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The TP53 and PTEN tumour suppressor genes are inactivated by nonsense mutations in a significant fraction of human tumours. TP53 nonsense mutant tumours account for approximately one million new cancer cases per year worldwide. We have screened chemical libraries with the aim of identifying compounds that induce translational readthrough and expression of full-length p53 protein in cells with nonsense mutation in this gene. Here we describe two novel compounds with readthrough activity, either alone or in combination with other known readthrough-promoting substances. Both compounds induced levels of full-length p53 in cells carrying R213X nonsense mutant TP53. Compound C47 showed synergy with the aminoglycoside antibiotic and known readthrough inducer G418, whereas compound C61 synergized with eukaryotic release factor 3 (eRF3) degraders CC−885 and CC−90009. C47 alone showed potent induction of full-length PTEN protein in cells with different PTEN nonsense mutations. These results may facilitate further development of novel targeted cancer therapy by pharmacological induction of translational readthrough.

Sentiment analysis, a subtask of affective computing, endows machines with the ability to sense and comprehend emotions. Recently, research attention has shifted from traditional isolated modality to ubiquitous multi-modalities, requiring to model the complex relationships between modalities and extract the task-relevant information. However, current methods only focus on modality consistency neglecting the complementary relationship and specificity information within each modality. Furthermore, most studies regard multimodal fusion as a mere process of information integration without considering the control of information flow. We propose a variational model that explicitly decomposes unimodal representations into two types, capturing consistency and specificity information, respectively. Following the information bottleneck principle, the implementation optimizes the fusion representation by maximizing its mutual information with consistency and specificity representations while minimizing mutual information with raw inputs. With information integrity constraints and task label supervision, the fusion representation preserves task-relevant information and discards irrelevant noise. Finally, quantitative and qualitative experiments on two benchmark datasets show that our method achieves competitive performance compared to recent baselines, for multimodal sentiment analysis.

This study conducted a questionnaire survey on the physical condition of high school students based on FIT. The correlation between sedentary behavior, exercise level and physical fitness was studied. In this paper, the fuzzy C-average clustering method of the BP neural network is used to make statistics and classification of students’ physical condition. This paper collates the biological quality data of college students. Then this paper makes a comprehensive classification, classification and quantitative assessment of the data. The study found that college students’ sedentary habits varied from individual and family backgrounds. Family factors influence students’ physical exercise. Physical exercise was positively correlated with sedentary behavior and body mass index in adolescents. The accuracy of clustering combined with the BP neural network can reach 94%.

In order to explore the influence of firing angle and projectile charge number on the muzzle disturbance of mortar, a nonlinear finite element model of mortar, projectile and soil is established, considering the coupling of projectile and barrel, plate and soil coupling, tripod and soil coupling, and the characteristics of buffer machine. Using explicit solver for mortar same firing angle of the projectile charge number, different projectile charge, different shooting angle and projectile charge, different shooting angle regularity of the muzzle disturbance for the sniper firing are analyzed, and the projectile charge number and the shooting angle and the muzzle disturbance are positive correlation. Aiming for a certain distance, using a small charge with smaller shot angle, it can effectively reduce the muzzle disturbance and improve the shooting accuracy. The conclusion has important guiding significance for the reliable use of mortars and the improvement of shooting accuracy.

Abstract Background There is a great association between the prevalence of obstructive sleep apnea (OSA) and asthma. Nonetheless, whether OSA impacts lung function, symptoms, and control in asthma and whether asthma increases the respiratory events in OSA are unknown. This meta-analysis aimed to examine the relationship between obstructive sleep apnea and asthma severity and vice versa. Methods We carried out a systematic search of PubMed, EMBASE, and Scopus from inception to September 2022. Primary outcomes were lung function, parameters of polysomnography, the risk of OSA in more severe or difficult-to-control asthmatic patients, and the risk of asthma in patients with more severe OSA. Heterogeneity was examined with the Q test and I2 statistics. We also performed subgroup analysis, Meta-regression, and Egger’s test for bias analysis. Results 34 studies with 27,912 subjects were totally included. The results showed that the comorbidity of OSA aggravated lung function in asthmatic patients with a consequent decreased forced expiratory volume in one second %predicted (%FEV1) and the effect was particularly evident in children. %FEV1 tended to decrease in adult asthma patients complicated with OSA, but did not reach statistical significance. Interestingly, the risk of asthma seemed to be slightly lower in patients with more severe OSA (OR = 0.87, 95%CI 0.763–0.998). Asthma had no significant effect on polysomnography, but increased daytime sleepiness assessed by the Epworth Sleepiness Scale in OSA patients (WMD = 0.60, 95%CI 0.16–1.04). More severe asthma or difficult-to-control asthma was independently associated with OSA (odds ratio (OR) = 4.36, 95%CI 2.49–7.64). Conclusion OSA was associated with more severe or difficult-to-control asthma with decreased %FEV1 in children. The effect of OSA on lung function in adult patients should be further confirmed. Asthma increased daytime sleepiness in OSA patients. More studies are warranted to investigate the effect of asthma on OSA severity and the impact of different OSA severity on the prevalence of asthma. It is strongly recommended that people with moderate-to-severe or difficult-to-control asthma screen for OSA and get the appropriate treatment.

In the live firing of mortar, the base plate is generally constructed at an angle of about 20° with the horizontal ground, so as to make the base plate more stable and improve the shooting accuracy. In order to explore the optimal matching angle between barrel and plate in live firing, a rigid-flexible coupling finite element model of a certain 82 mm mortar and soil is established. The dynamic response of launching is analyzed based on explicit solver under six working conditions with no. 4 charge, angle of fire 50°, angle of fire 60°, plate and horizontal ground 10°, 20° and 30° respectively. The relative change curves of the angle of firing of the first round of mortar under six conditions are obtained. It is found that when other firing conditions are consistent, the closer the angle between the plate and the barrel is to 90°, the smaller the relative change of the firing angle of the mortar is. When the angle between the plate and the barrel is to 90°, the relative change of the firing angle also reaches the minimum value, and the firing accuracy is the highest. The research results have reference value for the reliable use of mortars, the study of launch dynamic response and the design of related auxiliary devices.

ABSTRACTRectal cancer accounts for the second highest cancer-related mortality, which is predominant in Western civilizations. The treatment for rectal cancers includes surgery, radiotherapy, chemotherapy, and immunotherapy. Radiotherapy, specifically external beam radiation therapy, is the most common way to treat rectal cancer because radiation not only limits cancer progression but also significantly reduces the risk of local recurrence. However, therapeutic radiation-induced radioresistance to rectal cancer cells and toxicity to normal tissues are major drawbacks. Therefore, understanding the mechanistic basis of developing radioresistance during and after radiation therapy would provide crucial insight to improve clinical outcomes of radiation therapy for rectal cancer patients. Studies by various groups have shown that radiotherapy-mediated changes in the tumor microenvironment play a crucial role in developing radioresistance. Therapeutic radiation-induced hypoxia and functional alterations in the stromal cells, specifically tumor-associated macrophage (TAM) and cancer-associated fibroblasts (CAF), play a crucial role in developing radioresistance. In addition, signaling pathways, such as – the PI3K/AKT pathway, Wnt/β-catenin signaling, and the hippo pathway, modulate the radiation responsiveness of cancer cells. Different radiosensitizers, such as small molecules, microRNA, nanomaterials, and natural and chemical sensitizers, are being used to increase the effectiveness of radiotherapy. This review highlights the mechanism responsible for developing radioresistance of rectal cancer following radiotherapy and potential strategies to enhance the effectiveness of radiotherapy for better management of rectal cancer.

Due to the heterogeneity of colon cancer, surgery, chemotherapy, and radiation are ineffective in all cases. The genomic profile and biomarkers associated with the process are considered in personalized medicine, along with the patient's personal history. It is based on the response of the targeted therapies to specific genetic variations. The patient's genetic transcriptomic and epigenetic features are evaluated, and the best therapeutic approach and diagnostic testing are identified through personalized medicine. This review aims to summarize all the necessary, updated information on colon cancer related to personalized medicine. Personalized medicine is gaining prominence as generalized treatments are finding it challenging to contain colon cancer cases which currently rank fourth among global cancer incidence while being the fifth largest in total death cases worldwide. In personalized therapy, patients are grouped into specific categories, and the best therapeutic approach is chosen based on evaluating their molecular features. Various personalized strategies are currently being explored in the treatment of colon cancer involving immunotherapy, phytochemicals, and other biomarker-specific targeted therapies. However, significant challenges must be overcome to integrate personalized medicine into healthcare systems completely. We look at the various signaling pathways and genetic and epigenetic alterations associated with colon cancer to understand and identify biomarkers useful in targeted therapy. The current personalized therapies available in colon cancer treatment and the strategies being explored to improve the existing methods are discussed. This review highlights the advantages and limitations of personalized medicine in colon cancer therapy. The current scenario of personalized medicine in developed countries and the challenges faced in middle- and low-income countries are also summarized. Finally, we discuss the future perspectives of personalized medicine in colon cancer and how it could be integrated into the healthcare systems.

Background/purpose: Pulpectomy is the last means to preserve primary teeth with pulpitis or pulp necrosis. The aim of the study was to investigate the survival rate of primary teeth after pulpectomies and to explore the factors influencing the prognosis of pulpectomy. Materials and methods: This retrospective study was performed on patients who received primary tooth pulpectomy in the Department of Pediatric Dentistry at Peking University Hospital of Stomatology between January 2014 and February 2019. The demographic characteristics of children and the information of teeth treated were collected, and the clinical and radiographic examination after treatment were evaluated. Survival analysis was performed to determine the influencing factor of pulpectomy failure. Results: A total of 592 primary anterior teeth and 583 primary molars were included. The 30-month survival rate of primary anterior teeth was 58.5% and that of primary molars was 37.0%. The survival rate of postoperative primary molars was lower than that of primary anterior teeth (P

Detecting human head movement during sleep is important as it can help doctors to assess many physical or mental health problems, such as infantile eczema, calcium deficiency, insomnia, anxiety disorder, and even Parkinson’s disease, and provide useful clues for accurate diagnosis. To obtain the information of head movement during sleep, current solutions either use a camera or require the user to wear intrusive sensors to collect the image or motion data. However, the vision-based schemes rely on light conditions and raise privacy concerns. Many people, including the elderly and infants, may be reluctant to wear wearable devices during sleep. In this paper, we propose Wi-Senser, a nonintrusive and contactless smart monitoring system for detecting head movement during sleep. Wi-Senser directly reuses the existing WiFi infrastructure and exploits the fine-grained channel state information (CSI) of WiFi signals to capture the minute human head movement during sleep without attaching any sensors to the human body. Specifically, we constructed a filtering channel including a Hampel filter, wavelet filter, and mean filter to remove outliers and noises. We propose a new metric of carrier sensitivity to select an optimal subcarrier for recording the change in targeted body movement from 30 candidate subcarriers. Finally, we designed a peak-finding algorithm to capture the real peak set recording the change in human head movement. We designed and implemented Wi-Senser with just one commercial off-the-shelf (COTS) router and one laptop equipped with an Intel 5300 network interface card (NIC). We evaluated the performance of Wi-Senser with 10 volunteers (6 adults and 4 children). Extensive experiments demonstrate that Wi-Senser can achieve 97.95% accuracy for monitoring head movement during sleep. Wi-Senser provides a new solution for achieving noninvasive, continuous, and accurate detection of minute human movement without any additional cost.

(1) Background: CD163, a specific macrophage receptor, affects the progression of malignant tumors. Unfortunately, the regulation and expression of CD163 are poorly understood. In this study, we determined the expressions of CD163 in TMA samples from CRC patients and combined them with patient data from several Swedish hospitals. (2) Methods: The expressions of CD163 in tissue samples from CRC patients were examined. After combining 472 CRC patients’ gene expression and 438 CRC patients’ clinical data with the TCGA database, 964 cases from the GEO database, and experimental expression data from 1247 Swedish CRC patients, we selected four genes (PCNA, LOX, BCL2, and CD163) and analyzed the tumor-infiltrating immune cells (TICs) and CRC prognosis. (3) Results: Based on histopathological TMA analysis, CD163 was strongly expressed in the stroma of both normal and cancer tissues, and the expressions in normal and cancer cells varied from negative to strong. The results from public databases show decreased expression of CD163 in cancer tissue compared to normal mucosa (|log FC| > 1 and FDR < 0.01), and it is a negative prognostic factor for CRC patients (p-value < 0.05). Through tumor microenvironment (TME) analysis, we found a potential influence of CD163 on immune cell infiltration. Furthermore, the enrichment analysis indicated the possible interaction with other proteins and biological pathways. (4) Conclusions: CD163 is expressed differently in CRC tissue and is a negative prognostic factor. Its expression is associated with the TME and tumor purity of CRC. Considering all results, CD163 has the potential to be a predictive biomarker in the investigation of CRC.

Common detection methods in practice for diagnosing colorectal cancer (CRC) are painful and invasive leading to less participation of individuals for CRC diagnosis. Whereas, improved or enhanced imaging systems and other minimally invasive techniques with shorter detection times deliver greater detail and less discomfort in individuals. Thus, this review is a summary of the diagnostic tests, ranging from the simple potential use in developing a flexible CRC treatment to the patient's potential benefits in receiving less invasive procedures and the advanced treatments that might provide a better assessment for the diagnosis of CRC and reduce the mortality related to CRC. [ABSTRACT FROM AUTHOR]