Development and validation of a predictive model for acute-on-chronic liver failure after transjugular intrahepatic portosystemic shunt.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a cause of acute-on-chronic liver failure (ACLF). AIM: To investigate the risk factors of ACLF within 1 year after TIPS in patients with cirrhosis and construct a prediction model. METHODS: In total, 379 patients with decompensated cirrhosis treated with TIPS at Nanjing Drum Tower Hospital from 2017 to 2020 were selected as the training cohort, and 123 patients from Nanfang Hospital were included in the external validation cohort. Univariate and multivariate logistic regression analyses were performed to identify independent predictors. The prediction model was established based on the Akaike information criterion. Internal and external validation were conducted to assess the performance of the model. RESULTS: Age and total bilirubin (TBil) were independent risk factors for the incidence of ACLF within 1 year after TIPS. We developed a prediction model comprising age, TBil, and serum sodium, which demonstrated good discrimination and calibration in both the training cohort and the external validation cohort. CONCLUSION: Age and TBil are independent risk factors for the incidence of ACLF within 1 year after TIPS in patients with decompensated cirrhosis. Our model showed satisfying predictive value.

Structure and functional divergence of PIP peptide family revealed by functional studies on PIP1 and PIP2 in Arabidopsis thaliana.

PAMP-induced secreted peptide (PIP), one of the small post-translationally modified peptides (PTMPs), plays a crucial role in plant development and stress tolerance. However, little is known about functional divergence among this peptide family. Here, we studied the evolution of the PIP family in 23 plant species (10 monocotyledons and 13 dicotyledons from 7 families) and their functional divergence in Arabidopsis. A total of 128 putative PIP precursors were identified and classified into two subfamilies through phylogenetic analysis. Functional studies on AtPIP1 which represents Clade I family and AtPIP2 which represents Clade II family have shown that AtPIP2 displayed stronger immunity induction activity but weaker root growth inhibition than AtPIP1 in Arabidopsis. Transcriptome analysis of Arabidopsis seedlings treated with AtPIP1 and AtPIP2 showed that differential genes for both polypeptides were significantly enriched in similar plant defense pathways. However, Co-expression and Protein-protein interaction (PPI) analysis showed that the functions of AtprePIP2 co-expressed genes were more enriched in plant defense pathways than AtprePIP1. Molecular docking results show that AtPIP1 binds to RLK7 receptor with a more stable free energy and less binding area than AtPIP2, while hydrogen bond transfer occurs at the SGP motif position. The above results suggest that the PIP family have undergone functional divergence during evolution. Collectively, this work illustrates the relationship between PIP structure and function using Arabidopsis PIP as an example, and provides new insights into the current understanding between growth inhibition and immune responses which may be correlated but not fully coupled.

A Novel Zn2Cys6 Transcription Factor, TopC, Positively Regulates Trichodin A and Asperpyridone A Biosynthesis in Tolypocladium ophioglossoides.

Asperpyridone A represents an unusual class of pyridone alkaloids with demonstrated potential for hypoglycemic activity, primarily by promoting glucose consumption in HepG2 cells. Trichodin A, initially isolated from the marine fungus Trichoderma sp. strain MF106, exhibits notable antibiotic activities against Staphylococcus epidermidis. Despite their pharmacological significance, the regulatory mechanisms governing their biosynthesis have remained elusive. In this investigation, we initiated the activation of a latent gene cluster, denoted as "top", through the overexpression of the Zn2Cys6 transcription factor TopC in Tolypocladium ophioglossoides. The activation of the top cluster led to the biosynthesis of asperpyridone A, pyridoxatin, and trichodin A. Our study also elucidated that the regulator TopC exerts precise control over the biosynthesis of asperpyridone A and trichodin A through the detection of protein-nucleic acid interactions. Moreover, by complementing these findings with gene deletions involving topA and topH, we proposed a comprehensive biosynthesis pathway for asperpyridone A and trichodin A in T. ophioglossoides.

High-resolution feature based central venous catheter tip detection network in X-ray images.

Hospital patients can have catheters and lines inserted during the course of their admission to give medicines for the treatment of medical issues, especially the central venous catheter (CVC). However, malposition of CVC will lead to many complications, even death. Clinicians always detect the malposition based on position detection of CVC tip via X-ray images. To reduce the workload of the clinicians and the percentage of malposition occurrence, we propose an automatic catheter tip detection framework based on a convolutional neural network (CNN). The proposed framework contains three essential components which are modified HRNet, segmentation supervision module, and deconvolution module. The modified HRNet can retain high-resolution features from start to end, ensuring the maintenance of precise information from the X-ray images. The segmentation supervision module can alleviate the presence of other line-like structures such as the skeleton as well as other tubes and catheters used for treatment. In addition, the deconvolution module can further increase the feature resolution on the top of the highest-resolution feature maps in the modified HRNet to get a higher-resolution heatmap of the catheter tip. A public CVC Dataset is utilized to evaluate the performance of the proposed framework. The results show that the proposed algorithm offering a mean Pixel Error of 4.11 outperforms three comparative methods (Ma's method, SRPE method, and LCM method). It is demonstrated to be a promising solution to precisely detect the tip position of the catheter in X-ray images.

Learning Skill Characteristics From Manipulations.

Percutaneous coronary intervention (PCI) has increasingly become the main treatment for coronary artery disease. The procedure requires high experienced skills and dexterous manipulations. However, there are few techniques to model PCI skill so far. In this study, a learning framework with local and ensemble learning is proposed to learn skill characteristics of different skill-level subjects from their PCI manipulations. Ten interventional cardiologists (four experts and six novices) were recruited to deliver a medical guidewire to two target arteries on a porcine model for in vivo studies. Simultaneously, translation and twist manipulations of thumb, forefinger, and wrist are acquired with electromagnetic (EM) and fiber-optic bend (FOB) sensors, respectively. These behavior data are then processed with wavelet packet decomposition (WPD) under 1-10 levels for feature extraction. The feature vectors are further fed into three candidate individual classifiers in the local learning layer. Furthermore, the local learning results from different manipulation behaviors are fused in the ensemble learning layer with three rule-based ensemble learning algorithms. In subject-dependent skill characteristics learning, the ensemble learning can achieve 100% accuracy, significantly outperforming the best local result (90%). Furthermore, ensemble learning can also maintain 73% accuracy in subject-independent schemes. These promising results demonstrate the great potential of the proposed method to facilitate skill learning in surgical robotics and skill assessment in clinical practice.

Transmissive coding metasurface with dual-circularly polarized multi-beam.

The Pancharatnam-Berry (PB) phase can be used to control the phase of circularly polarized electromagnetic waves. However, there are few studies on the modulation of dual-circularly polarized multi-beam using the transmissive coding metasurface. A scheme of spin-controlling multi-beam by transmissive coding metasurface is proposed for dual-circular polarization simultaneously. The transmissive coding metasurface (TCMS) can transmit linearly polarized incidence into multi-beam with orthogonally circular polarization. The phase distribution is designed based the convolution theorem, and the elements of metasurface conforming to the PB phase are arranged according to the phase distribution. In order to compensate the emitting spherical waves into plane waves and realize the transmissive waves with dual-circular polarization, an interesting scheme of elements in different regions with different rotating phase are presented based on the principle of phase compensation. TCMS can transmit linearly polarized waves into two left-hand circularly polarized (LHCP) beams and two right-hand circularly polarized (RHCP) beams. The prototype of TCMS is fabricated and measured, and the experimental results agree well with the simulated data. The transmissive metasurface has potential application in holograms and satellite communication.

Assembly dynamics of East Asian subtropical evergreen broadleaved forests: New insights from the dominant Fagaceae trees.

The dominant species of a biome can be regarded as its genuine indicator. Evergreen broadleaved forests (EBLFs) in subtropical East Asia harbor high levels of species biodiversity and endemism and are vital to regional carbon storage and cycling. However, the historical assembly of this unique biome is still controversial. Fagaceae is the most essential family in East Asian subtropical EBLFs and its dominant species are vital for the existence of this biome. Here, we used the dominant Fagaceae species to shed light on the dynamic process of East Asian subtropical EBLFs over time. Our results indicate high precipitation in summer and low temperature in winter are the most influential climatic factors for the distribution of East Asian subtropical EBLFs. Modern East Asian subtropical EBLFs did not begin to appear until 23 Ma, subsequently experienced a long-lasting development in the Miocene and markedly deteriorated at about 4 Ma, driven jointly by orogenesis and paleoclimate. We also document that there is a lag time between when one clade invaded the region and when its members become dominant species within the region. This study may improve our ability to predict and mitigate the threats to biodiversity of East Asian subtropical EBLFs and points to a new path for future studies involving multidisciplinary methods to explore the assembly of regional biomes.

Gram-Level Production of Balanol through Regulatory Pathway and Medium Optimization in Herb Fungus Tolypocladium ophioglossoides.

As a potential protein kinase C inhibitor, the fungus metabolite balanol has become more attractive in recent decades. In our previous work, we revealed its biosynthetic pathway through overexpression of the cluster-situated regulator gene blnR in Chinese herb fungus Tolypocladium ophioglossoides. However, information on the regulation of blnR is still largely unknown. In this study, we further investigated the regulation of balanol biosynthesis by BlnR through the analysis of affinity binding using EMSA and RNA-seq analysis. The results showed that BlnR positively regulates balanol biosynthesis through binding to all promoters of bln gene members, including its own promoter. Microscopic observation revealed blnR overexpression also affected spore development and hypha growth. Furthermore, RNA-seq analysis suggested that BlnR can regulate other genes outside of the balanol biosynthetic gene cluster, including those involved in conidiospore development. Finally, balanol production was further improved to 2187.39 mg/L using the optimized medium through statistical optimization based on response surface methodology.

Space Squeeze Reasoning and Low-Rank Bilinear Feature Fusion for Surgical Image Segmentation.

Surgical image segmentation is critical for surgical robot control and computer-assisted surgery. In the surgical scene, the local features of objects are highly similar, and the illumination interference is strong, which makes surgical image segmentation challenging. To address the above issues, a bilinear squeeze reasoning network is proposed for surgical image segmentation. In it, the space squeeze reasoning module is proposed, which adopts height pooling and width pooling to squeeze global contexts in the vertical and horizontal directions, respectively. The similarity between each horizontal position and each vertical position is calculated to encode long-range semantic dependencies and establish the affinity matrix. The feature maps are also squeezed from both the vertical and horizontal directions to model channel relations. Guided by channel relations, the affinity matrix is expanded to the same size as the input features. It captures long-range semantic dependencies from different directions, helping address the local similarity issue. Besides, a low-rank bilinear fusion module is proposed to enhance the model's ability to recognize similar features. This module is based on the low-rank bilinear model to capture the inter-layer feature relations. It integrates the location details from low-level features and semantic information from high-level features. Various semantics can be represented more accurately, which effectively improves feature representation. The proposed network achieves state-of-the-art performance on cataract image segmentation dataset CataSeg and robotic image segmentation dataset EndoVis 2018.

A Multilayer and Multimodal-Fusion Architecture for Simultaneous Recognition of Endovascular Manipulations and Assessment of Technical Skills.

The clinical success of the percutaneous coronary intervention (PCI) is highly dependent on endovascular manipulation skills and dexterous manipulation strategies of interventionalists. However, the analysis of endovascular manipulations and related discussion for technical skill assessment are limited. In this study, a multilayer and multimodal-fusion architecture is proposed to recognize six typical endovascular manipulations. The synchronously acquired multimodal motion signals from ten subjects are used as the inputs of the architecture independently. Six classification-based and two rule-based fusion algorithms are evaluated for performance comparisons. The recognition metrics under the determined architecture are further used to assess technical skills. The experimental results indicate that the proposed architecture can achieve the overall accuracy of 96.41%, much higher than that of a single-layer recognition architecture (92.85%). In addition, the multimodal fusion brings significant performance improvement in comparison with single-modal schemes. Furthermore, the K -means-based skill assessment can obtain an accuracy of 95% to cluster the attempts made by different skill-level groups. These hopeful results indicate the great possibility of the architecture to facilitate clinical skill assessment and skill learning.

A Unified Framework for Multi-Guidewire Endpoint Localization in Fluoroscopy Images.

OBJECTIVE: In this paper, Keypoint Localization Region-based CNN (KL R-CNN) is proposed, which can simultaneously accomplish the guidewire detection and endpoint localization in a unified model. METHODS: KL R-CNN modifies Mask R-CNN by replacing the mask branch with a novel keypoint localization branch. Besides, some settings of Mask R-CNN are also modified to generate the keypoint localization results at a higher detail level. At the same time, based on the existing metrics of Average Precision (AP) and Percentage of Correct Keypoints (PCK), a new metric named APPCK is proposed to evaluate the overall performance on the multi-guidewire endpoint localization task. Compared with existing metrics, APPCK is easy to use and its results are more intuitive. RESULTS: Compared with existing methods, KL R-CNN has better performance when the threshold is loose, reaching a mean APPCK of 90.65% when the threshold is 9 pixels. CONCLUSION: KL R-CNN achieves the state-of-the-art performance on the multi-guidewire endpoint localization task and has application potentials. SIGNIFICANCE: KL R-CNN can achieve the localization of guidewire endpoints in fluoroscopy images, which is a prerequisite for computer-assisted percutaneous coronary intervention. KL R-CNN can also be extended to other multi-instrument localization tasks.

Optimizing nitrogen fertilizer amount for best performance and highest economic return of winter wheat under limited irrigation conditions.

Inappropriate water and fertilizer management can lead to unstable crop yields. Excessive fertilization can potentially cause soil degradation and nitrogen (N) leaching. The aim of this study was to explore the optimal N application rate on two wheat varieties with different nitrogen responding under limited water irrigation at three experimental sites in the Piedmont plain of the Taihang Mountains, China. A two-year field experiment was conducted to explore the effects of five N application rates (N0, N120, N180, N240, and N300) on winter wheat growth, leaf area index, aboveground biomass, grain yield, grain N accumulation, and net return. The results showed that N application rate significantly affected leaf area index, aboveground biomass, grain yield, and harvest index. Variety and variety × N rate interactions had a significant effect on few indicators. Compared with N0, N180 improved leaf area index, aboveground biomass, grain yield, and grain N accumulation. Compared with N240 and N300, N180 increased the harvest index and N harvest index, without significantly reducing grain yield or grain N accumulation, while enhancing a higher N use efficiency. Fertilizers applied in the ranges of 144.7-212.9 and 150.3-247.0 kg ha-1 resulted in the highest net return for the KN199 and JM585 varieties, respectively. Our study provides a sound theoretical basis for high-efficiency fertilizer utilization in sustainable winter wheat production in the Piedmont plains of the Taihang Mountains of China.

Real-Time Multi-Guidewire Endpoint Localization in Fluoroscopy Images.

The real-time localization of the guidewire endpoints is a stepping stone to computer-assisted percutaneous coronary intervention (PCI). However, methods for multi-guidewire endpoint localization in fluoroscopy images are still scarce. In this paper, we introduce a framework for real-time multi-guidewire endpoint localization in fluoroscopy images. The framework consists of two stages, first detecting all guidewire instances in the fluoroscopy image, and then locating the endpoints of each single guidewire instance. In the first stage, a YOLOv3 detector is used for guidewire detection, and a post-processing algorithm is proposed to refine the guidewire detection results. In the second stage, a Segmentation Attention-hourglass (SA-hourglass) network is proposed to predict the endpoint locations of each single guidewire instance. The SA-hourglass network can be generalized to the keypoint localization of other surgical instruments. In our experiments, the SA-hourglass network is applied not only on a guidewire dataset but also on a retinal microsurgery dataset, reaching the mean pixel error (MPE) of 2.20 pixels on the guidewire dataset and the MPE of 5.30 pixels on the retinal microsurgery dataset, both achieving the state-of-the-art localization results. Besides, the inference rate of our framework is at least 20FPS, which meets the real-time requirement of fluoroscopy images (6-12FPS).

One-Pot Preparation of Peptide-Doped Metal-Amino Acid Framework for General Encapsulation and Targeted Delivery.

Metal-organic frameworks (MOFs), especially those made by biological molecules (bio-MOFs), have been proved to be prospective candidates for biomedical applications. However, a simple and universal bio-MOF to load different substances for precise targeting is still lacking. In this work, we propose a facile one-pot method to prepare a peptide-doped bio-MOF for general encapsulation and targeted delivery. This bio-MOF is constructed by 9-fluorenylmethyloxycarbonyl-modified histidine (Fmoc-His) as a bridging linker that coordinates with Zn2+ ions, denoted as ZFH. The Fmoc-His-Asp-Gly-Arg peptide (Fmoc-HDGR) can be easily doped into the ZFH structure with different ratios to modulate the targeting ability of ZFH-DGR. Containing both hydrophobic Fmoc and hydrophilic His moieties, this framework is compatible with encapsulating various types of payloads, including hydrophobic chemotherapeutic, hydrophilic protein, and positively/negatively charged inorganic nanoparticles. It has also been proved to be highly biocompatible and stable in circulation, exhibit the capabilities to target ανß3 integrin overexpressed on tumor cells, and trigger drug release in a low pH microenvironment at the tumor site. As a proof of concept, Doxorubicin (Dox)-loaded ZFH-DGR (ZFH-DGR/Dox) demonstrated high cell selectivity between liver hepatocellular carcinoma (HepG2) cells and normal liver (L02) cells, which express high and low ανß3 integrin, respectively. This selectivity endows ZFH-DGR/Dox precise treatment and low toxicity in Heps-bearing liver cancer mice. This work develops a de novo approach to construct a peptide-doped bio-MOF system for universal load, precise delivery, and peptide drug combination therapy in the future.

The hornwort genome and early land plant evolution.

Hornworts, liverworts and mosses are three early diverging clades of land plants, and together comprise the bryophytes. Here, we report the draft genome sequence of the hornwort Anthoceros angustus. Phylogenomic inferences confirm the monophyly of bryophytes, with hornworts sister to liverworts and mosses. The simple morphology of hornworts correlates with low genetic redundancy in plant body plan, while the basic transcriptional regulation toolkit for plant development has already been established in this early land plant lineage. Although the Anthoceros genome is small and characterized by minimal redundancy, expansions are observed in gene families related to RNA editing, UV protection and desiccation tolerance. The genome of A. angustus bears the signatures of horizontally transferred genes from bacteria and fungi, in particular of genes operating in stress-response and metabolic pathways. Our study provides insight into the unique features of hornworts and their molecular adaptations to live on land.

Prevalence of Workplace Physical Violence against Health Care Professionals by Patients and Visitors: A Systematic Review and Meta-Analysis.

Workplace physical violence against health care professionals perpetrated by patients and visitors has been a persistent problem worldwide. Prevalence estimates varied vastly across studies and there was a lack of quantitative syntheses of prevalence studies. This review aimed to quantify pooled one-year prevalence estimates at the global and regional levels. A systematic literature search was performed in the databases of PubMed, PsycINFO, Web of Science, and Embase between 1 January 2000 and 8 October 2018. Studies providing information about one-year prevalence of self-reported workplace physical violence against health care professionals perpetrated by patients or visitors were included. Heterogeneity between studies was evaluated using Cochran's chi-squared test (Cochran's Q) and I2 values. Subgroup analysis and meta-regression were used to explore heterogeneity. A total of 65 eligible studies reported one-year prevalence estimates for 61,800 health care professionals from 30 countries. The pooled one-year prevalence of workplace physical violence against health care professionals perpetrated by patients or visitors was 19.33% (95% confidence interval (CI): 16.49%-22.53%) and the overall heterogeneity was high across studies. We noted geographic and staff categories variations for prevalence estimates through subgroup analysis. The meta-regression showed that sample size, type of health care setting, and quality score were significant moderators for heterogeneity. One in five health care professionals experienced workplace physical violence perpetrated by patients or visitors worldwide annually. Practical intervention was needed to ensure safety of health care professionals.

Prevalence of sleep disturbances in Chinese healthcare professionals: a systematic review and meta-analysis.

OBJECTIVE: The current review is a systematic, quantitative meta-analysis aimed at examining the pooled prevalence of sleep disturbances in Chinese healthcare professionals. Furthermore, we explore the possible causes of the inconsistencies in the current estimates. METHODS: Systematic searches of databases were conducted for literature published on English (EMBASE, PubMed and Web of Science) and Chinese (Chinese National Knowledge Infrastructure, Wan Fang database and Chinese Science & Technology journal database) databases until 25 May 2018. Statistical analyses were performed using SPSS and R software, the prevalence of sleep disturbances was pooled using random-effects model. RESULTS: A total of 52 studies with 31,749 participants were included. The pooled prevalence of sleep disturbances among Chinese healthcare professionals is 39.2% (95% CI: 36.0%-42.7%). Higher sleep disturbance rates are associated with being female, lower cut-off of Pittsburgh Sleep Quality Index (PSQI), later survey year, bigger sample size, the standardized assessment tool, being a nurse, and shift work. Sample size and cut-off of PSQI were significant moderators for heterogeneity. CONCLUSION: Sleep disturbances are common in Chinese healthcare professionals, and their prevalence is much higher than the general population. Further research is needed to identify effective strategies for preventing and treating sleep disturbances among healthcare professionals.

Qualitative and Quantitative Assessment of Technical Skills in Percutaneous Coronary Intervention: In Vivo Porcine Studies.

OBJECTIVE: Technical skill assessment plays an important role in the professional development of an interventionalist in percutaneous coronary intervention (PCI). However, most of the traditional assessment methods are time consuming and subjective. This paper aims to develop objective assessment techniques. METHODS: In this study, a natural-behavior-based assessment framework is proposed to qualitatively and quantitatively assess technical skills in PCI. In vivo porcine studies were conducted to deliver a medical guidewire to two target coronaries of left circumflex arteries by six novice and four expert interventionalists. Simultaneously, four types of natural behaviors (i.e., hand motion, proximal force, muscle activity, and finger motion) were acquired from the subjects' dominant hand and arm. The features extracted from the behaviors of different skill-level groups were compared using the Mann-Whitney U-test for effective behavior selection. The effective ones were further applied in the Gaussian-mixture-model-based qualitative assessment and Mahalanobis-distance-based quantitative assessment. RESULTS: The qualitative assessment achieves an accuracy of 92% to distinguish the novice and expert attempts, which is significantly higher than that of using single guidewire motions. Furthermore, the quantitative assessment can assign objective and effective scores for all attempts, indicating high correlation ( R = 0.9225) to those obtained by traditional methods. CONCLUSION: The objective, effective, and comprehensive assessment of technical skills can be provided by qualitatively and quantitatively analyzing interventionalists' natural behaviors in PCI. SIGNIFICANCE: This paper suggests a novel approach for the technical skill assessment and the promising results demonstrate the great importance and effectiveness of the proposed method for promoting the development of objective assessment techniques.

α-Amino Acetal: A Synthetic Intermediate for the Construction of Aza-Polycycles.

One-step construction of aza-polycyclic skeletons was realized through double cyclization of the oxocarbenium and carbocation intermediates generated from α-amino acetals, which were designed and synthesized by employing our α-amination protocol of aldehydes. A simple process, a broad substrate range, commercialized materials, and extensive applications demonstrated the generality and effectiveness of this method.

[Analysis of factors related to oil-spilling and establishment of limit standards of Asparagi Radix].

Some samples of Asparagi Radix were collected from medical markets.Colors of Asparagi Radix were observed by human vision and recorded to judge whether samples were degenerative.Water content of Asparagi Radix was determined by a drying method.The chroma value and color difference were determined and calculated by a colorimeter.With the deepening of color,the L*value was decreased and a*and ΔE*values were increased.It showed that the results determined by colorimeter can replace the results of visual observation.An HPLC method was established and used to determine the contents of 5-hydroxymethylfurfural(5-HMF) in Asparagi Radix.The results showed the 5-HMF contents were from 0.002 255 to 0.049 14 mg·g-1 in some samples with yellowish-white or yellowish-brown color,significantly increased from 0.080 80 to 0.105 1 mg·g-1 in some samples with brown color,and up to 1.033 mg·g-1 in an oil-spilling sample with dark brown color.This result demonstrated that the 5-HMF contents were significantly increased by accompanied with the deepening of color.There were the significant negatively correlation between the 5-HMF content and the L*value(P<0.01) and positively correlation between the 5-HMF content and the a*or ΔE*value(P<0.01) by the spearman analysis.The oil-spilling and qualified samples were clustered into two alone categories by the cluster analysis.That the limited standards of the 5-HMF content is not higher than 0.02% by HPLC method and of the L*value is not less than 50 by colorimeter method were suggested for Asparagi Radix.It is firstly reported the multiple-factor analysis about oil-spilling and discoloration and the establishment of limited standard of Asparagi Radix.