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Introduction: Fear memory formation has been implicated in fear- and stress-related psychiatric disorders, including post-traumatic stress disorder (PTSD) and phobias. Synapse deficiency and microglial activation are common among patients with PTSD, and induced in animal models of fear conditioning. Increasing studies now focus on explaining the specific mechanisms between microglia and synapse deficiency. Though newly-identified microglia regulator triggering receptor expressed on myeloid cells 2 (TREM2) plays a role in microglial phagocytic activity, its role in fear-formation remains unknown. Methods: We successfully constructed a fear- formation model by foot-shock. Four days after foot-shock, microglial capacity of synaptic pruning was investigated via western blotting, immunofluorescence and Golgi-Cox staining. Prelimbic chemical deletion or microglia inhibition was performed to detect the role of microglia in synaptic loss and neuron activity. Finally, Trem2 knockout mice or wild-type mice with Trem2 siRNA injection were exposed to foot-shock to identify the involvement of TREM2 in fear memory formation. Results: The results herein indicate that the foot-shock protocol in male mice resulted in a fear formation model. Mechanistically, fear conditioning enhanced the microglial capacity for engulfing synapse materials, and led to glutamatergic neuron activation in the prelimbic cortex. Prelimbic chemical deletion or microglia inhibition improved fear memory formation. Further investigation demonstrated that TREM2 regulates microglial phagocytosis, enhancing synaptic pruning. Trem2 knockout mice showed remarkable reductions in prelimbic synaptic pruning and reduced neuron activation, with decreased fear memory formation. Discussion: Our cumulative results suggest that prelimbic TREM2-mediated excessive microglial synaptic pruning is involved in the fear memory formation process, leading to development of abnormal stress-related behavior. [ABSTRACT FROM AUTHOR]

Background: This study aimed to identify the clinical predictors for the response of patients with mCRPC to ARATs. Materials and Methods: We retrospectively collected data on consecutive patients who were diagnosed with mCRPC and underwent ARAT treatment during this stage of the disease. Clinical parameters were obtained through medical chart reviews. ARAT failure was defined as a continuous increase in the serum prostate‐specific antigen (PSA) level above nadir to > 2 ng/mL, accompanied by radiographic progression. ARAT failure‐free survival and overall survival were assessed through Kaplan–Meier survival analysis and Cox regression survival analysis. Nomogram analysis based on significant predictors of ARAT failure‐free survival was performed. Results: In total, 319 patients with mCRPC who underwent ARAT were included. Multivariate analysis revealed that age, International Society of Urological Pathology (ISUP) grading, and chemotherapy‐naïve status were significant predictors of ARAT failure‐free survival. For overall survival, age, ISUP grading, and nadir PSA level during androgen deprivation therapy (ADT) were significant predictors. Through nomogram analysis based on age, ISUP grading, and chemotherapy‐naïve status, the likelihood of ARAT duration being more or less than 1 year could be predicted. Conclusion: For mCRPC patients, being older, having ISUP Grade 5 cancer, and having a history of chemotherapy were associated with a shorter duration of response to next‐line ARATs. Therefore, other therapeutic agents should be prioritized for such patients. Notably, among the included patients, those who were older, had a higher ISUP grade and a higher nadir PSA level during ADT exhibited worse overall survival. [ABSTRACT FROM AUTHOR]

Rice (Oryza sativa L.) endosperm is essential to provide nutrients for seed germination and determine grain yield. RNA editing, a post-transcriptional modification essential for plant development, unfortunately, is not fully characterized during rice endosperm development. Here, we perform systematic analyses to characterize RNA editome during rice endosperm development. We find that most editing sites are C-to-U CDS-recoding in mitochondria, leading to increased hydrophobic amino acids and changed structures of mitochondrial proteins. Comparative analysis of RNA editome reveals that CDS-recoding sites present higher editing frequencies with lower variabilities and their resultant recoded amino acids tend to exhibit stronger evolutionary conservation across many land plants. Furthermore, we classify mitochondrial genes into three groups, presenting distinct patterns in terms of CDS-recoding events. Besides, we conduct genome-wide screening to detect pentatricopeptide repeat (PPR) proteins and construct PPR-RNA binding profiles, yielding candidate PPR editing factors related to rice endosperm development. Taken together, our findings provide valuable insights for deciphering fundamental mechanisms of rice endosperm development underlying RNA editing machinery. A systematic study of the RNA editome during rice endosperm development suggests that predominant C-to-U CDS-recoding editing events produce conserved hydrophobic amino acids, and affect structures and functions of mitochondrial proteins. [ABSTRACT FROM AUTHOR]

Rice (Oryza sativa L.) endosperm is essential to provide nutrients for seed germination and determine grain yield. RNA editing, a post-transcriptional modification essential for plant development, unfortunately, is not fully characterized during rice endosperm development. Here, we perform systematic analyses to characterize RNA editome during rice endosperm development. We find that most editing sites are C-to-U CDS-recoding in mitochondria, leading to increased hydrophobic amino acids and changed structures of mitochondrial proteins. Comparative analysis of RNA editome reveals that CDS-recoding sites present higher editing frequencies with lower variabilities and their resultant recoded amino acids tend to exhibit stronger evolutionary conservation across many land plants. Furthermore, we classify mitochondrial genes into three groups, presenting distinct patterns in terms of CDS-recoding events. Besides, we conduct genome-wide screening to detect pentatricopeptide repeat (PPR) proteins and construct PPR-RNA binding profiles, yielding candidate PPR editing factors related to rice endosperm development. Taken together, our findings provide valuable insights for deciphering fundamental mechanisms of rice endosperm development underlying RNA editing machinery. A systematic study of the RNA editome during rice endosperm development suggests that predominant C-to-U CDS-recoding editing events produce conserved hydrophobic amino acids, and affect structures and functions of mitochondrial proteins. [ABSTRACT FROM AUTHOR]

Capsule endoscopy (CE) is non-invasive and painless during gastrointestinal examination. However, capsule endoscopy can increase the workload of image reviewing for clinicians, making it prone to missed and misdiagnosed diagnoses. Current researches primarily concentrated on binary classifiers, multiple classifiers targeting fewer than four abnormality types and detectors within a specific segment of the digestive tract, and segmenters for a single type of anomaly. Due to intra-class variations, the task of creating a unified scheme for detecting multiple gastrointestinal diseases is particularly challenging. A cascade neural network designed in this study, Cascade-EC, can automatically identify and localize four types of gastrointestinal lesions in CE images: angiectasis, bleeding, erosion, and polyp. Cascade-EC consists of EfficientNet for image classification and CA_stm_Retinanet for lesion detection and location. As the first layer of Cascade-EC, the EfficientNet network classifies CE images. CA_stm_Retinanet, as the second layer, performs the target detection and location task on the classified image. CA_stm_Retinanet adopts the general architecture of Retinanet. Its feature extraction module is the CA_stm_Backbone from the stack of CA_stm Block. CA_stm Block adopts the split-transform-merge strategy and introduces the coordinate attention. The dataset in this study is from Shanghai East Hospital, collected by PillCam SB3 and AnKon capsule endoscopes, which contains a total of 7936 images of 317 patients from the years 2017 to 2021. In the testing set, the average precision of Cascade-EC in the multi-lesions classification task was 94.55%, the average recall was 90.60%, and the average F1 score was 92.26%. The mean mAP@ 0.5 of Cascade-EC for detecting the four types of diseases is 85.88%. The experimental results show that compared with a single target detection network, Cascade-EC has better performance and can effectively assist clinicians to classify and detect multiple lesions in CE images. [ABSTRACT FROM AUTHOR]

Autonomous vehicles require more precise and reliable braking control, and electro-hydraulic braking (EHB) systems are better adapted to the development of autonomous driving. However, EHB systems inevitably suffer from unilateral dead zone nonlinearity, which adversely affects the position tracking control. Therefore, a finite-time adaptive control strategy was designed for unilateral dead zone nonlinearity. Initially, the unilateral dead zone nonlinearity was reformulated into a matched disturbance term and an unmatched disturbance term to reduce the adverse effects of disturbances, thereby enhancing system controllability. Then, the "complexity explosion" in the design of the control strategy was avoided by command filtering, and the design process of the controller was simplified. Furthermore, the finite-time control theory was employed to boost the system's convergence speed, thereby enhancing control performance. In order to ensure the stability of the system under the dead zone disturbance, the unknown disturbance terms were estimated. The stability of the control strategy was validated through the finite-time stability theorem and the Lyapunov function. Eventually, simulations and hardware-in-the-loop (HIL) experiments validated the feasibility and availability of the finite-time adaptive control strategy. [ABSTRACT FROM AUTHOR]

This study explores the role of the transcription factor FOXM1 in the initiation and progression of oesophageal squamous cell carcinoma (ESCC). Our findings reveal that FOXM1 is highly expressed in ESCC and correlates with the prognosis of the disease. The relationship between FOXM1 and asparagine synthetase (ASNS) is investigated, and the study demonstrates that FOXM1 activates ASNS, impacting the tumour stemness of ESCC. In this study, we reveal the association between FOXM1 and ESCC development, as well as FOXM1's promotion of migration and proliferation in ESCC cells. The study also highlights FOXM1's regulation of ASNS transcription and the functional role of ASNS in ESCC metastasis and growth. Furthermore, the study explores the impact of FOXM1 and ASNS on ESCC stemness and their potential implications for chemotherapy resistance. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to develop an innovative approach for monitoring and assessing labor pain through ECG waveform analysis, utilizing machine learning techniques to monitor pain resulting from uterine contractions. Methods: The study was conducted at National Taiwan University Hospital between January and July 2020. We collected a dataset of 6010 ECG samples from women preparing for natural spontaneous delivery (NSD). The ECG data was used to develop an ECG waveform-based Nociception Monitoring Index (NoM). The dataset was divided into training (80%) and validation (20%) sets. Multiple machine learning models, including LightGBM, XGBoost, SnapLogisticRegression, and SnapDecisionTree, were developed and evaluated. Hyperparameter optimization was performed using grid search and five-fold cross-validation to enhance model performance. Results: The LightGBM model demonstrated superior performance with an AUC of 0.96 and an accuracy of 90%, making it the optimal model for monitoring labor pain based on ECG data. Other models, such as XGBoost and SnapLogisticRegression, also showed strong performance, with AUC values ranging from 0.88 to 0.95. Conclusions: This study demonstrates that the integration of machine learning algorithms with ECG data significantly enhances the accuracy and reliability of labor pain monitoring. Specifically, the LightGBM model exhibits exceptional precision and robustness in continuous pain monitoring during labor, with potential applicability extending to broader healthcare settings. Trial registration: ClinicalTrials.gov Identifier: NCT04461704. [ABSTRACT FROM AUTHOR]

In our investigation of the influence rules and mechanisms of the building orientation on the surface properties of 316L stainless steel created via selective laser melting, we used X-ray diffractometry, scanning electron microscopy, and electron backscatter diffraction to investigate the phases, microstructures, and textures of specimens. In addition, we employed a digital microhardness tester, friction, and wear-testing apparatus, along with an electrochemical workstation, to examine variations in the surface properties. The results indicated that the surface phase compositions of the specimens with different building orientations were similar; however, they displayed anisotropic behavior in grain size, orientation, and texture. Notably, the surface densification of the specimens at 0°, 30°, 45°, and 60° initially decreased before subsequently increasing. In contrast, the surface roughness showed a pattern of first increasing and then declining. Moreover, the microhardness, wear resistance, and corrosion resistance decreased with an increasing inclination angle. [ABSTRACT FROM AUTHOR]

Background: Amidst the expansion of student enrollment in higher education, the well-being and retention rates of students have emerged as important concerns. Resilience, especially academic resilience, a multidimensional construct that can lead to academic success in adversity, is pivotal in enabling students to successfully cope with academic challenges. While the Academic Resilience Scale-30 (ARS-30) has been validated as an effective instrument in various languages, its applicability for Chinese students in higher education remains unexplored. Objective: This study aims to translate and validate the ARS-30 in Chinese, assessing its reliability and validity among Chinese college students in higher education. Methods: A convenience sample of 1,542 students participated in this study. The inventory included the demographic form, Chinese version of ARS-30 (C-ARS-30), 10-item Connor Davidson Resilience Scale (CD-RISC-10), and General Self-Efficacy Scale (GSES). The assessment of validity was conducted by analyzing content validity, construct validity, convergent and discriminant validity, as well as criterion-related validity. Construct validity was evaluated through Confirmatory Factor Analysis (CFA), Exploratory Factor Analysis (EFA) and Exploratory Structural Equation Modeling (ESEM). Reliability analysis was performed using Cronbach's alpha and test-retest reliability. Results: The C-ARS-30 demonstrated commendable content validity, with the CVI value of items ranging from 0.833 to 1.000, and a total scale CVI of 0.986. ESEM analysis revealed a solid four-factor structure, maintaining the scale's 30 items with excellent fit indices (χ2/df = 2.647, CFI = 0.937, TLI = 0.915, RMSEA = 0.057, SRMR = 0.027). The total score of C-ARS-30 exhibited positive correlations with the CD-RISC-10 (r = 0.542) and the GSES (r = 0.488). The scale demonstrated high internal consistency (Cronbach's a = 0.930) and test-retest reliability (0.794, p < 0.01). Conclusion: The C-ARS-30 is a reliable and valid instrument for assessing academic resilience among Chinese college students, offering a valuable tool for educational and psychological evaluations. [ABSTRACT FROM AUTHOR]

Purpose: Esophageal squamous cell carcinoma (ESCC) is an aggressive disease with a poor prognosis, caused by the inactivation of critical cell growth regulators that lead to uncontrolled proliferation and increased malignancy. Although Serine/Threonine Kinase 3 (STK3), also known as Mammalian STE20-like protein kinase 2 (MST2), is a highly conserved kinase of the Hippo pathway, plays a critical role in immunomodulation, organ development, cellular differentiation, and cancer suppression, its phenotype and function in ESCC require further investigation. In this study, we report for the first time on the role of STK3 kinase and its activation condition in ESCC, as well as the mechanism and mediators of kinase activation. Methods: In this study, we investigated the expression and clinical significance of STK3 in ESCC. We first used bioinformatics databases and immunohistochemistry to analyze STK3 expression in the ESCC patient cohort and conducted survival analysis. In vivo, we conducted a tumorigenicity assay using nude mouse models to demonstrate the phenotypes of STK3 kinase. In vitro, we conducted Western blot analysis, qPCR analysis, CO-IP, and immunofluorescence (IF) staining analysis to detect molecule expression, interaction, and distribution. We measured proliferation, migration, and apoptosis abilities in ESCC cells in the experimental groups using CCK-8 and transwell assays, flow cytometry, and EdU staining. We used RNA-seq to identify genes that were differentially expressed in ESCC cells with silenced STK3 or FOXO1. We demonstrated the regulatory relationship of the TP53INP1/P21 gene medicated by the STK3-FOXO1 axis using Western blotting and ChIP in vitro. Results: We demonstrate high STK3 expression in ESCC tissue and cell lines compared to esophageal epithelium. Cellular ROS induces STK3 autophosphorylation in ESCC cells, resulting in upregulated p-STK3/4. STK3 activation inhibits ESCC cell proliferation and migration by triggering apoptosis and suppressing the cell cycle. STK3 kinase activation phosphorylates FOXO1Ser212, promoting nuclear translocation, enhancing transcriptional activity, and upregulating TP53INP1 and P21. We also investigated TP53INP1 and P21's phenotypic effects in ESCC, finding that their knockdown significantly increases tumor proliferation, highlighting their crucial role in ESCC tumorigenesis. Conclusion: STK3 kinase has a high expression level in ESCC and can be activated by cellular ROS, inhibiting cell proliferation and migration. Additionally, STK3 activation-mediated FOXO1 regulates ESCC cell apoptosis and cell cycle arrest by targeting TP53INP1/P21. Our research underscores the anti-tumor function of STK3 in ESCC and elucidates the mechanism underlying its anti-tumor effect on ESCC. [ABSTRACT FROM AUTHOR]

As one of the most promising energy storage devices, supercapacitors exhibit a higher power density than batteries. However, its low energy density usually requires high-performance electrode materials. Although the RuO2 material shows desirable properties, its high cost and toxicity significantly limit its application in supercapacitors. Recent developments demonstrated that Co-based materials have emerged as a promising alternative to RuO2 for supercapacitors due to their low cost, favorable redox reversibility and environmental friendliness. In this paper, the morphological control and performance engineering of Co-based materials are systematically reviewed. Firstly, the principle of supercapacitors is briefly introduced, and the characteristics and advantages of pseudocapacitors are emphasized. The special forms of cobalt-based materials are introduced, including 1D, 2D and 3D nanomaterials. After that, the ways to enhance the properties of cobalt-based materials are discussed, including adding conductive materials, constructing heterostructures and doping heteroatoms. Particularly, the influence of morphological control and modification methods on the electrochemical performances of materials is highlighted. Finally, the application prospect and development direction of Co-based materials are proposed. [ABSTRACT FROM AUTHOR]

Comprehending the spatial–temporal characteristics, contributions, and evolution of driving factors in agricultural non-CO2 greenhouse gas (GHG) emissions at a macro level is pivotal in pursuing temperature control objectives and achieving China's strategic goals related to carbon peak and carbon neutrality. This study employs the Intergovernmental Panel on Climate Change (IPCC) carbon emissions coefficient method to comprehensively evaluate agricultural non-CO2 GHG emissions at the provincial level. Subsequently, the contributions and spatial–temporal evolution of six driving factors derived from the Kaya identity were quantitatively explored using the Logarithmic Mean Divisia Index (LMDI) and Geographical and Temporal Weighted Regression (GTWR) methods. The results revealed that the distribution of agricultural non-CO2 GHG emissions is shifting from the central provinces to the northwest regions. Moreover, the dominant driving factors of agricultural non-CO2 GHG emissions were primarily economic factor (EDL) with positive impact (cumulative promotion is 2939.61 million metric tons (Mt)), alongside agricultural production efficiency factor (EI) with negative impact (cumulative reduction is 2208.98 Mt). Influence of EDL diminished in the eastern coastal regions but significantly impacted underdeveloped regions such as the northwest and southwest. In the eastern coastal regions, EI gradually became the absolute dominant driver, demonstrating a rapid reduction effect. Additionally, a declining birth rate and rural-to-urban population migration have significantly amplified the driving effects of the population factor (RP) at a national scale. These findings, in conjunction with the disparities in geographic and socioeconomic development among provinces, can serve as a guiding framework for the development of a region-specific roadmap aimed at reducing agricultural non-CO2 GHG emissions. [ABSTRACT FROM AUTHOR]

Introduction: Depression is strongly associated with Alzheimer's disease (AD). Antidepressants are commonly used in patients before and after their diagnosis of AD. To date, the relationship between antidepressants and AD remains unclear. Methods: In our study, we administered sertraline or paroxetine to wild type (WT) and APPswe/PSEN1dE9 (APP/PSEN1) transgenic mouse models for up to 12 months. We quantified the drug concentrations using LC-MS/MS analysis and measured serum serotonin level using an ELISA assay. Additionally, we evaluated the amyloid burdens through thioflavin-S and Congo red stainings, and recognition memory using the novel object recognition test. Results: Our findings revealed that mice treated with paroxetine exhibited a significantly higher level of weight gain compared to the control group and increased mortality in APP/PSEN1 mice. After 12 months of antidepressant treatment, the sertraline level was measured at 289.8 ng/g for cerebellum, while the paroxetine level was 792.9 ng/g for cerebellum. Sertraline significantly increased thioflavin-S and Congo red depositions, along with gliosis, in both isocortex and hippocampus of APP/PSEN1 mice compared to the control group. Both antidepressants also led to a decreased recognition index in APP/PSEN1 mice. Conclusion: These findings suggest a potential role of sertraline in AD pathogenesis, emphasizing the need to reassess the use of these antidepressants in patients with AD. [ABSTRACT FROM AUTHOR]

Runway skid resistance should be evaluated and maintained periodically to sustain aircraft operation safety. This study focuses on evaluating runway skid resistance in terms of surface microtexture and macrotexture and determining how aircraft operations affect these characteristics. The friction–speed model developed by the Harmonisation of European Routine and Research Measuring Equipment for Skid Resistance of Roads and Runways–Laboratoire Central des Ponts et Chaussées was selected due to its consistent and rational results. The grip number values measured using a grip tester for 19 continuous months on 2 runways of the Taoyuan International Airport were analysed as a case study. Research outcomes showed that the microtexture of dense grade asphalt concrete was not considerably different from that of stone mastic asphalt concrete, but the latter exhibited markedly better macrotexture than the former. Aircraft landing operation significantly reduced skid resistance at the touchdown zone. In particular, macrotexture was decreased. However, aircraft behaviour at high-speed exits exerted more negative influences on microtexture than on macrotexture. Accordingly, designing a runway surface layer with improved macrotexture at the touchdown zone is recommended and special attention should be given to the microtexture evaluation of the area located immediately before a high-speed exit point. [ABSTRACT FROM AUTHOR]

Objectives: The elderly are disproportionately affected by age-related hearing loss (ARHL). Despite being a well-known tool for ARHL evaluation, the Hearing Handicap Inventory for the Elderly Screening version (HHIE-S) has only traditionally been used for direct screening using self-reported outcomes. This work uses a novel integration of machine learning approaches to improve the predicted accuracy of the HHIE-S tool for ARHL in older adults. Methods: We employed a dataset that was gathered between 2016 and 2018 and included 1,526 senior citizens from several Taipei City Hospital branches. 80% of the data were used for training (n = 1220) and 20% were used for testing (n = 356). XGBoost, Gradient Boosting, and LightGBM were among the machine learning models that were only used and assessed on the training set. In order to prevent data leakage and overfitting, the Light Gradient Boosting Machine (LGBM) model—which had the greatest AUC of 0.83 (95% CI 0.81–0.85)—was then only used on the holdout testing data. Results: On the testing set, the LGBM model showed a strong AUC of 0.82 (95% CI 0.79–0.86), far outperforming conventional techniques. Notably, several HHIE-S items and age were found to be significant characteristics. In contrast to traditional HHIE research, which concentrates on the psychological effects of hearing loss, this study combines cutting-edge machine learning techniques—specifically, the LGBM classifier—with the HHIE-S tool. The incorporation of SHAP values enhances the interpretability of the model's predictions and provides a more comprehensive comprehension of the significance of various aspects. Conclusions: Our methodology highlights the great potential that arises from combining machine learning with validated hearing evaluation instruments such as the HHIE-S. Healthcare practitioners can anticipate ARHL more accurately thanks to this integration, which makes it easier to intervene quickly and precisely. [ABSTRACT FROM AUTHOR]

The Radio Frequency Interference (RFI) generated by the surrounding environment will significantly reduce the observation efficiency of the large radio telescope. The Tian-Ma Radio Telescope (TMRT) has established a RFI monitoring system to keep watch on its surrounding RFI environment chronically in the L, S, C and X bands. The system consists of antennas, receivers, back-ends and control system. To achieve automatic system operation, we design and implement an automation software based on Tango Controls open source framework. This paper will briefly introduce the TMRT RFI Monitoring System (TRMS), and describe the functional design, architecture design and implementation of the automation software. Finally, with the help of this system, we carry out automatic remote monitoring of the RFI environment around the TMRT in the 1.12—12.4 GHz frequency band, and then analyze and verify the observation results. [ABSTRACT FROM AUTHOR]

This study aims to develop a mobile time-banking system on blockchain (MTBB), which can track service transaction records for community elderly care via mutual service exchange. The MTBB was developed to enable organizations, either corporate-social-responsibility organizations or nonprofit organizations to issue proprietary time tokens to members who participate in the organizations' volunteer activities. Database applications with smartphone apps integrated with MultiChain blockchain technology were developed. Metadata with the service transaction information are stored in the MultiChain blocks so that the transaction records are immutable and can be analyzed in the future. Cahn's time-banking guidelines were applied in developing this MTBB with MultiChain blockchain technology integrated for tracking service transaction records. The study also combines one-to-one mutual service exchange with organizations which offer volunteer activities and issue proprietary time tokens. With the blockchain transaction tracking mechanism, all elderly care service records via or within organizations can be tracked and analyzed to show their alignment with some of the Sustainable Development Goals of the United Nations. [ABSTRACT FROM AUTHOR]

Hepatocyte nuclear factor 1α (HNF1α) plays essential roles in controlling development and metabolism; its mutations are clearly linked to the occurrence of maturity-onset diabetes of the young (MODY3) in humans. Lysine 117 (K117) to glutamic acid (E117) mutation in the HNF1α gene has been clinically associated with MODY3, but no functional data on this variant are available. Here, we addressed the role of lysine 117 in HNF1α function using a knock-in animal model and site-directed mutagenesis. HNF1α K117E homozygous mice exhibited dwarfism, hepatic dysfunction, renal Fanconi syndrome, and progressive wasting syndrome. These phenotypes were very similar to those of mice with complete HNF1α deficiency, suggesting that K117 is critical to HNF1α functions. K117E homozygotes developed diabetes in the early postnatal period. The relative deficiency of serum insulin levels and the normal response to insulin treatment in homozygous mice were markedly similar to those in the MODY3 disorder in humans. Moreover, K117E heterozygous mutant causes age-dependent glucose intolerance, which is similar to the pathogenesis of MODY3 as well. K117 mutants significantly reduced the overall transactivation and DNA binding capacity of HNF1α by disrupting dimerization. Collectively, our findings reveal a previously unappreciated role of POU domain of HNF1α in homodimerization and provide important clues for identifying the molecular basis of HNF1α-related diseases such as MODY3. Article Highlights: HNF1α K117E homozygous mice exhibited dwarfism, hepatic dysfunction, renal Fanconi syndrome, and progressive wasting syndrome. K117E homozygotes developed diabetes in the early postnatal period. K117E heterozygous mutant causes age-dependent glucose intolerance, which is similar to the pathogenesis of maturity-onset diabetes of the young. K117 mutants significantly reduced the overall transactivation and DNA binding capacity of HNF1α by disrupting dimerization. [ABSTRACT FROM AUTHOR]

A comprehensive framework has been established for understanding immunological pathways, which can be categorized into eradicated and tolerable immune responses. Toll-like receptors (TLRs) are associated with specific immune responses. TH1 immunity is related to TLR7, TLR8, and TLR9, while TH2 immunity is associated with TLR1, TLR2, and TLR6. TH22 immunity is linked to TLR2, TLR4, and TLR5, and THαβ (Tr1) immunity is related to TLR3, TLR7, and TLR9. The chemokine receptor CXCR5 is a marker of follicular helper T cells, and other chemokine receptors can also be classified within a framework based on host immunological pathways. On the basis of a literature review on chemokines and immunological pathways, the following associations were identified: CCR5 with TH1 responses, CCR1 with TH1-like responses, CCR4 (basophils) and CCR3 (eosinophils) with TH2 and TH9 responses, CCR10 with TH22 responses, CCR6 with TH17 responses, CXCR3 with THαβ responses, CCR8 with regulatory T cells (Treg), and CCR2 with TH3 responses. These findings contribute to the identification of biomarkers for immune cells and provide insights into host immunological pathways. Understanding the chemokine and Toll-like receptor system is crucial for comprehending the function of the innate immune system, as well as adaptive immune responses. [ABSTRACT FROM AUTHOR]

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To address the challenging issues of large deformation, control difficulties, and susceptibility to failure in the support structure of soft coal roadways, this study utilizes the CVISC block creep model in UDEC software. The model incorporates Coulomb slip without cohesive contact to simulate the characteristics of soft coal, such as its loose, fragile, and small-block nature. Additionally, a soft coal nonlinear discrete element creep model is developed to investigate the creep characteristics of soft coal under triaxial compression, with the aim of revealing the underlying creep destabilization mechanism in soft coal tunnels. Based on the research findings, a primary, strong active support technology is proposed. This approach involves the use of high-preload, high-strength anchor rods and anchor cables, as well as the implementation of steel mesh and plastic woven mesh to enhance surface protection. The study highlights that: (1) The shear cracks inside the coal body of the soft coal specimen transform into tensile cracks under external force, leading to an increase in the number of tensile cracks. This is an important symbol of accelerated creep in soft coal. Improvement in peripheral pressure helps inhibit the generation of tensile cracks inside the specimen. (2) The rapid development of creep and inter-particle tensile fissures within the coal body particles themselves, along with the change in stress state after the excavation of the roadway, are the main reasons for the overall creep damage of the roadway. (3) The support force in the early stage of shed cable support is small, which cannot inhibit the accelerated development of tensile fissures. This leads to continuous deformation of the roadway, resulting in the failure of the support structure in the later stage and aggravated roadway damage. (4) The new support technology helps control surface deformation by enhancing the strength of the roadway protection surface. This suppresses the development speed and number of tensile fissures during roadway deformation, improves the starting strength of the roadway for accelerated creep, and enables effective control of the overall deformation of the soft coal roadway. Thus, the effectiveness of roadway support is remarkable. [ABSTRACT FROM AUTHOR]

Homeobox A7 (HOXA7) plays essential roles in multiple malignancies and was reported to be overexpressed in esophageal squamous cell carcinoma (ESCC). However, its functions in the ESCC tumor microenvironment remain to be explored. In this study, we showed that HOXA7 was overexpressed in ESCC among HOXA family members and correlated with tumor‐associated macrophage (TAM) infiltration both in The Cancer Genome Atlas database and ESCC clinical samples. Moreover, transactivation of C‐C motif chemokine ligand 2 (CCL2) by HOXA7 was identified (real‐time quantitative PCR [RT‐qPCR], western blot analysis, ELISA, and ChIP‐qPCR), which was detected to drive chemotaxis and M2 polarization of macrophages both in vitro (Transwell assay) and in vivo (xenograft tumors models). In addition, CCL2 triggers macrophage expression of epidermal growth factor (EGF) (RT‐qPCR and ELISA), which promotes tumor proliferation and metastasis by activating its receptor EGFR. In addition, EGF‐induced ESCC cell proliferation and migration can be abrogated by HOXA7 knockdown (CCK‐8 proliferation assay, EdU fluorescence, and Transwell assay). These results indicate a novel mechanistic role of HOXA7 in the cross‐talk between ESCC and TAMs, which could be an underlying therapeutic target for ESCC. [ABSTRACT FROM AUTHOR]

Background: Lymph node invasion is associated with poor outcome in patients with renal cell carcinoma (RCC). Patients and Methods: Patients with RCC within a single center from 2001 to 2018 were retrospectively obtained from the Chang Gung Research Database. Patient gender, physical status, Charlson Comorbidity Index, tumor side, histology, age at diagnosis, and body mass index (BMI) were compared. The overall survival (OS) and cancer-specific survival (CSS) of each group were estimated using the Kaplan–Meier method. Log-rank tests were used to compare between the subgroups. Results and Conclusions: A total of 335 patients were enrolled, of whom 76 had pT3N0M0, 29 had pT1–3N1M0, 104 had T1–4N0M1, and 126 had T1–4N1M1 disease. Significant OS difference was noted between pT3N0M0 and pT1–3N1M0 groups with 12.08 years [95% confidence interval (CI), 8.33–15.84] versus 2.58 years (95% CI, 1.32–3.85), respectively (P < 0.005). No significant difference was observed in OS between pT1–3N1M0 and T1–4N0M1 groups with 2.58 years (95% CI, 1.32–3.85) versus 2.50 years (95% CI, 1.85–3.15, P = 0.72). The OS of N1M1 group was worse than that of N0M1 group with 1.00 year (95% CI, 0.74–1.26) versus 2.50 years (95% CI, 1.85–3.15, P < 0.05). Similar results were also observed in CSS. In summary, we claim that RCC with lymph node (LN) invasion should be reclassified as stage IV disease in terms of survival outcome. [ABSTRACT FROM AUTHOR]

Background: There is an increased interest in the evaluation of post‐intensive care syndrome among adult patients who survive critical illness. However, there is little consensus regarding measurement instruments in clinical practice. Aim: To investigate the characteristics of existing instruments used to measure this syndrome in adults. Study design: A scoping review following the Arksey and O'Malley framework and Joanna Briggs Institute guideline was conducted. Studies published between 2010 and 2021 were identified in Medline via EBSCO, CINAHL complete, EMBASE, Web of Science, AMED, and PsycINFO databases, along with grey literature were included. The search retrieved 4134 references; eligible studies were independently identified, extracted, and appraised using the Crowe Critical Appraisal Tool. Results: Out of 4134 articles, 18 research articles underwent data extraction and analysis. Forty‐one instruments were identified. Most studies (n = 14) employed two or more instruments, generating single domain‐specific instruments that measured functioning within the physical (n = 10), cognitive (n = 7), psychological (n = 12), or social (n = 3) domains. Three studies detected post‐intensive care syndrome (without reference to the social domain) using a single assessment tool. Instruments used to measure psychological disorders were relatively consistent within studies, with little attention being paid to the social domain. Conclusion: While post‐intensive care syndrome is recognized as a growing phenomenon among patients globally, and international practice recommendations suggest a range of instruments to measure it, evaluation of this syndrome remains inconsistent. Also, identified instruments did not comprehensively assess this syndrome and lacked data pertaining to their psychometric properties. A psychometrically robust instrument that measures all domains of post‐intensive care syndrome in clinical practice is an urgent requirement. Relevance to clinical practice: Prompt recognition of post‐intensive care syndrome can facilitate prevention and management interventions. Urgent attention is needed to develop a valid, reliable, and practical instrument to measure this syndrome holistically. [ABSTRACT FROM AUTHOR]

Purpose: Gliomas and their surrounding microenvironment constantly interact to promote tumorigenicity, yet the underlying posttranscriptional regulatory mechanisms that govern this interplay are poorly understood. Methods: Utilizing our established PAC-seq approach and PolyAMiner bioinformatic analysis pipeline, we deciphered the NUDT21-mediated differential APA dynamics in glioma cells. Results: We identified LAMC1 as a critical NUDT21 alternative polyadenylation (APA) target, common in several core glioma-driving signaling pathways. qRT-PCR analysis confirmed that NUDT21-knockdown in glioma cells results in the preferred usage of the proximal polyA signal (PAS) of LAMC1. Functional studies revealed that NUDT21-knockdown-induced 3′UTR shortening of LAMC1 is sufficient to cause translational gain, as LAMC1 protein is upregulated in these cells compared to their respective controls. We demonstrate that 3′UTR shortening of LAMC1 after NUDT21 knockdown removes binding sites for miR-124/506, thereby relieving potent miRNA-based repression of LAMC1 expression. Remarkably, we report that the knockdown of NUDT21 significantly promoted glioma cell migration and that co-depletion of LAMC1 with NUDT21 abolished this effect. Lastly, we observed that LAMC1 3′UTR shortening predicts poor prognosis of low-grade glioma patients from The Cancer Genome Atlas. Conclusion: This study identifies NUDT21 as a core alternative polyadenylation factor that regulates the tumor microenvironment through differential APA and loss of miR-124/506 inhibition of LAMC1. Knockdown of NUDT21 in GBM cells mediates 3′UTR shortening of LAMC1, contributing to an increase in LAMC1, increased glioma cell migration/invasion, and a poor prognosis. [ABSTRACT FROM AUTHOR]

Myofibril proteins degradation constitutes an important factor in quality deterioration, procedural activation or inhibition of endogenous protease potential regulates autolytic proteolysis-induced softening of post mortem fish muscle. Based on the brief introduction of myofibril proteins degradation in fish skeletal muscle, a detailed description of the main myofibril degradation properties and the distinct role played by endogenous proteases were proposed, which reflects the limitations and challenges of the current research on myofibril hydrolysis mechanisms based on the varied surrounding conditions. In addition, the latest researches on the evaluation method of myofibril proteins degradation were comprehensively reviewed. The potential use of label-free proteomics combined with bioinformatics was also emphasized and has become an important means to in-depth understand protein degradation mechanism. [ABSTRACT FROM AUTHOR]

Background/aim: Breast cancer is the most common female malignancy in the world. Nearly ninety percent of screening-detected breast cancers were diagnosed with earlier stages of 0 to II in Taiwan. It's widely acknowledged that mammography screening of breast cancer can achieve the goal of early diagnosis and treatment in terms of preventive task while neglected interval cancers are associated with unfavorable tumor characteristics and worse outcomes. The purpose of this study was to explore the characteristics of screening-detected breast cancers in Taiwan. Materials and methods: Both screening and diagnostic mammography examinations with accompanied BI-RADS (breast imaging-reporting and data system) classification were extracted from the health information system and linked to cancer registry in Taiwan. Enrolled population included those attending their first mammography between 2012 and 2016, excluding subjects with previous breast cancer, or with missing or incomplete data. We compared treatment outcomes between breast cancers with either initial screening or diagnostic mammography (control group), and investigated the compositions of breast cancers detected by screening mammography through direct chart reviews. Results: A total of 84,246 screening and 61,230 diagnostic mammography sessions were performed from 2010 to 2020. More positive results (BI-RADS 0, 3, 4 and 5) were observed for those attending the first diagnostic than the first screening mammography (43.58% versus 16.12%, p < 0.001). Earlier stages (0 and I) distribution (92% versus 81%, p < 0.0001), better survivorship (overall survival: 96.91% versus 92.17%, p = 0.007) and a lower HER2 (human epidermal growth factor receptor II) positive status and lower tumor grade were noted in breast cancers with initial screening rather than diagnostic mammography. Among 26,103 mammography screening invitees between 2012 and 2016, 325 breast cancers were ascertained from cancer registry. Of these, 234 had one, 72 had two and 19 had three episodes of mammography before cancer diagnosis. Extensive chart reviews revealed that women with and without breast symptoms constituted 29.9 and 70.1% of the 325 screening-detected breast cancers, with the latter further divided into false negative results (interval cancer), diagnosed at the first mammography, diagnostic at the secondary or subsequent mammography and those with a delayed biopsy or confirmatory imaging constituted (5.2, 47, 10.5 and 7.4%). Conclusion: Screening-detected breast cancers were a mixture of women with and without symptoms, those with a false negative result, true negative results with cancer detected at subsequent mammography and non-adherers. Despite this, efficacy of mammography screening was ascertained in Taiwan from this study. To further enhance earlier detection and decrease false negativity, the impact of repeated mammography, and additional sonography for symptomatic women, compliance following a positive screening mammography should not be overemphasized. [ABSTRACT FROM AUTHOR]

Background There remain concerns regarding the technical feasibility of endoscopic resection for large gastrointestinal stromal tumors (GISTs), mainly relating to the risk of tumor rupture and the adequacy of the resection margins. This study aimed to evaluate the feasibility and therapeutic outcomes of the newly developed no-touch endoscopic full-thickness resection (NT-EFTR) technique for GISTs. Methods In this retrospective study, 92 patients with gastric GISTs undergoing NT-EFTR were included. Clinicopathological, endoscopic, and follow-up data were collected and analyzed. Results The median tumor size was 2.5 cm and en bloc resection was achieved in all patients with negative surgical margins. The median time of the NT-EFTR procedure was 59.5 minutes. Large tumors (> 3.0 cm), extraluminal tumor growth pattern, and large gastric defects were significant contributors to long operative times. Patients were discharged within 4 days postoperatively. During follow-up, all patients were free from local recurrence and distant metastasis. Conclusions NT-EFTR was a feasible method for the resection of gastric GISTs and can be expected to achieve complete radical resection. Large tumors with extraluminal growth and large gastric defects impact procedural difficulty. [ABSTRACT FROM AUTHOR]

With the vigorous development of industrial automation and the Internet of things, the transmission of data is more dependent on immediacy, so network devices have higher and higher requirements for time synchronization accuracy. The clock source of common network devices is provided by the transistor oscillator in the server, but the oscillator will change with factors such as aging and temperature, and it cannot be guaranteed that the oscillator in the server will work at the same frequency. Time synchronization can be achieved by technologies such as IRIG-B, NTP, or IEEE 1588 (PTP), but the hardware cost of building IRIG-B is high, and NTP has the lowest cost, but it can only provide time accuracy from milliseconds to microseconds. PTP can provide sub-microsecond or even nanosecond time precision. It is a system of time synchronization mechanisms through Ethernet transmission. In this article, we first propose a time synchronization system using the development board and PDP protocol. On the Xilinx Zynq-7000 SOC platform of Petalinux, we implement the hardware solution of Linux PTP. The hardware time stamp is 20 ns. To improve the accuracy, the congenital frequency error between the oscillators must be considered. Therefore, a PTP auxiliary time stamp with dynamic frequency compensation is proposed and designed into a chip. Experimental results show that at 45 nm (TN40G) it can operate at 370 MHz and achieve 2.7 ns resolution, which can be applied to more demands. [ABSTRACT FROM AUTHOR]

TAR DNA binding protein-43 (TDP-43) proteinopathies are accompanied by the pathological hallmark of cytoplasmic inclusions in the neurodegenerative diseases, including frontal temporal lobar degeneration (FTLD-TDP) and amyotrophic lateral sclerosis (ALS). We found that TTR accumulates with TDP-43 cytoplasmic inclusions in FTLD-TDP human patients and transgenic mice, in which TTR exhibits dramatic expression decline in elderly mice. The upregulation of TTR expression was demonstrated to facilitate the clearance of cytoplasmic TDP-43 inclusions through autophagy, whereof TTR induces autophagy upregulation via ATF4. Of interest, TTR upregulated ATF4 expression and promoted ATF4 nuclear import, presenting physical interaction. Neuronal expression of TTR in FTLD-TDP mice restored autophagy function and facilitated early soluble TDP-43 aggregates for autophagosome targeting, ameliorating neuropathology and behavioral deficits. Thus, TTR conducted two-way regulations by either inducing autophagy activation or escorting TDP-43 aggregates targeted autophagosomes, suggesting that TTR is a potential modulator therapy for neurological disorders caused by TDP-43 proteinopathy. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) has a poor prognosis and new effective treatments are needed. SLC12A5 plays important roles in multiple complex pathological states and is overexpressed in a variety of malignancies. However, the effects of SLC12A5 in HCC have not been determined. Methods: SLC12A5 expression was assessed by immunostaining and western blotting. A cell viability assay was used to detect cell proliferation. Flow cytometry was used to evaluate the intracellular calcium concentration and cell cycle. Ferroptosis was detected by transmission electron microscopy, lipid peroxidation, and glutathione assays. Subcutaneous tumor formation experiments were used to validate the tumorigenic effect of SLC12A5 in vivo. RNA‐seq was used to evaluate the molecular mechanisms underlying the effects of SLC12A5. The therapeutic efficacy of targeting SLC12A5 was assessed in a patient‐derived xenograft (PDX) model. Results: High SLC12A5 expression was strongly associated with a poor clinical prognosis and promoted HCC growth. Mechanistically, SLC12A5 promoted ER stress to enhance calcium release and upregulated PNCK expression levels. Concomitantly, PNCK was significantly activated by calcium ions released from the ER. PNCK activated and induced the phosphorylation of PI3K/AKT/mTOR pathway components. Furthermore, SLC12A5 inhibited ferroptosis in HCC by upregulating the expression of xCT, a cystine transporter. Conclusion: High SLC12A5 levels were correlated with a poor prognosis, promoted tumorigenesis, and inhibited ferroptosis in HCC. These findings suggested that SLC12A5 is a therapeutic target and provide insight into the link between ER stress and ferroptosis in HCC. [ABSTRACT FROM AUTHOR]

Objectives: Type 2 diabetes mellitus (T2DM) imposes a great burden on healthcare systems, and these patients experience higher long-term risks for developing end-stage renal disease (ESRD). Managing diabetic nephropathy becomes more challenging when kidney function starts declining. Therefore, developing predictive models for the risk of developing ESRD in newly diagnosed T2DM patients may be helpful in clinical settings. Methods: We established machine learning models constructed from a subset of clinical features collected from 53,477 newly diagnosed T2DM patients from January 2008 to December 2018 and then selected the best model. The cohort was divided, with 70% and 30% of patients randomly assigned to the training and testing sets, respectively. Results: The discriminative ability of our machine learning models, including logistic regression, extra tree classifier, random forest, gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and light gradient boosting machine were evaluated across the cohort. XGBoost yielded the highest area under the receiver operating characteristic curve (AUC) of 0.953, followed by extra tree and GBDT, with AUC values of 0.952 and 0.938 on the testing dataset. The SHapley Additive explanation summary plot in the XGBoost model illustrated that the top five important features included baseline serum creatinine, mean serum creatine within 1 year before the diagnosis of T2DM, high-sensitivity C-reactive protein, spot urine protein-to-creatinine ratio and female gender. Conclusions: Because our machine learning prediction models were based on routinely collected clinical features, they can be used as risk assessment tools for developing ESRD. By identifying high-risk patients, intervention strategies may be provided at an early stage. [ABSTRACT FROM AUTHOR]

Viral infection serves as the crucial etiology for the development of sudden sensorineural hearing loss (SSNHL). We aimed to investigate whether there is an association between concurrent Epstein–Barr virus (EBV) infection and SSNHL in an East Asian population. Patients who were older than 18 years of age and met the criteria of sudden hearing loss without an identifiable etiology were enrolled from July 2021 until June 2022, followed by the serological testing of IgA antibody responses against EBV-specific early antigen (EA) and viral capsid antigen (VCA) with an indirect hemagglutination assay (IHA) and real-time quantitative polymerase chain reaction (qPCR) of EBV DNA in serum before the treatment was initiated. After the treatment for SSNHL, post-treatment audiometry was performed to record the treatment response and degree of recovery. Among the 29 patients included during enrollment, 3 (10.3%) had a positive qPCR result for EBV. In addition, a trend of poor recovery of hearing thresholds was noted for those patients with a higher viral PCR titer. This is the first study to use real-time PCR to detect possible concurrent EBV infection in SSNHL. Our study demonstrated that approximately one-tenth of the enrolled SSNHL patients had evidence of concurrent EBV infection, as reflected by the positive qPCR test results, and a negative trend between hearing gain and the viral DNA PCR level was found within the affected cohort after steroid therapy. These findings indicate a possible role for EBV infection in East Asian patients with SSNHL. Further larger-scale research is needed to better understand the potential role and underlying mechanism of viral infection in the etiology of SSNHL. [ABSTRACT FROM AUTHOR]

Simple Summary: Most patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) fail to complete bacillus Calmette-Guérin (BCG) instillation due to toxicity or shortage. Our retrospective study aimed to assess the efficacy of intravesical chemotherapy replacement at the time of BCG interruption. We confirmed the chemotherapy replacement group had a better three-year bladder recurrence-free survival (RFS) than the BCG discontinuation group. Chemotherapy replacement is then a helpful strategy in patients with NMIBC facing BCG treatment stoppage. Background: To evaluate the efficacy of intravesical chemotherapy replacement in patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), who underwent bacillus Calmette-Guérin (BCG) instillation but discontinued due to global shortages or toxicity of BCG. Methods: This retrospective study included patients with intermediate- and high-risk NMIBC who received BCG intravesical instillation. Those who discontinued the treatment were divided into the pure BCG group and chemotherapy replacement group. Comparisons between these groups were performed. The primary endpoint was bladder recurrence-free survival (RFS). Results: A total of 480 patients were included. Baseline characteristics were similar between groups, but the total instillation times were higher in the chemotherapy replacement group than in the pure BCG group (n = 14.9 vs. 10.5). The chemotherapy replacement group had a better three-year RFS (p = 0.022). On multivariate analysis, the pure BCG group had significantly increased all-time and 3-year recurrences (hazard ratio 2.015 and 2.148) compared to the chemotherapy replacement group. Conclusions: Chemotherapy replacement has a better three-year RFS than no instillation in patients with intermediate- and high-risk NMIBC who received BCG instillation but facing treatment stoppage. [ABSTRACT FROM AUTHOR]

The main causes of damage to industrial machinery are aging, corrosion, and the wear of parts, which affect the accuracy of machinery and product precision. Identifying problems early and predicting the life cycle of a machine for early maintenance can avoid costly plant failures. Compared with other sensing and monitoring instruments, sound sensors are inexpensive, portable, and have less computational data. This paper proposed a machine tool life cycle model with noise reduction. The life cycle model uses Mel-Frequency Cepstral Coefficients (MFCC) to extract audio features. A Deep Neural Network (DNN) is used to understand the relationship between audio features and life cycle, and then determine the audio signal corresponding to the aging degree. The noise reduction model simulates the actual environment by adding noise and extracts features by Power Normalized Cepstral Coefficients (PNCC), and designs Mask as the DNN's learning target to eliminate the effect of noise. The effect of the denoising model is improved by 6.8% under Short-Time Objective Intelligibility (STOI). There is a 3.9% improvement under Perceptual Evaluation of Speech Quality (PESQ). The life cycle model accuracy before denoising is 76%. After adding the noise reduction system, the accuracy of the life cycle model is increased to 80%. [ABSTRACT FROM AUTHOR]

Purpose: Post-operative cystography has been used to predict the recovery of postprostatectomy urinary incontinence (PPI) in patients with localized prostate cancer. This study aimed to validate the predictive value of cystography for PPI and utilize a deep learning model to identify favorable and unfavorable features. Methods: Medical records and cystography images of patients who underwent robotic-assisted radical prostatectomy for localized prostate cancer were retrospectively reviewed. Specific cystography features, including anastomosis leakage, a downward bladder neck (BN), and the bladder neck angle, were analyzed for the prediction of PPI recovery. Favorable and unfavorable patterns were categorized based on the three cystography features. The deep learning model used for transfer learning was ResNet 50 and weights were trained on ImageNet. We used 5-fold cross-validation to reduce bias. After each fold, we used a test set to confirm the model's performance. Result: A total of 170 consecutive patients were included; 31.2% experienced immediate urinary continence after surgery, while 93.5% achieved a pad-free status and 6.5% were still incontinent in the 24 weeks after surgery. We divided patients into a fast recovery group (≤4 weeks) and a slow recovery group (>4 weeks). Compared with the slow recovery group, the fast recovery group had a significantly lower anastomosis leakage rate, less of a downward bladder neck, and a larger bladder neck angle. Test data used to evaluate the model's performance demonstrated an average 5-fold accuracy, sensitivity, and specificity of 93.75%, 87.5%, and 100%, respectively. Conclusions: Postoperative cystography features can predict PPI recovery in patients with localized prostate cancer. A deep-learning model can facilitate the identification process. Further validation and exploration are required for the future development of artificial intelligence (AI) in this field. [ABSTRACT FROM AUTHOR]

Objectives: Post-ESD esophageal stricture especially after wholly circumferential ESD remains an unresolved issue without ideal strategies. Our initiative novel self-control stricture-preventing water balloon may be an alternative. Methods: Patients with esophageal neoplastic lesions expected to result in a whole circular mucosa defect after esophageal ESD from February 2018 to August 2020 were included in the study. We used a novel self-control stricture-preventing water balloon combined with oral prednisolone as preventive strategy for the enrolled patients. Results: Thirty-seven patients (9 females and 28 males, patients aged 52 to 82 years) finished the 12-week treatment including steroid treatment and balloon placement. The median size of longitudinal diameter was 7 cm (range from 4 to 14 cm). All the lesions achieved curative resection and the median procedure time was 110 min (range 50 to 180 min). Balloons were found migration in 4 patients. As a result, there were 3 patients (8.1%) experienced stricture. Generally, patients could tolerate to balloons, only with mild uncomfortableness, such as occasional sore throat, cough, and retrosternal pain. In addition, during the follow-up period, no significant adverse events associated to oral steroid administration were observed and no recurrence was found. Conclusions: Our novel self-control stricture-preventing water balloon based on the oral steroid therapy is effective and safe. This strategy well prevents esophageal stricture after complete circumferential ESD. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the second most prevalent malignancy in men worldwide. The risk factors for PCa include obesity, age and family history. Increased visceral fat has been associated with high PCa risk, which has prompted previous researchers to investigate the influence of body composition and fat distribution on PCa prognosis. However, there is a lack of studies focusing on the mechanisms and interactions between periprostatic adipose tissue (PPAT) and PCa cells. The present study investigated the association between the composition of pelvic adipose tissue and PCa aggressiveness to understand the role played by this tissue in PCa progression. Moreover, PPAT-conditioned medium (CM) was prepared to assess the influence of the PPAT secretome on the pathophysiology of PCa. The present study included 50 patients with localized PCa who received robot-assisted radical prostatectomy. Medical records were collected, magnetic resonance imaging scans were analyzed and body compositions were calculated to identify the associations between adipose tissue volume and clinical PCa aggressiveness. In addition, CM was prepared from PPAT and perivesical adipose tissue (PVAT) collected from 25 patients during surgery, and its effects on the PCa cell lines C4-2 and LNCaP, and the prostate epithelial cell line PZ-HPV-7, were investigated using a cell proliferation assay and RNA sequencing (RNA-seq). The results revealed that the initial prostate-specific antigen level was significantly correlated with pelvic and periprostatic adipose tissue volumes. In addition, PPAT volume was significantly higher in patients with extracapsular tumor extension. PCa cell proliferation was significantly reduced when the cells were cultured in PPAT-CM compared with when they were cultured in control- and PVAT-CM. RNA-seq revealed that immune responses, and the cell death and apoptosis pathways were enriched in PPAT-CM-cultured cells indicating that the cytokines or other factors secreted from PPAT-CM induced PCa cell apoptosis. These findings revealed that the PPAT secretome may inhibit PCa cell proliferation by activating immune responses and promoting cancer cell apoptosis. This mechanism may act as a first-line defense during the early stages of PCa. [ABSTRACT FROM AUTHOR]

TTR (transthyretin) strikes a neuroprotective function in the prevention of amyloid-β (Aβ) deposition in Alzheimer disease (AD). Perturbation of the stringently controlled TARDBP/TDP-43 (TAR DNA binding protein) expression gives rise to cytoplasmic aggregation, characterized by TARDBP proteinopathy affiliated with several neurological disorders, including frontotemporal lobar degeneration with TARDBP pathology (FTLD-TDP) and amyotrophic lateral sclerosis/ALS. Proposedly, TTR can maintain cellular proteostasis susceptible to TARDBP aggregates and initiate its removal. Herein, we disclose that TTR upregulated in response to excessive TARDBP causes TARDBP aggregation in FTLD-TDP and co-accumulates with it. Moreover, TTR expression increases with age in FTLD-TDP but shows a downward decline in the elderly. TTR promotes macroautophagy/autophagy activity and facilitates aggregated TARDBP degradation via autophagy. Compellingly, TTR binds to ATF4 and boosts its nuclear import for autophagy upregulation. Therefore, TTR directs autophagy teamwork in bi-directional regulation through enhancing autophagy activity via ATF4 and chaperoning aggregated TARDBP to phagophores for degradation. Abbreviations: Aβ: amyloid-β; AD: Alzheimer disease; ER: endoplasmic reticulum; FTLD-TDP: frontotemporal lobar degeneration with TARDBP pathology; TARDBP/TDP-43: TAR DNA binding protein; TTR: transthyretin; UPR: unfolded protein response [ABSTRACT FROM AUTHOR]

One of the most challenging problems in autonomous driving is trajectory planning for lane changes. Conventional trajectory planning is generally realized by optimizing a specific cost function. However, the model performance required for different scenarios makes it repetitive and time-consuming to tune the cost function. Furthermore, to ensure driving safety, comfort as well as traffic efficiency, it is essential to interact with other vehicles by predicting their driving intentions. Therefore, this paper proposes a segmented-updated lane-change trajectory planning method for autonomous vehicles on closed highways. The maximum entropy inverse reinforcement learning (IRL) algorithm for human demonstration learning and the long short-term memory and Bayesian network (LSTM-BN)-based model for target vehicles' driving intentions are applied. Three contributions are made in this work: 1) The LSTM-BN is used to judge the intentions of surrounding vehicles based on its historical information to inform lane-change trajectory planning. 2) Different feature-based cost functions of the IRL algorithm are designed according to different lane-change scenarios, which enhances its adaptability to different scenarios. 3) Segmented-updated trajectory planning is used to dynamically optimize trajectories via an online optimization process, which reduces the model's limitations and improves overall lane-change performance. Finally, simulation experiments demonstrate that the proposed method has strong generalization ability, reliable accuracy, and can adjust lane-change trajectories reasonably according to the driving intentions of surrounding vehicles. [ABSTRACT FROM AUTHOR]

The chemotherapy instillation protocol also consisted of six weekly intravesical instillations as the induction course and monthly instillations at months 3 to 14 as the maintenance course. For patients who initiated a BCG instillation protocol but discontinued it due to shortage or toxicity, some had shifted to a chemotherapy instillation protocol, but others stopped instillation management. Data on tumour-related parameters, such as tumour stage, tumour histology, pathological grade, and intravesical instillation data, including the number of BCG instillations and chemotherapy instillations, and total intravesical instillations, were also recorded. There were two results in the BCG instillation group when facing BCG discontinuation, one is no further instillation plan, and the other is shifting to chemotherapy instillation. [Extracted from the article]

With the development of active noise cancellation (ANC) technology, ANC has been used to mitigate the effects of environmental noise on audiometric results. However, objective evaluation methods supporting the accuracy of audiometry for ANC exposure to different levels of noise have not been reported. Accordingly, the audio characteristics of three different ANC headphone models were quantified under different noise conditions and the feasibility of ANC in noisy environments was investigated. Steady (pink noise) and non-steady noise (cafeteria babble noise) were used to simulate noisy environments. We compared the integrity of pure-tone signals obtained from three different ANC headphone models after processing under different noise scenarios and analyzed the degree of ANC signal correlation based on the Pearson correlation coefficient compared to pure-tone signals in quiet. The objective signal correlation results were compared with audiometric screening results to confirm the correspondence. Results revealed that ANC helped mitigate the effects of environmental noise on the measured signal and the combined ANC headset model retained the highest signal integrity. The degree of signal correlation was used as a confidence indicator for the accuracy of hearing screening in noise results. It was found that the ANC technique can be further improved for more complex noisy environments. [ABSTRACT FROM AUTHOR]

Various peptide toxins in animal venom inhibit voltage-gated sodium ion channel Nav1.7, including Nav-targeting spider toxin (NaSpTx) Family I. Toxins in NaSpTx Family I share a similar structure, i.e., N-terminal, loops 1–4, and C-terminal. Here, we used Mu-theraphotoxin-Ca2a (Ca2a), a peptide isolated from Cyriopagopus albostriatus, as a template to investigate the general properties of toxins in NaSpTx Family I. The toxins interacted with the cell membrane prior to binding to Nav1.7 via similar hydrophobic residues. Residues in loop 1, loop 4, and the C-terminal primarily interacted with the S3–S4 linker of domain II, especially basic amino acids binding to E818. We also identified the critical role of loop 2 in Ca2a regarding its affinity to Nav1.7. Our results provide further evidence that NaSpTx Family I toxins share similar structures and mechanisms of binding to Nav1.7. [ABSTRACT FROM AUTHOR]