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BackgroundThe inappropriate use of prescription medication has recently garnered worldwide attention, but most national policies do not effectively provide for early detection or timely intervention. ObjectiveThis study aimed to develop and assess the validity of a model that can detect the inappropriate use of prescription medication. This effort combines a multiview and topic matching method. The study also assessed the validity of this approach. MethodsA multiview extension of the latent Dirichlet allocation algorithm for topic modeling was chosen to generate diagnosis-medication topics, with data obtained from the Chinese Monitoring Network for Rational Use of Drugs (CMNRUD) database. Topic mapping allowed for calculating the degree to which diagnoses and medications were similarly distributed and, by setting a threshold, for identifying prescription misuse. The Beijing Regional Prescription Review Database (BRPRD) database was used as the gold standard to assess the model’s validity. We also conducted a sensitivity analysis using random samples of validated prescriptions and evaluated the model’s performance. ResultsA total of 44 million prescriptions were used to generate topics using the diagnoses and medications from the CMNRUD database. A random sample (15,000 prescriptions) from the BRPRD was used for validation, and it was found that the model had a sensitivity of 81.8%, specificity of 47.4%, positive-predictive value of 14.5%, and negative-predictive value of 96.0%. The model showed superior stability under different sampling proportions. ConclusionsA method that combines multiview topic modeling and topic matching can detect the inappropriate use of prescription medication. This model, which has mediocre specificity and moderate sensitivity, can be used as a primary screening tool and will likely complement and improve the process of manually reviewing prescriptions.

BackgroundComprehensive safety data for vaccines from post-licensure surveillance, especially active surveillance, could guide administrations and individuals to make reasonable decisions on vaccination. Therefore, we designed a pilot study to assess the capability of a regional health care information platform to actively monitor the safety of a newly licensed vaccine. ObjectiveThis study aimed to conduct active surveillance of human papillomavirus (HPV) vaccine safety based on this information platform. MethodsIn 2017, one of China’s most mature information platforms with superior data linkage was selected. A structured questionnaire and open-ended interview guidelines were developed to investigate the feasibility of active surveillance following HPV vaccination using the regional health care information platform in Ningbo. The questionnaire was sent to participants via email, and a face-to-face interview was conducted to confirm details or resolve discrepancies. ResultsFive databases that could be considered essential to active surveillance of vaccine safety were integrated into the platform starting in 2015. Except for residents' health records, which had a coverage rate of 87%, the data sources covered more than 95% of the records that were documented in Ningbo. All the data could be inherently linked using the national identity card. There were 19,328 women who received the HPV vaccine, and 37,988 doses were administered in 2017 and 2018. Women aged 30-40 years accounted for the largest proportion. Quadrivalent vaccination accounted for 73.1% of total vaccination, a much higher proportion than that of bivalent vaccination. Of the first doses, 60 (60/19,328, 0.31%) occurred outside Ningbo. There were no missing data for vaccination-relevant variables, such as identity card, vaccine name, vaccination doses, vaccination date, and manufacturer. ICD-10 coding could be used to identify 9,180 cases using a predefined list of the outcomes of interest, and 1.88% of these cases were missing the identity card. During the 90 days following HPV vaccination, 4 incident cases were found through the linked vaccination history and electronic medical records. The combined incident rate of rheumatoid arthritis, optic neuritis, and Henoch-Schonlein purpura was 8.84/100,000 doses of bivalent HPV, and the incidence rate of rheumatoid arthritis was 3.75/100,000 doses of quadrivalent HPV. ConclusionsThis study presents an available approach to initiate an active surveillance system for adverse events following HPV vaccination, based on a regional health care information platform in China. An extended observation period or the inclusion of additional functional sites is warranted to conduct future hypothesis-generating and hypothesis-confirming studies for vaccine safety concerns.

The blood–brain barrier (BBB) is a protective barrier for brain safety, but it is also a major obstacle to the delivery of drugs to the cerebral parenchyma such as the hippocampus, hindering the treatment of central nervous system diseases such as Alzheimer’s disease (AD). In this work, an anti-AD brain-targeted nanodrug delivery system by co-loading icariin (ICA) and tanshinone IIA (TSIIA) into Aniopep-2-modified long-circulating (Ang2-ICA/TSIIA) liposomes was developed. Low-density lipoprotein receptor-related protein-1 (LRP1) was a receptor overexpressed on the BBB. Angiopep-2, a specific ligand of LRP1, exhibited a high binding efficiency with LRP1. Additionally, ICA and TSIIA, drugs with neuroprotective effects are loaded into the liposomes, so that the liposomes not only have an effective BBB penetration effect, but also have a potential anti-AD effect. The prepared Ang2-ICA/TSIIA liposomes appeared narrow dispersity and good stability with a diameter of 110 nm, and a round morphology. Cell uptake observations, BBB models in vitro, and imaging analysis in vivo showed that Ang2-ICA/TSIIA liposomes not only penetrate the BBB through endocytosis, but also accumulate in N2a cells or brain tissue. The pharmacodynamic analysis in vivo demonstrated that Ang2-ICA/TSIIA liposomes could improve AD-like pathological features in APP/PS1 mice, including inhibiting neuroinflammation and oxidative stress, reducing apoptosis, protecting neurons, and improving cognitive function. Therefore, Ang2-ICA/TSIIA liposomes are considered a potentially effective therapeutic strategy for AD.

Under the strategy of “Northeast Revitalizing”, Northeast China must correctly handles the coupling relationship of coordinated development among economy, energy, environment, and technology if it insists on the concept of green development. In this paper, by establishing an appropriate evaluation index system and introducing ”kernel function density” analysis method, the coupling problem and it’s time evolution characteristics of the coordinated development of the economy–energy–environment–technology of Liaoning Province, Jilin Province, Heilongjiang Province and Inner Mongolia Autonomous Region in Northeast China were studied. It was found that the coordination degree of the quaternary systems was between 0.71 and 0.97, and it was good. The development degree was between 0.25 and 0.58, and it was very bad. The ”weakness” of low development degree results in the low coupling degree (between 0.46 and 0.70) of the quaternary system. The coordination degree of the quaternary systems in Northeast China was increasing year by year, and the differences between provinces (regions) were also shrinking. The development degree generally presented ”wave” fluctuation characteristics, and the regional difference showed an increasing trend. The coupling degree of Heilongjiang Province, Jilin Province and Liaoning Province basically maintained a steady state of improvement, and Inner Mongolia Autonomous Region improved significantly after 2017. Finally, the paper put forward some countermeasures and suggestions to improve the coupling degree of the coordinated development of economy, energy, environment and technology in Northeast China, so as to provide reference for the revitalization of Northeast China.

Here, using whole-metagenome shotgun sequencing data from patients with COVID-19 and controls, the authors reconstruct 11,584 microbial metagenome-assembled genomes (MAGs) including 5,403 non-redundant MAGs, revealing microbiota and metabolic pathways associations with SARS-CoV-2 infection at strain-level resolution.

While liquid-liquid interface offers better contact and charge transfer potential than solid-based counterparts, fluidity still poses challenges for their application. Here, authors show that charge transfer exists in aqueous two-phase systems and propose a nanogenerator design based on the immiscible aqueous-aqueous interface.

Magnetic resonance imaging (MRI) can quantify characteristic values of tissues, serving as an important tool for scientific and clinical research. Magnetic resonance T1ρ relaxation time reflects the low-frequency motional processes between water and macromolecules. At high fields of 3 T and above, T1ρ is greatly affected by the chemical exchange between water and exchangeable protons, and T1ρ dispersion measured with varying spin-lock fields can be utilized to analyze and quantify the proton exchange process. However, it is time-consuming to obtain T1ρ-weighted images with different spin-lock fields, which limits its application. To solve this problem, a fast T1ρ dispersion imaging method based on multiple relaxation signal compensation strategy is proposed in this work, which compensates the T1ρ-weighted images at different locking frequencies to the same signal strength level, and combines the low-rank plus sparse model in the reconstruction. Experimental results show that the proposed method achieves good reconstruction results even when the acceleration factor is up to 7.

Rice bean is an underexploited legume crop that has many desirable properties against bio and abiotic stresses. Here, the authors report the genome assembly of this species, conduct population genetics studies and reveal the genetic variations associated with adaptation and yield traits.

RNA polymerase II (Pol II) transcription factories play a central role in gene expression and 3D chromatin organization. Here, the authors demonstrate that RUVBL2 directly regulates Pol II clustering at active gene promoters.

Abstract Background Fibulin‐4, namely, EFEMP2, is an essential matricellular protein associated with a variety of malignancies. The aim of this study was to explore the role of fibulin‐4 in the progression of esophageal squamous cell carcinoma (ESCC), as well as its effect on ESCC sensitivity to apatinib treatment. Methods The expression of fibulin‐4 in ESCC tissues and cell lines was detected. Stably transfected ESCC cells were established by transducing lentiviral vectors for silencing or overexpressing the fibulin‐4 gene into ESCC cells, and a subcutaneous xenograft tumor model of ESCC in mice was successfully established. IHC, RT–qPCR and western blotting were used to detect the expression of related genes and proteins. The CCK8 assay, EdU cell proliferation assay, wound healing assay, transwell assay and flow cytometry were used to evaluate the proliferation, invasion, migration and apoptosis of ESCC cells. After mice were sacrificed, the transplanted tumors were resected, and their volumes were measured. Results The expression of fibulin‐4 was significantly increased in both ESCC tissues and cell lines, and the high expression was closely related to the poor clinicopathological features. Downregulation of fibulin‐4 inhibited the proliferation, invasion and migration of ESCC cells in vitro and in vivo. Meanwhile, fibulin‐4 knockdown inhibited autophagy of tumor cells by activating the Akt–mTOR signaling pathway and significantly promoted apatinib‐induced apoptosis of ESCC cells. Conclusion Our study showed that fibulin‐4 is an oncogene that can promote ESCC progression and inhibit apoptosis. Downregulation of fibulin‐4 enhances the sensitivity of ESCC cells to apatinib by inhibiting cellular protective autophagy through activating the Akt–mTOR signaling pathway.

Abstract Purpose To explore the diagnostic value of integrated positron emission tomography/magnetic resonance imaging (PET/MRI) for the staging of endometrial carcinoma and to investigate the associations between quantitative parameters derived from PET/MRI and clinicopathological characteristics of endometrial carcinoma. Methods Altogether, 57 patients with endometrial carcinoma who underwent PET/MRI and PET/computed tomography (PET/CT) preoperatively were included. Diagnostic performance of PET/MRI and PET/CT for staging was compared by three readers. Associations between PET/MRI quantitative parameters of primary tumor lesions and clinicopathological characteristics of endometrial carcinoma were analyzed. Histopathological results were used as the standard. Results The overall accuracy of the International Federation of Gynecology and Obstetrics (FIGO) staging for PET/MRI and PET/CT was 86.0% and 77.2%, respectively. PET/MRI had higher accuracy in diagnosing myometrial invasion and cervical invasion and an equivalent accuracy in diagnosing pelvic lymph node metastasis against PET/CT, although without significance. All PET/MRI quantitative parameters were significantly different between stage I and stage III tumors. Only SUVmax/ADCmin were significantly different between stage I and II tumors. No parameters were significantly different between stage II and III tumors. The SUVmax/ADCmin in the receiving operating characteristic (ROC) curve had a higher area under the ROC curve for differentiating stage I tumors and other stages of endometrial carcinoma. Conclusions PET/MRI had a higher accuracy for the staging of endometrial carcinoma, mainly for FIGO stage I tumors compared to PET/CT. PET/MRI quantitative parameters, especially SUVmax/ADCmin, were associated with tumor stage and other clinicopathological characteristics. Hence, PET/MRI may be a valuable imaging diagnostic tool for preoperative staging of endometrial carcinoma.

Abstract Background Previous study found that C-reactive protein (CRP) can predict bleeding after on-pump CABG. To evaluate whether preoperative C-reactive protein (CRP) can be a novel marker of postoperative bleeding in patients having off-pump coronary artery bypass grafting (CABG). Methods This is a retrospective cohort study. Multiple variable regression analyses were performed. 537 patients undergoing off-pump isolated primary CABG at Fuwai Hospital from September 2017 to July 2018 were recorded. The primary endpoint was bleeding volume within 24 h after surgery. Results Data of 537 patients undergoing off-pump isolated primary CABG at Fuwai Hospital were recorded. The correlations between bleeding volume within 24 h after surgery and preoperative data were analyzed with univariate and multivariate linear regression. Much more preoperative CRP concentration (B = −0.089, P

Abstract Background The forkhead box O3a protein (FoxO3a) has been reported to be involved in the migration and invasion of trophoblast, but its underlying mechanisms unknown. In this study, we aim to explore the transcriptional and metabolic regulations of FoxO3a on the migration and invasion of early placental development. Methods Lentiviral vectors were used to knock down the expression of FoxO3a of the HTR8/SVneo cells. Western blot, matrigel invasion assay, wound healing assay, seahorse, gas-chromatography-mass spectrometry (GC–MS) based metabolomics, fluxomics, and RNA-seq transcriptomics were performed. Results We found that FoxO3a depletion restrained the migration and invasion of HTR8/SVneo cells. Metabolomics, fluxomics, and seahorse demonstrated that FoxO3a knockdown resulted in a switch from aerobic to anaerobic respiration and increased utilization of aromatic amino acids and long-chain fatty acids from extracellular nutrients. Furthermore, our RNA-seq also demonstrated that the expression of COX-2 and MMP9 decreased after FoxO3a knockdown, and these two genes were closely associated with the migration/invasion progress of trophoblast cells. Conclusions Our results suggested novel biological roles of FoxO3a in early placental development. FoxO3a exerts an essential effect on trophoblast migration and invasion owing to the regulations of COX2, MMP9, aromatic amino acids, energy metabolism, and oxidative stress.

Abstract Objectives To explore the association between CT-derived pectoralis muscle index (PMI) and COVID-19 induced lung injury. Methods We enrolled 116 elderly COVID-19 patients linked to the COVID-19 outbreak in Nanjing Lukou international airport. We extracted three sessions of their CT data, including one upon admission (T1), one during the first 2 weeks when lung injury peaked (T2) and one on day 14 ± 2 (T3). Lung injury was assessed by CT severity score (CTSS) and pulmonary opacity score (POS). Pneumonia evolution was evaluated by changes of CT scores at T2 from T1(Δ). Results The maximum CT scores in low PMI patients were higher than those of normal PMI patients, including CTSS1 (7, IQR 6–10 vs. 5, IQR 3–6, p 4. The presence of low PMI (OR = 5.98, p 4. Meanwhile, presence of low PMI (OR = 2.82, p = 0.042) and incrementally increasing D-dimer (OR = 0.088, p = 0.024) were predictors of lung injury aggravation with ΔPOS = 2. Conclusions PMI can be easily assessed on chest CT images and can potentially be used as one of the markers to predict the severity of lung injury in elderly COVID-19 patients.

Background: As a special reproductive hormone and ovarian reserve indicator, the role of anti-Müllerian hormone (AMH) in premenopausal women with breast cancer deserves further study. Methods: We conducted an in-depth analysis of the data from the EGOFACT study (NCT02518191), a phase Ⅲ, randomized, controlled trial involving premenopausal female breast cancer patients in two parallel groups: chemotherapy with or without gonadotropin-releasing hormone analogs (GnRHa). Three hundred thirty premenopausal women aged 25–49 years with operable stage I to III breast cancer were included in this study. The characteristics of ovarian reserve changes marked by AMH in the EGOFACT study and the factors affecting ovarian function in premenopausal women with breast cancer were analyzed. Results: The AMH level of the chemotherapy alone group decreased gradually within one year, while the AMH level of the GnRHa group was significantly higher as early as 6 months after chemotherapy and recovered to close to the baseline level 12 months after chemotherapy (F = 34.991, P

Bacillus spp. are known for their ability to control plant diseases; however, the mechanism of disease control by Bacillus spp. is still unclear. Previously, bacterial organic acids have been implicated in the process of disease suppression. We extracted the total organic acid from Bacillus cereus AR156 culture filtrate and identified oxalic acid (OA) as the programmed cell death–inducing factor. OA strongly suppressed the lesion caused by Botrytis cinerea without significant antagonism against the fungus. Low concentration of OA produced by Bacillus spp. inhibited cell death caused by high concentrations of OA in a concentration- and time-dependent manner. Pretreatment with a low concentration of OA led to higher accumulation of active oxygen-scavenging enzymes in tomato leaves and provoked the expression of defense-related genes. The activation of gene expression relied on the jasmonic acid (JA) signaling pathway but not the salicylic acid (SA) pathway. The disease suppression capacity of OA was confirmed on wild-type tomato and its SA accumulation–deficient line, while the control effect was diminished in JA synthesis–deficient mutant, suggesting that the OA-triggered resistance relied on JA and ethylene (ET) signaling transduction. OA secretion ability was widely distributed among the tested Bacillus strains and the final environmental OA concentration was under strict regulation by a pH-sensitive degradation mechanism. This study provides the first systematic analysis on the role of low-concentration OA secreted and maintained by Bacillus spp. in suppression of gray mold disease and determines the dependence of OA-mediated resistance on the JA/ET signaling pathway. [Graphic: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2022.

BackgroundThe community is the main place for people's daily activities. A livable environment will improve the subjective well-being of residents. ObjectiveTo understand the current status of subjective well-being of residents in Pudong, Shanghai, and explore the impact of community environmental factors on residents' subjective well-being. MethodsUsing quota sampling, 6000 permanent residents from 12 sub-districts or towns in Pudong, Shanghai were selected to participate in an questionnaire survey. The questionnaire included three parts: participants' basic information, community environmental factors (neighborhood aesthetics, fitness environment, public service and security, natural environment), and subjective well-being. Using a multiple regression model, the influence of community environmental factors on the subjective well-being of residents was analyzed. ResultsA total of 5887 questionnaires were recovered, and the valid recovery rate was 98.1%. The subjective well-being score of the survey respondents was (7.03±1.61) points. There was no statistical difference in the subjective well-being score of study subjects of different gender and marital status groups; while those with different ages, education levels, occupations, and self-evaluated economic status showed statistical differences in their subjective well-being score (P

Porosity defects and interfacial reaction are very serious problems in sand casting Al–Li alloy, which greatly affect the quality of castings. In this work, the characteristic and formation mechanism of the porosity defects in the sand casting Al–Li alloys were systematically investigated by scanning electron microscopy, transmission electron microscopy, energy spectrometry, and inductively coupled plasma mass spectrometry, in order to provide a theoretical basis for the prevention and control of the pore defects in the sand casting Al–Li alloys. The results found that the Al–Li alloys prepared by metal mold and graphite mold as casting molds had almost no pore defects and interfacial reaction layers, with the porosities of 5.81% and 5.05%, respectively, while the sand casting Al–Li alloys with furan resin, phenolic resin, and sodium silicate binder as binders all had serious pore defects and interfacial reaction layers, with the porosity of 15.67%, sharply weakening the mechanical properties of the Al–Li alloy casting. The types of the pore defects were mainly reactive pores and intrusive pores, and the interface reaction layer was mainly composed of LiAlO2 and C–H–O organics. The formation mechanism of the pore defects in the sand casting Al–Li alloys was caused by the reaction between Li and the hydroxyl groups in the binder of the sand mold to generate a large amount of hydrogen, which intruded into the melt or was sucked into the melt.

Abstract Background Early prediction model of hemodynamic instability has the potential to improve the critical care, whereas limited external validation on the generalizability. We aimed to independently validate the Hemodynamic Stability Index (HSI), a multi-parameter machine learning model, in predicting hemodynamic instability in Asian patients. Method Hemodynamic instability was marked by using inotropic, vasopressor, significant fluid therapy, and/or blood transfusions. This retrospective study included among 15,967 ICU patients who aged 20 years or older (not included 20 years) and stayed in ICU for more than 6 h admitted to Taipei Veteran General Hospital (TPEVGH) between January 1, 2010, and March 31, 2020, of whom hemodynamic instability occurred in 3053 patients (prevalence = 19%). These patients in unstable group received at least one intervention during their ICU stays, and the HSI score of both stable and unstable group was calculated in every hour before intervention. The model performance was assessed using the area under the receiver operating characteristic curve (AUROC) and was compared to single indicators like systolic blood pressure (SBP) and shock index. The hemodynamic instability alarm was set by selecting optimal threshold with high sensitivity, acceptable specificity, and lead time before intervention was calculated to indicate when patients were firstly identified as high risk of hemodynamic instability. Results The AUROC of HSI was 0.76 (95% CI, 0.75–0.77), which performed significantly better than shock Index (0.7; 95% CI, 0.69–0.71) and SBP (0.69; 95% CI, 0.68–0.70). By selecting 0.7 as a threshold, HSI predicted 72% of all 3053 patients who received hemodynamic interventions with 67% in specificity. Time-varying results also showed that HSI score significantly outperformed single indicators even up to 24 h before intervention. And 95% unstable patients can be identified more than 5 h in advance. Conclusions The HSI has acceptable discrimination but underestimates the risk of stable patients in predicting the onset of hemodynamic instability in an external cohort.

Abstract Background Liver fibrosis is a progressive liver injury response. Transforming growth factor β1 (TGF-β1) is oversecreted during liver fibrosis and promotes the development of liver fibrosis. Therapeutic approaches targeting TGF-β1 and its downstream pathways are essential to inhibit liver fibrosis. The N-terminal latency-associated peptide (LAP) blocks the binding of TGF-β1 to its receptor. Removal of LAP is critical for the activation of TGF-β1. Therefore, inhibition of TGF-β1 and its downstream pathways by LAP may be a potential approach to affect liver fibrosis. Methods Truncated LAP (tLAP) plasmids were constructed. Recombinant proteins were purified by Ni affinity chromatography. The effects of LAP and tLAP on liver fibrosis were investigated in TGF-β1-induced HSC-T6 cells, AML12 cells and CCl4-induced liver fibrosis mice by real time cellular analysis (RTCA), western blot, real-time quantitative PCR (RT-qPCR), immunofluorescence and pathological staining. Results LAP and tLAP could inhibit TGF-β1-induced AML12 cells inflammation, apoptosis and EMT, and could inhibit TGF-β1-induced HSC-T6 cells proliferation and fibrosis. LAP and tLAP could attenuate the pathological changes of liver fibrosis and inhibit the expression of fibrosis-related proteins and mRNAs in CCl4-induced liver fibrosis mice. Conclusion LAP and tLAP could alleviate liver fibrosis in vitro and in vivo via inhibition of TGF-β/Smad pathway. TLAP has higher expression level and more effective anti-fibrosis activity compared to LAP. This study may provide new ideas for the treatment of liver fibrosis.

Abstract Background As precision medicine gradually played an inaccessible role in cancer treatment, there was an urgent need to explore biomarkers or signatures for predicting cancer prognosis. Currently, little was known about the associations between COLGALT1 and kidney renal clear cell carcinoma (KIRC). Hence, this study was performed to reveal its roles in KIRC and to identify potential mechanisms of competing endogenous RNA (ceRNA) networks. Methods R 4.1.1 software was utilized to conduct bioinformatics analyses with the data derived from online databases. Difference analysis, survival analysis, univariate/multivariate cox regression analysis and correlation analysis were carried out successively in this article. Besides, we also investigated potential effects and mechanisms of COLGALT1 in KIRC. Results COLGALT1 expression was overexpressed in KIRC samples compared with the normal samples and it was associated with poor OS (P

Abstract Background Stem cell transplantation may improve visual acuity in patients with dry age-related macular degeneration. Herein, we aimed to summarise the evidence on the risks and benefits of stem cell transplantation for improving visual acuity, including the risk of adverse events. Methods Data were obtained from the PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases, and each database was interrogated from the date of inception until 19 March 2022. The rates of visual acuity outcomes and adverse events associated with stem cell transplantation were examined. All statistical analyses were conducted using Review Manager 5.4. The study was registered with PROSPERO (CRD 42022322902). Results The analysis examined 10 studies (102 patients), including one and three, randomised and non-randomised clinical trials, and one and five, multicentre prospective and prospective clinical trials, respectively. Meta-analysis showed changes in best-corrected visual acuity in the study eyes after stem cell transplantation (6 months: risk ratio [RR] = 17.00, 95% confidence interval [CI] 6.08–47.56, P

Triple-negative breast cancer (TNBC) presented as high heterogeneous immunogenicity that lacks useful clinical signatures to risk-stratify immune-benefit subtypes. We hypothesized that molecular-based phenotypic characterization of TNBC tumors and their immunity may overcome these challenges. We enrolled 1,145 patients with TNBC for analysis. Through combining algorithm integration analysis and TNBC datasets, a tumor immune risk score (TIRS) panel consisting of 8 potential biomarkers was identified. The TIRS panel represented excellent effectiveness as an independent predictor. High- and low risk stratification of patients was further achieved by TIRS, and significant survival and immune-infiltration pattern differences were found in each cohort, both at the transcriptome and protein levels. Non-negative matrix factorization clustering further identified four different tumor immune microenvironment types (TIMTs), among which TIMT-II was associated with the best prognosis and immune status, whereas TIMT-IV had the opposite effect, TIMT-III was associated with highly unstable genomes, and TIMT-I displayed stem-cell-related characteristics along with high stromal scores and may have extensive enrichment of tumor-associated fibroblasts and vascular cells. In conclusion, our TIRS panel could serve as a robust prognostic signature and provide therapeutic benefits for immunotherapy. Additionally, coordinating four TIMTs may be helpful for clinical decision-making in TNBC patients.

Abstract Background To evaluate whether the specific choroidal neovascularization (CNV) characteristics measured using optical coherence tomography angiography (OCTA) can predict the 6-month prognosis of neovascular age-related macular degeneration (nAMD) after anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods Patients with type 1, type 2, or mixed-type neovascularization (NV) were prospectively included. Participants underwent an initial loading phase of three consecutive monthly intravitreal injections of Conbercept (0.5 mg) and were switched to a pro re nata (PRN) treatment strategy. OCTA images were evaluated for eyes that underwent follow-up assessments for more than 6 months. CNV lesions were manually segmented, and the CNV area, vessel area, greatest vascular caliber (GVC), and greatest linear dimension (GLD) were compared between responders and non-responders. Two masked graders independently measured the above-mentioned parameters using OCTA, and consistency was assessed using the intraclass correlation coefficient (ICC) values. Multiple logistic regression analysis was performed to evaluate the effect of a 3-month change in the CNV area, GLD, and GVC on the 6-month response to anti-VEGF agents. Results Among the 60 eyes of 60 patients with nAMD, 39 were responders and 21 were non-responders. The proportion of CNV types was significantly different between responders and non-responders (P = 0.009). Patients with type 2 or mixed NV seemed more likely to respond to the treatment (28.2% vs. 0.0%, and 30.8% vs. 23.8%, respectively). The change in GVC showed a significant difference between responders (− 4.98 ± 17.17 μm) and non-responders (11.01 ± 14.10 μm) after three monthly intravitreal anti-VEGF injections. Multiple logistic regression analysis showed that only the change in GVC remained significant after controlling for baseline GVC, injection number, and CNV type (adjusted OR = 1.083; P = 0.008). Conclusions Type 2 and mixed-type NV were significantly associated with a better response to anti-VEGF therapy. Changes in GVC after 3 months of treatment were significantly associated with a response to anti-VEGF therapy at 6 months.

Abstract Background Solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) are rare mesenchymal tumors in the central nervous system with a high tendency to relapse, having a significant impact on quality of life (QoL). Due to the rarity of intracranial SFT/HPC, the prognostic factors and optimal treatment remain to be elucidated. Meanwhile, quality of life in patients with intracranial SFT/HPC is seldomly concerned. Thus, we aim to survey about the quality of life and underline some aspects demanding concern in intracranial SFT/HPC treatment through summarizing our case series in recent ten years. Methods Patients with intracranial SFT/HPC who underwent surgical resection from January 2009 to June 2019 were included in the study. Clinical features, such as age, gender, and resection extent, were collected. The EuroQol Five Dimensions Questionnaire (EQ-5D) was used to assess the patients’ quality of life (QoL). Prognosis factors related to progression-free survival (PFS) and overall survival (OS) were also evaluated. Results Thirty-six patients with a mean follow-up period of 61.6 months (range 13–123 months) were included in this study. Sixteen (44.4%) patients achieved gross total resection (GTR). Fourteen patients (38.9%) with tumor progression experienced adjuvant radiotherapy (11.1%) or Gamma Knife surgery (GKS, 27.8%). According to the 2016 WHO classification, there were 6 (16.7%) grade I SFT/HPC, 11 (30.5%) grade II SFT/HPC, and 19 (52.8%) grade III SFT/HPC. The PFS and OS were 29 months (range 4–96 months) and 38 months (range 4–125 months). The median EQ5D-3 L tariff with or without progression was 0.617 (95% CI 0.470–0.756) and 0.939 (95% CI 0.772–0.977) respectively. Gross total resection (GTR, p = 0.024) and grade I SFT/HPC (p = 0.017) were significantly associated with longer PFS. In multivariate analysis, GTR (HR 0.378, 95% CI 0.154–0.927) and adjuvant therapy (HR 0.336, 95% CI 0.118–0.956) result in significantly longer PFS in patients with SFT/HPC. Conclusions Patients underwent GTR and adjuvant therapy had longer PFS. Similarly, patients with lower WHO grade had relatively longer PFS. Therefore, GTR is advocated for the treatment of SFT/HPC. And adjuvant therapy such as GKS could be an alternative treatment for patients who underwent STR or with tumor progression. Further, the QoL decreased in patients with tumor progression and metastasis, and more attention is demanded to the QoL of intracranial SFT/HPC patients.

Abstract Background The deep-sea may be regarded as a hostile living environment, due to low temperature, high hydrostatic pressure, and limited food and light. Isopods, a species-rich group of crustaceans, are widely distributed across different environments including the deep sea and as such are a useful model for studying adaptation, migration, and speciation. Similar to other deep-sea organisms, giant isopods have larger body size than their shallow water relatives and have large stomachs and fat bodies presumably to store organic reserves. In order to shed light on the genetic basis of these large crustaceans adapting to the oligotrophic environment of deep-sea, the high-quality genome of a deep-sea giant isopod Bathynomus jamesi was sequenced and assembled. Results B. jamesi has a large genome of 5.89 Gb, representing the largest sequenced crustacean genome to date. Its large genome size is mainly attributable to the remarkable proliferation of transposable elements (84%), which may enable high genome plasticity for adaptive evolution. Unlike its relatives with small body size, B. jamesi has expanded gene families related to pathways of thyroid and insulin hormone signaling that potentially contribute to its large body size. Transcriptomic analysis showed that some expanded gene families related to glycolysis and vesicular transport were specifically expressed in its digestive organs. In addition, comparative genomics and gene expression analyses in six tissues suggested that B. jamesi has inefficient lipid degradation, low basal metabolic rate, and bulk food storage, suggesting giant isopods adopt a more efficient mechanism of nutrient absorption, storage, and utilization to provide sustained energy supply for their large body size. Conclusions Taken together, the giant isopod genome may provide a valuable resource for understanding body size evolution and adaptation mechanisms of macrobenthic organisms to deep-sea environments.

Abstract As emerging next-generation information technologies, blockchains have unique advantages in information transparency and transaction security. They have attracted great attentions in social and financial fields. However, the rapid development of quantum computation and the impending realization of quantum supremacy have had significant impacts on the advantages of traditional blockchain based on traditional cryptography. Here, we propose a blockchain algorithm based on asymmetric quantum encryption and a stake vote consensus algorithm. The algorithm combines a consensus algorithm based on the delegated proof of stake with node behaviour and Borda count (DPoSB) and quantum digital signature technology based on quantum state computational distinguishability with a fully flipped permutation ( $${\text{QSC}}{\text{D}}_{\text{ff}}$$ QSCD ff ) problem. DPoSB is used to generate blocks by voting, while the quantum signature applies quantum one-way functions to guarantee the security of transactions. The analysis shows that this combination offers better protection than other existing quantum-resistant blockchains. The combination can effectively resist the threat of quantum computation on blockchain technology and provide a new platform to ensure the security of blockchain.

Abstract Background Diabetic retinopathy (DR), one of the most common and severe microvascular complication of diabetes mellitus (DM), is mainly caused by diabetic metabolic disorder. So far, there is no effective treatment for DR. Eriocauli Flos, a traditional Chinese herb, has been used in treating the ophthalmic diseases including DR. However, the active ingredients and molecular mechanisms of Eriocauli Flos to treat diabetic retinopathy remain elusive. Methods Here, the systems pharmacology model was developed via constructing network approach. 8 active components which were screened by oral bioavailability (OB ≥ 30%) and drug-likeness (DL ≥ 0.18) and 154 targets were selected from Eriocauli Flos through TCMSP database. Another 3593 targets related to DR were obtained from Genecards, OMIM, TTD, and Drugbank databases. The 103 intersecting targets of DR and Eriocauli Flos were obtained by Draw Venn Diagram. In addition, protein-protein interaction network was established from STRING database and the compound-target network was constructed by Cytoscape which screened top 12 core targets with cytoNCA module. Then the overlapping targets were analyzed by GO and KEGG enrichment. Moreover, two core targets were selected to perform molecular docking simulation. Subsequently, CCK8 assay, RT-PCR and Western blotting were applied to further reveal the mechanism of new candidate active component from Eriocauli Flos in high glucose-induced HRECs. Results The results showed that the overlapping targets by GO analysis were enriched in cellular response to chemical stress, response to oxidative stress, response to reactive oxygen species, reactive oxygen species metabolic process and so on. Besides, the overlapping targets principally regulated pathways such as AGE-RAGE signaling pathway in diabetic complications, lipid atherosclerosis, fluid shear stress and atherosclerosis, and PI3K-Akt signaling pathway. Molecular docking exhibited that VEGFA and TNF-α, had good bindings to the great majority of compounds, especially the compound hispidulin. In vitro, hispidulin ameliorated high-glucose induced proliferation by down-regulating the expression of p-ERK, p-Akt, and VEGFA; meanwhile inhibited the mRNA levels of TNF-α. Conclusions In this study, through network pharmacology analysis and experimental validation, we found that hispidulin maybe has a potential targeted therapy effect for DR by decreasing the expression of p-Akt, p-ERK, and VEGFA, which resulted in ameliorating the proliferation in HRECs.

Abstract Unsupervised cross‐domain pedestrian detection has attracted attention in recent years. Although some works adopted unsupervised image translation frameworks to generate an intermediate domain to narrow the gap between source and target domains, the images in the intermediate domain tend to be distorted due to the instability of the generation network. In this work, we propose a new framework to improve the image quality of the generated intermediate domain via an end‐to‐end translation framework. First, an image quality assessment index is adopted and adjusted appropriately. The part that controls the image quality is kept, and the part that adversely affects the domain style translation is discarded. Secondly, the adjusted image quality assessment index is integrated into the unsupervised image translation framework, where a new loss with the index's weight is proposed. An end‐to‐end high‐quality‐awareness image translation framework is constructed to generate a high‐quality intermediate domain directly through this process. Finally, the intermediate domain with high‐quality images is applied for cross‐domain pedestrian detection. Experimental results on benchmark datasets show that the proposed framework can effectively improve unsupervised cross‐domain pedestrian detection performance. Compared with some state‐of‐the‐art works, the proposed framework can also achieve superior performance under miss rate metrics.

In this paper, a Ni coating was deposited on the surface of the A356 aluminum alloy by high velocity oxygen fuel spraying to improve the performance of the AZ91D magnesium/A356 aluminum bimetal prepared by a compound casting. The effects of the Ni coating as well as its thickness on microstructure and mechanical properties of the AZ91D/A356 bimetal were systematically researched for the first time. Results demonstrated that the Ni coating and its thickness had a significant effect on the interfacial phase compositions and mechanical properties of the AZ91D/A356 bimetal. The 10µm's Ni coating cannot prevent the generation of the Al-Mg intermetallic compounds (IMCs) at the interface zone of the AZ91D/A356 bimetal, while the Ni coating with the thickness of 45 µm and 190 µm can avoid the formation of the Al-Mg IMCs. When the Ni coating was 45 µm, the Ni coating disappeared and transformed into Mg-Mg2Ni eutectic structures+Ni2Mg3Al particles at the interface zone. With a thickness of 190µm's Ni coating, part of the Ni coating remained and the interface layer was composed of the Mg-Mg2Ni eutectic structures+ Ni2Mg3Al particles, Mg2Ni layer, Ni solid solution (SS) layer, Al3Ni2 layer, Al3Ni layer and sporadic Al3Ni+Al-Al3Ni eutectic structures from AZ91D side to A356 side in sequence. The interface layer consisting of the Mg-Ni and Al-Ni IMCs obtained with the Ni coating had an obvious lower hardness than the Al-Mg IMCs. The shear strength of the AZ91D/A356 bimetal with a Ni coating of 45 µm thickness enhanced 41.4% in comparison with that of the bimetal without Ni coating, and the fracture of the bimetal with 45µm's Ni coating occurred between the Mg matrix and the interface layer with a mixture of brittle fracture and ductile fracture.

Abstract Background Selinexor 80 mg combined with low-dose dexamethasone (Sd) demonstrated significant clinical benefit in patients with relapsed/refractory multiple myeloma (RRMM) who had disease refractory to a proteasome inhibitor (PI), an immunomodulator (IMiD), and an anti-CD38 monoclonal antibody based on a global phase II STORM study. The present study, MARCH, addresses China regulatory needs to further validate the data from STORM in Chinese patients with RRMM. Methods The MARCH study was conducted at 17 sites in China, where eligible Chinese RRMM patients who had disease refractory to PI and IMiD were enrolled. Selinexor 80 mg combined with dexamethasone 20 mg was administered orally on day 1 and day 3 of each week in 4-week cycles. The primary endpoint was the overall response rate (ORR) per an independent review committee, with the null hypothesis of ≤15%. Patients who received at least 1 dose of study treatment were included in the safety population. The pharmacokinetic (PK) profile was characterized by parameter and ethnicity sensitivity analyses. Results A total of 82 patients with RRMM were enrolled in the study, with a median age of 60 years. Of the 82 patients, 55 patients (67.1%) had high-risk cytogenetic abnormalities, defined as one or more of del 17p13, t(4;14), t(14;16), or 1q amplification identified by fluorescence in situ hybridization (FISH); 18 patients (22.0%) had abnormal renal function. Enrolled patients were heavily pre-treated with a median prior regimen number of 5. All 82 patients (100%) were refractory to both PI and IMiD, including 20 patients (24.4%) categorized as triple-class refractory population (refractory to PI, IMiD, and daratumumab). Ten patients (12.2%) had undergone CAR-T therapy. ORR was 29.3% (95% CI 19.7, 40.4) with a median DOR of 4.7 months. The median PFS and OS were 3.7 and 13.2 months, respectively. ORR was 25.0% (95% CI 8.7, 49.1) in the triple-class refractory population. Efficacy was consistent across various subgroups. The most frequent grade 3/4 adverse events (AEs) included anemia (57.3%), thrombocytopenia (51.2%), lymphopenia (42.7%), neutropenia (40.2%), hyponatremia (29.3%), and lung infection (26.8%). Serious AEs were reported in 54.9% of patients. No significant drug accumulation was shown following multiple administrations. No human PK ethnicity difference was identified between Chinese and western patients. Conclusions With an encouraging ORR, the MARCH study has demonstrated that selinexor combined with low-dose dexamethasone (Sd) delivers meaningful clinical benefit to Chinese patients with RRMM, including triple-class refractory patients. AEs were expected and manageable with supportive care and dose modification. Trial registration ClinicalTrials.gov, NCT03944057 (May 09, 2019); Chinadrugtrials.org.cn , CTR20190858 (June 05, 2019)

Labeling of the connected components is the key operation of the target recognition and segmentation in remote sensing images. The conventional connected-component labeling (CCL) algorithms for ordinary optical images are considered time-consuming in processing the remote sensing images because of the larger size. A dynamic run-length based CCL algorithm (DyRLC) is proposed in this paper for the large size, big granularity sparse remote sensing image, such as space debris images and ship images. In addition, the equivalence matrix method is proposed to help design the pre-processing method to accelerate the equivalence labels resolving. The result shows our algorithm outperforms 22.86% on execution time than the other algorithms in space debris image dataset. The proposed algorithm also can be implemented on the field programming logical array (FPGA) to enable the realization of the real-time processing on-board.

Abstract. Warfarin is a commonly used oral anticoagulant. Patients with artificial valve replacement, atrial fibrillation, pulmonary embolism, deep vein thrombosis, and other diseases require long-term anticoagulant oral treatment with warfarin. As warfarin exhibits prompt action with long maintenance time, it has become a key drug for the treatment of patients at risk of developing thrombosis or thromboembolism. Warfarin is a bican coumarin anticoagulant, that exhibits competitive action against vitamin K as its mechanism of action, thereby inhibiting the synthesis of coagulation factors—predominantly the vitamin K-dependent coagulation factors II, VII, IX, and X—in hepatocytes. Long-term warfarin is known to significantly increase the risk of organ bleeding in some patients, while some patients may need to reverse the anticoagulation effect. For instance, patients scheduled for emergency or invasive surgery may require rapid anticoagulation reversal. During such medical circumstances, fresh frozen plasma (FFP) is clinically used for the reversal of excess warfarin-associated anticoagulation, as it contains all the coagulation factors that can alleviate the abnormal blood anticoagulation status in such patients. Accordingly, this article aims to perform an in-depth review of relevant literature on the reversal of warfarin with FFP, and insightful deliberation of the application and efficacy of this clinical intervention.

ABSTRACTKirigami is an art of paper cutting, which can be used in mechanical metamaterials, actuators, and energy absorption based on its deployable and load-deflection characteristics. Traditional cuts with zero width produce undesirable plastic deformation or even tear fracture due to stress concentration in stretching. This study proposes to enlarge the cut width into a notch flexure, which is applied to an orthogonality-cutted kirigami sheet, which buckles out of plane into a 3D configuration patterns under uniaxial tension. The use of compliant beam as the notch makes the stress distribution around the cuts more uniform in both elastic and elastoplastic regime. The experimental and numerical results show that by tuning the geometric parameters of cuts and material properties of the sheets, the trigger condition of 3D patterns can be adjusted. Potential capability of tunable phononic wave propagation in this kirigami-inspired metamaterial is demonstrated. This design methodology offers a theoretical guide for kirigami-based structures.

Aiming at the problems of weak extensibility and difficulty in meeting personalized requirements in traditional trust evaluation models of cloud manufacturing service,a trust evaluation model of cloud manufacturing service for personalized needs is proposed.Firstly,a multi-level and multi-granularity trust evaluation framework of cloud manufacturing service is designed.Then,based on the framework,a trust evaluation method of cloud manufacturing services based on cloud model is proposed.In this method,the cloud model theory is used to characterize different types of evaluation indexes uniformly,and also used to describe the personalized needs.The standard deviations are used to calculate the weight coefficients of different evaluation indexes.Finally,the effectiveness and feasibility of the proposed model are verified through a case analysis and a comparative experiment of time overhead,respectively.Compared with traditional methods,the experimental results show that within a reasonable amount of time,according to the personalized requirements of users,the proposed model could make more accurate trust evaluations for different cloud manufacturing service providers,and then help users choose the cloud manufacturing service with the higher satisfaction.

Abstract Regardless of technical advancements, delayed bleeding is still a common adverse event after gastric endoscopic submucosal dissection (ESD), often occurring in the early postoperative phase. This study aimed to evaluate the efficacy of a newly designed polyethylene oxide (PEO) adhesive for preventing delayed gastric bleeding. Patients who underwent gastric ESD between December 2017 and December 2020 at three Chinese institutions were retrospectively reviewed. Patients receiving PEO application on gastric post-ESD ulcers were included in the PEO group, and patients without this procedure were included in the control group. To minimize potential bias, propensity score matching was performed, and sex, age, lesion size, lesion morphology, ulceration, localization, procedure time, frequency of major intraoperative bleeding, resected specimen size, lesion histopathology, submucosal invasion and the taking of antithrombotic drugs were included as matching factors. The incidence of delayed bleeding and time to bleeding were compared between both groups. After propensity score matching, 270 patients (135 per group) were included in the analysis. The delayed bleeding rate in the PEO group was significantly lower than that in the control group (1.5%, 2/135 vs. 8.9%, 12/135, P = 0.006). The median time (range) to bleeding was 4.5 (4–5) days in the PEO group and 2 (1–15) days in the control group, with no significant difference (P = 0. 198). PEO demonstrated a significant effect in reducing the rate of delayed bleeding. Further study is warranted to confirm the efficacy of PEO for bleeding that occurs in the early phase after gastric ESD.

BRAF-V600E mutation is common in patients with papillary thyroid carcinoma (PTC) and has been associated with an aggressive phenotype. Here the authors show that the mutation supports cancer progression by reactivating the developmental factor TBX3 and promoting the recruitment of myeloid derived suppressive cells.

Abstract Background Since 2010, the Blood Center of Zhejiang province, China, has conducted a pilot nucleic acid amplification testing (NAT) screening of blood donors for Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Human immunodeficiency virus (HIV). This study aims to assess the results of NAT testing over 10 years to establish the effects and factors influencing NAT yields of HBV, HCV, and HIV. Methods Blood donations from seven different blood services were screened for HBV DNA, HCV RNA, and HIV RNA using 6 mini pools (6MP) or individual donation (ID)-NAT method between August 1, 2010, and December 31, 2019, at the NAT centralized screening center. We compared 3 transcription-mediated amplification (TMA) assays and 2 polymerase chain reaction (PCR) assays. Further, HBV, HCV, and HIV NAT yields were calculated and donor characteristics and prevalence of HBV NAT yields analyzed. Donors with HCV and HIV NAT yield were also followed up. Results 1916.31 per million donations were NAT screening positive overall. The NAT yields for HBV, HCV, HIV and non-discriminating reactive were 1062.90 per million, 0.97 per million, 1.45 per million, and 850.99 per million, respectively, which varied in the seven blood services and different years. HBV NAT yields were higher than those of HCV and HIV and varied across demographic groups. Risk factors included being male, old age, low education level, and first-time donors. We found no differences in NAT yields of HBV, HCV, and HIV between the 3 TMA and 2 PCR assays; nonetheless, statistically, significant differences were noted between the five assays. Conclusion In summary, NAT screening in blood donations reduces the risk of transfusion-transmitted infections and shortens the window period for serological marker screening. Therefore, a sensitive NAT screening method, ID-NAT workflow, and recruitment of regular low-risk donors are critical for blood safety.

Self-stress grouting can effectively improve the weak reinforcement caused by shrinkage of the ordinary cement-based grouting materials (OGM). However, the research on self-stressing grouting materials is still not perfect, and the micro and macro performance discrepancies between it and OGM are rarely analyzed. Aiming to this, this paper developed a new cement-based self-stress grouting material (LS-1). By analysing the mechanical mechanism of self-stress reinforcement, it is found that self-stress reinforcement can reduce the effective shear stress of the rock fracture surface, thereby avoiding shear slip failure. Furthermore, by orthogonal testing, the optimal ratio of content of LS-1 was obtained as 10% of U-type expansive agent (UEA), 1.2% of polycarboxylic acid high-efficiency water-reducing agent (PC) and 1.2% of the early-strength concrete agent (EHD). The control experiment was conducted to investigate the performance discrepancy between the two types of grouting materials. The result showed that in terms of longitudinal restricted expansive displacement, under the same experimental conditions, the LS-1 expanded by 1.521 mm while OGM shrunk by 10.374 mm. Then, the damage model of both grouted coal specimens under the impact of acoustic emission (AE) with uniaxial load was established and analyzed. Besides, scanning electron microscope (SEM) was used to verify the effect of LS-1. It was found that for the OGM grouted coal specimen, the damage variable and degree was more extensive, and the bearing capacity is lower, indicating the expansive needle-shaped crystals that are formed after LS-1 solidification are beneficial to improve the density of the grout and avoid the shrinkage. This research will provide a reference for theoretical research and the engineering application of cement-based grouting material.

Abstract Study design Retrospective case–control radiographic study. Objective To identify main effects of preoperative pattern and global coronal malalignment (GCM) on postoperative coronal imbalance in degenerative lumbar scoliosis (DLS) patients and evaluate the rationality of the classification of coronal deformity based on preoperative GCM. Summary of background data A classification of coronal deformity based on preoperative GCM (20 mm set as the threshold of coronal imbalance) has been proposed recently, but whether it is practical is unclear. Methods One hundred twelve DLS patients treated with posterior instrumented fusion were reviewed. Coronal measurements included GCM and major Cobb angle. Based on relationship between C7 PL and major curve, preoperative patterns were classified into: Pattern 1(concave pattern), C7 PL shifted to the concave side of major curve; Pattern 2(convex pattern), C7 PL shifted to the convex side of major curve. Patients were separated into 4 groups (3 types): Type 0–1: GCM 20 mm plus Pattern 1; Type 2: GCM > 20 mm plus Pattern 2. After comparison within patterns or among 4 groups, further factorial analysis was performed. Results Significant differences regarding postoperative GCM or coronal imbalance/balance ratio existed among 4 groups (F = 6.219, p = 0.001; x 2 = 22.506, p

In this review, we summarize various site-selective reactions mediated by molecular containers. The emphasis is on those reactions that give different product distributions on the potential reactive sites inside the containers than they do outside, free in solution. Specific cases include site-selective cycloaddition and addition of arenes, reduction of epoxides, α,β-unsaturated aldehydes, azides, halides and alkenes, oxidation of remote C–H bonds and alkenes, and substitution reactions involving ring-opening cyclization of epoxides, nucleophilic substitution of allylic chlorides, and hydrolysis reactions. The product selectivity is interpreted as the consequence of the space shape and environment inside the container. The containers include supramolecular structures self-assembled through metal/ligand interactions or hydrogen bonding and open-ended covalent structures such as cyclodextrins and cavitands. Challenges and prospects for the future are also provided.

Objective To explore the risk factors of pain in de novo Parkinson's disease (PD) patients. Methods A total of 129 de novo PD patients collected from The Affiliated Brain Hospital of Nanjing Medical University from October 2018 to September 2021 were included. According to the Item ⁃17 of the Unified Parkinson's Disease Rating Scale Ⅱ (UPDRSⅡ⁃17th), patients were classified as PD patients without pain (UPDRSⅡ⁃17th was 0, n = 88) and PD patients with pain (UPDRSⅡ⁃17th ≥ 2, n = 41）. Mini⁃ Mental State Examination (MMSE) and corrected Montreal Cognitive Assessment (corrected MoCA) were used to assess cognitive function. Meanwhile, Hamilton Depression Rating Scale ⁃24 Items (HAMD ⁃24) was used to assess the depression status and the UPDRSⅢ was used to assess the motor function. The modified version of Hoehn ⁃Yahr staging was used to assess disease severity. The related risk factors of pain in PD patients were analyzed by univariate and multivariate forward Logistic regression. Results The in of pain in PD patients was 31.78% (41/129). Compared with PD without pain group, PD with pain group had lower scores in MMSE (Z = ﹣2.389, P = 0.017) and corrected MoCA (Z = ﹣2.166, P = 0.030), but higher scores in HAMD-24 (Z = ﹣4.024, P = 0.000), UPDRS Ⅲ (Z = ﹣3.639, P = 0.000）and Hoehn-Yahr staging grading (Z = ﹣2.232, P = 0.026). Further analysis of the differences between 2 groups in 7 domains of HAMD-24 showed PD with pain group had higher scores of the anxiety/somatization (Z = ﹣3.707, P = 0.000), mental disorder (Z = ﹣2.519, P = 0.012), retardation symptom (Z = ﹣2.048, P = 0.041), sleep disturbances (Z = ﹣3.484, P = 0.000) and despair symptom (Z = ﹣3.069, P = 0.002) than PD without pain group. Logistic regression analysis showed long duration (OR = 1.354, 95%CI: 1.013-1.809; P = 0.041), high HAMD-24 score (OR = 1.095, 95%CI: 1.033-1.162; P = 0.002) and high UPDRS Ⅲ score (OR = 1.040, 95%CI: 1.001- 1.082; P = 0.046) were risk factors of pain in PD patients. Conclusions Pain in PD has a high incidence in de novo PD patients. Long duration, a depressed state and severe motor symptoms are main risk factors for the development of pain in PD patients.

BackgroundLong working hours (LWH) and shift work are harmful to the physical and mental health of occupational groups.ObjectiveTo understand the status quo of LWH and shift work of migrant workers in Shanghai, and to analyze the influence of the above two factors on sleep of the population.MethodsFrom July to September 2018, a cross-sectional survey using questionnaires was conducted among 3215 in-service employees at seven workplaces with more than 300 employees in six selected districts of Shanghai using multi-stage random sampling method. A total of 2976 valid questionnaires were collected, with a valid response rate of 92.6%. The questionnaires included general demographic characteristics, personal health behavior, work-related factors, weekly working hours, shift work, and sleep. Univariate analysis and logistic regression analysis were used to investigate the relationships of LWH and shift work with sleep, and an interaction item was included to evaluate potential interaction between LWH and shift work.ResultThe average age of the subjects was (30.98±9.49) years old, the male to female ratio was 1∶1.20, and 2382 workers were reported without local residency (80.0%). Among the migrant workers, the average weekly working hours was (57.23±13.14) h, the proportions of LWH (weekly working hours>40 h), extra LWH (weekly working hours>55 h), and shift work were 80.6% (1919/2382), 60.3% (1436/2382), and 25.4% (600/2366), respectively, all above were significantly higher than those of local workers. The prevalence rates of insomnia and lack of sleep among the migrant workers were 46.3% (1091/2356) and 25.4% (597/2354), respectively. The results of logistic regression model showed that after adjusting demographic characteristics such as gender, age, education level, and monthly income, as well as occupation and personal health behavior, compared with working hours ≤40 h per week, working 55-60 h per week was a risk factor for insomnia of migrant workers (OR=1.33, 95%CI: 1.02-1.72), while working >60 h per week was a risk factor for both insomnia (OR=1.37, 95%CI: 1.05-1.78) and insufficient sleep (OR=1.73, 95%CI: 1.28-2.35) of migrant workers. Shift work was only associated with insomnia (OR=1.37, 95%CI: 1.11-1.69). Meanwhile, working hours>60 h per week and shift work had an interaction effect on insomnia of migrant workers (OR=2.35, 95%CI: 1.20-4.60).ConclusionLWH and shift work are prominent among migrant workers, and there is an interaction between LWH and shift work with insomnia.

This article summarized the treatment and nursing experience of a patient with stage II pressure sore after stroke. The main nursing measures of TCM included nursing evaluation, basic nursing and wine rhubarb drug external application. TCM nursing by syndrome differentiation is effective in would healing and pain relief in patient with stage II pressure sore after stroke. (本文总结了1例中风后II期压疮患者的治疗及护理经验。护理措施包括护理评估、基础护理、中药酒大黄涂药治疗, 通过辨证施护, 以充分改善患者压疮症状, 减轻患者痛苦。)

Spatially resolved transcriptomics provides a new way to define spatial contexts and understand the pathogenesis of complex human diseases. Although some computational frameworks can characterize spatial context via various clustering methods, the detailed spatial architectures and functional zonation often cannot be revealed and localized due to the limited capacities of associating spatial information. We present RESEPT, a deep-learning framework for characterizing and visualizing tissue architecture from spatially resolved transcriptomics. Given inputs such as gene expression or RNA velocity, RESEPT learns a three-dimensional embedding with a spatial retained graph neural network from spatial transcriptomics. The embedding is then visualized by mapping into color channels in an RGB image and segmented with a supervised convolutional neural network model. Based on a benchmark of 10x Genomics Visium spatial transcriptomics datasets on the human and mouse cortex, RESEPT infers and visualizes the tissue architecture accurately. It is noteworthy that, for the in-house AD samples, RESEPT can localize cortex layers and cell types based on pre-defined region- or cell-type-enriched genes and furthermore provide critical insights into the identification of amyloid-beta plaques in Alzheimer's disease. Interestingly, in a glioblastoma sample analysis, RESEPT distinguishes tumor-enriched, non-tumor, and regions of neuropil with infiltrating tumor cells in support of clinical and prognostic cancer applications.

Automatic incident detection (AID) has always been one of the focus issues in the field of transportation. However, due to the contingency and randomness of traffic incident, traffic incident samples are scarce and far less than non-incident samples. Therefore, unlike other scenarios using large-scale deep networks, traffic incident detection tackle at small and imbalanced sample size. Imbalanced, small sample data sets, inappropriate and incomplete initial variable sets make the AID model insensitive to incident samples, resulting in unsatisfactory model performance (low detection rate or high false alarm rate). Therefore, a hybrid AID method (SASYNO-RF-RSKNN) is proposed using self-adaptive synthetic over-sampling, random forest and random subspace k nearest neighbor. First, the spatial-temporal and real-time characteristics of traffic stream are used for the selection of appropriate initial variables to construct a relatively complete set of initial variables. Second, the SASYNO oversampling method is used to expand the original imbalanced sample database, so that the number of minority class samples is consistent with the number of most class samples. Then, feature variables are selected from the initial variables using the RF algorithm. Finally, the RSKNN ensemble algorithm with feature variables as input is employed to detect traffic incident. In addition, six indexes are used to evaluate model performance, including accuracy (ACC), false alarm rate (FAR), detection rate (DR), precision, Matthews correlation coefficient (MCC) and F1-score. Simultaneously, we also designed horizontal and vertical contrast experiments, and the experimental results show that SASYNO-RF-RSKNN model has superior performance. It is worth mentioning that experiments are implemented on two real-world datasets. Most indexes of the proposed model are the best compared with other five excellent machine learning algorithms. On the whole, the proposed model has a dependable and high-performance for traffic incident detection.

Aggregate thermostatically controlled loads (ATCLs) are a suitable candidate for power imbalance on demand side to smooth the power fluctuation of renewable energy. A new control scheme based on an improved bilinear aggregate model of ATCLs is investigated to suppress power imbalance. Firstly, the original bilinear aggregate model of ATCLs is extended by the second-order equivalent thermal parameter model to optimize accumulative error over a long time scale. Then, to ensure the control performance of tracking error, an improved model predictive control algorithm is proposed by integrating the Lyapunov function with the error transformation, and theoretical stability of the proposed control algorithm is proven. Finally, the simulation results demonstrate that the accuracy of the improved bilinear aggregate model is enhanced; the proposed control algorithm has faster convergence speed and better tracking accuracy in contrast with the Lyapunov function-based model predictive control without the prescribed performance.

Abstract Employing a family of dimpled and slotted spherical resonators, and a set of X‐band waveguide bandpass filters (BPFs) is presented in this study. The resonators originated from spherical resonators with depression (hence, dimples are formed) and cutting slots into the resonator shell. With a large number of experiments, the combination of using the twisted coupling topology, depression and slotting on the resonators results in filters with simultaneous low insertion loss (IL), good out‐of‐band rejection and wide spurious‐free stopband. Several BPFs are designed and 3D printed using the selective laser melting (SLM) technique where they are made in one piece. The monolithic implementation of these filters is allowed by the compatibility of the microwave and the mechanical design, which minimises the required supporting structures inside the filters. The measurement results show ILs of 0.2–0.3 dB and are better than 15 dB return loss. There is a small frequency shift of less than 0.9%, and a measured spurious‐free stopband covering the entire X–Ku bands (8.2–18 GHz) with rejection over 34 dB. Additionally, for the SLM printed devices, the influences of temperature to the S‐parameter responses, as well as polishing, which lowers the losses, are included in this study.

Abstract Objective To evaluate the biomechanical influence after percutaneous endoscopic lumbar facetectomy in different diameters on segmental range of motion (ROM) and intradiscal pressure (IDP) of the relevant segments by establishing three dimensional finite element (FE) model. Methods An intact L3–5 model was successfully constructed from the CT of a healthy volunteer as Model A (MA). The Model B (MB), Model C (MC) and Model D (MD) were obtained through facetectomy on L4 inferior facet in diameters 7.5 mm, 10 mm and 15 mm on MA for simulation. The ROM and IDP of L3/4 and L4/5 of four models were all compared in forward flexion, backward extension, left and right bending, left and right rotation. Results Compared with MA, the ROM of L4/5 of MB, MC and MD all increased. MD changed more significantly than MB and MC in backward extension, right bending and right rotation. But that of MB and MC on L3/4 had no prominent change, while MD had a slight increase in backward extension. The IDP of MB and MC on L4/5 in six states was similar to MA, yet MD increased obviously in backward extension, right bending, left and right rotation. The IDP on L3/4 of MB and MC was resemble to MA in six conditions, nevertheless MD increased slightly only in backward extension. Conclusion Compared with the facetectomy in diameters 7.5 mm and 10 mm, the mechanical effect brought by facetectomy in diameter 15 mm on the operating segment changed more significantly, and had a corresponding effect on the adjacent segments.