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Background: Alternative polyadenylation (APA) events may be modulated by single nucleotide polymorphisms (SNPs). Therefore, this study aims to evaluate the association between APA quantitative trait loci (apaQTLs)-related SNPs (apaQTL-SNPs) and non-small-cell lung cancer (NSCLC) risk. Methods: APA-related genes associated with NSCLC (LUAD and LUSC) were first identified, and the respective apaQTL-SNPs of those genes were selected. Then, a two-phase case-control study was performed to evaluate the association between candidate apaQTL-SNPs and NSCLC risk. Results: A total of 7 LUAD- and 21 LUSC-associated apaQTL-SNPs were selected. In the first phase, the apaQTL-SNP rs10138506 was significantly associated with LUAD risk (p < 0.05), whereas the other two apaQTL-SNPs (rs1130698 and rs1130719) were significantly associated with LUSC risk (p < 0.05). In the second phase, the variant G allele of rs10138506 was still significantly associated with an increased risk of LUAD (OR = 1.42, 95%CI = 1.02–1.98, p = 0.038). Functional annotation indicated that the variant G allele of rs10138506 was significantly associated with a higher PDUI value of CHURC1. Meanwhile, 3′RACE experiments verified the presence of two poly(A) sites (proximal and distal) in CHURC1, while qRT-PCR results indicated that different genotypes of rs1127968 which, in perfect LD with rs10138506, can mediate changes in the lengths of the 3′UTR of CHURC1 isoforms. Conclusion: The variant G allele of rs10138506 in CHURC1 was correlated with a longer 3′UTR of CHURC1 mRNA and an increased LUAD risk. Further studies should evaluate the interaction between rs10138506 and different 3′UTR lengths of CHURC1 that regulate LUAD development.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. Recently a juvenile ALS patient was reported carrying the c.757delG mutation of the sorbitol dehydrogenase (

China's rapid economic growth over the past few decades has been fueled by the fossil-fuel dominated energy system. In Northern China, coal and biomass are important fuel types for household cooking and heating. The use of coal and biomass not only contributes to CO

With the advancement of imaging technology, high dynamic range (HDR) images can now be captured and displayed to produce realistic effects. Tone mapping operators (TMOs) are used to map HDR radiance to the displayable range. A reliable TMO would play a significant role in the accurate reproduction of HDR scenes. The present study aimed to establish an image quality metric based on external references to evaluate various TMOs. Two psychophysical experiments were conducted to develop reference images and to investigate the performance of TMOs. In experiment 1, a set of high quality reference images was developed by rendering image features in terms of contrast, sharpness, and colorfulness, to achieve good rendering for each image. The images were used as reference in experiment 2 to evaluate the performance of 14 TMOs using a six-point categorical judgment method. The TMOs were evaluated using four scales, i.e., contrast, sharpness, colorfulness, and overall performance. The hierarchical relationship among TMOs was established. The results were further compared with previous studies, and high correlation was found between the current experiments and previous studies.

BACKGROUND The majority of children with ulcerative colitis present with extensive colitis at diagnosis, but the response to therapy is heterogenous. Identifying the optimal window for biologic treatment and risk stratification of patients remains an unmet need. AIM To develop a pathology based histomic model to predict corticosteroid free clinical remission (CSF) with mesalamine alone at one year. METHODS 292 hematoxylin and eosin diagnostic treatment naïve rectal mucosal biopsies from the multi-center PROTECT study were digitized. Whole slide images (WSIs) underwent two-step pre-processing a)stain normalization and b)informative patch selection (size 512x512). We trained machine learning (ML) models using 250 histomic features (texture, color, histogram and nuclei features) with 5-fold cross-validation, for patch-level classification. Feature importance was determined by the Gini index. We re-trained the classifier using the top features. Slide-level prediction was defined by threshold voting. Performance metrics at the patch and WSI level was evaluated. A total of 161 patients underwent high-throughput RNA sequencing to define rectal gene expression. We undertook unsupervised weighted gene co-expression network analysis (WGCNA) to discover networks of co-expressed genes with shared biologic functions correlated with histomic features, histological traits, and outcomes. RESULTS 187571 informative patches from 292 patients (Male:55%; Age:12.7y (IQR:11-15); CSF remission:41%) were trained on 23 ML classifiers. The best model trained on 250 features at the patch-level was random forest (RF). At a remission ratio threshold of 0.48, WSI area under the receiver operator curve (AUROC) was 0.90 (95%CI:0.70, 1.00), accuracy 90.4%, precision 90.9% and recall 84.7%. 18 top features were identified and trained, and the corresponding WSI AUROC was 0.87 (95%CI:0.72, 1.00), accuracy 90.1%, precision 89.4%, and recall 83.9% (Fig. 1). We re-trained the 18 features on an independent real-world dataset of 131 UC patients and the model WSI AUROC was 0.85 (95%CI:0.74, 1.00) and an accuracy of 88.5%. Of the 13 modules identified by WGCNA analysis, six modules significantly correlated with clinical and/or histomic features (Fig. 2). Two of the gene co-expression modules were negatively associated with baseline clinical, endoscopic, and histologic measures of severity, and positively associated with nuclei features (Otsu area, perimeter, and equivalent diameter) and the outcome measure of CSF remission. Intersection of genes with adult single cell RNA seq data demonstrated enrichment for enterocytes (SLC26A3) and extracellular matrix (IHH) CONCLUSION We developed a predictive model for UC disease course using histomic features from standard of care pre-treatment pathology images. Characterization of the underlying molecular basis of the histomic features is ongoing.

A series of novel modified waterborne polyurethane acrylate (WPU-EA) emulsions were prepared with isophorone diisocyanate (IPDI), polycarbonate diol, 2,2-bis-hydroxymethyl-propionic acid (DMPA), 1,4-butanediol (BDO), epoxy acrylate (EA), and pentaerythritol triacrylate (PETA). The structure of WPU-EA was confirmed by FTIR and 1H NMR spectroscopy. The effects of different dosages of epoxy acrylate on the cured film were investigated by tensile properties, dynamic mechanical analysis and thermogravimetric analysis. The results indicate that with increasing content of epoxy acrylate, the average particle size of the emulsion gradually increases. With the rise in epoxy acrylate concentration from 0%, 3.0%, 6.0% to 9.0%, the gel fraction of the cured film increases from 83.7%, 92.5%, 93.0% to 93.6%, respectively, and the glass transition temperature rises from 90.3 °C, 107.5 °C, 141.9 °C to 146.6 °C. The tensile strength and the thermal stability of the cured film increases, and the elongation at break decreases. Moreover, the WPU-EA emulsions were sprayed on polycarbonate sheets and exhibited the advantages of high hardness, better gloss and good adhesion, which is promising for the application of plastic coatings.

Background: Type 2 diabetes (T2D) is characterised by the loss of pulsatile insulin secretion. We studied mice with β-cell specific loss of the glucagon receptor (GCGRflox/flox X Ins-1 cre) , to investigate the role of intra-islet glucagon signalling on pan-islet calcium oscillations and islet pulsatility. Methods: Frequently sampled intravenous glucose tolerance tests were conducted on GCGRKOβ-cells-/-and littermate controls. Crossing with GCaMP6f (STOP flox) animals allowed for β-cell specific expression of a fluorescent calcium indicator. These islets were functionally imaged in vitro and in vivo. Wild-type mice were transplanted with islets expressing GCaMP6f in β-cells into the anterior eye chamber and placed on a high fat diet. Half of the cohort received a glucagon analogue (GCG-analogue) for 40 days and the control group were fed to achieve weight matching. Calcium imaging was performed regularly during the development of hyperglycaemia and in response to GCG-analogue treatment. Results: GCGRKOβ-cells-/- mice had poorer glucose tolerance in an intraperitoneal glucose tolerance test (control 12.7mmol/L ±0.6 vs. GCGRKOβ-cells-/- 15.4mmol/L ±0.0 at 15 min, p=0.002) ; fasting glycaemia was not different to controls. In vitro, GCGRKOβ-cells-/- islets showed profound loss of synchronised calcium waves in response to glucose which is only partially rescued in vivo. First-phase insulin pulsatility on peripheral blood sampling (n=5) was significantly disordered in GCGRKOβ-cells-/- mice (burst mass GCGRKOβ-cells-/- 0.30 ±0.03 versus 0.84 ±0.23 for controls p=0.04) . Diet induced obesity and hyperglycaemia resulted in a loss of co-ordinated calcium waves in transplanted islets. This was reversed with GCG-analogue treatment, independently of weight-loss (n=8) . Conclusion: These data provide novel evidence for the role of intra-islet glucagon in sustaining synchronised calcium oscillations and support a possible therapeutic role for glucagonergic agents to restore the insulin pulsatility lost in T2D. Disclosure K.Suba: n/a. B.Jones: None. T.M.Tan: Consultant; Zihipp Ltd. B.Owen: None. D.J.Drucker: Consultant; Kallyope, Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Other Relationship; Eli Lilly and Company. S.Bloom: None. K.Murphy: None. V.Salem: None. Y.S.Patel: Employee; PerkinElmer. A.Roberts: None. J.V.Shrewsbury: None. S.Chen: None. R.Kwok: None. V.Kalogianni: None. X.Liu: None. G.A.Rutter: Advisory Panel; Sun Pharmaceutical Industries Ltd., Research Support; Sun Pharmaceutical Industries Ltd.

Reporting guidelines are structured tools developed using explicit methodology that specify the minimum information required by researchers when reporting a study. The use of artificial intelligence (AI) reporting guidelines that address potential sources of bias specific to studies involving AI interventions has the potential to improve the quality of AI studies, through improvements in their design and delivery, and the completeness and transparency of their reporting. With a number of guidance documents relating to AI studies emerging from different specialist societies, this Review article provides researchers with some key principles for selecting the most appropriate reporting guidelines for a study involving an AI intervention. As the main determinants of a high-quality study are contained within the methodology of the study design rather than the intervention, researchers are recommended to use reporting guidelines that are specific to the study design, and then supplement them with AI-specific guidance contained within available AI reporting guidelines.

Current advances of immunotherapy have greatly changed the way of cancer treatment. At the same time, a great number of nanoparticle-based cancer immunotherapies (NBCIs) have also been explored to elicit potent immune responses against tumors. However, few NBCIs are nearly in the clinical trial which is mainly ascribed to a lack understanding of in vivo fate of nanoparticles (NPs) for cancer immunotherapy. NPs for cancer immunotherapy mainly target the immune organs or immune cells to enable efficient antitumor immune responses. The physicochemical properties of NPs including size, shape, elasticity and surface properties directly affect their interaction with immune systems as well as their in vivo fate and therapeutic effect. Hence, systematic analysis of the physicochemical properties and their effect on in vivo fate is urgently needed. In this review, we first recapitulate the fundamentals for the in vivo fate of NBCIs including physio-anatomical features of lymphatic system and strategies to modulate immune responses. Moreover, we highlight the effect of physicochemical properties on their in vivo fate including lymph nodes (LNs) drainage, cellular uptake and intracellular transfer. Challenges and opportunities for rational design of NPs for cancer immunotherapy are also discussed in detail.

Data-driven digital health technologies have the power to transform health care. If these tools could be sustainably delivered at scale, they might have the potential to provide everyone, everywhere, with equitable access to expert-level care, narrowing the global health and wellbeing gap. Conversely, it is highly possible that these transformative technologies could exacerbate existing health-care inequalities instead. In this Viewpoint, we describe the problem of health data poverty: the inability for individuals, groups, or populations to benefit from a discovery or innovation due to a scarcity of data that are adequately representative. We assert that health data poverty is a threat to global health that could prevent the benefits of data-driven digital health technologies from being more widely realised and might even lead to them causing harm. We argue that the time to act is now to avoid creating a digital health divide that exacerbates existing health-care inequalities and to ensure that no one is left behind in the digital era.

Pain is common in athletes which should be well managed. To identify risk factors for shoulder pain, and the association between shoulder pain, lower back pain and knee pain among elementary school-aged badminton players, we conducted a cross-sectional study to collect data of the past year among 611 elementary school age (7–12 years old) badminton players belonging to the Japan Schoolchildren Badminton Federation using a questionnaire. Odds ratio (OR) and 95% confidence interval (CI) were estimated by multivariate logistic regression analysis. The overall incidence rate of shoulder injuries, lower back injuries and knee injuries was 0.38 injuries per 1000 h of badminton training. Players with training time per day > 2.5 h were 2.64 times (95% CI 1.03–6.78, p = 0.043) more likely to sustain shoulder pain than those with training time per day ≤ 2.5 h. A significant association was revealed between shoulder pain and knee pain as well as between lower back pain and knee pain as training hours per day > 2.5 h. Moreover, lower back pain was significantly associated with shoulder pain independent of training hours per day (≤ 2.5 h: p = 0.001; > 2.5 h: p

A number of large technology companies have created code-free cloud-based platforms that allow researchers and clinicians without coding experience to create deep learning algorithms. In this study, we comprehensively analyse the performance and featureset of six platforms, using four representative cross-sectional and en-face medical imaging datasets to create image classification models. The mean (s.d.) F1 scores across platforms for all model–dataset pairs were as follows: Amazon, 93.9 (5.4); Apple, 72.0 (13.6); Clarifai, 74.2 (7.1); Google, 92.0 (5.4); MedicMind, 90.7 (9.6); Microsoft, 88.6 (5.3). The platforms demonstrated uniformly higher classification performance with the optical coherence tomography modality. Potential use cases given proper validation include research dataset curation, mobile ‘edge models’ for regions without internet access, and baseline models against which to compare and iterate bespoke deep learning approaches. Several technology companies offer platforms for users without coding experience to develop deep learning algorithms. This Analysis compares the performance of six ‘code-free deep learning’ platforms (from Amazon, Apple, Clarifai, Google, MedicMind and Microsoft) in creating medical image classification models.

IntroductionInfectious keratitis (IK) represents the 5thleading cause of blindness worldwide. A delay in diagnosis is often a major factor in progression to irreversible visual impairment and/or blindness from IK. The diagnostic challenge is further compounded by low microbiological culture yield, long turnaround time, poorly differentiated clinical features, and polymicrobial infections. In recent years, deep learning (DL), a subfield of artificial intelligence, has rapidly emerged as a promising tool in assisting automated medical diagnosis, clinical triage and decision making, and improving workflow efficiency in healthcare services. Recent studies have demonstrated the potential of using DL in assisting the diagnosis of IK, though the accuracy remains to be elucidated. This systematic review and meta-analysis aims to critically examine and compare the performance of various DL models with clinical experts and/or microbiological results (the current “gold standard”) in diagnosing IK, with an aim to inform practice on the clinical applicability and deployment of DL-assisted diagnostic models.Methods and analysisThis review will consider studies that included application of any DL models to diagnose patients with suspected IK, encompassing bacterial, fungal, protozoal and/or viral origins. We will search various electronic databases, including EMBASE and MEDLINE. There will be no restriction to the language and publication date. Two independent reviewers will assess the titles, abstracts and full-text articles. Extracted data will include details of each primary studies, including title, year of publication, authors, types of DL models used, populations, sample size, decision threshold, and diagnostic performance. We will perform meta-analyses for the included primary studies when there are sufficient similarities in outcome reporting.Ethics and disseminationNo ethical approval is required for this systematic review. We plan to disseminate our findings via presentation/publication in a peer-reviewed journal.Protocol registrationThis systematic review protocol will be registered with the PROSPERO after peer review.STRENGTH AND LIMITATIONS OF THIS STUDY- This study will serve as the most up-to-date systematic review and meta-analysis specifically evaluating the diagnostic performance of deep learning in infectious keratitis.- The quality of the study will depend on the quality of the available published literature related to this topic.- This study will help identify the gaps in the current clinical evidence, which may be related to study design, quality of the research methodologies, setting of reference standard, risk of bias, and outcome reporting.

To ensure the domestic water and landscape water supply requirements of Hejin Sakura Valley Scenic Area, the water supply scheme of the artificial lake and scenic spot domestic water consumption assessment machine is optimized. Firstly, in view of the water resources situation in the area where the cherry blossom valley garden scenic spot is located, the necessity of pumping groundwater is pointed out; Secondly, combined with the basic information of hydrogeology and mountainous terrain, a scheme for pumping water supply from natural pipe wells is proposed; Finally, relying on FLAC3D software, three different pipe diameter pumping well models of 600mm, 700mm and 800mm are established, three-dimensional jet field analysis is carried out, and the optimal layout scheme of pipe diameter and position of pipe well is given. Studies have shown that the larger the well diameter, the greater the outlet flow rate, and the water output can be increased by 50~80m3/d for each 100mm tube well; The number of tube wells arranged is about 6, and it is recommended that a sufficient distance should be maintained between wells; The demand for pipe wells with different apertures varies between 1 and 2 mouths. The results of this paper can provide guidance for the construction of gardens in central China to solve the problem of water supply, and support and serve the construction of garden landscape.

Quantifying biomarkers at the early stage of the disease is challenging due to the low abundance of biomarkers in the sample and the lack of sensitive techniques. This article reports the development of a novel microfluidic electrochemical biosensing platform to address this challenge. The electrochemical sensing is achieved by utilizing a micropillar array electrode (μAE) coated with 3D bimetallic Pt-Pd nanotrees to enhance the sensitivity. A bubble-based acoustic microstreaming technique is integrated with the device to increase the contact of analyte molecules with the surface of electrodes to further enhance the electrochemical performance. The current density of Pt-Pd NTs/μAE with acoustic microstreaming is nearly 22 times that of the bare planar electrode in potassium ferrocyanide solution. The developed biosensor has demonstrated excellent sensing performance. For hydrogen peroxide detection, both the Pt-Pd NTs/μAE and acoustic microstreaming contribute to the sensitivity enhancement. The current density of the Pt-Pd NTs/μAE is approximatively 28 times that of the bare μAE. With acoustic microstreaming, this enhancement is further increased by nearly 1.6 times. The platform has a linear detection range of 5-1000 μM with a LOD of 1.8 μM toward hydrogen peroxide detection, while for sarcosine detection, the linear range is between 5 and 100 μM and LOD is 2.2 μM, respectively. Furthermore, the sarcosine biosensing shows a high sensitivity of 667 μA mM

The European Space Agency Climate Change Initiative Land Cover data (ESA CCI-LC, from 1992 to 2015) is introduced to the National Center for Atmospheric Research Community Earth System Model version 1.2.1 (NCAR CESM1.2.1). In comparison with the original land surface data in the Community Land Model version 4 (ORG), the new data features notable land use and land cover change (LULCC) with increased forests over northeastern Asia and Alaska by decreasing shrublands and grasslands. Overestimated bare land cover over the Tibetan Plateau (TP) and the Rocky Mountains in the ORG are corrected with the replacements by grasslands and shrublands respectively in the new data. The model simulation results show that with the introduction of the ESA CCI-LC, the simulated surface albedo, surface net radiation flux, sensible and latent heat fluxes are relatively improved over the regions where significant LULCC exists, such as northeastern Asia, Alaska, the TP, and Australia. Surface air temperature, precipitation, and atmospheric circulation are improved in boreal winter but degraded in summer. The winter warming over northeastern Asia results from increased longwave downwelling flux and adiabatic heating while the notable winter cooling over Alaska is attributed to strong cold advection followed by reduced longwave downwelling flux. LULCC alters precipitation by influencing water vapor content. In winter, LULCC affects atmospheric circulation via modulating baroclinicity while in summer, it influences land-sea thermal contrast, thus affecting the intensity of East Asian summer monsoon. LULCC also alters the simulated dust burden.

Several sulfonium salts as efficient unimolecular photoinitiators capable of initiating upconversion nanoparticle-assisted cationic and radical/cationic hybrid photopolymerization are reported. The obtained luminescent polymeric materials, with curing depths of more than 10 cm and good network uniformity, are dual-wavelength responsive and show great potential in sensing and anti-counterfeiting applications.

International audience; Metrics & More Article Recommendations CONSPECTUS: Dendrimers, a special family of polymers, are particularly promising materials for various biomedical applications by virtue of their well-defined dendritic structure and cooperative multivalency. Specifically, in this Account, we present state-of-the-art amphiphilic dendrimers for nucleic acid delivery. Ribonucleic acid (RNA) molecules are fast becoming an important drug modality, particularly since the recent success of mRNA vaccines against COVID-19. Notably, RNA therapeutics offer the unique opportunity to treat diseases at the gene level and address "undruggable" targets. However, RNA therapeutics are not stable and have poor bioavailability, imposing the need for their protection and safe delivery by vectors to the sites-of-action to allow the desired therapeutic effects. Currently, the two most advanced nonviral vectors are based on lipids and polymers, with lipid vectors primarily exploiting the membrane-fusion mechanism and polymer vectors mainly endocytosis-mediated delivery. Notably, only lipid vectors have been advanced through to their clinical use in the delivery of, for example, the first siRNA drug and the first mRNA vaccine. The success of lipid vectors for RNA delivery has motivated research for further innovative materials as delivery vectors. Specifically, we have pioneered lipid/dendrimer conjugates, referred to as amphiphilic dendrimers, for siRNA delivery with the view to harnessing the delivery advantages of both lipid and polymer vectors while enjoying the unique structural features of dendrimers. These amphiphilic dendrimer vectors are lipid/dendrimer hybrids and are thus able to mimic lipid vectors and exploit membranefusion-mediated delivery, while simultaneously retaining the multivalent properties of polymer vectors that allow endocytosis-based delivery. In addition, they have precisely controllable and stable nanosized chemical structures and offer nanotechnology-based delivery. Effective amphiphilic dendrimer vectors share two important elements: chemical hydrophilic entities to bind RNA and RNA complex-stabilizing hydrophobicity. These two combined features allow the encapsulation of RNA within a stable complex before its release into the cytosol following endocytosis. This hydrophilic/hydrophobic balance permitted by the structural features of amphiphilic dendrimers plays a determining role in RNA delivery success. In this Account, we provide a conceptual overview of this exciting field with the latest breakthroughs and key advances in the design of amphiphilic dendrimers for the delivery of siRNA and mRNA. Specifically, we start with a short introduction to siRNA-and mRNA-based therapeutics and their delivery challenges. We then outline the pioneering and representative studies on amphiphilic dendrimer vectors to highlight their historical development and promising features that offer to facilitate the once challenging RNA delivery. We conclude by offering perspectives for the future of amphiphilic dendrimer vectors for nucleic acid delivery in general.

PurposeRetinal signatures of systemic disease (‘oculomics’) are increasingly being revealed through a combination of high-resolution ophthalmic imaging and sophisticated modelling strategies. Progress is currently limited not mainly by technical issues, but by the lack of large labelled datasets, a sine qua non for deep learning. Such data are derived from prospective epidemiological studies, in which retinal imaging is typically unimodal, cross-sectional, of modest number and relates to cohorts, which are not enriched with subpopulations of interest, such as those with systemic disease. We thus linked longitudinal multimodal retinal imaging from routinely collected National Health Service (NHS) data with systemic disease data from hospital admissions using a privacy-by-design third-party linkage approach.ParticipantsBetween 1 January 2008 and 1 April 2018, 353 157 participants aged 40 years or older, who attended Moorfields Eye Hospital NHS Foundation Trust, a tertiary ophthalmic institution incorporating a principal central site, four district hubs and five satellite clinics in and around London, UK serving a catchment population of approximately six million people.Findings to dateAmong the 353 157 individuals, 186 651 had a total of 1 337 711 Hospital Episode Statistics admitted patient care episodes. Systemic diagnoses recorded at these episodes include 12 022 patients with myocardial infarction, 11 735 with all-cause stroke and 13 363 with all-cause dementia. A total of 6 261 931 retinal images of seven different modalities and across three manufacturers were acquired from 1 54 830 patients. The majority of retinal images were retinal photographs (n=1 874 175) followed by optical coherence tomography (n=1 567 358).Future plansAlzEye combines the world’s largest single institution retinal imaging database with nationally collected systemic data to create an exceptional large-scale, enriched cohort that reflects the diversity of the population served. First analyses will address cardiovascular diseases and dementia, with a view to identifying hidden retinal signatures that may lead to earlier detection and risk management of these life-threatening conditions.

With improved productivity, the impact of social and economic development on the ecological environment is becoming more and more significant, and the transformation of transportation modes often accompanies the transformation of the economic development mode. It is essential to study the impact of high-speed rail (HSR) on the environment. This article constructs a compiled index Ecological Environment Pressure (EEP) evaluation system. The spatial analysis tool is then used to explore the temporal and spatial evolution characteristics of EEP in China. The Difference-in-Difference (DID) method and the Propensity Score Matching (PSM) method are used to quantitatively calculate the impact of HSR operations on EEP based on Panel Data. The results show that the EEP in China decreased significantly from 2003 to 2018, and therefore the quality of China’s ecological environment is improving. The regression coefficient of HSR on EEP is significantly negative, indicating that HSR operations will reduce EEP. Additionally, the HSR operation in the eastern and central regions negatively impacts the EEP. At the same time, the HSR operations will also reduce the EEP of resource-based cities, especially for resource-based cities in the central region. The degree of industrial transformation (DIT) and degree of employment transformation (DET), combined with the implementation of HSR operations, can significantly reduce the EEP. It is suggested to formulate more focused actions and policies to reduce EEP and effectively promote sustainable social development.

Small interfering RNA (siRNA)-based RNA interference has emerged as a promising therapeutic strategy for the treatment of a wide range of incurable diseases. However, the safe and effective delivery of siRNA therapeutics into the interior of target cells remains challenging. Here, we disclosed novel amphiphilic peptide dendrimers (AmPDs) that composed of hydrophobic two lipid-like alkyl chains and hydrophilic poly(lysine) dendrons with different generations (2C18-KK2 and 2C18-KK2K4) as nanovehicles for siRNA delivery. These AmPDs are able to self-assemble into supramolecular nanoassemblies that are capable of entrapping siRNA molecules into nanoparticles to protect siRNA from enzymatic degradation and promote efficient intracellular uptake without evident toxicity. Interestingly, by virtue of the optimal balance of hydrophobic lipid-like entity and hydrophilic poly(lysine) dendron generations, AmPD 2C18-KK2K4 bearing bigger hydrophilic dendron can package siRNA to form stable, but more ready to disassemble complexes, thereby resulting in more efficient siRNA releasing and better gene silencing effect in comparison with AmPD 2C18-KK2 bearing smaller dendron. Additional studies confirmed that 2C18-KK2K4 can capitalize on the advantages of lipid and peptide dendrimer vectors for effective siRNA delivery. Collectively, our AmPD-based nanocarriers indeed represent a safe and effective siRNA delivery system. Our findings also provide a new perspective on the modulation of self-assembly amphiphilic peptide dendrimers for the functional and adaptive delivery of siRNA therapeutics.

PURPOSE This systematic review aims to identify instrument-based tests for quantifying vitreous inflammation in uveitis, report the test reliability and the level of correlation with clinician grading. METHODS Studies describing instrument-based tests for detecting vitreous inflammation were identified by searching bibliographic databases and trials registers. Test reliability measures and level of correlation with clinician vitreous haze grading are extracted. RESULTS Twelve studies describing ultrasound, optical coherence tomography (OCT), and retinal photography for detecting vitreous inflammation were included: Ultrasound was used for detection of disease features, whereas OCT and retinal photography provided quantifiable measurements. Correlation with clinician grading for OCT was 0.53-0.60 (three studies) and for retinal photography was 0.51 (1 study). Both instruments showed high inter- and intra-observer reliability (>0.70 intraclass correlation and Cohen's kappa), where reported in four studies. CONCLUSION Retinal photography and OCT are able to detect and measure vitreous inflammation. Both techniques are reliable, automatable, and warrant further evaluation.

The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials–Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials–Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human–AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial., The CONSORT-AI and SPIRIT-AI extensions improve the transparency of clinical trial design and trial protocol reporting for artificial intelligence interventions.

Fragile angular-shaped granular materials, such as calcareous sand, rockfill material, and ballast, show complex stress–strain–volumetric relationships due to the effects of particle breakage. This...

International audience; RNA interference (RNAi) holds great promise for therapeutic applications. However, safe and successful clinical translation essentially requires further advancement of developing efficient delivery systems. Herein, we report that amphiphilic phospholipid peptide dendrimers (AmPPDs) could mediated effective delivery of siRNA targeting Hsp27 for treating castration-resistant prostate cancer (CRPC). AmPPDs bears natural lipid derivative DSPE as the hydrophobic tail and different dendritic l-lysine as the hydrophilic head, capable of compacting siRNA into nanoparticles to protect it from enzymatic degradation. Interestingly, DSPE-KK2, AmPPD bearing smaller hydrophilic dendron, promoting more efficient intracellular uptake and endosome release of the so-formed siRNA complexes, as well as better siRNA releasing ability, ultimately resulting in more potent gene silencing and anticancer effects both in vitro and in vivo. Such outstanding performance of DSPE-KK2 in siRNA delivery may attribute to its optimal balance between the hydrophobic tail and hydrophilic dendritic portion. Our findings provide guidance for the development of safe and effective dendrimer-based siRNA delivery system, thus bringing new hope for combating various diseases.

Annual land use land cover (LULC) change information at medium spatial resolution (i.e. at 30 m) is required in numerous subjects, such as biophysical modelling, land management and global change studies. Annual LULC information, however, is usually not available at continental or national scale due to reasons such as insufficient remote sensing data coverage or lack of computational capabilities. Here we integrate high temporal resolution and coarse spatial resolution satellite images (i.e., Moderate Resolution Imaging Spectroradiometer (MODIS) and Global Inventory Modelling and Mapping Studies (GIMMS) normalized difference vegetation index (NDVI)) with high spatial resolution datasets (China’s Land-Use/cover Datasets (CLUDs) derived from 30-meter Landsat TM/ETM+/OLI) to generate reliable annual nominal 30 m LULC maps for the whole of China between 1980 and 2015. We also test the performance of a statistical based change detection algorithm (Breaks for Additive Seasonal and Trend), originally designed for tracking forest change, in classifying all-type LULC change. As a result, a nominal 30 m annual land use/land cover datasets (CLUD-A) from 1980 to 2015 was developed for the whole China. The mapping results were assessed with a change sample dataset, a regional annual validation sample set and a three-year China sample set. Of the detected change years, 75.61% matched the exact time of conversion within ±1 year. Annual mapping results provided a detail process of urbanization, deforestation, afforestation, water and cropland dynamics over the past 36 years. The consistent characterization of land change dynamics for China can be further used in scientific research and to support land management for policy-makers.

The flank faces of diamond cutting tools are characterized by the groove wear when the tools are used to machine single crystal silicon workpieces precisely, which significantly affects the quality of the machined surface. Many researchers confirmed the existence of SiC hard particles and inferred that hard particles scratch led to the groove wear on tools flank face. However, little literature can be found to reveal the formation process of tools groove wear. Therefore, in this paper, a scratch model of SiC hard particles and diamond tool is proposed by molecular dynamics simulation method to investigate the formation mechanism of the groove wear on the tools flank face. The two basic scratch conditions, namely mechanical scratch and rolling scratch, are utilized to simulate hard particles motion on diamond tools surface respectively, and the tools wear are suggested by the variation in coordination numbers. It can be concluded that owing to the high temperature, the locally softened performance of diamond tools combined with continuous effects of SiC hard particles are the main factors that lead to the formation of the groove wear on the tools flank face.

Elastomer materials integrated with high mechanical strength and excellent self-healing ability can be used as substrates in electronic skins, soft robots, and electrical devices. However, simultaneously enhancing the mechanical and self-healing properties of elastomers is still a great challenge because the self-healing ability of polymer materials is usually antagonistic to its mechanical strength. Herein, a novel healable polyurethane elastomer was developed using a double-network (DN) structure system. In the DN system, a loosely cross-linked chemical network was obtained via a photo-curable acrylic double bond, acting as a robust molecular framework and maintaining the elasticity of the polymer. Simultaneously, the physical cross-linked network produced by quadruple H-bonds of ureidopyrimidinone (UPy) units can not only achieve rapid reformation after fracture but also dissipate strain energy as a weak dynamic bond, endowing the elastomer with excellent self-healing ability and high stretchability. Owing to the accurate design, the synthesized elastomer exhibits excellent properties, including high tensile stress (13.71 MPa), high stretchability (∼500%), exceptional resilience and self-healing ability (90%). The robust healable elastomer enables the easy fabrication of composite conductors, which the prominent performance suggests as a great potential of the healable flexible sensor in next-generation wearable stretchable electronic devices, soft robots, and strain sensors.

International audience; Novel nucleoside derivatives were developed using the strategy of “terminal N,N-dimethylation” to impart tertiary amines to a 1,2,4-triazole nucleoside. The obtained lead compounds displayed significantly improved anticancer activity with dual mechanisms of cell death via apoptosis and autophagy, offering a fresh perspective to searching for new anticancer candidates.

Nighttime Light Emission (NLE) is associated with diminished mental and physical health. The present study examines how NLE and associated urban features (e.g., air pollution, low green space) impact mental and physical wellbeing. We included 200,393 UK Biobank Cohort participants with complete data. The study was carried out in two steps. In Step1, we assessed the relationship between NLE, deprivation, pollution, green space, household poverty and mental and physical symptoms. In Step2, we examined the role of NLE on environment-symptom networks. We stratified participants into high and low NLE and used gaussian graphical model to identify nodes which bridged urban features and mental and physical health problems. We then compared the global strength of these networks in high vs low NLE. We found that higher NLE associated with higher air pollution, less green space, higher economic and neighborhood deprivation, higher household poverty and higher depressed mood, higher tiredness/lethargy and obesity (Rtraining_mean = 0.2624, Ptraining_mean test_mean = 0.2619, Ptest_mean P

Hainan Wen,1,&ast; Weigang Wang,1,2,&ast; Shoujun Xie,3 Qian Sun,1 Yueyi Liang,3 Baojiang Wen,1,2 Yanchao Liu,3 Lihong Sun,3 Zongwei Zhang,3 Jing Cao,1,2 Xiaoxuan Liu,1,2 Xiaoran Niu,1,2 Zirou Ouyang,1,2 Ning Dong,1,2 Jianhong Zhao1,2 1The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Hebei Provincial Center for Clinical Laboratories, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Laboratory, the Affiliated Hospital of Chengde Medical university, Chengde, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianhong Zhao, Email zhaojh_2002@hebmu.edu.cnBackground: Although the principles for blood cultures (BCs) guidelines provide a recommendation for collection patterns, the complexity of clinical practice occasionally prompts clinicians to adopt non-standard collection patterns. Here, we investigate the influences of different BC collection patterns on detection of pathogens.Methods: The BC collection patterns of 96 hospitals were surveyed online. And a retrospective study of BC data from a tertiary hospital was conducted.Results: The results showed that 53.1% of hospitals adopted the recommended patterns. Among the 1439 episodes of true-positive BCs, 67.4% were found in both the left- and right-sided bottles; 58.2% were found in both aerobic and anaerobic bottles.Conclusion: The present study suggested that the rate of standard collection patterns of blood culture was low and the non-standard collection patterns were associated with decreased detection of pathogens. Simultaneous collection of blood on the left and right sides was recommended as an effective pattern of BC collection.Keywords: blood culture, collection pattern, online survey, time-to-positivity, pathogen detection

IntroductionRecent years have witnessed an upsurge of demand in eye care services in the UK. With a large proportion of patients referred to Hospital Eye Services (HES) for diagnostics and disease management, the referral process results in unnecessary referrals from erroneous diagnoses and delays in access to appropriate treatment. A potential solution is a teleophthalmology digital referral pathway linking community optometry and HES.Methods and analysisThe HERMES study (Teleophthalmology-enabled and artificial intelligence-ready referral pathway for community optometry referrals of retinal disease: a cluster randomised superiority trial with a linked diagnostic accuracy study) is a cluster randomised clinical trial for evaluating the effectiveness of a teleophthalmology referral pathway between community optometry and HES for retinal diseases. Nested within HERMES is a diagnostic accuracy study, which assesses the accuracy of an artificial intelligence (AI) decision support system (DSS) for automated diagnosis and referral recommendation. A postimplementation, observational substudy, a within-trial economic evaluation and discrete choice experiment will assess the feasibility of implementation of both digital technologies within a real-life setting. Patients with a suspicion of retinal disease, undergoing eye examination and optical coherence tomography (OCT) scans, will be recruited across 24 optometry practices in the UK. Optometry practices will be randomised to standard care or teleophthalmology. The primary outcome is the proportion of false-positive referrals (unnecessary HES visits) in the current referral pathway compared with the teleophthalmology referral pathway. OCT scans will be interpreted by the AI DSS, which provides a diagnosis and referral decision and the primary outcome for the AI diagnostic study is diagnostic accuracy of the referral decision made by the Moorfields-DeepMind AI system. Secondary outcomes relate to inappropriate referral rate, cost-effectiveness analyses and human–computer interaction (HCI) analyses.Ethics and disseminationEthical approval was obtained from the London—Bromley Research Ethics Committee (REC 20/LO/1299). Findings will be reported through academic journals in ophthalmology, health services research and HCI.Trial registration numberISRCTN18106677 (protocol V.1.1).