC-3 displays an outstanding electrocatalytic ability for ORR and OER, a high specific capacity of 1023.6 mAh gZn−1, and excellent reversibility after 80 h at 10 mA cm−2 in a Zn-air battery system. This work presents a new strategy for the design and synthesis of efficient multifunctional carbon-based catalysts for energy storage and conversion devices

A single micro-LED manipulation system based on micro-gripper

Micro-LEDs (μLEDs) have advantages in terms of brightness, power consumption, and response speed. In addition, they can also be used as micro-sensors implanted in the body via flexible electronic skin. One of the key techniques involved in the fabrication of μLED-based devices is transfer printing. Although numerous methods have been proposed for transfer printing, improving the yield of μLED arrays is still a formidable task. In this paper, we propose a novel method for improving the yield of μLED arrays transferred by the stamping method, using an innovative design of piezoelectrically driven asymmetric micro-gripper. Traditional grippers are too large to manipulate μLEDs, and therefore two micro-sized cantilevers are added at the gripper tips. A μLED manipulation system is constructed based on the micro-gripper together with a three-dimensional positioning system. Experimental results using this system show that it can be used successfully to manipulate μLED arrays

Prospective study of AI-assisted prediction of breast malignancies in physical health examinations: role of off-the-shelf AI software and comparison to radiologist performance

ObjectiveIn physical health examinations, breast sonography is a commonly used imaging method, but it can lead to repeated exams and unnecessary biopsy due to discrepancies among radiologists and health centers. This study explores the role of off-the-shelf artificial intelligence (AI) software in assisting radiologists to classify incidentally found breast masses in two health centers.MethodsFemale patients undergoing breast ultrasound examinations with incidentally discovered breast masses were categorized according to the 5th edition of the Breast Imaging Reporting and Data System (BI-RADS), with categories 3 to 5 included in this study. The examinations were conducted at two municipal health centers from May 2021 to May 2023.The final pathological results from surgical resection or biopsy served as the gold standard for comparison. Ultrasonographic images were obtained in longitudinal and transverse sections, and two junior radiologists and one senior radiologist independently assessed the images without knowing the pathological findings. The BI-RADS classification was adjusted following AI assistance, and diagnostic performance was compared using receiver operating characteristic curves.ResultsA total of 196 patients with 202 breast masses were included in the study, with pathological results confirming 107 benign and 95 malignant masses. The receiver operating characteristic curve showed that experienced breast radiologists had higher diagnostic performance in BI-RADS classification than junior radiologists, similar to AI classification (AUC = 0.936, 0.806, 0.896, and 0.950, p < 0.05). The AI software improved the accuracy, sensitivity, and negative predictive value of the adjusted BI-RADS classification for the junior radiologists’ group (p< 0.05), while no difference was observed in the senior radiologist group. Furthermore, AI increased the negative predictive value for BI-RADS 4a masses and the positive predictive value for 4b masses among radiologists (p < 0.05). AI enhances the sensitivity of invasive breast cancer detection more effectively than ductal carcinoma in situ and rare subtypes of breast cancer.ConclusionsThe AI software enhances diagnostic efficiency for breast masses, reducing the performance gap between junior and senior radiologists, particularly for BI-RADS 4a and 4b masses. This improvement reduces unnecessary repeat examinations and biopsies, optimizing medical resource utilization and enhancing overall diagnostic effectiveness

Angiotensin II Type I Receptor Agonistic Autoantibody Induces Podocyte Injury via Activation of the TRPC6- Calcium/Calcineurin Pathway in Pre-Eclampsia

Background/Aims: Angiotensin II type I receptor agonistic autoantibody (AT1-AA) is closely related to pre-eclampsia, which is characterized by proteinuria and hypertension. AT1-AA has been shown to enhance the effect of AngII in pre-eclampsia, such as production of endothelin-1, activation of ROS, and vasoconstriction, which are considered to be associated with hypertension; however, whether or not AT1-AA participates in podocyte damage leading to the generation of proteinuria has not been reported. In this study we investigated the role of pre-eclamptic serum AT1-AA on podocytes and the mechanism underlying the generation of proteinuria. Methods: The levels of AT1-AA isolated from pre-eclamptic sera were determined by an enzyme-linked immunosorbent assay. Human podocytes were cultured in vitro and treated with various concentrations of AT1-AA. Whether or not an ERK1/2 inhibitor and TRPC6 siRNA inhibit the effect of AT1-AA on podocytes was determined. Western blot was used to detect the expression of podocyte-specific proteins (nephrin, synaptopodin, and podocin) and the phosphorylation of ERK1/2 and TRPC6. The arrangement of F-actin was observed by immunofluorescence. A Calcineurin Cellular Activity Assay Kit was used to detect calcineurin activity. Changes in the intracellular Ca2+ concentration was determined by confocal laser. Results: AT1-AA induced a decrease in podocyte-specific protein expression and calcineurin activity and increased expression of p-ERK1/2 and TRPC6 protein and the intracellular Ca2+ concentration. Immunofluorescence revealed rearrangement of F-actin. PD98059, an inhibitor of ERK1/2, and TRPC6 siRNA attenuated the decreased expression of podocyte-specific proteins and decreased intracellular Ca2+ concentration. The expression of TRPC6 was reduced following the addition of ERK1/2 inhibitor. Conclusion: AT1-AA induced podocyte damage in a dose-dependent manner. The underlying mechanism might involve activation of the TRPC6 –calcium/calcineurin pathway. This study provides new details regarding podocyte injury and the mechanism underlying the generation of proteinuria in pre-eclampsia