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Longitudinal evaluation of circulating tumor DNA in patients undergoing neoadjuvant therapy for early breast cancer using a tumor-informed assay

Simulation and experimental verification of the precision finishing method for optical free-form surface segmentation

Optical free-form surfaces are often used to manufacture optical components such as lenses and mirrors, and free zone surface optical components are widely used in aerospace optics. To address the issues of low processing quality and overall efficiency in the machining of aluminum alloy free-form surfaces, an efficient numerical control machining method based on surface segmentation has been proposed. The segmentation of free-form surfaces is divided into two stages: the recognition of surface partitions and the determination of surface boundaries. Initially, the free-form surface is roughly classified into three types of regions: convex (planar), concave, and saddle-shaped, based on its curvature characteristics. The surface is then further segmented using the fuzzy c-means clustering algorithm. Subsequently, the Voronoi diagram algorithm is employed to construct the boundaries of the free-form surface ultimately. In a UG simulation, the segmentation machining method was compared with the conventional overall machining method, demonstrating a reduction in the machining path by 12.18% and machining time by 13.92%. Finally, experiments revealed a 12.28% reduction in machining path length and a 12.56% reduction in machining time using the segmentation machining method. This verifies the practicality of the free-form surface segmentation approach and proves that it can effectively enhance machining efficiency and quality.

Heparan sulfate regulates myofibroblast heterogeneity and function to mediate niche homeostasis during alveolar morphogenesis

Electron paramagnetic resonance spectroscopy for analysis of free radicals in zebrafish

Electron paramagnetic resonance (EPR) is an excellent choice for detecting free radicals in biological samples. Biologically relevant radicals are extremely short-lived and cannot be detected directly, emphasizing the need for an appropriate compound to generate stable adducts that can be measured by EPR. Spin trapping with nitrone compounds like 5,5-dimethyl-1-pyrroline N-oxide (DMPO) is a method commonly employed for detecting free radicals. However, due to the instability of nitrone radical adducts, using the cell-permeable 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl pyrrolidine (CMH) appears to be a more effective approach within biological tissues. Here, we compare the use of DMPO and CMH to detect the most abundant reactive oxygen species radical, superoxide (O2⋅-), in zebrafish and present an optimized protocol for performing EPR with a CMH spin probe in both zebrafish hearts and larvae. Together, our data suggest that EPR using the CMH probe is a reliable method to detect O2⋅- in zebrafish pathologies linked to oxidative stress, such as cardiovascular diseases.

Targeted delivery of TGF-β mRNA to murine lung parenchyma using one-component ionizable amphiphilic Janus Dendrimers

Spatial relationship between carbon emissions and ecosystem service value based on land use: A case study of the Yellow River Basin

Land use changes significantly impact both carbon emissions and ecosystem service value (ESV). However, few studies have been conducted on the spatial relationship between land use carbon emissions (LUCE) and ESV. Thus, focused on the Yellow River Basin (YRB), this study independently calculates carbon emissions from land use change (LUCE) and ecosystem service values (ESV) in the region. Utilizing spatial autocorrelation methods, we analyze the spatiotemporal pattern of LUCE and ESV and subsequently apply the bivariate spatial autocorrelation method to explore their spatial relationship. The results prove that: (1) The YRB’s LUCE has continuously increased, with construction land acting as the dominant carbon source and woodland acting as the main carbon sink. The LUCE in the YRB had a positive spatial autocorrelation. (2) The YRB’s ESV increased. Spatially, the ESV in the YRB showed a positive autocorrelation. (3) Both LUCE and ESV exhibited negative spatial autocorrelation, with predominant patterns of bivariate localized spatial autocorrelation identified as High-Low agglomeration (H-L) and Low-High agglomeration (L-H). Cities with the L-H pattern were primarily located in Qinghai Province and Inner Mongolia. In contrast, cities with the H-L pattern were mainly observed in the western section of Shandong and the northeastern region of Henan. The study revealed the negative impact of increased carbon emissions from land use on the value of ecosystem services, providing assistance in the development of relevant environmental policies and promoting sustainable development in the YRB.

Phosphorylation of FOXN3 by NEK6 promotes pulmonary fibrosis through Smad signaling

Impact of geopolitical risks and innovation on global defense stock return

This study conducts a comparative analysis of how geopolitical risk (GPR) and innovation impact stock returns in the defense industry based on data from 75 defense companies across 17 countries and 4 continents. With daily datasets spanning from January 1, 2014 to March 29, 2024, wavelet coherence and wavelet phase differences were used to conduct the analysis. The results revealed that innovation had a greater and more pronounced impact during the entire analysis period compared with the influence of GPR events. GPRs exerted an uneven and heterogeneous impact on global defense stocks and had a concentrated impact during events that generated uncertainty. Overall, we found significant time-varying dependence across a large number of companies at different time frequencies. The COVID-19 pandemic did not have a major impact on companies in the defense industry. Further, GPR events led to increased volatility during the Russia–Ukraine war, leading to increased uncertainty. In addition to the dominant role they play in the world defense market, US companies served as a robust hedge, especially from 2021 to 2022. Defense companies in the UK are more sensitive to both GPR events and innovation, followed by companies in Germany and France. Comparative analysis of the scalograms of China reveals a greater influence of innovation compared with GPR events. Thus, diversification opportunities have been extended from the defense industry in China, offering investors a promising way to capitalize on refuge opportunities during periods of disruption. To mitigate the global rearmament trend, we suggest alternative investment opportunities for different time horizons.

The physical roles of different posterior tissues in zebrafish axis elongation

Abstract Shaping embryonic tissues requires spatiotemporal changes in genetic and signaling activity as well as in tissue mechanics. Studies linking specific molecular perturbations to changes in the tissue physical state remain sparse. Here we study how specific genetic perturbations affecting different posterior tissues during zebrafish body axis elongation change their physical state, the resulting large-scale tissue flows, and posterior elongation. Using a custom analysis software to reveal spatiotemporal variations in tissue fluidity, we show that dorsal tissues are most fluid at the posterior end, rigidify anterior of this region, and become more fluid again yet further anteriorly. In the absence of notochord (noto mutants) or when the presomitic mesoderm is substantially reduced (tbx16 mutants), dorsal tissues elongate normally. Perturbations of posterior-directed morphogenetic flows in dorsal tissues (vangl2 mutants) strongly affect the speed of elongation, highlighting the essential role of dorsal cell flows in delivering the necessary material to elongate the axis.

qlifetable: An R package for constructing quarterly life tables

The big data revolution has greatly expanded the availability of microdata on vital statistics, providing researchers with unprecedented access to large and complex datasets on birth, death, migration, and population, sometimes even including exact dates of demographic events. This has led to the development of a novel methodology for estimating sub-annual life tables that offers new opportunities for the insurance industry, also potentially impacting on the management of pension funds and social security systems. This paper introduces the qlifetable package, an R implementation of this methodology. It begins by detailing how basic summary statistics are computed by the package from detailed individual records, including the length of age years, which should be observed as relative (subjective) to ensure congruency between age and calendar time when measuring exposure times and exact ages of individuals at events. This is a new result that compels the observation of time as relative in the disciplines of actuarial science, risk management and demography. Afterwards, the paper demonstrates the use of the package, which integrates a set of functions for estimating crude quarterly (and annual) death rates, calculating seasonal-ageing indexes (SAIs) and building quarterly life tables for a (general or insured) population by exploiting either microdata of dates of births and events or summary statistics.

Comparative studies of 2168 plasma proteins measured by two affinity-based platforms in 4000 Chinese adults

Abstract Proteomics offers unique insights into human biology and drug development, but few studies have directly compared the utility of different proteomics platforms. We measured plasma levels of 2168 proteins in 3976 Chinese adults using both Olink Explore and SomaScan platforms. The correlation of protein levels between platforms was modest (median rho = 0.29), with protein abundance and data quality parameters being key factors influencing correlation. For 1694 proteins with one-to-one matched reagents, 765 Olink and 513 SomaScan proteins had cis-pQTLs, including 400 with colocalising cis-pQTLs. Moreover, 1096 Olink and 1429 SomaScan proteins were associated with BMI, while 279 and 154 proteins were associated with risk of ischaemic heart disease, respectively. Addition of Olink and SomaScan proteins to conventional risk factors for ischaemic heart disease improved C-statistics from 0.845 to 0.862 (NRI: 12.2%) and 0.863 (NRI: 16.4%), respectively. These results demonstrate the utility of these platforms and could inform the design and interpretation of future studies.

Leveraging large language models for data analysis automation

Data analysis is constrained by a shortage of skilled experts, particularly in biology, where detailed data analysis and subsequent interpretation is vital for understanding complex biological processes and developing new treatments and diagnostics. One possible solution to this shortage in experts would be making use of Large Language Models (LLMs) for generating data analysis pipelines. However, although LLMs have shown great potential when used for code generation tasks, questions regarding the accuracy of LLMs when prompted with domain expert questions such as omics related data analysis questions, remain unanswered. To address this, we developed mergen , an R package that leverages LLMs for data analysis code generation and execution. We evaluated the performance of this data analysis system using various data analysis tasks for genomics. Our primary goal is to enable researchers to conduct data analysis by simply describing their objectives and the desired analyses for specific datasets through clear text. Our approach improves code generation via specialized prompt engineering and error feedback mechanisms. In addition, our system can execute the data analysis workflows prescribed by the LLM providing the results of the data analysis workflow for human review. Our evaluation of this system reveals that while LLMs effectively generate code for some data analysis tasks, challenges remain in executable code generation, especially for complex data analysis tasks. The best performance was seen with the self-correction mechanism, in which self-correct was able to increase the percentage of executable code when compared to the simple strategy by 22.5% for tasks of complexity 2. For tasks for complexity 3, 4 and 5, this increase was 52.5%, 27.5% and 15% respectively. Using a chi-squared test, it was shown that significant differences could be found using the different prompting strategies. Our study contributes to a better understanding of LLM capabilities and limitations, providing software infrastructure and practical insights for their effective integration into data analysis workflows.

Metallaphotoredox-catalyzed alkynylcarboxylation of alkenes with CO2 and alkynes for expedient access to β-alkynyl acids

Does integration matter? an international cross-sectional study on the relationship between perceived public health and primary care integration and COVID-19 vaccination rates

Background Immunisation against COVID-19 is crucial for controlling the pandemic, yet global challenges persist in vaccine coverage and equitable distribution. A well-integrated primary health care approach can enhance vaccination programmes. Aim To explore the relationship between perceived PC (primary care)-PH (public health) integration, as well as other vaccination program implementation factors, and national COVID-19 vaccination coverage. Design and setting A convenience sample of self-identified primary care professionals completed an online survey on COVID-19 vaccination programme implementation and their perceptions of PC-PH integration. Methods Countries with ≥5 responses were included in the data analysis. COVID-19 vaccination implementation approach and perceived PC-PH integration against COVID-19 vaccination coverage was investigated using bivariate and subgroup analyses, Spearman correlation, and linear regression. Results A total of 394 responses from 32 countries were analysed. Participants included primary care providers, academics, and researchers. The median national COVID-19 vaccination coverage was 28.41% at time of study. Perceived barriers included patient hesitancy and vaccine supply shortages, while facilitators included vaccine product choices, equity, and community engagement. The study revealed a positive relationship between perceptions of PC-PH integration and national vaccination coverage in upper-middle and lower-middle income countries. Conclusion Perceived PC-PH integration increased with decreasing economic quartiles and this perception was linked to actual national vaccination coverage. Integration may be especially important for countries with lesser vaccine supply. High-income countries may benefit from increased collaboration between PC and PH to enhance vaccination efficiency. The findings contribute to understanding the role of PC-PH integration in vaccination programmes in different settings.

Grain boundary diffusion cannot explain the W isotope heterogeneities of the deep mantle

PGLYRP1-mediated intracellular peptidoglycan detection promotes intestinal mucosal protection

Magnetic Bloch states at integer flux quanta induced by super-moiré potential in graphene aligned with twisted boron nitride

Early Alzheimer’s Disease with frequent neuritic plaques harbors neocortical tau seeds distinct from primary age-related tauopathy

Distorted learning from local metacognition supports transdiagnostic underconfidence

Abstract Individuals experiencing symptoms of anxiety and depression have been shown to exhibit persistent underconfidence. The origin of such metacognitive biases presents a puzzle, given that individuals should be able to learn appropriate levels of confidence from observing their own performance. In two large general population samples ( N  = 230 and N  = 278), we measure both 'local' confidence in individual task instances and 'global' confidence as longer-run self-performance estimates while manipulating external feedback. Global confidence is sensitive to both local confidence and feedback valence—more frequent positive (negative) feedback increases (respectively decreases) global confidence, with asymmetries in feedback also leading to shifts in affective self-beliefs. Notably, however, global confidence exhibits reduced sensitivity to instances of higher local confidence in individuals with greater subclinical anxious-depression symptomatology, despite sensitivity to feedback valence remaining intact. Our finding of blunted sensitivity to increases in local confidence offers a mechanistic basis for how persistent underconfidence is maintained in the face of intact performance.

Entanglement growth from squeezing on the MPS manifold

Abstract Finding suitable characterizations of quantum chaos is a major challenge in many-body physics, with a central difficulty posed by the linearity of the Schrödinger equation. A possible solution for recovering non-linearity is to project the dynamics onto some variational manifold. The classical chaos induced via this procedure may be used as a signature of quantum chaos in the full Hilbert space. Here, we demonstrate analytically a previously heuristic connection between the Lyapunov spectrum from projection onto the matrix product state (MPS) manifold and the growth of entanglement. This growth occurs by squeezing a localized distribution on the variational manifold. The process qualitatively resembles the Cardy-Calabrese picture, where local perturbations to a moving MPS reference are interpreted as bosonic quasi-particles. Taking careful account of the number of distinct channels for these processes recovers the connection to the Lyapunov spectrum. Our results rigorously establish the physical significance of the projected Lyapunov spectrum, suggesting it as an alternative method of characterizing chaos in quantum many-body systems, one that is manifestly linked to classical chaos.