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Abstract Globally, breast cancer continues to be the leading cause of cancer-related incidence and mortality among females. Research has shown that sleep patterns significantly influence tumor onset and progression. In this research, the association was examined through the application of a two-sample Mendelian randomization (MR) approach. For the analysis of seven sleep patterns, genetic tools were sourced from both the UK Biobank and 23andMe, including morning/evening person (chronotype) n = 177,604, morning person (chronotype) n = 248,094, daytime dozing/sleepiness n = 193,472, getting up in the morning n = 193,717, and sleeplessness n = 193,987; sleep duration n = 192,810; and nap during the day n = 166,853. The Breast Cancer Association Consortium (BCAC) supplied genome-wide association studies (GWAS) data, including 133,384 breast cancer cases and 113,789 controls, alongside subtype-specific data with 106,278 cases and 91,477 controls. We discovered that chronotype encompasses both morning and evening types contributes to the risk of overall breast cancer. While daytime dozing and morning person (chronotype) are linked to a lower risk of breast cancer in general, In subtype-specific analyses, morning person (chronotype) was negatively associated with luminal B, HER2-negative-like, and daytime dozing was negatively correlated with luminal A-like, luminal B-like, and HER2-enriched-like. The study corroborates that chronotype is a danger element for breast cancer, aligning with previous observational findings. The association between being a morning person (chronotype) or having daytime dozing and a decreased risk of breast cancer underscores the significance of sleep patterns in formulating strategies for cancer prevention.

Abstract The Span-based model can effectively capture the complex entity structure in the text, thus becoming the mainstream model for nested named entity recognition (Nested NER) tasks. However, traditional Span-based models decode each entity span independently. They do not consider the semantic connections between spans or the entities’ positional information, which limits their performance. To address these issues, we propose a Bi-Directional Context-Aware Network (Bi-DCAN) for the Nested NER. Specifically, we first design a new span-level semantic relation model. Then, the Bi-DCAN is implemented to capture this semantic relationship. Furthermore, we incorporate Rotary Position Embedding into the bi-affine mechanism to capture the relative positional information between the head and tail tokens, enabling the model to more accurately determine the position of each entity. Experimental results show that compared to the latest model Diffusion-NER, our model reduces 20M parameters and increases the F1 scores by 0.24 and 0.09 on the ACE2005 and GENIA datasets respectively, which proves that our model has an excellent ability to recognise nested entities.

Abstract Capsaicin derivatives with thiourea structure (CDTS) is highly noteworthy owing to its higher analgesic potency in rodent models and higher agonism in vitro. However, the direct synthesis of CDTS remains t one or more shortcomings. In this study, we present reported a green, facile, and practical synthetic method of capsaicin derivatives with thiourea structure is developed by using an automated synthetic system, leading to a series of capsaicin derivatives with various electronic properties and functionalities in good to excellent yields.

Abstract In face-to-face communication, multimodal cues such as prosody, gestures, and mouth movements can play a crucial role in language processing. While several studies have addressed how these cues contribute to native (L1) language processing, their impact on non-native (L2) comprehension is largely unknown. Comprehension of naturalistic language by L2 comprehenders may be supported by the presence of (at least some) multimodal cues, as these provide correlated and convergent information that may aid linguistic processing. However, it is also the case that multimodal cues may be less used by L2 comprehenders because linguistic processing is more demanding than for L1 comprehenders, leaving more limited resources for the processing of multimodal cues. In this study, we investigated how L2 comprehenders use multimodal cues in naturalistic stimuli (while participants watched videos of a speaker), as measured by electrophysiological responses (N400) to words, and whether there are differences between L1 and L2 comprehenders. We found that prosody, gestures, and informative mouth movements each reduced the N400 in L2, indexing easier comprehension. Nevertheless, L2 participants showed weaker effects for each cue compared to L1 comprehenders, with the exception of meaningful gestures and informative mouth movements. These results show that L2 comprehenders focus on specific multimodal cues – meaningful gestures that support meaningful interpretation and mouth movements that enhance the acoustic signal – while using multimodal cues to a lesser extent than L1 comprehenders overall.

Abstract This study aimed to estimate the healthcare costs of kidney transplantation compared with dialysis using a propensity score approach to handle potential treatment selection bias. We included 693 adult wait-listed patients who started renal replacement therapy between 1998 and 2012 in Region Skåne and Stockholm County Council in Sweden. Healthcare costs were measured as annual and monthly healthcare expenditures. In order to match the data structure of the kidney transplantation group, a hypothetical kidney transplant date of persons with dialysis were generated for each dialysis patient using the one-to-one nearest-neighbour propensity score matching method. Applying propensity score matching and inverse probability-weighted regression adjustment models, the potential outcome means and average treatment effect were estimated. The estimated healthcare costs in the first year after kidney transplantation were €57,278 (95% confidence interval (CI) €54,467–60,088) and €47,775 (95% CI €44,313–51,238) for kidney transplantation and dialysis, respectively. Thus, kidney transplantation leads to higher healthcare costs in the first year by €9,502 (p = 0.066) compared to dialysis. In the following two years, kidney transplantation is cost saving [€36,342 (p

Abstract Provide reference data on which EQ-5D-3L value set should be used with Chinese patients with chronic kidney disease (CKD); assess differences in health-related quality of life (HRQoL) based on the use of the Chinese (from 2014 and 2018), the UK, and the Japanese value sets; and examine differences in utility scores for key preventive influencing factors. Data from 373 patients with CKD recruited for a cross-sectional multicenter HRQoL survey were used. Differences among utility scores based on the four value sets were determined using Wilcoxon signed rank test. Intra-class correlation coefficient (ICCs) and Bland–Altman plots were used to evaluate consistency among utility scores and Tobit regression model was used to analyze the influencing factors of utility scores. There were significant differences between utility scores based on the four value sets, with the Chinese 2018 value set yielding the highest utility (0.957). ICCs between the value sets for China 2014, the UK, and Japan were all greater than 0.9, whereas the ICCs between the value sets for China 2018 and the other three were all less than 0.7. The influencing factors of utility scores included CKD stages, age, education level, city, and primary renal disease. This was the first study to report findings on the health utility of patients with CKD based on the two Chinese EQ-5D-3L value sets. Overall, the Chinese value sets performed similarly to the other two value sets (UK and Japan) commonly used in the Chinese population; however, value sets for different countries were not interchangeable. In Chinese contexts, the two value sets for China were recommended and the choice of which one should consider whether the value set of choice was established with a sample that is consistent with the targeted population.

Abstract Fetal aberrant right subclavian artery (ARSA) is a relatively common sonographic finding. Congenital heart disease (CHD) is the most common structural abnormality in patients with ARSA. We aimed to assess the prevalence of genetic abnormalities, particularly sequence variants, in fetuses with CHD and ARSA. By clinical phenotyping and genomic sequencing, we retrospectively reviewed all fetuses with a prenatal diagnosis of CHD combined with ARSA at a single center. As a result, we identified 30 fetuses with ARSA combined with CHD, with conotruncal anomalies being the most common (n = 12, 40%), followed by left ventricular outflow tract obstruction (n = 6, 20%) and atrioventricular septal defects (n = 6, 20%). Overall, 18 (60%) cases had a genetic diagnosis. Copy number variation sequencing analysis identified six (20%) fetuses with aneuploidy and seven (23%) with pathogenic copy-number variants. Whole-exome sequencing (WES) analysis of the remaining 17 cases revealed diagnostic genetic variants in five (29%) cases, indicating that the diagnostic yield of WES for the entire cohort was 17% (5/30). Our findings reveal the high burden of genetic abnormalities in fetal CHD with ARSA. Single-gene disorders contribute substantially to the genetic etiology of fetal CHD with ARSA.

Abstract Pyrimidine catabolism is implicated in hepatic steatosis. Dihydropyrimidine dehydrogenase (DPYD) is an enzyme responsible for uracil and thymine catabolism, and DPYD human genetic variability affects clinically observed toxicity following 5-Fluorouracil administration. In an in vitro model of fatty acid-induced steatosis, the pharmacologic inhibition of DPYD resulted in protection from lipid accumulation. Additionally, a gain-of-function mutation of DPYD, created through clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR-Cas9) engineering, led to an increased lipid burden, which was associated with altered mitochondrial functionality in a hepatocarcionma cell line. The studies presented herein describe a novel role for DPYD in hepatocyte metabolic regulation as a modulator of hepatic steatosis.

Abstract To provide an effective risk assessment of water inrush for coal mine safety production, a BP neural network prediction method for water inrush based on principal component analysis and deep confidence network optimization was proposed. Because deep belief network (DBN) is disadvantaged by a long training time when establishing a high-dimensional data classification model, the principal component analysis (PCA) method is used to reduce the dimensionality of many factors affecting the water inrush of the coal seam floor, thus reducing the number of variables of the research object, redundancy and the difficulty of feature extraction and shortening the training time of the model. Then, a DBN network was used to extract secondary features from the processed nonlinear data, and a more abstract high-level representation was formed by combining low-level features to find the expression of the nonlinear relationship between the characteristics of water in bursts. Finally, a prediction model was established to predict the water inrush in coal mines. The superiority of this method was verified by comparing the prediction of the actual working face with the actual situation in typical mining areas of North China. The prediction accuracy of coal mine water inrush obtained by this algorithm is 94%, while the prediction accuracy of traditional BP algorithm is 70%, and the prediction accuracy of SVM algorithm is 88%.

Abstract Novel modalities such as PROTAC and RNAi have the ability to inadvertently alter the abundance of endogenous proteins. Currently available in vitro secondary pharmacology assays, which evaluate off-target binding or activity of small molecules, do not fully assess the off-target effects of PROTAC and are not applicable to RNAi. To address this gap, we developed a proteomics-based platform to comprehensively evaluate the abundance of off-target proteins. First, we selected off-target proteins using genetics and pharmacology evidence. This process yielded 2813 proteins, which we refer to as the “selected off-target proteome” (SOTP). An iterative algorithm was then used to identify four human cell lines out of 932. The 4 cell lines collectively expressed ~ 80% of the SOTP based on transcriptome data. Second, we used mass spectrometry to quantify the intracellular and extracellular proteins from the selected cell lines. Among over 10,000 quantifiable proteins identified, 1828 were part of the predefined SOTP. The SOTP was designed to be easily modified or expanded, owing to the rational selection process developed and the label free LC–MS/MS approach chosen. This versatility inherent to our platform is essential to design fit-for-purpose studies that can address the dynamic questions faced in investigative toxicology.

Abstract Infants who are small for gestational age (SGA) are at increased risk of neonatal and infant death, non-communicable diseases and growth retardation. However, the epidemiological characteristics of SGA remain unclear. We aim to explore the prevalence of SGA and to examine its socioeconomic associations by using data from 21 cities. 10,515,494 single live birth records between 2014 and 2019 from the Guangdong Women and Children Health Information System were included in the study. Descriptive statistical methods were used to analyze the prevalence trend of SGA and its distribution. We also analyze the associations between the prevalence of SGA and per-capita GDP. The prevalence of SGA in Guangdong Province from the years 2014–2019 was 13.17%, 12.96%, 11.96%, 12.72%, 11.45%, 11.30% respectively, and the overall prevalence was 12.28%. The prevalence of term SGA infants in Guangdong Province was 12.50%, which was much higher than that of preterm SGA (7.71%). There was a significant negative correlation between the SGA prevalence and per-capita GDP in 21 cities of Guangdong Province. The level of economic development may affect the prevalence of SGA. The prevalence of SGA in full term infants is significantly higher than in premature infants, suggesting that most SGA infants may be born at a later gestational age.

Abstract Space radiation consists of energetic protons and other heavier ions. During the International Space Station program, chromosome aberrations in lymphocytes of astronauts have been analyzed to estimate received biological doses of space radiation. More specifically, pre-flight blood samples were exposed ex vivo to varying doses of gamma rays, while post-flight blood samples were collected shortly and several months after landing. Here, in a study of 43 crew-missions, we investigated whether individual radiosensitivity, as determined by the ex vivo dose–response of the pre-flight chromosome aberration rate (CAR), contributes to the prediction of the post-flight CAR incurred from the radiation exposure during missions. Random-effects Poisson regression was used to estimate subject-specific radiosensitivities from the preflight dose–response data, which were in turn used to predict post-flight CAR and subject-specific relative biological effectiveness (RBEs) between space radiation and gamma radiation. Covariates age, gender were also considered. Results indicate that there is predictive value in background CAR as well as radiosensitivity determined preflight for explaining individual differences in post-flight CAR over and above that which could be explained by BFO dose alone. The in vivo RBE for space radiation was estimated to be approximately 3 relative to the ex vivo dose response to gamma irradiation. In addition, pre-flight radiosensitivity tended to be higher for individuals having a higher background CAR, suggesting that individuals with greater radiosensitivity can be more sensitive to other environmental stressors encountered in daily life. We also noted that both background CAR and radiosensitivity tend to increase with age, although both are highly variable. Finally, we observed no significant difference between the observed CAR shortly after mission and at > 6 months post-mission.

Abstract Several previous studies of eye movements have put forward that, during face recognition, Easterners spread their attention across a greater part of their visual field than Westerners. Recently, we found that culture’s effect on the perception of faces reaches mechanisms deeper than eye movements, therefore affecting the very nature of information sampled by the visual system: that is, Westerners globally rely more than Easterners on fine-grained visual information (i.e. high spatial frequencies; SFs), whereas Easterners rely more on coarse-grained visual information (i.e. low SFs). These findings suggest that culture influences basic visual processes; however, the temporal onset and dynamics of these culture-specific perceptual differences are still unknown. Here, we investigate the time course of SF use in Western Caucasian (Canadian) and East Asian (Chinese) observers during a face identification task. Firstly, our results confirm that Easterners use relatively lower SFs than Westerners, while the latter use relatively higher SFs. More importantly, our results indicate that these differences arise as early as 34 ms after stimulus onset, and remain stable through time. Our research supports the hypothesis that Westerners and Easterners initially rely on different types of visual information during face processing.

Abstract T cell receptor (TCR) signaling is important for T cell homeostasis and function. However, how surface TCR levels are regulated and its biological significance on T cells remains largely unknown. Here, we show that the T cell-specific deletion of Arpc2, a component of Arp2/3 complex, results in compromised peripheral T cell homeostasis. Arp2/3 complex-nucleated actin filaments are essential for maintaining surface TCR levels by regulating TCR+ endosome trafficking in resting state and controlling polarization of TCR+ endosomes during immune synapse formation in T cells. Additionally, Arpc2-TKO T cells are unable to form immune synapse. Interestingly, defected T cell homeostasis is caused by reduced surface TCR levels but not impaired immune synapse formation. Collectively, our findings suggest that Arp2/3 complex-nucleated actin filaments are required for maintaining surface TCR levels via regulating TCR+ endosome trafficking which is essential for T cell homeostasis.

Abstract The fabrication and application of polystyrene (PS)-assisted ITO nanowire (NW) networks are reported. The ITO-NW networks are fabricated by means of electron-beam deposition via PS. This method has the advantages of low-temperature (~300 °C), low-cost, facile and efficient operation. The growth mechanism of PS-assisted ITO NWs was analyzed in detail, and the morphology of which could be regulated by the size of PS. X-ray diffraction and high-resolution transmission electron microscope show that the ITO NWs are close to an integral cubic lattice. The transmittance of ITO-NW networks layer is above 90% after 400 nm and the sheet resistance is ~200 Ω/□. When they applied on vertical blue and green LEDs, the light output power all has been improved ~30%. And, the resistive switching behaviors of ITO-NWs were measured and analyzed in Ag/ITO-NW networks/Al capacitor. The application of ITO-NW networks on special morphological devices was discussed. The PS-assisted ITO-NW networks show a strong researching and application value.

Abstract Prognostic biomarkers for the pancreatic neuroendocrine tumors are needed. Proteomic study on insulinoma has been rarely reported. We identified the differential expression of proteins between insulinoma and their paired tissues by proteomic analysis, and evaluated the prognostic significance of specific proteins in pancreatic neuroendocrine tumors including insulinoma. The differential expression of select proteins was validated in more than 300 tumors using immunohistochemical staining and western blot. Methylation of UCH-L1 promoter in tumors was examined by methylation specific PCR and validated by sequencing. The concurrent expression of UCH-L1 and α-internexin was correlated with the prognosis in 2 independent collectives of patients with tumors. Sixty-two and 219 proteins were significantly down-regulated and up-regulated in insulinomas, respectively. Demethylation of UCH-L1 promoter was associated with UCH-L1 expression in tumors (p = 0.002). The concurrent expression of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors was significantly associated with better overall survival and disease-free survival in the combination of both cohorts (log rank p = 3.90 × 10−4 and p = 3.75 × 10−5, respectively) and in each of cohorts. The prognostic value of both proteins was also validated in patients with stage II and III tumors (p = 0.017 and p = 0.006, respectively). The proteins UCH-L1 and α-internexin could be independent prognostic biomarkers of pancreatic neuroendocrine tumors.

Abstract Previous studies have shown that intuitive moral cognition occurs at an early stage. However, inconsistent findings indicate that moral information is recognized at a relatively late stage. This study uses the recognition potential (RP) as a neural index and simultaneously measures individuals’ moral preferences using the Moral Foundation Questionnaire. We aim to investigate how individual differences in moral preferences modulate the processing of morality in the pre-semantic stage and provide some insights to explain the variation in rapid information processing linked to morality. The participants performed an implicit task in which recognizable words depicting geographical names or behaviors related to moral, disgusting or neutral content alternated with background stimuli at high rates of presentation. The results showed that the early recognition of moral information manifested in the RP depended on an individual’s moral concerns. Participants with a higher level of endorsement of the harm/care foundation exhibited a greater net moral effect, namely, greater mean amplitudes of the moral-neutral RP difference waves. Meanwhile, only the group that was more sensitive to the harm/care foundation showed a distinctively larger RP for the moral words than for the neutral words. Overall, these findings suggest that the early processing of moral cognition may hinge on individual differences in moral concerns about other people’s suffering.