Background:Intratumor heterogeneity (ITH) has been shown to be inversely associated with immune infiltration in several cancers including clear cell renal cell carcinoma (ccRCC), but it remains unclear whether ITH is associated with response to immunotherapy (e.g. PD-1 blockade) in ccRCC.Methods:We quantified ITH using mutant-allele tumor heterogeneity, investigated the association of ITH with immune parameters in patients with ccRCC (n = 336) as well as those with papillary RCC (pRCC, n = 280) from The Cancer...

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the ninth member of the proprotein convertase family that regulates lipoprotein homeostasis and altered PCSK9 expression was reportedly associated with tumor development and progression. This study assessed PCSK9 expression and functions in human colon cancer and then explored the underlying molecular events. Methods Colon cancer tissues were utilized for analysis of PCSK9 expression for association with clinicopathological factors from patients by immunohistochemistry assay. Manipulation of PCSK9...

Abstract Background Emerging evidence have revealed that circRNAs exert important biological effects in the development and progression of various diseases, including cancer. Our study aimed to elaborated the biological effects of hsa-circ_0003570 in hepatocellular carcinoma (HCC) development at the molecular level. Results The results of functional experiments showed that knockdown of circ_0003570 induced HCC cell growth, migration and invasion, whereas overexpression of circ_0003570 presented the opposite effects. In vivo experiments, xenograft tumors grown from circ-overexpressed...

Mid-infrared (MIR) single-photon detection is emerging as an important technology for various applications. Superconducting nanowire single photon detectors (SNSPDs) fabricated with superconducting films with energy gaps of a few meV are natural broadband single-photon detectors. Recently, extending SNSPDs’ operation wavelengths into the MIR region is highly attractive. γ-Nb₄N₃ has a reduced N content and lower energy gap than the commonly used δ-NbN, making SNSPDs based on γ-Nb₄N₃ film more sensitive to low energy photons. We...

Wall shear stress (WSS) is of fundamental physiological and pathological significance. Current measurement technologies suffer from poor spatial resolution, or cannot measure instantaneous values in a label-free manner. Here we demonstrate dual-wavelength third-harmonic-generation (THG) line-scanning imaging, for instantaneous wall shear rate and WSS measurement in vivo. We used soliton self-frequency shift to generate dual-wavelength femtosecond pulses. Simultaneous acquisition of dual-wavelength THG line-scanning signals extract blood flow velocities at adjacent radial positions for instantaneous wall shear...

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with invasive and metastatic characteristics and poor prognosis. Intracellular protein homeostasis is associated with invasion and metastasis of pancreatic cancer, but the specific molecular mechanism remains unclear. Our previous studies have revealed that DNAJB11, a key protein in protein homeostasis, is secreted by exosomes in the supernatant of dissociated pancreatic cancer cells with high metastasis. The results from transcriptome sequencing and co-immunoprecipitation (Co-IP)-based liquid chromatography with...

Abstract Background Diabetes is a major public health concern with a considerable impact on healthcare expenditures. Deciding on health insurance coverage for new drugs that meet patient needs is a challenge facing policymakers. Our study aimed to assess patients’ preferences for public health insurance coverage of new anti-diabetic drugs in China. Methods We identified six attributes of new anti-diabetic drugs and used the Bayesian-efficient design to generate choice sets for a discrete choice experiment (DCE)....

Abstract Background Most cancer disability-adjusted life year (DALY) studies worldwide have used broad, generic disability weights (DWs); however, differences exist among populations and types of cancers. Using breast cancer as example, this study aimed to estimate the population-level DALYs in females in China and the impact of screening as well as applying local DWs. Methods Using multisource data, a prevalence-based model was constructed. (1) Overall years lived with disability (YLDs) were estimated by using numbers...

Abstract Background Sedative gastrointestinal endoscopy is extensively used worldwide. An appropriate degree of sedation leads to more acceptability and satisfaction. Artificial intelligence has rapidly developed in the field of digestive endoscopy in recent years and we have constructed a mature computer-aided diagnosis (CAD) system. This system can identify the remaining parts to be examined in real-time endoscopic procedures, which may help anesthetists use anesthetics properly to keep patients in an appropriate degree of sedation. Aims...

Ti₂AlC is a kind of ternary layered structured ceramic metal compound, combing advantages of both ceramic and metal. Herein, the saturable absorption performance of Ti₂AlC at 1 μm waveband is investigated for the first time. The Ti₂AlC behaves with excellent saturable absorption, which has a modulation depth of 14.53% and a saturable intensity of 13.27 MW/cm². An all-normal dispersion fiber laser based on the Ti₂AlC saturable absorber (SA) is constructed. The repetition frequency of the...

Abstract Background This study aimed to evaluate the artificial intelligence (AI)-based coronary artery calcium (CAC) quantification and regional distribution of CAC on non-gated chest CT, using standard electrocardiograph (ECG)-gated CAC scoring as the reference. Methods In this retrospective study, a total of 405 patients underwent non-gated chest CT and standard ECG-gated cardiac CT. An AI-based algorithm was used for automated CAC scoring on chest CT, and Agatston score on cardiac CT was manually quantified. Bland-Altman...

Abstract Background Midazolam (MDZ) is an anaesthetic that is widely used for anxiolysis and sedation. More recently, MDZ has also been described to be related to the outcome of various types of carcinomas. However, how MDZ influences the progression of hepatocellular carcinoma (HCC) and its effects on the biological function and tumour immune microenvironment of this type of tumour remain unknown. Methods The effects of MDZ on the proliferation, invasion, and migration of HCC cell...

Abstract Background Evidence supports therapeutic drug monitoring of polymyxin B, but clinical data for establishing an area under the concentration–time curve across 24 h at steady state (AUCss,24 h) threshold are still limited. This study aimed to examine exposure–response/toxicity relationship for polymyxin B to establish an AUCss,24 h threshold in a real-world cohort of patients. Methods Using a validated Bayesian approach to estimate AUCss,24 h from two samples, AUCss,24 h threshold that impacted the risk...

Dynamic treatment regimes are a set of time-adaptive decision rules that can be used to personalize treatment across multiple stages of care. Grounded in causal inference methods, dynamic treatment regimes identify variables that differentiate the treatment effect and may be used to tailor treatments across individuals based on the patient’s own characteristics – thereby representing an important step toward personalized medicine. In this manuscript we introduce Penalized Spline-Involved Tree-based Learning, which seeks to improve upon...

Abstract Background As systematically developed statements regarding possible courses of action, health system guidance (HSG) can assist with making decisions about addressing problems or achieving goals in health systems. However, there are conceptual and methodological challenges in HSG implementation due to the complexity of health-system policy-making, the diversity of available evidence and vast differences in contexts. To address these gaps, we aim to develop a theoretical framework for supporting HSG implementation as part of a...

Abstract Background Visits to the emergency department (ED) are inflection points in patients’ illness trajectories and are an underutilized setting to engage seriously ill patients in conversations about their goals of care. We developed an intervention (ED GOAL) that primes seriously ill patients to discuss their goals of care with their outpatient clinicians after leaving the ED. The aims of this study are (i) to test the impact of ED GOAL administered by trained nurses...

Abstract Background Maize rough dwarf disease (MRDD), caused by rice black-streaked dwarf virus (RBSDV) belonging to the Fijivirus genus, seriously threatens maize production worldwide. Three susceptible varieties (Ye478, Zheng 58, and Zhengdan 958) and two resistant varieties (P138 and Chang7–2) were used in our study. Results A set of ATP-binding cassette subfamily B (ABCB) transporter genes were screened to evaluate their possible involvements in RBSDV resistance. In the present study, ZmABCB15, an ABCB transporter family...

Abstract Background Liver metastasis (LM) is a major obstacle to the prognosis of gastric cancer (GC) patients, but the molecular mechanism underlying gastric cancer liver metastasis (GC-LM) remains unknown. Exosomes have been identified as an important mediator of communication between tumor cells and the microenvironment. Therefore, we sought to investigate the effects of primary GC cells on the liver microenvironment and the role of exosomal microRNAs (exo-miRNA) in GC-LM. Methods Sequential differential centrifugation, transmission electron...

Abstract Background The functional alterations of eRNAs have been reported to be correlated with tumorigenesis. However, the roles of eRNAs in thyroid cancer (THCA) remain still unclear. This study aimed to construct an immune-related eRNA prognostic signature that could effectively predict the survival and prognosis for THCA. Methods The Weighted Gene Co-Expression Network Analysis (WGCNA) was performed to identify THCA-specific immune-related hub genes and immune-related eRNAs were obtained using Pearson correlation analysis. Univariate and least...

BackgroundThe purpose of this study was to construct a nomogram based on classical parameters and immunohistochemical markers to predict the recurrence of early low-risk endometrial cancer patients.MethodsA total of 998 patients with early low-risk endometrial cancer who underwent primary surgical treatment were enrolled (668 in the training cohort, 330 in the validation cohort). Prognostic factors identified by univariate and multivariate analysis in the training cohort were used to construct the nomogram. Prediction performance of the...

BackgroundThe purpose of this study was to construct a nomogram based on classical parameters and immunohistochemical markers to predict the recurrence of early low-risk endometrial cancer patients.MethodsA total of 998 patients with early low-risk endometrial cancer who underwent primary surgical treatment were enrolled (668 in the training cohort, 330 in the validation cohort). Prognostic factors identified by univariate and multivariate analysis in the training cohort were used to construct the nomogram. Prediction performance of the...

Abstract Background Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiological data of dengue virus (DENV) is essential for research studies and collaborative surveillance. Methods Targeting DENV-1 spreading prominently in recent decades, by reconciling all qualified complete E gene sequences of 5003 DENV-1 strains with epidemiological information from 78 epidemic countries/areas ranging from 1944 to 2018, we established and...

Abstract Background Birth weight is considered not only to undermine future growth, but also to induce lifelong diseases; the aim of this study is to explore the relationship between birth weight and adult bone mass. Methods We performed multivariable regression analyses to assess the association of birth weight with bone parameters measured by dual-energy X-ray absorptiometry (DXA) and by quantitative ultrasound (QUS), independently. We also implemented a systemic Mendelian randomization (MR) analysis to explore the...

In general, 𝑘 lenses with different materials can achieve at most (𝑘+1)-color correction (𝑘≥2). In this paper, a superachromat containing three lenses is designed to achieve five-color correction in the 600 - 1600 nm waveband, where the maximum chromatic focal shift is controlled within 1/100,000 of the focal length, achieving an almost unprecedented result. Conditions for lens power combination of three thin lenses in contact are firstly derived based on the Buchdahl dispersion equation, then...

Abstract Background Oxidative stress plays an important role in the progression of various types of tumors. However, its role in esophageal squamous cell carcinoma (ESCC) has seldom been explored. This study aimed to discover prognostic markers associated with oxidative stress in ESCC to improve the prediction of prognosis and help in the selection of effective immunotherapy for patients. Results A consensus cluster was constructed using 14 prognostic differentially expressed oxidative stress-related genes (DEOSGs) that were...