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Crashes caused by distracted driving result in more than 3000 deaths every year in the U.S. Distracted driver behavior detection is instrumental for driver assist systems. Researchers have focused on autonomously detecting distracted driver behavior so that drivers can be alerted in time to reduce the risk of crashes. Despite the large number of approaches presented in the literature, there are still issues related to proper performance evaluation, reproducibility and lack of or very slow adoption of these approaches by the transportation industry. Most existing approaches either do not provide documented and usable codes or use private datasets, or do not present the experiment details, such as data split, sometimes resulting in inflated accuracy numbers. Moreover, these factors also make many results not reproducible. In addition, the performance metrics should be chosen carefully to measure various aspects of different methods, including their generalizability, and action localization ability in time. In this work, we perform a commensurate comparison of different state-of-the-art methods by using different data splits and performance metrics on the StateFarm distracted driving and AI CITY Challenge datasets. With the data split experiments, we highlight the importance of leave-N-driver-out cross validation, since these models should perform well in real-world testing with never-before-seen drivers. The results show the importance of data splitting and the performance metric for the comparison and evaluation of different methods, and their significant effects on the results.

Abstract: Purpose: We evaluated the effect of potential clinical factors on surgical recurrence of ileal Crohn’s disease after initial ileocolic resection. Methods: One hundred seventy-six patients with ileal Crohn’s disease who underwent an ileocolic resection with anastomosis were identified from our database. The outcome of interest was time from first to second ileocolic resection. Survival analysis was used to assess the significance of the Montreal phenotype classification, smoking habit, a family history of inflammatory bowel disease and other clinical variables. Results: In our final Cox model, a family history of inflammatory bowel disease (hazard ratio 2.24, 95 percent confidence interval 1.16–4.30, P = 0.016), smoking at time of initial ileocolic resection (hazard ratio 2.08, 95 percent confidence interval 1.11–3.91, P = 0.023) was associated with an increased risk of a second ileocolic resection while postoperative prescription of immunomodulators (hazard ratio 0.40, 95 percent confidence interval 0.18–0.88, P = 0.022) was associated with a decreased risk of a second ileocolic resection. Conclusions: Both a family history of inflammatory bowel disease and smoking at the time of the initial ileocolic resection are associated with an increased risk of a second ileocolic resection. Postoperative prescription of immunomodulators is associated with a reduced risk of surgical recurrence. This study supports the concept that both genetic and environmental factors influence the risk of surgical recurrence of ileal Crohn’s disease.

Driver behavior analysis plays an important role in driver assistance systems. A driver’s face and head pose hold the key towards understanding whether the driver’s attention and concentration are on the road while driving. Naturalistic driving studies (NDS) allow observing drivers in real-time under naturalistic traffic conditions. Yet, data collected in NDS often comprise low-resolution videos usually with more challenging camera positions compared to controlled studies. For instance, when the camera is not directly facing the driver, classifying head pose becomes more challenging, since the variation between different classes becomes much smaller. In this paper, we propose three different approaches to classify a driver’s head pose from naturalistic videos, which were captured by a camera providing a side view, instead of directly facing the driver. These approaches employ a sequence of five key points on the driver’s face. We compare these three proposed approaches with each other as well as with three different baselines by using leave-one-driver-out cross-validation on nine different drivers. Results show that our proposed method employing a Bidirectional Gated Recurrent Unit (BiGRU) outperforms the best performing baseline by 11% in terms of overall accuracy.

Therapeutic cancer vaccines, which are designed to amplify tumor-specific T cell responses, have been envisioned as one of the most powerful tools for effective cancer immunotherapy. However, increasing the potency, quality and durability of the vaccine response remains a big challenge. In recent years, materials-based delivery systems focusing on the co-delivery of antigens and adjuvants to enhance cancer vaccination therapy have attracted increasing interest. Among various materials, polymeric nanoparticles (NPs) with different physicochemical properties which can incorporate multiple immunological cues are of great interest. In this review, the recent progress in the design and construction of both ex vivosubunit and in situcancer vaccines using polymeric NPs is summarized. Especially, we will focus on how these NPs improve the adjuvanticity of vaccines. The design principles of polymeric NPs for ex vivosubunit cancer vaccines and in situcancer vaccination are also discussed. Finally, we want to briefly discuss molecular chaperones in cancer immunity and the applications of our unique self-assembly mixed shell polymeric micelle-based nanochaperones for cancer vaccines.

Citrus fruits have abundant flavonoid glycosides (FGs), an important class of natural functional and flavor components. However, there have been few reports about the modification of UDP-glycosyltransferases (UGTs) on flavonoids in citrus. Notably, in flavonoid biosynthesis, 7-O-glucosylation is the initial and essential step of glycosylation prior to the synthesis of flavanone disaccharides, the most abundant and iconic FGs in citrus fruits. Here, based on the accumulation of FGs observed at the very early fruit development stage of two pummelo varieties, we screened six novel flavonoid 7-O-glucosyltransferase genes (7GlcTs) viatranscriptomic analysis and then characterized them in vitro. The results revealed that four Cg7GlcTs possess wide catalytic activities towards various flavonoid substrates, with CgUGT89AK1 exhibiting the highest catalytic efficiency. Transient overexpression of CgUGT90A31and CgUGT89AK1led to increases in FG synthesis in pummelo leaves. Interestingly, these two genes had conserved sequences and consistent functions across different germplasms. Moreover, CitUGT89AK1was found to play a role in the response of citrus to Huanglongbing infection by promoting FG production. The findings improve our understanding of flavonoid 7-O-glucosylation by identifying the key genes, and may help improve the benefits of flavonoid biosynthesis for plants and humans in the future.

It is extremely challenging to design photocontrolled molecular switches with absorption and fluorescence dual-mode outputs that are suited for a solid surface and interface. Herein, we report a group of furan-containing tetraarylethene derivatives with unique photophysical behavior of aggregation-induced emission (AIE) and distinct photochemical reaction-triggered photochromic behaviors by combining a photoactive furan or benzofuran group and an AIE-active triphenylethene molecule. The introduction of a furyl or benzofuryl group into the AIE luminogen endows the molecules with significant reversible photochromism and solid-state fluorescence. The coloration and decoloration of these molecules can be switched by respective irradiation of UV and visible light in a reversible way, and the photochromic changes are accompanied by a switch-on and switch-off of the solid-state fluorescence. It is revealed that the photocontrolled cyclization and cycloreversion reactions are responsible for the reversible photochromism and fluorescence switching based on experimental data and theoretical analysis. Both the position and conjugation of the introduced photoactive units have significant influence on the color and strength of the photochromism, and the simultaneous occurrence of photoinduced fluorescence change in the solid state is perfectly suited for surface-involved applications. The demonstrations of dual-mode signaling in photoswitchable patterning on a filter paper and anti-counterfeiting of an anti-falsification paper strongly highlight the unique advantage of these photochromic molecules with an aggregation-induced emission characteristic in various practical applications. This work proposes a general strategy to design photochromic molecules with AIE activity by introducing photoactive functionals into an AIEgen and demonstrates incomparable advantage in dual-mode signaling and multifunctional applications of these molecules.

In this Letter, triazoles as carbene reagents were used for sulfonamide-directed C–H insertion carbenoid functionalization to construct benzylpyridine sulfonamide dual-pharmacophore compounds. This method is simple and efficient and can be used for the late-stage modification of sulfonamide drugs.

Background: As one of the most important reversible protein post-translation modification types, ubiquitination plays a significant role in the regulation of many biological processes, such as cell division, signal transduction, apoptosis and immune response. Protein ubiquitination usually occurs when ubiquitin molecule is attached to a lysine on a target protein, which is also known as “lysine ubiquitination”. Objective: In order to investigate the molecular mechanisms of ubiquitination-related biological processes, the crucial first step is the identification of ubiquitination sites. However, conventional experimental methods in detecting ubiquitination sites are often time-consuming and a large number of ubiquitination sites remain unidentified. In this study, a ubiquitination site prediction method for Arabidopsis thaliana was developed using a Support Vector Machine (SVM). Methods: We collected 3009 experimentally validated ubiquitination sites on 1607 proteins in A. thaliana to construct the training set. Three feature encoding schemes were used to characterize the sequence patterns around ubiquitination sites, including AAC, Binary and CKSAAP. The maximum Relevance and Minimum Redundancy (mRMR) feature selection method was employed to reduce the dimensionality of input features. Five-fold cross-validation and independent tests were used to evaluate the performance of the established models. Results: As a result, the combination of AAC and CKSAAP encoding schemes yielded the best performance with the accuracy and AUC of 81.35% and 0.868 in the independent test. We also generated an online predictor termed as AraUbiSite, which is freely accessible at: http://systbio.cau.edu.cn/araubisite. Conclusion: We developed a well-performed prediction tool for large-scale ubiquitination site identification in A. thaliana. It is hoped that the current work will speed up the process of identification of ubiquitination sites in A. thaliana and help to further elucidate the molecular mechanisms of ubiquitination in plants.

The aroma quality of citrus fruit is determined by volatiles that are present at extremely low levels in the citrus fruit juice sacs; it can be greatly improved by increasing volatiles. In this study, we showed that the contents of cis- and trans-linalool oxides were significantly increased in the juice sacs of three pummelos artificially pollinated with the Citrus mangshanensis(MS) pollen. A novel cytochrome P450 78A7 gene (CitLO1) was significantly upregulated in the juice sacs of Huanong Red pummelo pollinated with MS pollen in comparison to that with open pollination. Compared to wild-type tobacco Bright-Yellow2 cells, transgenic cells overexpressing CitLO1 promoted a 3- to 4-fold more conversion of (−)-linalool to cis- and trans-linalool oxides. Overall, our results suggest that MS pollen has a xenia effect on pummelo fruit aroma quality, and CitLO1 is a linalool oxide synthase gene that played an important role in the xenia effect.

To describe the treatment patterns and the predictors of different treatment standards in recently diagnosed diabetic macular edema (DME) patients in a nationally representative sample.

Pretransplant cancer screening and improvement of management protocols before and after transplant reduce an expensive treatment cost and improve poor outcome of recipients with early posttransplant de novo malignancy within the first 3 years. Supplemental digital content is available in the text.

Volatile terpenoids accumulate in citrus and play important roles in plant defense against various stressors. However, the broad-spectrum response of terpenoid biosynthesis to ubiquitous stressors in citrus has not been comparatively investigated. In this study, volatile terpenoids were profiled under six stressors: high temperature, citrus miner, citrus red mite, citrus canker, Alternaria brown spot, and huanglongbing (HLB). Significant content changes in 15 terpenoids, including β-ocimene, were observed in more than four of the six stressors, implying their possibly universal stress-response effects. Notably, the emission of terpenoids, including β-caryophyllene, β-ocimene, and nerolidol glucoside, was significantly increased by HLB in HLB-tolerant “Shatian” pomelo leaves. The upregulation of CgTPS1and CgTPS2and their characterization in vivoidentified them as mono- or sesquiterpenoid biosynthetic genes. This study provides a foundation for determining stress resistance mechanisms in citrus and biopesticide designations for future industrial applications.

Saccharides are a sort of ubiquitous and vital molecules within the whole life. However, the application of saccharides analysis with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is restricted by their low ionization efficiency and the instability of the sialic acid fraction. Derivatization strategy based on nonreductive amination provides a good solution, however, this is often time consuming and may result in sample loss due to removal of excessive derivatization reagents. Herein, hydralazine (HZN) was utilized as a reactive matrix for labeling reducing saccharides directly on MALDI target which eliminated tedious sample preparation and avoided sample loss. After optimization, effective and reproducible on-MALDI-target derivatization of neutral and acidic saccharides was achieved in both positive and negative modes. Compared with 2,5-dihydroxybenzoic acid (DHB) and 9-Aminoacridine (9-AA), HZN improved the detection sensitivity of reducing saccharides and provided more abundant fragment ions in MS/MS analysis. Moreover, 26 kinds of neutral glycans and 5 kinds of sialic glycans were identified from ovalbumin (OVA) and bovine fetuin, respectively. Combined with the statistical models, this strategy could be used to distinguish and predict samples of 6 brands of beer, and discriminate 2 kinds of beer fermentation modes. In addition, HZN was applied for quantitative analysis of glucose in urine samples, and the obtained urine glucose concentrations of diabetic patients were consistent with the clinical test results, showing the potential of qualitative and quantitative analysis of reducing saccharides in complex samples.

Traditional Chinese tongue diagnosis plays an irreplaceable role in disease diagnosis. This study aimed to describe the tongue characteristics of patients with granulomatous lobular mastitis (GLM). Forty GLM patients and 40 non-GLM controls were evaluated using the Traditional Chinese Medicine subjective clinical interpretation and a TDA-1 Tongue Diagnostic and Analysis system. The associations between the image features of the tongue body and coating and the profiling of immune-inflammatory parameters were analyzed. GLM patients were prone to a reddish tongue bodies with thick, white, and greasy coatings. Thick and greasy tongue coating features are risk factors for GLM. GLM patients had higher levels of white blood cells (WBC), platelets, C-reactive protein, interleukin-2, and transforming growth factor-β (TGF-β) than non-GLM controls (P < .05). Also, tongue coating contrast and entropy values were significantly correlated with WBC or TGF-β levels in GLM patients (r < −0.310 and P < .05). We demonstrated that the hot evil and phlegm-dampness constitutions are the main characteristics of GLM. This might provide a reference for GLM diagnosis.

BACKGROUND AND OBJECTIVE:Diabetic blindness occurs most often among working-age people. Panretinal photocoagulation (PRP) can prevent this outcome. Administrative data examined changes in PRP incidence rates.PATIENTS AND METHODS:Anonymous data from the “claims submitted” files of an insurer with nationwide representation was used. This health insurance was a job benefit, and the sample included 6,085,750 U.S. employees and their dependents. Those who received PRP for diabetic retinopathy were compared to all others with diabetes mellitus. Although some enrollees had more than one PRP procedure, each procedure was considered a unique event. The rate change was evaluated by chi-square tests with post hoc tests for pair-wise comparisons.RESULTS:A total of 14,856 PRP procedures were performed. An incidence rate reduction from 0.95% to 0.67% (chi-square = 243.6818, A total of 14,856 PRP procedures were performed. An incidence rate reduction from 0.95% to 0.67% (chi-square = 243.6818, P< .0001) was found within the study interval.CONCLUSION:The incidence of PRP was reduced in this sample of U.S. workers and their dependents.

BABY BOOM (BBM) is a member of the APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) family and its expression has been shown to improve herbaceous plant transformation and regeneration. However, this improvement has not been shown clearly for tree species. This study demonstrated that the efficiency of transgenic apple (Malus domestica Borkh.) plant production was dramatically increased by ectopic expression of the MdBBM1gene. “Royal Gala” apple plants were first transformed with a CaMV35S-MdBBM1construct (MBM) under kanamycin selection. These MBMtransgenic plants exhibited enhanced shoot regeneration from leaf explants on tissue culture media, with most plants displaying a close-to-normal phenotype compared with CaMV35S-GUStransgenic plants when grown under greenhouse conditions, the exception being that some plants had slightly curly leaves. Thin leaf sections revealed the MBMplants produced more cells than the GUSplants, indicating that ectopic-expression of MdBBM1enhanced cell division. Transcriptome analysis showed that mRNA levels for cell division activators and repressors linked to hormone (auxin, cytokinin and brassinosteroid) signalling pathways were enhanced and reduced, respectively, in the MBMplants compared with the GUSplants. Plants of eight independent MBMlines were compared with the GUSplants by re-transforming them with an herbicide-resistant gene construct. The number of transgenic plants produced per 100 leaf explants was 0–3% for the GUSplants, 3–8% for five MBMlines, and 20–30% for three MBMlines. Our results provided a solution for overcoming the barriers to transgenic plant production in apple, and possibly in other trees.

In citrus, 1,6-rhamnosytransferase (1,6RhaT) and 1,2-rhamnosytransferase (1,2RhaT) catalyze flavanone-7-O-glucosides to form nonbitter flavanone rutinosides (FRs) and bitter flavanone neohesperidosides (FNs), respectively. As revealed in this study of fruit peels from 36 citrus accessions, FRs varied from undetectable levels in pummelo and kumquat to being the dominant flavonoids in sweet orange and loose-skin mandarins. Furthermore, a previously annotated full-length 1,6RhaT-likegene was identified as another 1,6RhaT-encoding gene by in vitroexperiments. In total, 28 alleles of full-length 1,6RhaTswere isolated and classified into A, B and C types with only type A alleles encoding a functional protein. Coincidently, only the accessions that contained FRs harbored type A alleles, as was further verified in two F1 hybrid populations. Moreover, the inferior substrate conversion efficiency of 1,6RhaTs in comparison with that of 1,2RhaT in vitromight partly explain the lower proportions of FRs to total flavanone disaccharides in citrus hybrids harboring both functional rhamnosyltransferases. Our findings provide a better understanding of FR content variations among citrus and are meaningful for a mechanistic illustration of citrus flavonoid metabolism and fruit quality improvement practices.

The effects of dipeptidyl peptidase-4 inhibitors (DPP4Is) on joint pain have been controversial.

Increasing evidence shows that the CXC chemokine receptor 2 (CXCR2) signaling pathway is essentially implicated in the recruitment of myeloid-derived suppressor cells (MDSCs) to the tumor microenvironment and leads to MDSC-mediated immune suppression. Therefore, CXCR2 has recently emerged as a promising drug target for cancer immunotherapy. In this paper, benzocyclic sulfone derivatives were designed as potent CXCR2 antagonists. Structure–activity relationship studies resulted in two lead compounds 9band 11h, which demonstrated double-digit nanomolar potencies against CXCR2 and significantly inhibited neutrophil infiltration into the air pouch in an in vivosetting. More importantly, 9band 11hdose-dependently inhibited the tumor growth through oral administration in the Pan02 mouse model. Further cytometry and immunohistochemical analyses revealed that 9band 11hcould reduce the infiltration of neutrophils and MDSCs and enhance the infiltration of CD3+T lymphocytes into the Pan02 tumor tissues, shedding light on their mechanisms of action in cancer immunotherapy.

1,2-Rhamnosyltransferase (1,2RhaT) catalyzes the final step of production of flavanone neohesperidoside (FNH) that is responsible for the primary bitter taste of citrus fruits. In this study, species-specific flavonoid profiles were determined in 87 Citrusaccessions by identifying eight main flavanone glycosides (FGs). Accumulation of FNHs was completely correlated to the presence of the 1,2RhaTgene in 87 citrus accessions analyzed using a novel 1,2RhaT-specific DNA marker. Pummelo (Citrus grandis) was identified as the genetic origin for a function allele of 1,2RhaTthat underpinned FNH-bitterness in modern citrus cultivars. In addition, genes encoding six MYB and five bHLH transcription factors were shown to coexpress with 1,2RhaTand other flavonoid pathway genes related to FNH accumulation, indicating that these transcription factors may affect the fruit taste of citrus. This study provides a better understanding of bitterness formation in Citrusvarieties and a genetic marker for the early selection of nonbitterness lines in citrus breeding programs.

Eggs with the same total weight may have considerable differences in yolk weight. Eggs with a high percentage of yolk have a higher nutritional value, more flavor, and are more desirable to consumers. However, a large yolk proportion means more dry matter in the eggs, which reduces the feed efficiency. The elucidation of the genetic factors of yolk quantity in eggs is of scientific and practical significance. Through RNA sequencing, we explored the transcriptome of ovarian tissue from 12 Wenchang chickens, including 6 chickens that laid eggs with a high yolk percentage (32%) and 6 that laid low yolk percentage eggs (25%). We identified a total of 362 differentially expressed genes (P-value < 0.01, log2fold change < −1, log2fold change > 1), of which 220 were upregulated and 142 were downregulated in high yolk percentage hens. According to the Gene Ontology terms annotation and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, the differentially expressed genes were associated with the regulation of various cell functions, cell differentiation and development, neuroactive ligand–receptor interactions, and calcium and ubiquitin-mediated proteolysis signaling pathways. To further filter for genes that were directly involved in yolk accumulation, the chicken quantitative trait loci database, genes within 100 kb upstream and downstream of the yolk weight trait SNP, and intersection genes in protein–protein interaction network diagrams were used to detect genes that overlapped with the differentially expressed genes. We found 7 candidate genes in total, MNR2, AOX1, ANTXRL, GRAMD1C, EEF2, COMP, and JUND, which affect female reproductive performance and the growth and development of follicles, supporting cell transport, cell proliferation, and differentiation. All candidate genes and several randomly selected genes were verified by quantitative real time PCR, and the results were consistent with the RNA sequencing. In conclusion, investigating the molecular mechanisms of high yolk percentage traits will allow breeding strategies to be optimized to alter the percentage of yolk in chicken eggs.