Search

Abstract Melanoma is the most dangerous form of skin cancer. Hence, a better understanding of molecular mechanisms in melanoma pathogenesis is urgently needed, which provides a new insight into the therapy of melanoma. DTL gene is screened out in melanoma pathogenesis by integrated bioinformatics analysis, and its expression is validated in the tissue and cell samples of melanoma. Forced DTL expression facilitates the proliferation, invasion, migration and EMT of melanoma cells, while DTL knockdown suppresses the biological behavior of melanoma cells. In addition, DTL promotes the malignancy of melanoma in vivo. Mechanistically, BUB1 is the crucial downstream target of DTL. Reduced DTL expression suppresses BUB1 expression, while enhanced DTL expression induces BUB1 upregulation. Rescue experiments showed that growing and migrating of melanoma cells induced by DTL are partially impaired by BUB1 inhibition. In addition, the expression of phosphorylated ERK (p-ERK) and the downstream transcription factor E2F1 are reduced when DTL expression is blocked. Meanwhile, BUB1 levels are decreased when the expression of p-ERK or E2F1 is repressed. Notably, the growth and migration of melanoma cells by inhibition of ERK and knockdown of E2F1 was rescued by overexpressing BUB1. DTL gene may be a prognosis marker and represent a unique potential target for melanoma patients. DTL supports the biologically malignant activity of melanoma cells via the ERK/E2F1/BUB1 axis.

BackgroundSOX13 is a transcription factor belonging to the SOX family. SOX proteins are critical regulators of multiple cancer progression, and some are known to control carcinogenesis. Nevertheless, the functional and clinical significance of SOX13 in human thyroid cancer (THCA) remain largely unelucidated.MethodsData on SOX13 expression were obtained through The Cancer Genome Atlas together with Gene Expression Omnibus. Co-expression, differential expression, and functional analyses of genes were investigated by databases. Associations between SOX13 levels, immune infiltration, ferroptosis, and immune checkpoint gene levels were analyzed. Genetic changes in SOX13 were investigated using CBioPortal. Associations between SOX13 levels and THCA clinicopathological features were analyzed and nomogram modeling for diagnostic and prognostic prediction. The influence of SOX13 on proliferation, migration, and metastasis was determined in KTC-1 and TPC-1 cell lines.ResultsSOX13 was significantly lower in THCA tumors compared to controls. In addition, upregulated SOX13 gene mutation were evident in thyroid cancer. SOX13-associated genes exhibited differential expression in pathways associated with thyroid cancer development. Significant associations were found between SOX13 levels, immune infiltration, ferroptosis, and immune checkpoint genes in THCA tissue. SOX13 levels correlated with THCA stage, histologic grade, and primary neoplasm focus types, and independently predicted overall and progression-free intervals. SOX13 expression effectively distinguished between tumor and normal thyroid tissue. Spearman correlations highlighted a significant relationship between SOX13 and ferroptosis-associated genes. Overexpression of SOX13 enhances the inhibition of RSL3 (iron death activator) on the cell viability of TPC-1. Higher SOX13 levels in Thyroid cancer cells may lead to reduced proliferation, migration, and metastasis by regulating ferroptosis.ConclusionReduced SOX13 expression inversely impacts patient prognosis. In addition, SOX13 strongly regulates cancer immunity and Ferroptosis. Hence, SOX13 has great promise as a bioindicator for both thyroid cancer prognosis and immune cell invasion.

Objective To delineate the efficacy and safety profile of hemodiafiltration with endogenous reinfusion (HFR) for uremic toxin removal in patients undergoing maintenance hemodialysis (MHD).Methods Patients who have been on MHD for a period of at least 3 months were enrolled. Each subject underwent one HFR and one hemodiafiltration (HDF) treatment. Blood samples were collected before and after a single HFR or HDF treatment to test uremic toxin levels and to calculate clearance rate. The primary efficacy endpoint was to compare uremic toxin levels of indoxyl sulfate (IS), λ-free light chains (λFLC), and β2-microglobulin (β2-MG) before and after HFR treatment. Secondary efficacy endpoints was to compare the levels of urea, interleukin-6 (IL-6), P-cresol, chitinase-3-like protein 1 (YKL-40), leptin (LEP), hippuric acid (HPA), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), tumor necrosis factor-α (TNF-α), fibroblast growth factor 23 (FGF23) before and after HFR treatment. The study also undertook a comparative analysis of uremic toxin clearance between a single HFR and HDF treatment. Meanwhile, the lever of serum albumin and branched-chain amino acids before and after a single HFR or HDF treatment were compared. In terms of safety, the study was meticulous in recording vital signs and the incidence of adverse events throughout its duration.Results The study enrolled 20 patients. After a single HFR treatment, levels of IS, λFLC, β2-MG, IL-6, P-cresol, YKL-40, LEP, HPA, TMAO, ADMA, TNF-α, and FGF23 significantly decreased (p 0.05), while post-HDF, levels of serum albumin significantly decreased (p = 0.000).Conclusion HFR treatment effectively eliminates uremic toxins from the bloodstream of patients undergoing MHD, especially protein-bound toxins and large middle-molecule toxins. Additionally, it retains essential physiological compounds like albumin and branched-chain amino acids, underscoring its commendable safety profile.

BackgroundTousled-like kinase 2 (TLK2) gene variant-related neurodevelopmental disorder was recently described. The haploinsufficiency of TLK2 was considered the most likely underlying disease mechanism, leading to a consistent neurodevelopmental phenotype. So far, only four studies, conducted on 49 patients from North America and Europe, have been reported.Case presentationIn this study, we reported a Chinese family with a TLK2-related neuropsychiatric phenotype. The proband, a boy aged 2 years and 6 months, presented with temper tantrums, mood lability, aggressiveness, congenital astigmatism, and distinctive facial dysmorphism. Whole-exome sequencing identified a novel heterozygous variation in TLK2 gene (c.49dupG, p. E17Gfs*10) in them. His father carried the same TLK2 gene variant and exhibited anxiety and irritability. The parental grandparents and other family members had no such variation. Moreover, the proband was found to have global developmental delay, autism-like symptoms, and mild elevated homo-vanillic acid (HVA) and 2,3-dihydroxy-2-methylbutyric acid levels tested in urine.ConclusionHerein, we identified a novel TLK2 variant from a Chinese family and reported a new neuropsychiatric phenotype. This study also expanded the genotype profile of the newly defined TLK2-related neurodevelopmental disorder.

Airborne LiDAR bathymetry (ALB) system is an attractive and efficient method for nearshore bathymetry and underwater topography mapping. To ensure and improve the measurement accuracy and reliability in various water environments, different receivers using a segmented field of view (FOV) have been designed and are implemented in ALB. These are used to obtain various echo data of multiple channels and perform bathymetry at various water depths. However, in echo waveform processing, detailed information about the water body described by the different echo waveforms is lacking, making it difficult to overcome severe waveform superposition in extremely shallow areas or to separate the weak echo of the water bottom from the noise in extremely deep areas. Therefore, we employed a novel method of multi-channel waveform fusion bathymetry (MWFB) to achieve information complementarity, gain multi-channel waveforms, and detect the robustness of water and bottom echo signals. This method uses an adaptive signal waveform extraction of a multichannel fusion mechanism to eliminate systematic and random noise, and the waveform curvature is used to reconstruct the energy–waveform curves. Iterative decomposition based on waveform curvature and energy curves was conducted to improve the correctness of waveform decomposition and the reliability of waveform components. Furthermore, the water surface and bottom peaks were detected based on the multichannel waveform curvature, which enabled acquisition of the accurate temporal positions of the peaks and achieve high-accuracy bathymetry. According to the experimental results and a comparison with reference datasets, the highest bathymetric accuracy of the MWFB method reached an RMSE of 0.22. For the different study areas, the bathymetric accuracy of the slope reached 95%, 92%, and 97% at Ganquan Island, Lingyang Reef, and Bei Island, respectively. Furthermore, the bathymetric point numbers were effectively increased and bathymetric accuracy was also improved in shallow and deep water, which illustrates the superior bathymetric performance of the MWFB method and its ability to provide a high-efficiency waveform dataset through multi-channel data fusion. The novel LiDAR bathymetric method proposed in this study can effectively achieve high-accuracy nearshore bathymetry and seafloor topographical mapping.

Forecasting hypersonic glide vehicle (HGV) trajectories accurately is crucial for defense, but traditional methods face challenges due to the scarce real-world data and the intricate dynamics of these vehicles. Data-driven approaches based on deep learning, while having emerged in recent years, often exhibit limitations in predictive accuracy and long-term forecasting. Whereas, physics-informed neural networks (PINNs) offer a solution by incorporating physical laws, but they treat these laws as constraints rather than fully integrating them into the learning process. This paper presents PhysNODE, a novel physics-embedded neural ODE model for the precise forecasting of HGV trajectories, which directly integrates the equations of HGV motion into a neural ODE. PhysNODE leverages a neural network to estimate the hidden aerodynamic parameters within these equations. These parameters are then combined with observable physical quantities to form a derivative function, which is fed into an ODE solver to predict the future trajectory. Comprehensive experiments using simulated datasets of HGV trajectories demonstrate that PhysNODE outperforms the state-of-the-art data-driven and physics-informed methods, particularly when training data is limited. The results highlight the benefit of embedding the physics of the HGV motion into the neural ODE for improved accuracy and stability in trajectory predicting.

In recent years, artificial intelligence (AI) has undergone remarkable advancements, exerting a significant influence across a multitude of fields. One area that has particularly garnered attention and witnessed substantial progress is its integration into the realm of the nervous system. This article provides a comprehensive examination of AI’s applications within the peripheral nervous system, with a specific focus on AI-enhanced diagnostics for peripheral nervous system disorders, AI-driven pain management, advancements in neuroprosthetics, and the development of neural network models. By illuminating these facets, we unveil the burgeoning opportunities for revolutionary medical interventions and the enhancement of human capabilities, thus paving the way for a future in which AI becomes an integral component of our nervous system’s interface.

Unmanned aerial vehicle (UAV)-based object detection methods are widely used in traffic detection due to their high flexibility and extensive coverage. In recent years, with the increasing complexity of the urban road environment, UAV object detection algorithms based on deep learning have gradually become a research hotspot. However, how to further improve algorithmic efficiency in response to the numerous and rapidly changing road elements, and thus achieve high-speed and accurate road object detection, remains a challenging issue. Given this context, this paper proposes the high-efficiency multi-object detection algorithm for UAVs (HeMoDU). HeMoDU reconstructs a state-of-the-art, deep-learning-based object detection model and optimizes several aspects to improve computational efficiency and detection accuracy. To validate the performance of HeMoDU in urban road environments, this paper uses the public urban road datasets VisDrone2019 and UA-DETRAC for evaluation. The experimental results show that the HeMoDU model effectively improves the speed and accuracy of UAV object detection.

Background: Postoperative cognitive dysfunction (POCD) is characterized by impaired learning and memory. 6 h duration isoflurane anesthesia is an important factor to induce POCD, and the dysfunction of ryanodine receptor (RyR) in the hippocampus may be involved in this process. We investigated the expression of RyR3 in the hippocampus of mice after 6-h duration isoflurane anesthesia, as well as the improvement of RyR receptor agonist caffeine on POCD mice, while attempting to identify the underlying molecular mechanism. Materials: We constructed a POCD model using 8-week-old male C57BL/6J mice that were exposed to 6-h duration isoflurane. Prior to the three-day cognitive behavioral experiment, RyR agonist caffeine were injected. Fear conditioning and location memory tests were used in behavioral studies. We also exposed the mouse neuroblastoma cell line Neuro-2a (N2A) to 6-h duration isoflurane exposure to simulate the conditions of in vivo cognitive dysfunction. We administered ryanodine receptor agonist (caffeine) and inhibitor (ryanodine) to N2a cells. Following that, we performed a series of bioinformatics analysis to discover proteins that are involved in the development of cognitive dysfunction. Rt-PCR and Western blot were used to assess mRNA level and protein expression. Results: 6-h duration isoflurane anesthesia induced cognitive dysfunction and increased RyR3 mRNA levels in hippocampus. The mRNA levels of RyR3 in cultured N2a cells after anesthesia were comparable to those in vivo, and the RyR agonist caffeine corrected the expression of some cognitive-related phenotypic proteins that were disturbed after anesthesia. Intraperitoneal injection of RyR agonist caffeine can improve cognitive function after isoflurane anesthesia in mice, and bioinformatics analyses suggest that CaMKⅣ may be involved in the molecular mechanism. Conclusion: Ryanodine receptor agonist caffeine may improve cognitive dysfunction in mice after isoflurane anesthesia.

Introduction: Obesity has detrimental influences on women reproductive health. There is little experience in optimizing controlled ovarian hyperstimulation (COH) protocols to treat Chinese obese patients who are undergoing in vitro fertilization and embryo transfer (IVF-ET) therapy. Methods: The clinical outcome differences were retrospectively analyzed among obese patients who received gonadotrophin-releasing hormone agonist (GnRH-a), GnRH antagonist (GnRH-ant), micro dose GnRH-a (mGnRH-a) and GnRH-a long protocol in IVF-ET cycle at Chengdu Jinjiang Hospital for Women's and Children's Health from January 2014 to December 2019. Results: The transplantation rate of the GnRH-a long protocol group (59.1%) was higher than that of the GnRH-ant (25.9%) and mGnRH-a (36.7%) groups. The total live birth rate of the GnRH-a long protocol group (46.2%) was higher than that of the GnRH-a group (25.9%) and GnRH-ant group (40.3%). The total number of frozen embryos in the GnRH-ant group was higher than in the other groups (P

The importance of named entity identification in traditional Chinese medicine (TCM) as the basis for supporting downstream tasks is receiving increasing attention. Deep learning-based methods have been widely used for related tasks. However, most current methods do not deal well with two common TCM entity recognition problems: an unbalanced number of entities and sparse entities. To solve these problems, we propose an ensemble learning method based on dynamic optimization. In this study, we first use bidirectional encoder representations from transformers (BERT) to extract word vectors and then further extract features based on BERT-bidirectional long short-term memory (BiLSTM). Then, we dynamically adjust the entity class and fusion weights of ensemble learning according to the entity distribution and sparsity of each batch. Finally, the prediction results are output through the conditional random field (CRF) layer. This approach allows the model to dynamically focus on difficult samples and to improve the update weights of the most beneficial learning tasks. In addition, we introduce a reduction factor to reduce the magnitude of the parameter updates when the entities are sparse. This prevents the model from being unduly disrupted by nonentity information. Therefore, our model can effectively reduce the negative impact of unbalanced numbers of entities and sparse entities. The experimental results show that our model achieves the best results on a publicly available TCM entity recognition dataset and has a faster convergence rate than the baseline model. Compared to the baseline model BERT-BiLSTM-CRF, our method improves the F1-score by 0.56, further demonstrating its effectiveness.

Abstract Background Peritoneal dialysis (PD) is an effective and successful renal replacement therapy. The baseline peritoneal solute transfer rate (PSTR) is related to local membrane inflammation and may be partially genetically determined. Herein, we focused on vascular endothelial growth factor (VEGF) and its receptor, kinase insert domain containing receptor (KDR). Methods This study recruited 200 PD patients from Renji Hospital in Shanghai, China. We analysed the association between the polymorphisms of VEGF and KDR and the 4-hour dialysate-to-plasma ratio for creatinine (4 h D/P Cr), which was measured between one and three months after initiating PD. Results The CC genotype in VEGF rs3025039 and the AA genotype in KDR rs2071559 were both positively associated with a fast baseline PSTR (VEGF rs3025039 CC vs. TT + TC: 0.65 ± 0.12 vs. 0.61 ± 0.11; P = 0.029; KDR rs2071559 AA vs. GA + GG: 0.65 ± 0.12 vs. 0.62 ± 0.12; P = 0.039). Conclusion Baseline PSTR was partly determined by VEGF and KDR gene polymorphisms.

BackgroundEqualization of medical services is fundamental to the development of people-centered urbanization in Chinese-style modernization. In the past few decades, the achievements of the Chinese economy have remarkably increased the quantity and quality of healthcare services. Under rapid urbanization, large-scale population floating has led to a mismatch between supply and demand for healthcare services and raised the tension between spatial demographic reorganization and the relative stability of public healthcare service facilities. The current studies of healthcare spatial deprivation (HSD) mainly are focus on either supply, or demand, or accessibility based on census data. Therefore, it is necessary to build a multiple index that could give a physical result by using ordinary indices and mixing them together by relative methods to overcome this problem.MeasureWe chose Ningbo city, Zhejiang province, located in the eastern coastal region of China, as the study area. Moreover, from 2000 to 2020, the urbanization rate of Ningbo rapidly increased from 55.75 to 78.0%. In order to show the HSD in a rapidly urbanizing city, we first consider the subdistrict as the scale, innovatively absolve the medical accessibility to the IRD (Index of Relative Disadvantage), and construct the Index of Healthcare Relative Spatial Deprivation (IHRSD) framework. Based on the seventh national census data, we apply an IHRSD with Entropy Weight Method, 2SFCA (Two-step Floating Catchment Area Method) and GDM (Geographical Detector Model) to measure where and who are vulnerable to deprive in healthcare.ResultMeasured by IHRSD, (1) There is stronger healthcare spatial deprivation in peri-urban and developed-town in Ningbo; (2) Young childhood and fertile-women are vulnerable to healthcare spatial deprivation, in fact, they are spatially deprived in healthcare; (3) The socio-demographic attribute is a significant factor in healthcare spatial deprivation, especially the level of aging and population clustering; and (4) The relationship between healthcare spatial deprivation and accessibility shows an inverted U-shaped structure.ConclusionOur experiments show that the problems of HSD are mainly from the characteristics of the population, the layout of healthcare service institutions, the accessibility of the traffic system and the natural conditions. Although the constructions of equalization of primary medical and health services, hierarchical diagnosis, and treatment, and the “healthcare complex” are currently trying to reduce the phenomenon of HSD. Faced with groups and location, the acquisition of the accurately healthcare service supply is the key to realizing healthcare spatial equity.

This paper introduces freight buses as a novel solution for city logistics, aiming to replace other freighters currently operated by various private logistics firms within city centers. The focus lies on investigating the route planning challenge associated with integrating freight buses into an city distribution framework. Each freight bus follows a predefined route, repeatedly traversing from a distribution center to multiple depots before returning to the distribution center. All depots are serviced by multiple freight buses on a consistent basis. This route planning problem presents a fresh iteration of the periodic vehicle routing problem. To tackle this challenge, the paper proposes a Mixed-Integer Linear Programming model, serving as a fundamental framework for future research endeavors concerning freight buses.

Clustering ensemble integrates multiple base clustering results to improve the stability and robustness of the single clustering method. It consists of two principal steps: a generation step, which is about the creation of base clusterings, and a consensus function, which is the integration of all clusterings obtained in the generation step. However, most of the existing base clustering algorithms used in the generation step are shallow clustering algorithms such as k-means. These shallow clustering algorithms do not work well or even fail when dealing with large-scale, high-dimensional unstructured data. The emergence of deep clustering algorithms provides a solution to address this challenge. Deep clustering combines the unsupervised commonality of deep representation learning to address complex high-dimensional data clustering, which has achieved excellent performance in many fields. In light of this, we introduce deep clustering into clustering ensemble and propose an improved selective deep-learning-based clustering ensemble algorithm (ISDCE). ISDCE exploits the deep clustering algorithm with different initialization parameters to generate multiple diverse base clusterings. Next, ISDCE constructs ensemble quality and diversity evaluation metrics of base clusterings to select higher-quality and rich-diversity candidate base clusterings. Finally, a weighted graph partition consensus function is utilized to aggregate the candidate base clusterings to obtain a consensus clustering result. Extensive experimental results on various types of datasets demonstrate that ISDCE performs significantly better than existing clustering ensemble approaches.

Abstract The COVID-19 pandemic is a serious public health threat that many countries in the world are facing. While several measures are being taken to minimize the spread of infection, mental health efforts must address psychological challenges due to the pandemic. This commentary reflects on original research from earlier epicenters of COVID-19 and identifies effective practices and suggestions applicable to mental health interventions in the North American context. Tailored mental health services need to be provided for populations that are at high risk of infection. Suggested interventions targeting specific population groups, such as healthcare workers, COVID-19 patients, and vulnerable populations, are discussed.

Background: Chronic fatigue syndrome (CFS) is characterized by significant and persistent fatigue. Ginseng is a traditional anti-fatigue Chinese medicine with a long history in Asia, as demonstrated by clinical and experimental studies. Ginsenoside Rg1 is mainly derived from ginseng, and its anti-fatigue metabolic mechanism has not been thoroughly explored.Methods: We performed non-targeted metabolomics of rat serum using LC-MS and multivariate data analysis to identify potential biomarkers and metabolic pathways. In addition, we implemented network pharmacological analysis to reveal the potential target of ginsenoside Rg1 in CFS rats. The expression levels of target proteins were measured by PCR and Western blotting.Results: Metabolomics analysis confirmed metabolic disorders in the serum of CFS rats. Ginsenoside Rg1 can regulate metabolic pathways to reverse metabolic biases in CFS rats. We found a total of 34 biomarkers, including key markers Taurine and Mannose 6-phosphate. AKT1, VEGFA and EGFR were identified as anti-fatigue targets of ginsenoside Rg1 using network pharmacological analysis. Finally, biological analysis showed that ginsenoside Rg1 was able to down-regulate the expression of EGFR.Conclusion: Our results suggest ginsenoside Rg1 has an anti-fatigue effect, impacting the metabolism of Taurine and Mannose 6-phosphate through EGFR regulation. This demonstrates ginsenoside Rg1 is a promising alternative treatment for patients presenting with chronic fatigue syndrome.

In this work, the authors report a sophisticated combination of genetic, biophysical, and biochemical analyses to identifies the cycling conformational states of PPM1D. The findings reveal how an allosteric inhibitor locks the protein into a conformationally inactive state, and explain the distribution of PPM1D activating mutations in cancer.

Abstract Background In frozen embryo transfer (FET), there is limited consensus on the best means of endometrial preparation in terms of the reproductive outcomes in women with polycystic ovary syndrome (PCOS). The present study aimed to compare the pregnancy and neonatal outcomes following artificial cycle FET (AC-FET) with or without gonadotropin-releasing hormone agonist (GnRH-a) pretreatment among women with PCOS. Methods A total of 4503 FET cycles that satisfied the inclusion criteria were enrolled in this retrospective cohort study between 2015 and 2020. The GnRH-a group received GnRH-a pretreatment while the AC-FET group did not. Propensity score matching (PSM) method and multivariate logistic regression analysis were performed to adjust for potential confounding factors. Results After PSM, women in the GnRH-a group suffered a significantly lower miscarriage rate (11.2% vs. 17.1%, P = 0.033) and a higher live birth rate (LBR) compared with those in the AC-FET group (63.1% vs. 56.8%, P = 0.043). No differences were observed in the rates of biochemical pregnancy, clinical pregnancy and ectopic pregnancy between the two groups. A higher mean gestational age at birth was observed in the GnRH-a group than in the AC-FET group (39.80 ± 2.01 vs. 38.17 ± 2.13, P = 0.009). The incidence of neonatal preterm birth (PTB) in the GnRH-a group was lower than that in the AC-FET group (7.4% vs. 14.9%, P = 0.009). Singleton newborns conceived after GnRH-a group were more likely to be small for gestational age (SGA) than those born after AC-FET group (16.4% vs. 6.8%, P = 0.009). However, no significant differences were found between the two groups in terms of mean birthweight, apgar score, the rates of macrosomia, large for gestational age and low birth weight. Conclusion(s) In women with PCOS who underwent AC-FET, GnRH-a pretreatment was significantly associated with a higher live birth rate and a reduced risk of neonatal PTB. However, there was a concomitant increase in the risk of developing SGA babies.

This paper considers the stability and L2- $\text{L}_\infty $ control problem for It $\hat {o}$ stochastic systems with the sawtooth-like input delay. Compared with previously-known results on systems with the sawtooth-like input delay, a new auxiliary system is introduced to reduce the conservatism of the system. Besides, the influence of stochastic noises is investigated. For the delayed stochastic system without the disturbance, an LMI type mean-square asymptotical stability criterion is derived by using the Bessel-Legendre stochastic inequality and a modified finite-interval quadratic polynomial inequality. Then a linear feedback controller is proposed to realize the stability of the system with a prescribed L2- $\text{L}_\infty $ performance under the influence of disturbances, where the controller gain matrix is designed by introducing slack variables. To be pointed out that the augmented Lyapunov-Krasovskii functional (LKF) used in this paper is new, which is constructed by introducing an auxiliary system to increase the delay-dependent function terms in the discriminant. Finally, two numerical examples are given to show the validness and effectiveness of the theoretical results.

Objective: To explore potential risk factors of postoperative nausea and vomiting (PONV) following ambulatory surgery. Method: Clinical data of 1670 cases receiving ambulatory surgery in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from September 2017 to December 2019 were retrospectively analyzed. They were categorized to PONV group and non-PONV group, and perioperative data in both groups were analyzed for assessing risk factors of PONV following ambulatory laparoscopy. Results: There were 156/1,670 (9.3%) PONV cases, and the female and male incidence in recruited cases was 12.0% and 6.0%, respectively. Analyses on perioperative data of them identified that female gender [adjusted odds ratio (aOR) = 2.060, P < 0.001], operation time >1 h (aOR = 1.554, P = 0.011), postoperative pain at rest (aOR = 1.909, P = 0.013) and postoperative pain during activities (aOR = 3.512, P < 0.001) were independent risk factors of PONV following ambulatory surgery. Furthermore, postoperative pain at rest and during activities were linearly, positively correlated to the incidence of PONV. Conclusion: Female gender, operation time >1 h and postoperative pain are closely related with the incidence of PONV following ambulatory surgery. Alleviating postoperative pain properly is one of the methods to reduce risk factors of PONV following ambulatory surgery.

Objectives To establish visualised prediction models of low fertilisation rate (LFR) and total fertilisation failure (TFF) for patients in conventional in vitro fertilisation (IVF) cycles.Design A retrospective cohort study.Setting Data from August 2017 to August 2021 were collected from the electronic records of a large obstetrics and gynaecology hospital in Sichuan, China.Participants A total of 11 598 eligible patients who underwent the first IVF cycles were included. All patients were randomly divided into the training group (n=8129) and the validation group (n=3469) in a 7:3 ratio.Primary outcome measure The incidence of LFR and TFF.Results Logistic regressions showed that ovarian stimulation protocol, primary infertility and initial progressive sperm motility were the independent predictors of LFR, while serum luteinising hormone and P levels before human chorionic gonadotropin injection and number of oocytes retrieved were the critical predictors of TFF. And these indicators were incorporated into the nomogram models. According to the area under the curve values, the predictive ability for LFR and TFF were 0.640 and 0.899 in the training set and 0.661 and 0.876 in the validation set, respectively. The calibration curves also showed good concordance between the actual and predicted probabilities both in the training and validation group.Conclusion The novel nomogram models provided effective methods for clinicians to predict LFR and TFF in traditional IVF cycles.

Using the 2017–2018 American Time Use Survey, the authors investigate how a comprehensive set of temporal conditions of paid work affects parental child care time, with attention to gender and education. Temporal work conditions include access to leave, inflexible start and end times, short advance notice of work schedules, types of work shifts, and usual days worked. Among mothers, the only significant relationship is between usual days worked and routine care time. Among fathers, lacking access to paid leave and having inflexible start and end times are associated with reduced routine care time, and working on variable days of the week is related to less developmental care time. Temporal work conditions also shape the educational gap in parental child care time. Importantly, nonstandard shifts and working on weekends widen the educational gradient in mothers’ developmental care time. The findings imply that temporal work conditions amplify gender inequality in work-family lives and families as agents of class reproduction.

China Jinping Underground Laboratory (CJPL) has the deepest rock overburden in the world, which considerably shields the detectors from muons. Thus, it has ultra-low radiation background level and is useful for experiments investigating rare physical events. Previously, experiments including the CDEX (China Dark matter EXperiment), PandaX (Particle and Astrophysical Xenon Experiments), JUNA (Jinping Underground Nuclear Astrophysics Experiment), and neutrino experiment have been carried out at CJPL and have given good results in dark matter detection, neutrinoless double beta decay, and more. This review introduces the construction process of CJPL, and introduces the facilities, results, and future plans of the aforementioned experiments. The CDEX used a high-purity germanium detector array for the dark matter detection and neutrinoless double-beta decay searches; whereas, for the same searches, PandaX used a dual-phase liquid xenon time projection chamber detector. A proton and helium accelerator was used by JUNA to simulate four nuclear reactions that occur in the Universe. A 103-kg prototype was constructed for feasibility verification by the neutrino experiment. The CDEX, PandaX, and JUNA collaboration groups give their latest results, all of which have approached or replaced the best results in the world. These experiments verify the extraordinary experimental conditions at CJPL. With the construction of CJPL-II, we expect an increase in the number of experiments based in Jinping and for further significant results to be achieved.

Aggregate figures unequivocally depict an increase in anti-Asian sentiment in the United States and other Western countries since the start of the COVID-19 pandemic, but there is limited understanding of the contexts under which Asians encounter discrimination. The authors examine how coethnic concentration shapes Asians’ experiences of discrimination across U.S. counties during COVID-19 and also assess whether county-level context (e.g., COVID-19 infection rates, unemployment rates) could help explain this relationship. The authors analyze the Understanding Coronavirus in America tracking survey, a nationally representative panel of American households, along with county-level contextual data. The authors find an n-shaped relationship between coethnic concentration and Asians’ perceived discrimination. This relationship is explained largely by county-level COVID-19 infection rates. Together, the context of medium Asian concentration and high COVID-19 cases created a particularly hostile environment for Asians during COVID-19.

In this article, we describe a gender peak effect that women's relative share in COVID-19 infections increases when there is a sharp increase in cases, and it reaches the highest level during peak times in each wave of the COVID-19 outbreak. We demonstrate this gender peak effect by analyzing detailed, sex-disaggregated Public Health Agency of Canada (PHAC) data. The data include 1,045,998 men and women who were confirmed cases of COVID-19 from March 2020 to February 2022. We show that women's relative share in COVID-19 infections always increases and reaches the level exceeding men's share when we see a sharp peak in case number. We further show that women's higher share in care work (e.g., captured by occupation and age variables) largely explains their elevated infections during COVID-19 peaks. Effective public health interventions during infectious disease outbreaks must recognize this potential gender peak effect and take appropriate measures to curb women's health vulnerabilities.

Background: Rising median age at marriage and increasing lifestyle differentials across occupations suggest that occupations increasingly offer important signals of the economic and cultural resources of potential spouses. Scant attention has been paid to occupational assortative mating in recent years. Rarer are studies about racial, ethnic, and nationality differences in occupational homogamy rates. Objective: We document variations in occupational homogamy rates by race, ethnicity, and national origin and identify factors contributing to group differences in occupational homogamy rates. Methods: Using data from the 2006 and 2008-2019 American Community Survey, we compared occupational homogamy rates by race, ethnicity, and nationality. We also used logistic regression models to identify the correlates of occupational homogamy and used Fairlie decomposition models to assess the extent to which individual traits, occupational traits, and place of residence contribute to group differences in occupational homogamy. Results: Asian American men have higher occupational homogamy rates than non-Asian men. Differences in occupational homogamy rates among Asian national origin groups are greater than group differences among non-Asian men. Among Asian men, Indians have the highest occupational homogamy rates and Koreans have the lowest. Differences in educational attainment and representation in STEM occupations explain a significant portion of group differences in occupational homogamy rates. Contribution: We reveal that, in addition to educational and occupational attainment, marital sorting on occupation may represent a dimension of "strategic adaptation" in Asian Americans' social mobility.

Abstract Background This study aimed to assess the independent prognostic value of tumor size compared with other clinical and pathologic features of primary invasive cutaneous melanoma (CM). Methods This study included 28,593 patients with primary invasive CM in Surveillance, Epidemiology, and End Results Program database diagnosed from 2004 through 2016. Tumor size was divided into five subgroups (≤6, 7‐12, 13‐30, 31‐42, and >42 mm). The primary endpoint was melanoma‐specific survival (MSS). Results The relationship between tumor size and survival was piecewise. After adjusting for age, sex, primary site, histopathologic cell type, Breslow thickness, ulceration, mitotic rate, regional metastasis, and distant metastasis, the hazard ratio (HR) of MSS increased with increasing tumor size until a peak at 31‐42 mm (HRs, 1.33, 1.59, 2.41, respectively; all P 42 mm subgroup had the shortest MSS in T4. In addition, tumor size with a cutoff value of 12 mm showed stronger prognostic value for MSS (HR, 2.32; 95% CI, 1.80‐2.98; P

Context Oxidative imbalance-induced cognitive impairment is among the most urgent clinical concerns. Isoflurane has been demonstrated to impair cognitive function via an increase in oxidative stress. GSP has strong antioxidant capacities, suggesting potential cognitive benefits. Objective This study investigates whether GSP pre-treatment can alleviate isoflurane-induced cognitive dysfunction in mice. Materials and methods C57BL/6J mice were pre-treated with either GSP 25–100 mg/kg/d for seven days or GSP 100–400 mg/kg as a single dose before the 6 h isoflurane anaesthesia. Cognitive functioning was examined using the fear conditioning tests. The levels of SOD, p-NR2B and p-CREB in the hippocampus were also analysed. Results Pre-treatment with either a dose of GSP 50 mg/kg/d for seven days or a single dose of GSP 200 mg/kg significantly increased the % freezing time in contextual tests on the 1st (72.18 ± 12.39% vs. 37.60 ± 8.93%; 78.27 ± 8.46% vs. 52.72 ± 2.64%), 3rd (93.80 ± 7.62% vs. 52.94 ± 14.10%; 87.65 ± 10.86% vs. 52.89 ± 1.73%) and 7th (91.36 ± 5.31% vs. 64.09 ± 14.46%; 93.78 ± 3.92% vs. 79.17 ± 1.79%) day after anaesthesia. In the hippocampus of mice exposed to isoflurane, GSP 200 mg/kg increased the total SOD activity on the 1st and 3rd day and reversed the decreased activity of the NR2B/CREB pathway. Discussion and conclusions These findings suggest that GSP improves isoflurane-induced cognitive dysfunction by protecting against perturbing antioxidant enzyme activities and NR2B/CREB pathway. Therefore, GSP may possess a potential prophylactic role in isoflurane-induced and other oxidative stress-related cognitive decline.

Accumulating evidence indicates that inhalation anesthetics induce or increase the risk of cognitive impairment. GLYX-13 (rapastinel) acts on the glycine site of N-methyl-D-aspartate receptors (NMDARs) and has been shown to enhance hippocampus-dependent learning and memory function. However, the mechanisms by which GLYX-13 affects learning and memory function are still unclear. In this study, we investigated these mechanisms in a mouse model of long-term anesthesia exposure. Mice were intravenously administered 1 mg/kg GLYX-13 at 2 hours before isoflurane exposure (1.5% for 6 hours). Cognitive function was assessed using the contextual fear conditioning test and the novel object recognition test. The mRNA expression and phosphorylated protein levels of NMDAR pathway components, N-methyl-D-aspartate receptor subunit 2B(NR2B)-Ca2+/calmodulin dependent protein kinase II (CaMKII)-cyclic adenosine monophosphate response element binding protein (CREB), in the hippocampus were evaluated by quantitative RT-PCR and western blot assay. Pretreatment with GLYX-13 ameliorated isoflurane exposure-induced cognitive impairment and restored NR2B, CaMKII and CREB mRNA and phosphorylated protein levels. Intracerebroventricular injection of KN93, a selective CaMKII inhibitor, significantly diminished the effect of GLYX-13 on cognitive function and NR2B, CaMKII and CREB levels in the hippocampus. Taken together, our findings suggest that GLYX-13 pretreatment alleviates isoflurane-induced cognitive dysfunction by protecting against perturbation of the NR2B/CaMKII/CREB signaling pathway in the hippocampus. Therefore, GLYX-13 may have therapeutic potential for the treatment of anesthesia-induced cognitive dysfunction. This study was approved by the Experimental Animal Ethics Committee of Drum Tower Hospital affiliated to the Medical College of Nanjing University, China (approval No. 20171102) on November 20, 2017.

BackgroundChronic diseases may impact older adults’ health outcomes, health care costs, and quality of life. Self-management is expected to encourage individuals to make autonomous decisions, adhere to treatment plans, deal with emotional and social consequences, and provide choices for healthy lifestyle. New eHealth solutions significantly increase the health literacy and empower patients in self-management of chronic conditions. ObjectiveThis study aims to develop a Community-Based e-Health Program (CeHP) for older adults with chronic diseases and conduct a pilot evaluation. MethodsA pilot study with a 2-group pre- and posttest repeated measures design was adopted. Community-dwelling older adults with chronic diseases were recruited from senior activity centers in Singapore. A systematic 3-step process of developing CeHP was coupled with a smart-device application. The development of the CeHP intervention consists of theoretical framework, client-centric participatory action research process, content validity assessment, and pilot testing. Self-reported survey questionnaires and health outcomes were measured before and after the CeHP. The instruments used were the Self-care of Chronic Illness Inventory (SCCII), Healthy Aging Instrument (HAI), Short-Form Health Literacy Scale, 12 Items (HLS-SF 12), Patient Empowerment Scale (PES), and Social Support Questionnaire, 6 items. The following health outcomes were measured: Montreal Cognitive Assessment, Symbol Digit Modalities Test, total cholesterol (TC), high-density lipoproteins, low-density lipoproteins/very-low-density lipoproteins (LDL/VLDL), fasting glucose, glycated hemoglobin (HbA1c), and BMI. ResultsThe CeHP consists of health education, monitoring, and an advisory system for older adults to manage their chronic conditions. It is an 8-week intensive program, including face-to-face and eHealth (Care4Senior App) sessions. Care4Senior App covers health education topics focusing on the management of hypertension, hyperlipidemia, and diabetes, brain health, healthy diet, lifestyle modification, medication adherence, exercise, and mindfulness practice. Content validity assessment indicated that the content of the CeHP is valid, with a content validity index (CVI) ranging 0.86-1 and a scale-CVI of 1. Eight participants in the CeHP group and 4 in the control group completed both baseline and post intervention assessments. Participants in the CeHP group showed improvements in fasting glucose, HbA1c, TC, LDL/VLDL, BMI, SCCII indices (Maintenance, Monitoring, and Management), HAI, and PES scores post intervention, although these changes were not significant. For the participants in the control group, the scores for SCCII (management and confidence) and HLS-SF 12 decreased post intervention. ConclusionsThe CeHP is feasible, and it engages and empowers community-dwelling older adults to manage their chronic conditions. The rigorous process of program development and pilot evaluation provided valid evidence to expand the CeHP to a larger-scale implementation to encourage self-management, reduce debilitating complications of poorly controlled chronic diseases, promote healthy longevity and social support, and reduce health care costs.

High dielectric constants in organic semiconductors have been identified as a central challenge for the improvement in not only piezoelectric, pyroelectric, and ferroelectric effects but also photoelectric conversion efficiency in OPVs, carrier mobility in OFETs, and charge density in charge-trapping memories. Herein, we report an ultralong persistence length (lp≈41 nm) effect of spiro-fused organic nanopolymers on dielectric properties, together with excitonic and charge carrier behaviors. The state-of-the-art nanopolymers, namely, nanopolyspirogrids (NPSGs), are synthesized via the simple cross-scale Friedel-Crafts polygridization of A2B2-type nanomonomers. The high dielectric constant (k=8.43) of NPSG is firstly achieved by locking spiro-polygridization effect that results in the enhancement of dipole polarization. When doping into a polystyrene-based dielectric layer, such a high-k feature of NPSG increases the field-effect carrier mobility from 0.20 to 0.90 cm2 V-1 s-1 in pentacene OFET devices. Meanwhile, amorphous NPSG film exhibits an ultralow energy disorder (

General anesthetics can induce cognitive impairments and increase the risk of Alzheimer’s disease (AD). However, the underlying mechanisms are still unknown. Our previous studies shown that long-term isoflurane exposure induced peripheral and central insulin resistance (IR) in adult mice and aggravated IR in type 2 diabetes mellitus (T2DM) mice. Clinical and preclinical studies revealed an association between impaired insulin signaling and tau pathology in AD and other tauopathies. We investigated if alleviation of hippocampal IR by the antidiabetic agent metformin could reduce tau hyperphosphorylation and cognitive decline induced by isoflurane in mice. The effects of prolonged (6 h) isoflurane anesthesia on hippocampal IR, hippocampal tau hyperphosphorylation, and hippocampus-dependent cognitive function were evaluated in wild type (WT) adult mice and the high-fat diet plus streptozotocin (HFD/STZ) mouse model of T2DM. Here we shown that isoflurane and HFD/STZ dramatically and synergistically induced hippocampal IR and fear memory impairment. Metformin pretreatment strongly ameliorated hippocampal IR and cognitive dysfunction caused by isoflurane in WT mice, but was less effective in T2DM mice. Isoflurane also induced hippocampal tau hyperphosphorylation and metformin reversed this effect. In addition, isoflurane significantly increased blood glucose levels in both adult and T2DM mice, and metformin reversed this effect as well. Administration of 25% glucose to metformin-pretreated mice induced hyperglycemia, but surprisingly did not reverse the benefits of metformin on hippocampal insulin signaling and fear memory following isoflurane anesthesia. Our findings show hippocampal IR and tau hyperphosphorylation contribute to acute isoflurane-induced cognitive dysfunction. Brief metformin treatment can mitigate these effects through a mechanism independent of glycemic control. Future studies are needed to investigate whether long-term metformin treatment can also prevent T2DM-induced hippocampal IR and cognitive decline.

Interacting with family members and friends from other households is a key part of everyday life and is crucial to people’s mental well-being. The COVID-19 pandemic severely curtailed face-to-face contact between households, particularly for older adults (aged 60 and above), due to their high risk of developing severe illness if infected by COVID-19. In-person contact, where possible, was largely replaced by virtual interaction during the pandemic. This article examines how inter-household contact in face-to-face and virtual forms, as well as combinations of the two forms of contact, related to older adults’ mental well-being during the pandemic. Data from two national longitudinal surveys, collected from the same respondents before (2018–2019) and during (June 2020) the pandemic, were comparatively analysed: the Health and Retirement Study in the US and Understanding Society in the UK. The findings showed a notable increase in loneliness in the US and a decline in general mental well-being in the UK following the outbreak of COVID-19. In both countries, more frequent inter-household face-to-face contact during the pandemic was associated with better general mental well-being, but inter-household virtual contact, via means such as telephone and digital media, was not associated with general mental well-being in either the US or the UK. In the US, older adults who engaged more frequently in virtual contact were more likely to feel lonely during the pandemic, particularly if their face-to-face contact was limited. In both countries, the increase in loneliness following the outbreak of the pandemic was greater for older adults who reported more virtual contact. The findings suggest that household-centred crisis management during the COVID-19 pandemic had unintended mental health implications in both the US and the UK, despite contextual differences between the two countries. Although face-to-face contact between households helped to sustain older adults’ mental well-being, virtual contact was not a qualitatively equivalent alternative. The findings also provide an important evidence base for informing policy developments and for supporting the mental health of older people during the COVID-19 pandemic and in the longer term.

Underground Nuclear Astrophysics Experiment in China (JUNA) has been commissioned by taking the advantage of the ultra-low background in Jinping underground lab. High current mA level 400 KV accelerator with an ECR source and BGO detectors were commissioned. JUNA studies directly a number of nuclear reactions important to hydrostatic stellar evolution at their relevant stellar energies. In the first quarter of 2021, JUNA performed the direct measurements of 25Mg(p,γ)26Al, 19F(p,α)16O, 13C(α,n)16O and 12C(α,γ)16O near the Gamow window. The experimental results reflect the potential of JUNA with higher statistics, precision and sensitivity of the data. The preliminary results of JUNA experiment and future plan are given.

In China, the oil and natural gas resources of Bohai Bay are mainly marginal oil fields. It is necessary to build both iceresistant and economical offshore platforms. However, there are many risks during the life cycle of offshore platforms due to the imperfect preliminary design for the Bohai Sea economical ice-resistant structures. As a result, the whole life-cycle design should be considered, including plan, design, construction, management and maintenance design. Based on the demand of existing codes and research of the basic design, structural ice-resistant performance and the reasonable management and maintenance, the life-cycle design theory is discussed. It was concluded that the life-cycle cost-effective optimum design proposed will lead to a minimum risk.

Bohai is a typical marginal oil field in an ice region, where most of the oil and gas platforms are economical. Sea ice is the main factor that affects the safety of oil and gas platforms in Bohai. Due to the complexity of the ice load and ice-induced vibrations, there are large security risks when developing Bohai oil and gas in the winter. It is difficult to ensure the safe production of oil and gas in winter using existing sea ice disaster warning technologies. Based on winter oil and gas production in the Bohai Sea’s Liaodong Bay, a set of suitable sea ice management systems is proposed in this paper. These systems integrate sea ice monitoring, risk assessment and risk prediction technologies. Based on the risk warning system, an ice management model of a Bohai ice platform has been put into practice, which ensures the safe production of the platform in winter.

ABSTRACT Most scholars' comprehension on labour are ambiguous because of the variety of philosophical contradictions embedded in their plausible theories being not explicitly stated but irrationally taken for granted. We, therefore, inquisitively direct sole attention to social spacetime in which, and by which, labour in totality takes place. And then consider the division of labour in natural spacetime as just the appearance of the alienation of labour in social spacetime by our Marxist renewal of the notion of labour - thus manifesting its benefaction to an essential up-to-date explanation of human being, on which a labourer could struggle to survive as still a human being within social spacetime, to fight against the almighty empire of capitalism in the era of globalisation.

Background: Prostate cancer is one of the most prevalent cancers in men. Exposure to heavy metals and their association with prostate cancer risk has been studied extensively, but combined effects remain largely inconclusive. Objectives: To elucidate the association between serum concentrations of heavy metals and prostate cancer risk. Methods: Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the concentrations of a panel of 10 heavy metals (Mn, Cu, Zn, As, Se, Sb, Co, Cu, Cd and Pb) in serum samples of 141 cases and 114 controls in the Singapore Prostate Cancer Study. Linear probit regression models were used to estimate risk differences (RDs) and 95% confidence intervals (CIs) for the associations between log-centered serum metal concentrations and prostate cancer risk with adjustment for potential confounders. Bayesian kernel machine regression (BKMR) models were used to account for nonlinear, interactive, and joint metal effects. Results: Using probit regression, four heavy metals (As, Zn, Mn, Sb) were significantly and positively associated with prostate cancer risk in the unadjusted models. Using BKMR analysis, both As and Zn had positive risk differences on prostate cancer risk when all other metals were held fixed at the 25th and 50th percentiles (RD, 25th percentile: As: 0.15, Zn: 0.19, RD, 50th percentile: As: 0.45, Zn: 0.37). In addition, the overall mixture risk difference was positive and the 95% credible intervals did not include 0 when all metals in the mixture were jointly above their 55th percentile, as compared to when all metals were below their median values. Conclusions: In summary, we found positive associations between the serum levels of As and Zn and prostate cancer risk on the risk difference scale using BKMR models. The overall mixture effect was also associated with increased prostate cancer risk. Future studies are warranted to validate these findings in prospective studies. Keywords: Combined effects, Heavy metals, Joint exposure, Mixtures, Prostate cancer

In all metazoan species, sperm is produced from germline stem cells. These self-renew and produce daughter cells that amplify and differentiate dependent on interactions with somatic support cells. In the male gonad of Drosophila melanogaster, the germline and somatic cyst cells co-differentiate as cysts, an arrangement in which the germline is completely enclosed by cytoplasmic extensions from the cyst cells. Notch is a developmentally relevant receptor in a pathway requiring immediate proximity with the signal sending cell. Here, we show that Notch is expressed in the cyst cells of wild-type testes. Notch becomes activated in the transition zone, an apical area of the testes in which the cyst cells express stage-specific transcription factors and the enclosed germline finalizes transit-amplifying divisions. Reducing the ligand Delta from the germline cells via RNA-Interference or reducing the receptor Notch from the cyst cells via CRISPR resulted in cell death concomitant with loss of germline cells from the transition zone. This shows that Notch signaling is essential for the survival of the germline stem cell lineage.

The buckling behavior of rod strings in wellbore is one of the key issues in petroleum engineering. The slender rod strings in vertical wellbore were selected as research objects. Based on the energy method, the critical load formulas of sinusoidal and helical buckling were derived for the string with the bottom of the wellbore pressure. According to the sinusoidal and helical buckling’s geometry of the pressurized column, the contact friction state of post-buckling between the rod strings and the wellbore was considered. This paper adopted Lagrange multiplier method to describe sliding displacement boundary conditions of wellbore and introduced gravitational potential energy and friction resistance dissipated energy in the energy method. The contact forces and friction resistances between the rod string and wellbore were derived in vertical wells. The post buckling experimental apparatus was also developed in this paper. The sinusoidal and helical buckling critical loads and friction resistances were derived under different loads. The experimental results are consistent with the theoretical results. Therefore, this article would provide an effective method for buckling column such as drilling and coiled tubing.