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Background: Mutations of the PIK3CA/AKT/mTOR axis are common events in metastatic breast cancers (MBCs). This study was designed to evaluate the extent to which genetic alterations of the PIK3CA/AKT/mTOR can predict protein activation of this signalling axis in MBCs. Methods: Molecular profiles were generated by CLIA-certified laboratories from a real-world evidence cohort of 171 MBC patients. Genetic alterations of the PIK3CA pathway were measured using next-generation sequencing. Activation levels of AKT and downstream signalling molecules were quantified using two orthogonal proteomic methods. Protein activity was correlated with underlying genomic profiles and response to CDK4/6 inhibition in combination with endocrine treatment (ET). Results: Oncogenic alterations of the PIK3CA/AKT/PTEN pathway were identified in 49.7% of cases. Genomic profiles emerged as poor predictors of protein activity (AUC:0.69), and AKT phosphorylation levels mimicked those of mutant lesions in 76.9% of wild-type tumours. High phosphorylation levels of the PI3K/AKT/mTOR downstream target p70S6 Kinase (T389) were associated with shorter PFS in patients treated with CDK4/6 inhibitors in combination with ET (HR:4.18 95%CI:1.19–14.63); this association was not seen when patients were classified by mutational status. Conclusions: Phosphoprotein-based measurements of drug targets and downstream substrates should be captured along with genomic information to identify MBCs driven by the PI3K/AKT/mTOR signalling. [ABSTRACT FROM AUTHOR]

Inorganic carbon acquisition is essential to algal growth, while the limitations of dissolved inorganic carbon (DIC) on phytoplankton are still less known in lakes. Sediment is an active hot spot for microbial metabolism, driving the migration and transformation of elements in shallow lakes, which may control the DIC availability to influence algal spatiotemporal dynamics. Hence, we investigated the spatiotemporal changes of phytoplankton, DIC and sediment respiration rates in a eutrophic shallow freshwater lake under non-bloom conditions. There was a widespread deficiency of DIC in the lake, except the estuary. Sediment respiration was positively associated with changes in DIC concentrations, indicating that carbon metabolic activity of sedimentary microorganisms was an important inorganic carbon source for water columns. The availability of DIC in water columns regulated by sediment microbial respiration influenced the algal biomass, composition and productivity. The synergistic effects of seasonal temperature changes and sediment microbial respiration influenced the vertical distribution and migration of phytoplankton. Our results emphasized that carbon metabolic intensity of sediment microorganisms might play a key role in dynamics of phytoplankton, further impacting the spatiotemporal pattern and formation of algal bloom in eutrophic shallow freshwater lakes. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death protein 1 and its ligand (PD-1/PD-L1) as well as anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4), have been widely used for treating solid tumors. Myocarditis is a potentially lethal immune-related adverse events (irAEs) caused by ICIs therapy. The treatment of steroid-refractory myocarditis is challenging. We reported two non-small-cell lung cancer patients with steroid-refractory myocarditis induced by ICI. The symptoms were not resolved after pulse corticosteroid therapy and subsequent treatment including intravenous immunoglobulin and mycophenolate mofetil. Considering the level of serum interleukin (IL)-6 decreased by > 50% and level of serum tumor necrosis factor-α (TNF-α) increased during the course of the disease, infliximab was used. Myocarditis gradually alleviated after infliximab treatment. The cases revealed that specific cytokine inhibitors have promising roles in the treatment of steroid-refractory myocarditis. Infliximab could be considered for patients with low level of IL-6 and elevated level of TNF-α. [ABSTRACT FROM AUTHOR]

Background: Pregnant women are significantly underrepresented in clinical trials, yet most of them take medication during pregnancy despite the limited safety data. The objective of this study was to characterize medication use during pregnancy and apply propensity score matching method at scale on patient records to accelerate and prioritize the drug effect signal detection associated with the risk of preterm birth and other adverse pregnancy outcomes. Methods: This was a retrospective study on continuously enrolled women who delivered live births between 2013/01/01 and 2022/12/31 (n = 365,075) at Providence St. Joseph Health. Our exposures of interest were all outpatient medications prescribed during pregnancy. We limited our analyses to medication that met the minimal sample size (n = 600). The primary outcome of interest was preterm birth. Secondary outcomes of interest were small for gestational age and low birth weight. We used propensity score matching at scale to evaluate the risk of these adverse pregnancy outcomes associated with drug exposure after adjusting for demographics, pregnancy characteristics, and comorbidities. Results: The total medication prescription rate increased from 58.5 to 75.3% (P < 0.0001) from 2013 to 2022. The prevalence rate of preterm birth was 7.7%. One hundred seventy-five out of 1329 prenatally prescribed outpatient medications met the minimum sample size. We identified 58 medications statistically significantly associated with the risk of preterm birth (P ≤ 0.1; decreased: 12, increased: 46). Conclusions: Most pregnant women are prescribed medication during pregnancy. This highlights the need to utilize existing real-world data to enhance our knowledge of the safety of medications in pregnancy. We narrowed down from 1329 to 58 medications that showed statistically significant association with the risk of preterm birth even after addressing numerous covariates through propensity score matching. This data-driven approach demonstrated that multiple testable hypotheses in pregnancy pharmacology can be prioritized at scale and lays the foundation for application in other pregnancy outcomes. [ABSTRACT FROM AUTHOR]

The concept of probabilistic interval preference ordering sets (PIPOSs) provides a scientific and intuitive framework for solving real-life multi-criteria group decision-making problems. In some areas such as investment decision-making and supplier selection, PIPOSs have a wider application space, and the development of similarity and distance measures based on PIPOSs holds great significance. Similarity measure is a basic and prominent tool for dealing with imperfect and ambiguous information in fuzzy sets, but it can also be used to deal with uncertain information in preference ordering. These metrics play an important role in the actual decision-making process, as they effectively quantify the degree of similarity between two PIPOSs, and further allow for the prioritization of different scenarios. In this article, we sort out the definitions and arithmetic rules of PIPOSs, and creatively propose several new similarity measures based on PIPOSs. Then, we propose a group decision-making method based on similarity measures and conduct a comparative study with three existing similarity measures to illustrate its advantages over existing metrics. Finally, we confirm its validity through numerical illustrations in the case study, and also conduct a comparative assessment to verify the scientific validity and effectiveness of the newly introduced measure against the existing metrics. [ABSTRACT FROM AUTHOR]

This study develops a theoretical model to capture volatility-managed portfolios' risk-adjusted returns affected by investor sentiment, and uses Chinese A-share market data to analyze the volatility-managed effect based on the small-minus-big (SMB) factor and explain the abnormal returns of volatility-managed portfolios from the investor sentiment perspective. Our results show that the Sharpe ratio of the SMB factor significantly increases after volatility management, especially in low-sentiment periods. Moreover, the mechanism analysis shows that in low-sentiment periods, small-cap stock investors overreact to volatility compared to large-cap stock investors, making the SMB factor significantly positively correlated with lagged volatility. Additional analyses show that volatility-managed portfolios constructed through stocks with gambling characteristics can achieve higher abnormal returns, and the abnormal returns of volatility-managed portfolios cannot be corrected by arbitrage traders as arbitrage is ineffective, reflecting the immaturity of China's emerging capital market. [ABSTRACT FROM AUTHOR]

Satisfactory reduction of some displaced pediatric supracondylar humerus fractures is not achievable via closed reduction, thus necessitating open procedure, which increases the incidence of complications. Using percutaneous prying-up technique to assist closed reduction may reduce the requirement for transform to an open operation. We retrospectively reviewed displaced pediatric supracondylar humerus fractures treated by the same surgeon from September 2021 to January 2024,with 134 subjects meeting criteria for inclusion. These children were divided into two groups. In Group A(n = 61),the prying-up technique was used to assist with closed reduction of fractures. Group B(n = 73) included fractures treated with conventional manual traction. To balance group size,12 fractures from group A were randomly removed, leaving a final 61 patients in each group. Demographics, operative time, the rate of failed closed reduction, complications and radiographic results were analyzed. The operative time was significantly less in Group A as compared with Group B(mean difference, − 7.22; [95% confidence interval (CI), − 8.49 to − 5.94]; p < 0.001). The rate of failed closed reduction were significantly lower in Group A as compared to Group B(2 of 61 vs. 10 of 61, p = 0.015). However, we found no difference in terms of the radiographic results and complications between the two groups(p > 0.05). percutaneous prying-up technique significantly improves the efficiency of surgery and reduces rate of failed closed reduction of supracondylar humeral fractures in pediatric patients. Level III, retrospective comparative study.See Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Sharing a dementia diagnosis with others is a prerequisite to accessing important support for social, cognitive, and physical activity. However, due to the stigma associated with dementia, individuals may be hesitant to disclose their diagnosis. Despite the importance of this issue, there is limited research on personal experiences with sharing one's diagnosis. This study explored how people with young-onset dementia disclose their diagnosis to other people, also known as self-disclosure, and how time affects self-disclosure. Methods: We conducted an exploratory qualitative study, using semi-structured interviews with nine people with young-onset dementia living in the United Kingdom (UK). A narrative approach to analysis was applied, focusing on understanding the core narratives, themes, tone, and imagery of each participant's narratives as well as providing a cross-case analysis to identify patterns across narratives. Results: Participants openly disclosed their diagnosis, accepting it as an illness that did not define their identity. Several were met with stigmatizing reactions, which affected their levels of openness, and a lack of understanding, which caused shrinking social networks for some. Peer support groups, advocacy activities, and strategic concealment were used to support self-disclosure. Conclusion: This study provides a holistic understanding of people with young-onset dementia's experiences with self-disclosure and how these evolved. Policies should prioritize the creation of dementia-friendly communities, while recommendations for practice include integrating empowerment interventions and peer support into post-diagnostic support. These efforts will support individuals in their self-disclosure journey, promote social engagement and reduce stigma. [ABSTRACT FROM AUTHOR]

Background: Uterine Fibroids (UFs) are common benign tumors in the female reproductive tract, but their progression to intravascular leiomyomatosis (IVL) is rare. Presently, there are few reports on single-stage resection of UFs and IVL. Case presentation: A 47-year-old woman, G2P2, had been diagnosed multiple UFs four years ago and now developed heart failure. Imaging examinations revealed that UFs had invaded the right iliac vein and extended into the right atrium through the inferior vena cava. Through multidisciplinary collaboration and a single-stage resection, the patient has survived for over 24 months post-surgery, and her heart function has significantly improved compared to preoperative levels, with no recurrence of UFs observed. Conclusions: Single-stage resection of IVL and UF is feasible and advantageous for this case, and selecting the appropriate surgical approach is crucial. [ABSTRACT FROM AUTHOR]

As one of the most important fertilizers in agriculture, the fate of urea-derived nitrogen (urea-N) in agricultural ecosystems has been well documented. However, little is known about the function of urea-derived carbon (urea-C) in soil ecosystems, especially which soil microorganisms benefit most from the supply of urea-C and whether the utilization of urea-C by the rhizosphere and bulk soil microorganisms is affected by irrigation regimes. To address this, a soil pot experiment was conducted using 13C-labeled urea to investigate changes in the composition of the rhizosphere and bulk soil microbial communities and differences in the incorporation of urea-derived C into the rhizosphere and bulk soil phospholipid fatty acids (PLFA) pool under flooded irrigation (FI) and water-saving irrigation (CI). Our results suggest that the size and structure of the rhizosphere and bulk soil microbial communities were strongly influenced by the irrigation regime. The CI treatment significantly increased the total amount of PLFA in both the rhizosphere and bulk soil compared to the FI treatment, but it only significantly affected the abundance of Gram-positive bacteria (G+) in the bulk soil. In contrast, shifts in the microbial community structure induced by irrigation regimes were more pronounced in the rhizosphere soil than in the bulk soil. Compared to the FI treatment, the CI treatment significantly increased the relative abundances of the G+ and Actinobacteria in the rhizosphere soil (p < 0.05). According to the PLFA-SIP, most of the labeled urea-derived C was incorporated into 16:1ω7c, 16:0 and 18:1ω7c under both treatments. Despite these general trends, the pattern of 13C incorporation into the PLFA pool differed between the treatments. The factor loadings of individual PLFAs suggested that 18:1ω7c, 16:1ω7c and 16:1ω5c were relatively enriched in urea-C in the bulk soil, while 17:1ω8c, i16:0 and 16:0 were relatively enriched in urea-C in the rhizosphere soil under different irrigation regimes. The loadings also confirmed that 10-me16:0, cy17:0 and cy19:0 were relatively enriched in urea-C under the CI treatment, whereas 14:0, a15:0 and 15:0 were relatively enriched in urea-C under the FI treatment. These results are helpful not only in revealing the interception mechanism of urea-C in soil but also in understanding the functions of key microbes in element cycles. [ABSTRACT FROM AUTHOR]

Objectives Phenotyping is a core task in observational health research utilizing electronic health records (EHRs). Developing an accurate algorithm demands substantial input from domain experts, involving extensive literature review and evidence synthesis. This burdensome process limits scalability and delays knowledge discovery. We investigate the potential for leveraging large language models (LLMs) to enhance the efficiency of EHR phenotyping by generating high-quality algorithm drafts. Materials and Methods We prompted four LLMs—GPT-4 and GPT-3.5 of ChatGPT, Claude 2, and Bard—in October 2023, asking them to generate executable phenotyping algorithms in the form of SQL queries adhering to a common data model (CDM) for three phenotypes (ie, type 2 diabetes mellitus, dementia, and hypothyroidism). Three phenotyping experts evaluated the returned algorithms across several critical metrics. We further implemented the top-rated algorithms and compared them against clinician-validated phenotyping algorithms from the Electronic Medical Records and Genomics (eMERGE) network. Results GPT-4 and GPT-3.5 exhibited significantly higher overall expert evaluation scores in instruction following, algorithmic logic, and SQL executability, when compared to Claude 2 and Bard. Although GPT-4 and GPT-3.5 effectively identified relevant clinical concepts, they exhibited immature capability in organizing phenotyping criteria with the proper logic, leading to phenotyping algorithms that were either excessively restrictive (with low recall) or overly broad (with low positive predictive values). Conclusion GPT versions 3.5 and 4 are capable of drafting phenotyping algorithms by identifying relevant clinical criteria aligned with a CDM. However, expertise in informatics and clinical experience is still required to assess and further refine generated algorithms. [ABSTRACT FROM AUTHOR]

Nickel-based superalloys with high Al + Ti content are considered non-weldable, and hot cracking is a major challenge in their thermal fabrication processes. In this study, the microstructure liquefaction characteristics and liquation cracking behavior of laser-remelted as-cast K447A superalloy have been investigated. In the heat-affected zone (HAZ), the special liquefaction phenomenon of the coarse script carbides consists of cracking, breakdown, and liquefaction successively. The whole liquefaction sequence observed in the as-cast K447A substrate encompasses: IMRs (Ni7Hf2-γ + γ–γ′ + M5B3-γ), primary γ′, MC-γ, matrix γ, and MC phases. Liquefaction of IMRs during the laser thermal cycle easily forms a continuous liquid film and evolves into liquation cracking. In the remelted zone (RZ), the fine MC particles and IMRs just form isolated liquefaction points. These isolated liquefaction points are interconnected due to micro-cracks generated by thermal stresses and solidification shrinkage stresses. Finally, crack-free remelted specimens have been obtained by process optimization and preheating the substrate. The tensile strength and elongation of the RZ are increased by 32 and 227 pct, which is beneficial for the RZ acting as a buffer layer to relax or inhibit the stress and cracks generated by subsequent additive repair of K447A. [ABSTRACT FROM AUTHOR]

Atomic stabilization is a universal phenomenon that occurs when atoms interact with intense and high-frequency laser fields. In this work, we systematically study the influence of the ponderomotive (PM) force, present around the laser focus, on atomic stabilization. We show that the PM force could induce tunneling and even over-barrier ionization to the otherwise stabilized atoms. Such effect may overweigh the typical multiphoton ionization under moderate laser intensities. Our work highlights the importance of an improved treatment of atomic stabilization that includes the influence of the PM force. [ABSTRACT FROM AUTHOR]

FOXO transcription factors modulate aging-related pathways and influence longevity in multiple species, but the transcriptional targets that mediate these effects remain largely unknown. Here, we identify an evolutionarily conserved FOXO target gene, Oxidative stress-responsive serine-rich protein 1 (OSER1), whose overexpression extends lifespan in silkworms, nematodes, and flies, while its depletion correspondingly shortens lifespan. In flies, overexpression of OSER1 increases resistance to oxidative stress, starvation, and heat shock, while OSER1-depleted flies are more vulnerable to these stressors. In silkworms, hydrogen peroxide both induces and is scavenged by OSER1 in vitro and in vivo. Knockdown of OSER1 in Caenorhabditis elegans leads to increased ROS production and shorter lifespan, mitochondrial fragmentation, decreased ATP production, and altered transcription of mitochondrial genes. Human proteomic analysis suggests that OSER1 plays roles in oxidative stress response, cellular senescence, and reproduction, which is consistent with the data and suggests that OSER1 could play a role in fertility in silkworms and nematodes. Human studies demonstrate that polymorphic variants in OSER1 are associated with human longevity. In summary, OSER1 is an evolutionarily conserved FOXO-regulated protein that improves resistance to oxidative stress, maintains mitochondrial functional integrity, and increases lifespan in multiple species. Additional studies will clarify the role of OSER1 as a critical effector of healthy aging. FOXO transcription factors are known to promote longevity via effects on transcriptional targets. In this study, the authors identify OSER1 as an evolutionarily conserved target of FOXO. OSER1 expression improves resistance to oxidative stress, supports mitochondrial function, and extends lifespan across multiple species. [ABSTRACT FROM AUTHOR]

Background: Dietary diversity has been suggested as a potential preventive measure against frailty in older adults, but the effect of changes in dietary diversity on frailty is unclear. This study was conducted to examine the association between the dietary diversity score (DDS) and frailty among older Chinese adults. Methods: A total of 12,457 adults aged 65 years or older were enrolled from three consecutive and nonoverlapping cohorts from the Chinese Longitudinal Healthy Longevity Survey (the 2002 cohort, the 2005 cohort, and the 2008 cohort). DDS was calculated based on nine predefined food groups, and DDS changes were assessed by comparing scores at baseline and the first follow-up survey. We used 39 self-reported health items to assess frailty. Cox proportional hazard models were performed to examine the association between DDS change patterns and frailty. Results: Participants with low-to-low DDS had the highest frailty incidence (111.1/1000 person-years), while high-to-high DDS had the lowest (41.1/1000 person-years). Compared to the high-to-high group of overall DDS pattern, participants in other DDS change patterns had a higher risk of frailty (HRs ranged from 1.25 to 2.15). Similar associations were observed for plant-based and animal-based DDS. Compared to stable DDS changes, participants with an extreme decline in DDS had an increased risk of frailty, with HRs of 1.38 (1.24, 1.53), 1.31 (1.19, 1.44), and 1.29 (1.16, 1.43) for overall, plant-based, and animal-based DDS, respectively. Conclusions: Maintaining a lower DDS or having a large reduction in DDS was associated with a higher risk of frailty among Chinese older adults. These findings highlight the importance of improving a diverse diet across old age for preventing frailty in later life. [ABSTRACT FROM AUTHOR]

Waste categorization and recycling are critical approaches for converting waste into valuable and functional materials, thereby significantly aiding in land preservation, reducing pollution, and optimizing resource usages. However, real-world classification and identification of recyclable waste face substantial hurdles due to the intricate and unpredictable nature of wastes, as well as the limited availability of comprehensive waste datasets. These factors limit efficacy of the existing research work in the domain of waste management. In this paper, we utilize semantic segmentation at individual pixel level and introduce a semi-supervised metod for authentic waste classification scenarios, leveraging the Zerowaste dataset. We devise a non-standard data augmentation strategy that mimics the ever-changing conditions of real-world waste environments. Additionally, we introduce an adaptive weighted loss function and dynamically adjust the ratio of positive to negative samples through a masking method, ensuring the model learns from relevant samples. Lastly, to maintain consistency between predictions made on data-augmented images and the original counterparts, we remove input perturbations. Our method proves to be effective, as verified by an array of standard experiments and ablation studies, achieved an accuracy improvement of 3.74% over the baseline Zerowaste method. [ABSTRACT FROM AUTHOR]

In this pilot study, we investigated the utility of handheld ultrasound-guided photoacoustic (US-PA) imaging probe for analyzing ex-vivo breast specimens obtained from female patients who underwent breast-conserving surgery (BCS). We aimed to assess the potential of US-PA in detecting biochemical markers such as collagen, lipids, and hemoglobin, and compare these findings with routine imaging modalities (mammography, ultrasound) and histopathology results, particularly across various breast densities. Twelve ex-vivo breast specimens were obtained from female patients with a mean age of 59.7 ± 9.5 years who underwent BCS. The tissues were illuminated using handheld US-PA probe between 700 and 1100 nm across all margins and analyzed for collagen, lipids, and hemoglobin distribution. The obtained results were compared with routine imaging and histopathological assessments. Our findings revealed that lipid intensity and distribution decreased with increasing breast density, while collagen exhibited an opposite trend. These observations were consistent with routine imaging and histopathological analyses. Moreover, collagen intensity significantly differed (P < 0.001) between cancerous and normal breast tissue, indicating its potential as an additional biomarker for risk stratification across various breast conditions. The study results suggest that a combined assessment of PA biochemical information, such as collagen and lipid content, superimposed on grey-scale ultrasound findings could aid in distinguishing between normal and malignant breast conditions, as well as assist in BCS margin assessment. This underscores the potential of US-PA imaging as a valuable tool for enhancing breast cancer diagnosis and management, offering complementary information to existing imaging modalities and histopathology. [ABSTRACT FROM AUTHOR]

Pseudo-labeling methods are popular in semi-supervised learning (SSL). Their performance heavily relies on a proper threshold to generate hard labels for unlabeled data. To this end, most existing studies resort to a manually pre-specified function to adjust the threshold, which, however, requires prior knowledge and suffers from the scalability issue. In this paper, we propose a novel method named Meta-Threshold, which learns a dynamic confidence threshold for each unlabeled instance and does not require extra hyperparameters except a learning rate. Specifically, the instance-level confidence threshold is automatically learned by an extra network in a meta-learning manner. Considering limited labeled data as meta-data, the overall training objective of the classifier network and the meta-net can be formulated as a nested optimization problem that can be solved by a bi-level optimization scheme. Furthermore, by replacing the indicator function existed in the pseudo-labeling with a surrogate function, we theoretically provide the convergence of our training procedure, while discussing the training complexity and proposing a strategy to reduce its time cost. Extensive experiments and analyses demonstrate the effectiveness of our method on both typical and imbalanced SSL tasks. [ABSTRACT FROM AUTHOR]

The currency exchange rate is a crucial link between all countries related to economic and trade activities. With increasing volatility, exchange rate fluctuations have become frequent under the combined effects of global economic uncertainty and political risks. Consequently, accurate exchange rate prediction is significant in managing financial risks and economic instability. In recent years, the Transformer models have attracted attention in the field of time series analysis. Transformer models, such as Informer and TFT (Temporal Fusion Transformer), have also been extensively studied. In this paper, we evaluate the performance of the Transformer, Informer, and TFT models based on four exchange rate datasets: NZD/USD, NZD/CNY, NZD/GBP, and NZD/AUD. The results indicate that the TFT model has achieved the highest accuracy in exchange rate prediction, with an R2 value of up to 0.94 and the lowest RMSE and MAE errors. However, the Informer model offers faster training and convergence speeds than the TFT and Transformer, making it more efficient. Furthermore, our experiments on the TFT model demonstrate that integrating the VIX index can enhance the accuracy of exchange rate predictions. [ABSTRACT FROM AUTHOR]

In agriculture, the timely and accurate assessment of fruit ripeness is crucial to optimizing harvest planning and reduce waste. In this article, we explore the integration of two cutting-edge deep learning models, YOLOv9 and Swin Transformer, to develop a complex model for detecting strawberry ripeness. Trained and tested on a specially curated dataset, our model achieves a mean precision (mAP) of 87.3% by using the metric intersection over union (IoU) at a threshold of 0.5. This outperforms the model using YOLOv9 alone, which achieves an mAP of 86.1%. Our model also demonstrated improved precision and recall, with precision rising to 85.3% and recall rising to 84.0%, reflecting its ability to accurately and consistently detect different stages of strawberry ripeness. [ABSTRACT FROM AUTHOR]

Rehabilitation from musculoskeletal injuries focuses on reestablishing and monitoring muscle activation patterns to accurately produce force. The aim of this study is to explore the use of a novel low-powered wearable distributed Simultaneous Musculoskeletal Assessment with Real-Time Ultrasound (SMART-US) device to predict force during an isometric squat task. Participants (N = 5) performed maximum isometric squats under two medical imaging techniques; clinical musculoskeletal motion mode (m-mode) ultrasound on the dominant vastus lateralis and SMART-US sensors placed on the rectus femoris, vastus lateralis, medial hamstring, and vastus medialis. Ultrasound features were extracted, and a linear ridge regression model was used to predict ground reaction force. The performance of ultrasound features to predict measured force was tested using either the Clinical M-mode, SMART-US sensors on the vastus lateralis (SMART-US: VL), rectus femoris (SMART-US: RF), medial hamstring (SMART-US: MH), and vastus medialis (SMART-US: VMO) or utilized all four SMART-US sensors (Distributed SMART-US). Model training showed that the Clinical M-mode and the Distributed SMART-US model were both significantly different from the SMART-US: VL, SMART-US: MH, SMART-US: RF, and SMART-US: VMO models (p < 0.05). Model validation showed that the Distributed SMART-US model had an R2 of 0.80 ± 0.04 and was significantly different from SMART-US: VL but not from the Clinical M-mode model. In conclusion, a novel wearable distributed SMART-US system can predict ground reaction force using machine learning, demonstrating the feasibility of wearable ultrasound imaging for ground reaction force estimation. [ABSTRACT FROM AUTHOR]

Although oxygen vacancies (Ovs) have been intensively studied in single semiconductor photocatalysts, exploration of intrinsic mechanisms and in‐depth understanding of Ovs in S‐scheme heterojunction photocatalysts are still limited. Herein, a novel S‐scheme photocatalyst made from WO3‐Ov/In2S3 with Ovs at the heterointerface is rationally designed. The microscopic environment and local electronic structure of the S‐scheme heterointerface are well optimized by Ovs. Femtosecond transient absorption spectroscopy (fs‐TAS) reveals that Ovs trigger additional charge movement routes and therefore increase charge separation efficiency. In addition, Ovs have a synergistic effect on the thermodynamic and kinetic parameters of S‐scheme photocatalysts. As a result, the optimal photocatalytic performance is significantly improved, surpassing that of single component WO3‐Ov and In2S3 (by 35.5 and 3.9 times, respectively), as well as WO3/In2S3 heterojunction. This work provides new insight into regulating the photogenerated carrier dynamics at the heterointerface and also helps design highly efficient S‐scheme photocatalysts. [ABSTRACT FROM AUTHOR]

Although oxygen vacancies (Ovs) have been intensively studied in single semiconductor photocatalysts, exploration of intrinsic mechanisms and in‐depth understanding of Ovs in S‐scheme heterojunction photocatalysts are still limited. Herein, a novel S‐scheme photocatalyst made from WO3‐Ov/In2S3 with Ovs at the heterointerface is rationally designed. The microscopic environment and local electronic structure of the S‐scheme heterointerface are well optimized by Ovs. Femtosecond transient absorption spectroscopy (fs‐TAS) reveals that Ovs trigger additional charge movement routes and therefore increase charge separation efficiency. In addition, Ovs have a synergistic effect on the thermodynamic and kinetic parameters of S‐scheme photocatalysts. As a result, the optimal photocatalytic performance is significantly improved, surpassing that of single component WO3‐Ov and In2S3 (by 35.5 and 3.9 times, respectively), as well as WO3/In2S3 heterojunction. This work provides new insight into regulating the photogenerated carrier dynamics at the heterointerface and also helps design highly efficient S‐scheme photocatalysts. [ABSTRACT FROM AUTHOR]

Background: Atherogenic index of plasma (AIP), a marker of atherosclerosis and cardiovascular disease (CVD). However, few studies have investigated association between AIP and all-cause mortality and specific-mortality in the general population. Methods: This study included data from 14,063 American adults. The exposure variable was the AIP, which was defined as log10 (triglycerides/high-density lipoprotein cholesterol). The outcome variables included all-cause mortality and specific-mortality. Survey-weighted cox regressions were performed to evaluate the relation between AIP and all-cause mortality and specific-mortality. Weighted restricted cubic spline was conducted to examin the non-linear relationship. Results: During 10 years of follow-up, we documented 2,077, 262, 854, and 476 cases of all-cause mortality, diabetes mortality, CVD mortality and cancer mortality, respectively. After adjustment for potential confounders, we found that atherogenic index of plasma (AIP) was significantly associated with an increased risk of diabetes mortality when comparing the highest to the lowest quantile of AIP in female (p for trend = 0.001) or participants older than 65 years (p for trend = 0.002). AIP was not significantly associated with all-cause mortality, CVD mortality and cancer mortality (p > 0.05). Moreover, a non-linear association was observed between AIP and all-cause mortality in a U-shape (p for non-linear = 0.0011), while a linear relationship was observed with diabetes mortality and non-diabetes mortality (p for linear < 0.0001). Conclusions: In this study, there is a no significant association between high AIP levels and a high risk of all-cause and cardiovascular mortality. Besides, a higher AIP was significantly associated with an increased risk of diabetes mortality, which only found in women older than 65 years. AIP was associated with all-cause mortality in a U-shape. This association could be explained by the finding that higher AIP predicted a higher risk of death from diabetes, and that lower AIP predicted a higher risk of death from non-diabetes causes. Highlight: We used a large national database and a prospective cohort study with a long follow-up period. Higher AIP was significantly associated with an increased risk of diabetes mortality, only in women older than 65 years. There is a no significant association between high AIP levels and a high risk of all-cause and cardiovascular mortality. AIP was associated with all-cause mortality in a U-shape. This finding suggest that controlling AIP levels may have a positive effect on reducing diabetes mortality. [ABSTRACT FROM AUTHOR]

Lead-free alkali halides have gained increasing attention owing to their desired optoelectronic properties across a variety of light-emitting applications. However, state-of-the-art alkali halide emitters commonly are bulky crystals functionalized with highly toxic elemental doping, hindering their integration into emerging flexible, wearable and large-area optoelectronic devices. Herein, we have developed environmental friendly and solution-processable alkali halide nanocrystals that exhibit intense self-trapped emission facilitated by Sn2+ ionic doping. We find that the presence of Sn2+-interstitial leads to the tilting of cubic structures of RbI and thus triggers the self-trapped emission. The resultant tin(II)-doped RbI and RbxCs1−xI nanocrystals display an impressive maximum photoluminescence quantum yield of 91.9% and exhibit remarkable stability under ambient conditions. These findings pave the way for a new class of bright, solution-processable alkali halides, with diverse applications such as energy down conversion and flexible scintillation technologies. [ABSTRACT FROM AUTHOR]

Conventional photovoltaic (PV)‐photodetectors are hard to detect fainted signals, while photomultiplication (PM)‐capable devices indispensable for detecting weak light and are prone to degrade under strong light illumination and large bias, and it is urgent to realize highly efficient integrated detecting system with both PM and PV operation modes. In this work, one lead‐free Cs3Cu2I5 nanocrystals with self‐trapping exciton nature was introduced as interfacial layer adjacent to bulk and layer‐by‐layer heterojunction structure, and corresponding organic photodetectors with bias‐switchable dual modes are demonstrated. The fabricated device exhibits low operating bias (0 V for PV mode and 0.8 V for PM mode), high specific detectivity (~1013 Jones), fast response speed as low as 1.59 μs, large bandwidth over 0.2 MHz and long‐term operational stability last for 4 months in ambient condition. This synergy strategy also validated in different materials and device architectures, providing a convenient and scalable production process to develop highly efficient bias‐switchable multi‐functional organic optoelectrical applications. [ABSTRACT FROM AUTHOR]

Conventional photovoltaic (PV)‐photodetectors are hard to detect fainted signals, while photomultiplication (PM)‐capable devices indispensable for detecting weak light and are prone to degrade under strong light illumination and large bias, and it is urgent to realize highly efficient integrated detecting system with both PM and PV operation modes. In this work, one lead‐free Cs3Cu2I5 nanocrystals with self‐trapping exciton nature was introduced as interfacial layer adjacent to bulk and layer‐by‐layer heterojunction structure, and corresponding organic photodetectors with bias‐switchable dual modes are demonstrated. The fabricated device exhibits low operating bias (0 V for PV mode and 0.8 V for PM mode), high specific detectivity (~1013 Jones), fast response speed as low as 1.59 μs, large bandwidth over 0.2 MHz and long‐term operational stability last for 4 months in ambient condition. This synergy strategy also validated in different materials and device architectures, providing a convenient and scalable production process to develop highly efficient bias‐switchable multi‐functional organic optoelectrical applications. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths and represents a substantial disease burden worldwide. Immune checkpoint inhibitors combined with chemotherapy are the standard first-line therapy for advanced NSCLC without driver mutations. Programmed death-ligand 1 (PD-L1) is currently the only approved immunotherapy marker. PD-L1 detection methods are diverse and have developed rapidly in recent years, such as improved immunohistochemical detection methods, the application of liquid biopsy in PD-L1 detection, genetic testing, radionuclide imaging, and the use of machine learning methods to construct PD-L1 prediction models. This review focuses on the detection methods and challenges of PD-L1 from different sources, and discusses the influencing factors of PD-L1 detection and the value of combined biomarkers. Provide support for clinical screening of immunotherapy-advantage groups and formulation of personalized treatment decisions. [ABSTRACT FROM AUTHOR]

A stable mitochondrial pool is crucial for healthy cell function and survival. Altered redox biology can adversely affect mitochondria through induction of a variety of cell death and survival pathways, yet the understanding of mitochondria and their dysfunction in primary human cells and in specific disease states, including asthma, is modest. Ferroptosis is traditionally considered an iron dependent, hydroperoxy-phospholipid executed process, which induces cytosolic and mitochondrial damage to drive programmed cell death. However, in this report we identify a lipoxygenase orchestrated, compartmentally-targeted ferroptosis-associated peroxidation process which occurs in a subpopulation of dysfunctional mitochondria, without promoting cell death. Rather, this mitochondrial peroxidation process tightly couples with PTEN-induced kinase (PINK)−1(PINK1)-Parkin-Optineurin mediated mitophagy in an effort to preserve the pool of functional mitochondria and prevent cell death. These combined peroxidation processes lead to altered epithelial cell phenotypes and loss of ciliated cells which associate with worsened asthma severity. Ferroptosis-targeted interventions of this process could preserve healthy mitochondria, reverse cell phenotypic changes and improve disease outcomes. Altered redox biology causes mitochondrial dysfunction, yet mechanisms and implications vary. Here, the authors identify 15 lipoxygenase-linked mitochondrial ferroptosis and mitophagy driving epithelial cell differentiation and asthma outcomes. [ABSTRACT FROM AUTHOR]

Gene targeting (GT) allows precise manipulation of genome sequences, such as knock-ins and sequence substitutions, but GT in seed plants remains a challenging task. Engineered sequence-specific nucleases (SSNs) are known to facilitate GT via homology-directed repair (HDR) in organisms. Here, we demonstrate that Cas12a and a temperature-tolerant Cas12a variant (ttCas12a) can efficiently establish precise and heritable GT at two loci in Arabidopsis thaliana (Arabidopsis) through a sequential transformation strategy. As a result, ttCas12a showed higher GT efficiency than unmodified Cas12a. In addition, the efficiency of transcriptional and translational enhancers for GT via sequential transformation strategy was also investigated. These enhancers and their combinations were expected to show an increase in GT efficiency in the sequential transformation strategy, similar to previous reports of all-in-one strategies, but only a maximum twofold increase was observed. These results indicate that the frequency of double strand breaks (DSBs) at the target site is one of the most important factors determining the efficiency of genetic GT in plants. On the other hand, a higher frequency of DSBs does not always lead to higher efficiency of GT, suggesting that some additional factors are required for GT via HDR. Therefore, the increase in DSB can no longer be expected to improve GT efficiency, and a new strategy needs to be established in the future. This research opens up a wide range of applications for precise and heritable GT technology in plants. Key message: The combination of enhancers, Cas12a, and sequential transformation strategies enables efficient and precise heritable gene targeting in Arabidopsis. [ABSTRACT FROM AUTHOR]

In the context of the "Belt and Road Initiative", the sustainable development of border cities is paramount for facilitating intergovernmental exchanges. Using the system dynamics approach, we integrated border policy factors to create the Border City Coordinated Development (BCCD-SD) model, encompassing three dimensions: Economic, Social, and Resource-Environment. Furthermore, a comprehensive evaluation indicator, the City Coordinated Development Index (CCDI), was devised. Using Lincang City in Southwest China as a case study, this article examines the trends in city development under three scenarios: Inertial Development, Rapid Development, and Green Development. The research findings demonstrate that the model adeptly captures trends in the city coordinated development indicators. Among the three scenarios, the rapid development scenario stands out, yielding the most favorable economic indicators, superior public infrastructure, and the highest employed population. However, the rapid development path, which is heavily focused on economic growth, intensifies resource and environmental pressures, giving rise to sustainability challenges. In contrast, although the green development scenario trails slightly in economic performance compared to rapid development, it fosters a larger urban population and transition of the employed population into citizens while excelling in resource and environmental aspects. Overall, the CCDI attains its highest score under the green development scenario, surpassing those of rapid and inertia development, signifying superior city development coordination along the green path. This scenario effectively combines economic growth, social progress, and resource-environment protection. This study also emphasizes the pivotal role of ports in the coordinated development of border cities and underscores the necessity of expediting the transition from a "gateway" economy to a "port+" economy. One objective of this article is to encourage border cities to serve as more effective windows to the outside world, promote regional coordination, and achieve high-quality development. [ABSTRACT FROM AUTHOR]

Background: Conflicting results have been reported on the association of dietary unsaturated fatty acids (UFAs) with longevity and cardiovascular health. Most previous studies have focused only on the amount of UFAs consumed, not the timing of intake. Methods: This prospective cohort study used data from 30,136 adults aged 18 years and older. Intakes of UFAs by meal time and types were assessed by a 24-h dietary recall for two days. The covariate-adjusted survey-weighted Cox proportional hazards models were performed to evaluate the associations of dietary total unsaturated fatty acid (TUFA), polyunsaturated fatty acid (PUFA), and monounsaturated fatty acid (MUFA) intakes throughout the day and three meals with mortality. Results: During a median of 10.0 years of follow-up, 4510 total deaths occurred. All-cause mortality decreased with increasing intakes at dinner of TUFA (HR: 0.87 [0.77–0.98]), PUFA (HR: 0.81 [0.73–0.91]), and MUFA (HR: 0.88 [0.77–0.99]). With an increased intake of PUFA at dinner, CVD mortality showed a decreasing trend. However, the inverted L-shaped non-linear trend in all-cause mortality was found with increasing intake at breakfast of TUFA (HR: 1.35 [1.17–1.57], Q3 vs. Q1), PUFA (HR: 1.30 [1.13–1.50]), and MUFA (HR: 1.28 [1.13–1.45]). Meanwhile, increased breakfast intake of UFAs was associated with increased CVD and heart disease mortality. Conclusions: Meal timing influences the association of UFAs with all-cause and CVD-related mortality. [ABSTRACT FROM AUTHOR]

Background: The CRC‐VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. Methods: This study performed an analysis of the CRC‐VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. Results: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow‐up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. Conclusions: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery. [ABSTRACT FROM AUTHOR]

In this work, we mainly consider the Cauchy problem for the reverse space-time nonlocal Hirota equation with the initial data rapidly decaying in the solitonless sector. Start from the Lax pair, we first construct the basis Riemann-Hilbert problem for the reverse space-time nonlocal Hirota equation. Furthermore, using the approach of Deift-Zhou nonlinear steepest descent, the explicit long-time asymptotics for the reverse space-time nonlocal Hirota is derived. For the reverse space-time nonlocal Hirota equation, since the symmetries of its scattering matrix are different with the local Hirota equation, the ϑ(λi) (i = 0, 1) would like to be imaginary, which results in the δ λ i 0 contains an increasing t ± I m ϑ (λ i) 2 , and then the asymptotic behavior for nonlocal Hirota equation becomes differently. [ABSTRACT FROM AUTHOR]

The design and synthesis of porous carbons with unique structures and diverse functionalities as CO2 adsorbents constitute a challenging and intriguing research topic. In this study, the synthesis of hollow micro-mesoporous nitrogen-doped carbon nanoparticles (NPCS) and its adsorption of CO2 were investigated. Highly porous nitrogen-doped carbon nanoparticles were successfully synthesized by using economically available resorcinol and formaldehyde as carbon precursors, with N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (KH-792) as a soft template and silica sol as a hard template. The hollow nitrogen-doped carbon nanoparticles exhibit an evident microporous-mesoporous structure and have two different scales of mesopores with 9 nm and 12 nm, respectively. The effects of various synthetic parameters on the formation of hollow nitrogen-doped carbon nanoparticles were analyzed. The hollow nitrogen-doped carbon nanoparticles exhibited specific surface area of 1090 to 1716 m2/g and nitrogen content of 2.83 to 5.28%. At 273 K and 1 bar, the experimental results demonstrated the positive effects of the enriched pore structure and nitrogen doping on CO2 adsorption. The optimum adsorption capacity of activated NPCS (ANPCS) was 5.11 mmol/g with excellent CO2/N2 selectivity value of 20.44 at 273 K and 1 bar. The initial heat of adsorption value for ANPCS was 30.90 KJ/mol. Additionally, the hollow nitrogen-doped carbon nanoparticles retained 99.2% of the initial adsorbed amount after 5 cycles of adsorption. The excellent adsorption performance of the material can be ascribed not only to its extensive specific surface area and enriched nitrogen but also to its mesoporous and hollow structure, which facilitates rapid CO2 transport. Highlights: The combination of soft and hard templates was used to prepare hollow micro-mesoporous nitrogen-doped carbon nanoparticles. N-(2-aminoethyl)-3-aminopropyltrimethoxysilane is used not only as structure-directing and pore-forming agent, but also nitrogen source. The carbon nanoparticles have excellent CO2 adsorption due to their large specific surface area, high nitrogen content and mesoporous hollow structures. The mesoporous and hollow structures leads to high CO2 transport rates in carbon nanoparticles. [ABSTRACT FROM AUTHOR]

This paper presents a high-resolution 18-bit SAR ADC with a high 10-bit capacitor DAC and a low 8-bit resistor DAC. The total required number of the unit capacitors is decreased to 512. Foreground digital calibration based on capacitive recombination is introduced to improve linearity. Preamplifiers and output offset storage(OOS) enhance the noise and offset performance of the comparator. As a result, the design under 180 nm process achieves a signal-to-noise and distortion ratio(SNDR) of 105.5dB and a spurious-free dynamic range (SFDR) of 116.3dB under 1 MS/s sampling rate with a single channel. The effective number of bits (ENOB) can reach 17.23 bits with a Nyquist-rate input while consuming 46 mW from a 5 V supply. The resultant Schreier and Walden figures of merit (FoM) are 178.92 dB and 295.34 fJ/conversion-step, respectively. The proposed SAR ADC occupies an actual area of 3850 μ m by 2810 μ m. [ABSTRACT FROM AUTHOR]

Objective: To investigate the macular morphological and visual outcomes of combined idiopathic epiretinal membrane (iERM) removal with triamcinolone acetonide (TA) injection based on consideration of the ectopic inner foveal layer (EIFL) staging scheme. Methods: Retrospective case–control study. The clinical data of 84 eyes of 84 patients who underwent vitrectomy for iERM between 2018 and 2022 were reviewed. The enrolled subjects were divided into the TA and non-TA groups. Fifty-one eyes received intravitreal TA injection following vitrectomy and ERM peeling (TA group), and 33 were only treated by standard vitrectomy and ERM peeling (non-TA group). Preoperative and postoperative EIFL stages, central foveal thickness (CFT), and best-corrected visual acuity (BCVA) were compared between both groups. Results: After a mean follow-up of 7.69 ± 3.68 months, both groups exhibited significant improvement in EIFL stages (P < 0.01), with no discernible advantage observed in the TA group. The TA and non-TA groups demonstrated improvement in the EIFL stages in 56.86 and 63.64% of eyes, respectively (P = 0.43). The CFT and BCVA significantly improved in both groups at the final visit (P < 0.01). However, CFT in the non-TA group displayed a more significant reduction during the follow-up (P < 0.03). Subgroup analysis revealed no significant differences in postoperative CFT and BCVA between the two groups in cases with or without continuous EIFL (P > 0.10). Conclusion: Our findings indicate that combined intravitreal TA injection following ERM removal conferred no significant benefits in alleviating macular thickening or improving visual acuity in iERM. [ABSTRACT FROM AUTHOR]