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Objective Arterial aneurysms are life-threatening but usually asymptomatic before requiring hospitalization. Oculomics of retinal vascular features (RVFs) extracted from retinal fundus images can reflect systemic vascular properties and therefore were hypothesized to provide valuable information on detecting the risk of aneurysms. By integrating oculomics with genomics, this study aimed to (i) identify predictive RVFs as imaging biomarkers for aneurysms and (ii) evaluate the value of these RVFs in supporting early detection of aneurysms in the context of predictive, preventive and personalized medicine (PPPM). Methods This study involved 51,597 UK Biobank participants who had retinal images available to extract oculomics of RVFs. Phenome-wide association analyses (PheWASs) were conducted to identify RVFs associated with the genetic risks of the main types of aneurysms, including abdominal aortic aneurysm (AAA), thoracic aneurysm (TAA), intracranial aneurysm (ICA) and Marfan syndrome (MFS). An aneurysm-RVF model was then developed to predict future aneurysms. The performance of the model was assessed in both derivation and validation cohorts and was compared with other models employing clinical risk factors. An RVF risk score was derived from our aneurysm-RVF model to identify patients with an increased risk of aneurysms. Results PheWAS identified a total of 32 RVFs that were significantly associated with the genetic risks of aneurysms. Of these, the number of vessels in the optic disc (‘ntreeA’) was associated with both AAA (β = −0.36, P = 6.75e−10) and ICA (β = −0.11, P = 5.51e−06). In addition, the mean angles between each artery branch (‘curveangle_mean_a’) were commonly associated with 4 MFS genes (FBN1: β = −0.10, P = 1.63e−12; COL16A1: β = −0.07, P = 3.14e−09; LOC105373592: β = −0.06, P = 1.89e−05; C8orf81/LOC441376: β = 0.07, P = 1.02e−05). The developed aneurysm-RVF model showed good discrimination ability in predicting the risks of aneurysms. In the derivation cohort, the C-index of the aneurysm-RVF model was 0.809 [95% CI: 0.780–0.838], which was similar to the clinical risk model (0.806 [0.778–0.834]) but higher than the baseline model (0.739 [0.733–0.746]). Similar performance was observed in the validation cohort, with a C-index of 0.798 (0.727–0.869) for the aneurysm-RVF model, 0.795 (0.718–0.871) for the clinical risk model and 0.719 (0.620–0.816) for the baseline model. An aneurysm risk score was derived from the aneurysm-RVF model for each study participant. The individuals in the upper tertile of the aneurysm risk score had a significantly higher risk of aneurysm compared to those in the lower tertile (hazard ratio = 17.8 [6.5–48.8], P = 1.02e−05). Conclusion We identified a significant association between certain RVFs and the risk of aneurysms and revealed the impressive capability of using RVFs to predict the future risk of aneurysms by a PPPM approach. Our finds have great potential to support not only the predictive diagnosis of aneurysms but also a preventive and more personalized screening plan which may benefit both patients and the healthcare system. Graphical abstract

Background We aimed to evaluate the tolerability and efficacy of linezolid in children for treating suspected and diagnosed Gram-positive bacterial infections. Methods A systematic literature search was conducted up to April 23, 2021, using linezolid and its synonyms as search terms. Two reviewers independently identified and extracted relevant randomized controlled trials and prospective cohort studies. The extracted studies were included in a single-rate meta-analysis of adverse events and clinical outcomes using random-effects models. Results A total of 1082 articles were identified, and nine studies involving 758 children were included in the meta-analysis. The overall proportion of adverse events was 8.91% [95% confidence interval (CI) = 1.64%–36.52%], with diarrhea (2.24%), vomiting (2.05%), and rash (1.72%) being the most common. The incidences of thrombocytopenia and anemia were 0.68% and 0.16%, respectively. Some specific adverse events, including rash and gastrointestinal events, were more frequent in the oral administration subgroup. In terms of efficacy, the overall proportion of clinical improvement was 88.80% (95% CI = 81.31%–93.52%). Children with a history of specific bacteriological diagnosis or concomitant antibiotic therapy had a 1.13-fold higher clinical improvement than children without such histories. The proportion of microbial eradication was 92.68% (95% CI = 84.66%–96.68%). The proportion of all-cause mortality was 0.16% (95% CI = 0.00%–7.75%). Conclusions Linezolid was well-tolerated in pediatric patients and was associated with a low frequency of adverse events, such as anemia, thrombocytopenia, and neutropenia. Moreover, linezolid was effective in children with diagnosed and suspected Gram-positive infections.

The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of "eat me" signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.

Integrating light-harvesting materials with microbial biochemistry is a viable approach to produce chemicals with high efficiency from the air, water, and sunlight. Yet it remains unclear whether all absorbed photons in the materials can be transferred through the material-biology interface for solar-to-chemical production and whether the presence of materials beneficially affect the microbial metabolism. Here we report a microbe-semiconductor hybrid by interfacing CO(2)/N(2)-fixing bacterium Xanthobacter autotrophicus with CdTe quantum dots for light-driven CO(2) and N(2) fixation with internal quantum efficiencies of 47.2 ± 7.3% and 7.1 ± 1.1%, respectively, reaching the biochemical limits of 46.1% and 6.9% imposed by the stoichiometry in biochemical pathways. Photophysical studies suggest fast charge-transfer kinetics at the microbe-semiconductor interfaces, while proteomics and metabolomics indicate a material-induced regulation of microbial metabolism favoring higher quantum efficiencies compared to the biological counterparts alone.

The miniaturization of silicon-based electronics has motivated considerable efforts in exploring new electronic materials, including two-dimensional semiconductors and halide perovskites, which are usually too delicate to maintain their intrinsic properties during the harsh device fabrication steps. Here we report a convenient plug-and-probe approach for one-step simultaneous van der Waals integration of high-k dielectrics and contacts to enable top-gated transistors with atomically clean and electronically sharp dielectric and contact interfaces. By applying the plug-and-probe top-gate transistor stacks on two-dimensional semiconductors, we demonstrate an ideal subthreshold swing of 60 mV per decade. Using this approach on delicate lead halide perovskite, we realize a high-k top-gate CsPbBr

The platinum-catalysed hydrogen evolution reaction (HER) generally shows poorer kinetics in alkaline electrolyte and represents a key challenge for alkaline water electrolysis. In the presence of alkali metal cations and hydroxyl anions, the electrode–electrolyte (platinum–water) interface in an alkaline electrolyte is far more complex than that in an acidic electrolyte. Here we combine electrochemical impedance spectroscopy and an electrical transport spectroscopy approach to probe and understand the fundamental role of different cations (Li+, Na+ and K+) in HER kinetics. Our integrated studies suggest that the alkali metal cations play an indirect role in modifying the HER kinetics, with the smaller cations being less destabilizing to the hydroxyl adsorbate (OHad) species in the HER potential window, which favours a higher coverage of OHad on the platinum surface. The surface OHad species are highly polar and act as both electronically favoured proton acceptors and geometrically favoured proton donors to promote water dissociation in alkaline media, thus boosting the Volmer-step kinetics and the HER activity. [Figure not available: see fulltext.]

In this paper, we address the issue of solving problems with multiple components, multiple objectives, and target values for each objective. There are limitations in managing these multi-component, multi-goal problems such as the need for domain expertise to combine or prioritize the goals. In this paper, we propose a domain-independent method, Adaptive Leveling-Weighting-Clustering (ALWC), to manage the exploration of design scenarios of multi-goal, engineering-design problems. Using ALWC, designers explore combinations and priorities of the goals based on their interrelationships. Through iteration, design scenarios are obtained with higher goal achievements and an improved understanding of the relationship among subsystems. This is achieved without increasing computational complexity. This knowledge is helpful for multi-component design. The ALWC method is demonstrated using a thermal-system design problem.

More accurate source analysis of potentially toxic elements (PTEs) in atmospheric fallout that endanger biodiversity and human health remains needed. This study determined the concentrations of seven PTEs, including Pb, Cd, As, Cu, Zn, Ni, and Cr, by inductively coupled plasma mass spectrometry (ICP-MS), and the sources of PTE pollution were quantified using multivariate statistical analysis, including principal component analysis (PCA), cluster analysis (CA), and Pearson correlation analysis, and Moran index was applied for mutual verification and supplementation. PCA and CA revealed that the same mixed sources of Pb, Cd, As, Cu, and Zn were found in the atmospheric dust fall in the study area, while Ni and Cr had the same source of pollution. Pearson correlation analysis provided that there were strong correlations between Pb-Cd, Pb-As, Pb-Cu, Cd-As, Cd-Cu, As-Cu, and Ni-Cr, indicating commonality between the two sources of heavy metal pollution. Additionally, the Moran index showed that strong spatial correlations were observed between Pb, Cd, As, Cu, and Zn, whose sources were mainly related to non-ferrous metal processing smelter smelting slag sites and an environmental company in the study area. However, no spatial correlation was found between Ni and Cr, which mainly originated from the local geological background.

Anastomotic leakage is a serious complication in laparoscopic colorectal surgeries. To resolve this problem, a new stapling technology (Tri-staple) is developed. In this study, we aim to compare the short-term outcomes of Tri-staple versus Universal staple in laparoscopic anterior resection of rectal and distal sigmoid colonic cancer.A total of 446 patients were admitted to our hospital and received laparoscopic anterior resection for rectal and distal sigmoid colonic cancer between January 2016 and December 2020. Among them, Tri-staples were used in 202 patients, and the Universal staples were used in 244 patients. Propensity score matching was performed, followed by a comparison between the two groups (Tri-staple vs. Universal staple) in the incidences of anastomotic leakage, bleeding, and reoperation.In total, 270 patients were included in this retrospective cohort study by the propensity score matching, with each group having 135 patients. Tri-staple group had a significant lower incidence of anastomotic leakage compared with the Universal staple group (4.44% vs. 11.11%, P lt; 0.05). The reoperation rate was also lower in Tri-staple group than the Universal staple group (3.70% vs. 8.15%, P lt; 0.05). The anastomotic bleeding rates, average postoperative hospital stay, average drain indwelling period, and average fasting period had no statistical differences between the two groups.The usage of Tri-staple in laparoscopic anterior resection of rectal and distal sigmoid colonic cancer is associated with lower postoperative complications compared with Universal staple. Future high-quality randomized controlled trials are needed to confirm our findings.

To establish the optimal dose of indocyanine green (ICG) to administer intravenously 30 min before laparoscopic cholecystectomy (LC).In this randomized controlled trial (RCT), patients undergoing LC for cholecystitis, cholelithiasis, and/or cholecystic polyps were randomized into four groups given four different ICG doses (0.025, 0.1, 0.25, 2.5 mg). Using OptoMedic endoscopy combined with a near-infrared fluorescent imaging system, we evaluated the fluorescence intensity (FI) of the common bile duct and liver at three timepoints: before surgical dissection of the cystohepatic triangle, before clipping of the cystic duct, and before closure. The bile duct-to-liver ratio (BLR) of the FI was analyzed to assess the cholangiography effect.Sixty-four patients were allocated to one of four groups, with 40 patients included in the final analysis. Generally, with increasing ICG doses, the levels of FI in the bile duct and liver increased gradually at each of the three timepoints. Before surgical dissection of the cystohepatic triangle, 0.1-mg ICG showed the highest BLR (F = 3.47, p = 0.0259). Before clipping the cystic duct and before closure, the 0.025- and 0.1-mg groups showed a higher BLR than the 0.25- and 2.5-mg groups (p 0.05). When setting the ideal cholangiography at a BLR ≥ 1, ≥ 3, or ≥ 5, the 0.1-mg group showed the highest qualified case number at the three timepoints.The intravenous administration of 0.1-mg ICG, 30 min before LC, is significantly better for fluorescent cholangiography of the extrahepatic biliary structures before dissection and clipping of the cystohepatic triangle.This study was registered in the Chinese Clinical Trial Registry (ChiCTR) (ChiCTR2200057933).

Purpose Robotic ophthalmic microsurgery has significant potential to help improve the success of challenging procedures and overcome the physical limitations of the surgeon. Intraoperative optical coherence tomography (iOCT) has been reported for the visualisation of ophthalmic surgical manoeuvres, where deep learning methods can be used for real-time tissue segmentation and surgical tool tracking. However, many of these methods rely heavily on labelled datasets, where producing annotated segmentation datasets is a time-consuming and tedious task. Methods To address this challenge, we propose a robust and efficient semi-supervised method for boundary segmentation in retinal OCT to guide a robotic surgical system. The proposed method uses U-Net as the base model and implements a pseudo-labelling strategy which combines the labelled data with unlabelled OCT scans during training. After training, the model is optimised and accelerated with the use of TensorRT. Results Compared with fully supervised learning, the pseudo-labelling method can improve the generalisability of the model and show better performance for unseen data from a different distribution using only 2% of labelled training samples. The accelerated GPU inference takes less than 1 millisecond per frame with FP16 precision. Conclusion Our approach demonstrates the potential of using pseudo-labelling strategies in real-time OCT segmentation tasks to guide robotic systems. Furthermore, the accelerated GPU inference of our network is highly promising for segmenting OCT images and guiding the position of a surgical tool (e.g. needle) for sub-retinal injections.

Artificial intelligence has been successfully applied in various fields, one of which is computer vision. In this study, a deep neural network (DNN) was adopted for Facial emotion recognition (FER). One of the objectives in this study is to identify the critical facial features on which the DNN model focuses for FER. In particular, we utilized a convolutional neural network (CNN), the combination of squeeze-and-excitation network and the residual neural network, for the task of FER. We utilized AffectNet and the Real-World Affective Faces Database (RAF-DB) as the facial expression databases that provide learning samples for the CNN. The feature maps were extracted from the residual blocks for further analysis. Our analysis shows that the features around the nose and mouth are critical facial landmarks for the neural networks. Cross-database validations were conducted between the databases. The network model trained on AffectNet achieved 77.37% accuracy when validated on the RAF-DB, while the network model pretrained on AffectNet and then transfer learned on the RAF-DB results in validation accuracy of 83.37%. The outcomes of this study would improve the understanding of neural networks and assist with improving computer vision accuracy.

Background The contributive role of the microbiome in tumor progression has been reported in multiple studies, such as the Fusobacterium nucleatum (F. nucleatum) in breast cancer (BC). This study aimed to explore the role of F. nucleatum-derived small extracellular vesicles (Fn-EVs) in BC and preliminarily uncover the mechanism. Methods Ten normal and 20 cancerous breast tissues were harvested to investigate the gDNA expression of F. nucleatum and its relation with the clinical characteristics of BC patients. After isolating Fn-EVs by ultracentrifugation from F. nucleatum (ATCC 25,586), both MDA-MB-231 and MCF-7 cells were treated with PBS, Fn, or Fn-EVs, followed by being subjected to CCK-8, Edu staining, wound healing, and Transwell assays to detect their cell viability, proliferation, migration, and invasion. TLR4 expression in BC cells with diverse treatments was assessed by western blot. In vivo experiments were performed to verify its role in tumor growth and liver metastasis. Results The F. nucleatum gDNA levels of breast tissues in BC patients were significantly higher than those in normal subjects, and positively associated with tumor size and metastasis. Fn-EVs administration significantly enhanced the cell viability, proliferation, migration, and invasion of BC cells, while knocking down TLR4 in BC cells could block these effects. Furthermore, in vivo study verified the contributive role of Fn-EVs in tumor growth and metastasis of BC, which might rely on its regulation of TLR4. Conclusions Collectively, our results suggest that F. nucleatum plays an important role in BC tumor growth and metastasis by regulating TLR4 through Fn-EVs. Thus, a better understanding of this process may aid in the development of novel therapeutic agents.