Advancing Out-of-Distribution Detection through Data Purification and Dynamic Activation Function Design

In the dynamic realms of machine learning and deep learning, the robustness and reliability of models are paramount, especially in critical real-world applications. A fundamental challenge in this sphere is managing Out-of-Distribution (OOD) samples, significantly increasing the risks of model misclassification and uncertainty. Our work addresses this challenge by enhancing the detection and management of OOD samples in neural networks. We introduce OOD-R (Out-of-Distribution-Rectified), a meticulously curated collection of open-source datasets with enhanced noise reduction properties. In-Distribution (ID) noise in existing OOD datasets can lead to inaccurate evaluation of detection algorithms. Recognizing this, OOD-R incorporates noise filtering technologies to refine the datasets, ensuring a more accurate and reliable evaluation of OOD detection algorithms. This approach not only improves the overall quality of data but also aids in better distinguishing between OOD and ID samples, resulting in up to a 2.5\% improvement in model accuracy and a minimum 3.2\% reduction in false positives. Furthermore, we present ActFun, an innovative method that fine-tunes the model's response to diverse inputs, thereby improving the stability of feature extraction and minimizing specificity issues. ActFun addresses the common problem of model overconfidence in OOD detection by strategically reducing the influence of hidden units, which enhances the model's capability to estimate OOD uncertainty more accurately. Implementing ActFun in the OOD-R dataset has led to significant performance enhancements, including an 18.42\% increase in AUROC of the GradNorm method and a 16.93\% decrease in FPR95 of the Energy method. Overall, our research not only advances the methodologies in OOD detection but also emphasizes the importance of dataset integrity for accurate algorithm evaluation

Dynamic control of working slope shape and optimization of advance speed in seasonally stripped open-pit coal mine

Due to the discontinuity of the stripping project in seasonal stripping open-pit coal mines, the untimely advance distance of the working slope is huge. In order to reduce the advance stripping and save the stripping distance, research was carried out on dynamic control of the shape of the working slope and optimization of the limit advance speed of the working slope in seasonal stripped open-pit coal mines. This paper explains the shape and operation procedure of the working slope in seasonal stripped open-pit coal mines and analyzes factors that influence working slope shape and advance speed. Based on structural form of working slope and stripping operation mode of seasonally stripped open-pit coal mines, an engineering model for shape optimization of working slope is established. The relationship between circular advance distance of working slope with working bench width and exposed coal mode of stope is discussed. Bench group cycle advance engineering quantity and production capacity of layered equipment, advance time of the working slope cycle and calculation method for reliability of side slope transportation system are given. With optimization goal of minimizing transport work of stripping material and time-space continuity of stripping engineering as constraint condition, mathematical model for shape optimization of working slope in seasonally stripped open-pit coal mine is established. Sequential quadratic programming algorithm (SQP) is introduced to solve nonlinear programming. A method to realize dynamic control of shape of working slope of seasonally stripped open-pit coal mine by determining combination mode of stripping benches and working bench width and a method to optimize limit advance speed of stripped working slope are proposed. Taking Shengli West No.2 Open-pit Coal Mine as an engineering background, above-mentioned optimization control method is applied for research and calculation and solution are carried out by establishing form optimization model of stripping working slope and substituting actual parameters of West No.2 Open-pit Mine. Results show that when the number of benches in bench group is 5 and working bench width is 89 m, advance of working slope meets the requirements of space-time continuity in stripping engineering and transport work of stripped objects is smallest. In this shape, limit advance speed of the working slope is 320 m/a, and change of limit advance speed of the working slope is analyzed and determined when combination of benches and cyclic advance distance is changed

Reverse atrial remodeling in heart failure with recovered ejection fraction

Background Heart failure with recovered ejection fraction (HFrecEF) has been a newly recognized entity since 2020. However, the concept has primarily focused on left ventricular ejection fraction improvement, with less focus on the recovery of the left atrium. In this study, we investigated changes in left atrial (LA) echocardiographic indices in HFrecEF. Methods and Results An inpatient cohort with heart failure with reduced ejection fraction (HFrEF) was identified retrospectively and followed up prospectively in a single tertiary hospital. The enrolled patients were classified into HFrecEF and persistent HFrEF groups. Alternations in LA parameters by echocardiography were calculated. The primary outcome was a composite of cardiovascular death or heart failure rehospitalization. A total of 699 patients were included (HFrecEF: n=228; persistent HFrEF: n=471). Compared with persistent HFrEF, the HFrecEF group had greater reductions in LA diameter, LA transverse diameter, LA superior–inferior diameter, LA volume, and LA volume index but not in LA sphericity index. Cox regression analysis showed that the HFrecEF group experienced lower risks of prespecified end points than the persistent HFrEF group after adjusting for confounders. Additionally, 136 (59.6%) and 62 (13.0%) patients showed LA reverse remodeling (LARR) for the HFrecEF and persistent HFrEF groups, respectively. Among the HFrecEF subgroup, patients with LARR had better prognosis compared with those without LARR. Multivariate logistic analysis demonstrated that age and coronary heart disease were 2 independent negative predictors for LARR. Conclusions In HFrecEF, both left ventricular systolic function and LA structure remodeling were improved. Patients with HFrecEF with LARR had improved clinical outcomes, indicating that the evaluation of LA size provides a useful biomarker for risk stratification of heart failure

Unleashing the Power of Prompt-driven Nucleus Instance Segmentation

Nucleus instance segmentation in histology images is crucial for a broad spectrum of clinical applications. Current dominant algorithms rely on regression of nuclear proxy maps. Distinguishing nucleus instances from the estimated maps requires carefully curated post-processing, which is error-prone and parameter-sensitive. Recently, the Segment Anything Model (SAM) has earned huge attention in medical image segmentation, owing to its impressive generalization ability and promptable property. Nevertheless, its potential on nucleus instance segmentation remains largely underexplored. In this paper, we present a novel prompt-driven framework that consists of a nucleus prompter and SAM for automatic nucleus instance segmentation. Specifically, the prompter learns to generate a unique point prompt for each nucleus while the SAM is fine-tuned to output the corresponding mask for the prompted nucleus. Furthermore, we propose the inclusion of adjacent nuclei as negative prompts to enhance the model's capability to identify overlapping nuclei. Without complicated post-processing, our proposed method sets a new state-of-the-art performance on three challenging benchmarks. Code is available at \url{github.com/windygoo/PromptNucSeg}Comment: under revie

Tyrosine Phosphatase PTPRO Deficiency in ERBB2-Positive Breast Cancer Contributes to Poor Prognosis and Lapatinib Resistance

Despite the initial benefit from treating ERBB2-positive breast cancer with tyrosine kinase inhibitor lapatinib, resistance develops inevitably. Since the expression of protein tyrosine phosphatase receptor-type O (PTPRO), a member of the R3 subfamily of receptor protein tyrosine phosphatases (PTPs), is inversely correlated with the aggressiveness of multiple malignancies, we decided to explore the correlation between PTPRO and lapatinib resistance in ERBB2-positive breast cancer. Results of immunohistochemical (IHC) staining and the correlation analysis between the expression levels of PTPRO and the clinicopathological parameters indicate that PTPRO is downregulated in cancer tissues as compared with normal tissues and negatively associated with differentiation, tumor size, tumor depth, as well as the expression of ERBB2 and Ki67. Results from Kaplan–Meier analyses indicate that lower expression of PTPRO is correlated with shorter relapse-free survival for patients with ERBB2-positive breast cancer, and multivariable Cox regression analysis found that PTPRO can potentially serve as an independent prognostic indicator for ERBB2-positive breast cancer. Results from both human breast cancer cells with PTPRO knockdown or overexpression and mouse embryonic fibroblasts (MEFs) which derived from Ptpro ( +/+ ) and Ptpro ( −/− ) mice with then stably transfected plasmid FUGW-Erbb2 consistently demonstrated the essentiality of PTPRO in the lapatinib-mediated anticancer process. Our findings suggest that PTPRO is not only able to serve as an independent prognostic indicator, but upregulating PTPRO can also reverse the lapatinib resistance of ERBB2-positive breast cancer

Generation and Application of Inducible Chimeric RNA ASTN2-PAPPA(as) Knockin Mouse Model

Chimeric RNAs (chiRNAs) play many previously unrecognized roles in different diseases including cancer. They can not only be used as biomarkers for diagnosis and prognosis of various diseases but also serve as potential therapeutic targets. In order to better understand the roles of chiRNAs in pathogenesis, we inserted human sequences into mouse genome and established a knockin mouse model of the tamoxifen-inducible expression of ASTN2-PAPPA antisense chimeric RNA (A-P(as)chiRNA). Mice carrying the A-P(as)chiRNA knockin gene do not display any apparent abnormalities in growth, fertility, histological, hematopoietic, and biochemical indices. Using this model, we dissected the role of A-P(as)chiRNA in chemical carcinogen 4-nitroquinoline 1-oxide (4NQO)-induced carcinogenesis of esophageal squamous cell carcinoma (ESCC). To our knowledge, we are the first to generate a chiRNA knockin mouse model using the Cre-loxP system. The model could be used to explore the roles of chiRNA in pathogenesis and potential targeted therapies

Targeting PELP1 Attenuates Angiogenesis and Enhances Chemotherapy Efficiency in Colorectal Cancer

SIMPLE SUMMARY: Excessive angiogenesis is a distinct feature of colorectal cancer (CRC) and plays a pivotal role in tumor development and metastasis. Therefore, it is essential to clarify the underlying mechanism of angiogenesis. In this study, we found that the level of proline-, glutamic acid, and leucine-rich protein 1 (PELP1) was positively correlated with microvessel density (MVD). In vitro and in vivo assays further showed PELP1 regulated angiogenesis via the Signal transducer and activator of transcription 3 (STAT3)/Vascular endothelial growth factor (VEGFA). Notably, we found that inhibition of PELP1 enhanced the efficacy of chemotherapy due to vascular normalization. Thus, targeting of PELP1 may be a potentially therapeutic strategy for CRC. ABSTRACT: Abnormal angiogenesis is one of the important hallmarks of colorectal cancer as well as other solid tumors. Optimally, anti-angiogenesis therapy could restrain malignant angiogenesis to control tumor expansion. PELP1 is as a scaffolding oncogenic protein in a variety of cancer types, but its involvement in angiogenesis is unknown. In this study, PELP1 was found to be abnormally upregulated and highly coincidental with increased MVD in CRC. Further, treatment with conditioned medium (CM) from PELP1 knockdown CRC cells remarkably arrested the function of human umbilical vein endothelial cells (HUVECs) compared to those treated with CM from wildtype cells. Mechanistically, the STAT3/VEGFA axis was found to mediate PELP1-induced angiogenetic phenotypes of HUVECs. Moreover, suppression of PELP1 reduced tumor growth and angiogenesis in vivo accompanied by inactivation of STAT3/VEGFA pathway. Notably, in vivo, PELP1 suppression could enhance the efficacy of chemotherapy, which is caused by the normalization of vessels. Collectively, our findings provide a preclinical proof of concept that targeting PELP1 to decrease STAT3/VEGFA-mediated angiogenesis and improve responses to chemotherapy due to normalization of vessels. Given the newly defined contribution to angiogenesis of PELP1, targeting PELP1 may be a potentially ideal therapeutic strategy for CRC as well as other solid tumors

Neoantigen-based cancer vaccination using chimeric RNA-loaded dendritic cell-derived extracellular vesicles

Cancer vaccines critically rely on the availability of targetable immunogenic cancer-specific neoepitopes. However, mutation-based immunogenic neoantigens are rare or even non-existent in subgroups of cancer types. To address this issue, we exploited a cancer-specific aberrant transcription-induced chimeric RNA, designated A-Pas chiRNA, as a possible source of clinically relevant and targetable neoantigens. A-Pas chiRNA encodes a recently discovered cancer-specific chimeric protein that comprises full-length astrotactin-2 (ASTN2) C-terminally fused in-frame to the antisense sequence of the 18th intron of pregnancy-associated plasma protein-A (PAPPA). We used extracellular vesicles (EVs) from A-Pas chiRNA-transfected dendritic cells (DCs) to produce the cell-free anticancer vaccine DEXA-P . Treatment of immunocompetent cancer-bearing mice with DEXA-P inhibited tumour growth and prolonged animal survival. In summary, we demonstrate for the first time that cancer-specific transcription-induced chimeric RNAs can be exploited to produce a cell-free cancer vaccine that induces potent CD8+ T cell-mediated anticancer immunity. Our novel approach may be particularly useful for developing cancer vaccines to treat malignancies with low mutational burden or without mutation-based antigens. Moreover, this cell-free anticancer vaccine approach may offer several practical advantages over cell-based vaccines, such as ease of scalability and genetic modifiability as well as enhanced shelf life