RmdnCache: Dual-Space Prefetching Neural Network for Large-Scale Volume Visualization.

Volume visualization plays a significant role in revealing important intrinsic patterns of 3D scientific datasets. However, these datasets are often large, making it challenging for interactive visualization systems to deliver a seamless user experience because of high input latency that arises from I/O bottlenecks and limited fast memory resources with high miss rates. To address this issue, we have proposed a deep learning-based prefetching method called RmdnCache, which optimizes the data flow across the memory hierarchy to reduce the input latency of large-scale volume visualization. Our approach accurately prefetches the content of the next view to fast memory using learning-based prediction while rendering the current view. The proposed deep learning architecture consists of two networks, RNN and MDN in respective spaces, which work together to predict both the location and likelihood distribution of the next view for defining an optimal prefetching range. Our method outperforms existing state-of-the-art prefetching algorithms in reducing overall input latency for visualizing real-world large-scale volumetric datasets.

Nur77 mitigates endothelial dysfunction through activation of both nitric oxide production and anti-oxidant pathways.

BACKGROUND: Nur77 belongs to the member of orphan nuclear receptor 4A family that plays critical roles in maintaining vascular homeostasis. This study aims to determine whether Nur77 plays a role in attenuating vascular dysfunction, and if so, to determine the molecular mechanisms involved. METHODS: Both Nur77 knockout (Nur77 KO) and Nur77 endothelial specific transgenic mice (Nur77-Tg) were employed to examine the functional significance of Nur77 in vascular endothelium in vivo. Endothelium-dependent vasodilatation to acetylcholine (Ach) and reactive oxygen species (ROS) production was determined under inflammatory and high glucose conditions. Expression of genes was determined by real-time PCR and western blot analysis. RESULTS: In response to tumor necrosis factor alpha (TNF-α) treatment and diabetes, the endothelium-dependent vasodilatation to Ach was significantly impaired in aorta from Nur77 KO as compared with those from the wild-type (WT) mice. Endothelial specific overexpression of Nur77 markedly prevented both TNF-α- and high glucose-induced endothelial dysfunction. Compared with WT mice, after TNF-α and high glucose treatment, ROS production in aorta was significantly increased in Nur77 KO mice, but it was inhibited in Nur77-Tg mice, as determined by dihydroethidium (DHE) staining. Furthermore, we demonstrated that Nur77 overexpression substantially increased the expression of several key enzymes involved in nitric oxide (NO) production and ROS scavenging, including endothelial nitric oxide synthase (eNOS), guanosine triphosphate cyclohydrolase 1 (GCH-1), glutathione peroxidase-1 (GPx-1), and superoxide dismutases (SODs). Mechanistically, we found that Nur77 increased GCH1 mRNA stability by inhibiting the expression of microRNA-133a, while Nur77 upregulated SOD1 expression through directly binding to the human SOD1 promoter in vascular endothelial cells. CONCLUSION: Our results suggest that Nur77 plays an essential role in attenuating endothelial dysfunction through activating NO production and anti-oxidant pathways in vascular endothelium. Targeted activation of Nur77 may provide a novel therapeutic approach for the treatment of cardiovascular diseases associated with endothelial dysfunction.

AnyFace++: A Unified Framework for Free-style Text-to-Face Synthesis and Manipulation.

Human faces contain rich semantic information that could hardly be described without a large vocabulary and complex sentence patterns. However, most existing text-to-image synthesis methods could only generate meaningful results based on limited sentence templates with words contained in the training set, which heavily impairs the generalization ability of these models. In this paper, we define a novel 'free-style' text-to-face generation and manipulation problem, and propose an effective solution, named AnyFace++, which is applicable to a much wider range of open-world scenarios. The CLIP model is involved in AnyFace++ for learning an aligned language-vision feature space, which also expands the range of acceptable vocabulary as it is trained on a large-scale dataset. To further improve the granularity of semantic alignment between text and images, a memory module is incorporated to convert the description with arbitrary length, format, and modality into regularized latent embeddings representing discriminative attributes of the target face. Moreover, the diversity and semantic consistency of generation results are improved by a novel semi-supervised training scheme and a series of newly proposed objective functions. Compared to state-of-the-art methods, AnyFace++ is capable of synthesizing and manipulating face images based on more flexible descriptions and producing realistic images with higher diversity.

Developing and validating clinical models to identify candidates for allergic rhinitis pre-exposure prophylaxis.

PURPOSE: Few risk-forecasting models of allergic rhinitis (AR) exist that may aid AR pre-exposure prophylaxis (PrEP) in clinical practice. Therefore, this study aimed to develop and validate an effective clinical model for identifying candidates for AR PrEP using a routine medical questionnaire. METHODS: This study was conducted in 10 Chinese provinces with 13 medical centers (n = 877) between 2019 and 2021. Clinical characteristics and exposure history were collected via face-to-face interviews. Well-trained physicians diagnosed patients with AR based on skin prick test results and clinical performance. The least absolute shrinkage and selection operator model was used to identify potential risk factors for AR, and the logistic regression model was used to construct the risk-forecasting model. Predictive power and model reliability were assessed using area under the receiver operating characteristic curve and calibration curves, respectively. RESULTS: This study diagnosed 625 patients with AR who had positive responses to at least one indoor or outdoor allergen and 460 to at least one outdoor pollen allergen. Two nomograms were established to identify two types of AR with various sensitization patterns. Both models had an area under curve of approximately 0.7 in the development and internal validation datasets. Additionally, our findings found good agreement for the calibration curves of both models. CONCLUSION: Early identification of candidates for AR PrEP using routine medical information may improve the deployment of limited resources and effective health management. Our models showed good performance in predicting AR; therefore, they can serve as potential automatic screening tools to identify AR PrEP candidates.

Inhibiting endothelial cell Mst1 attenuates acute lung injury in mice.

Background: Lung endothelium plays a pivotal role in the orchestration of inflammatory and injury responses to acute pulmonary insults. Mammalian sterile 20-like kinase 1 (Mst1), a mammalian homolog of Hippo, is a serine/threonine kinase that is ubiquitously expressed in many tissues and has been shown to play an important role in the regulation of apoptosis, inflammation, stress responses, and organ growth. While Mst1 exhibits high expression in the lung, its involvement in the endothelial response to pulmonary insults remains largely unexplored. Methods: Mst1 activity was assessed in lung endothelium by western blot. Mst1 endothelial specific knockout mice and a pharmacological inhibitor were employed to assess the effects of Mst1 on homeostatic and lipopolysaccharide (LPS)-induced endothelial responses. Readouts for these studies included various assays, including NF-κB activation and levels of various inflammatory cytokines and adhesion molecules. The role of Mst1 in lung injury was evaluated in a LPS-induced murine model of acute lung injury (ALI). Results: Mst1 phosphorylation was significantly increased in lung endothelial cells after exposure to tumor necrosis factor (TNF)-alpha (TNF-α) and mouse lung tissues after LPS exposure. Overexpression of full length Mst1 or its kinase domain promoted nuclear factor kappaB (NF-κB) activation through promoting JNK and p38 activation, whereas dominant negative forms of Mst1 (DN-Mst1) attenuated endothelial responses to TNF-α and interleukin-1ß. Consistent with this, targeted deletion of Mst1 in lung endothelium reduced lung injury to LPS in mice. Similarly, wild-type mice were protected from LPS-induced lung injury following treatment with a pharmacological inhibitor of Mst1/2. Conclusions: Our findings identified Mst1 kinase as a key regulator in the control of lung EC activation and suggest that therapeutic strategies aimed at inhibiting Mst1 activation might be effective in the prevention and treatment of lung injury to inflammatory insults.

Epigenetic regulation of vascular smooth muscle cell phenotypic switch and neointimal formation by PRMT5.

AIMS: Phenotypic transition of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic state is involved in the development of cardiovascular diseases, including atherosclerosis, hypertension, and post-angioplasty restenosis. Arginine methylation catalyzed by protein arginine methyltransferases (PRMTs) has been implicated in multiple cellular processes, however, its role in VSMC biology remains undetermined. The objective of this study was to determine the role of PRMTs in VSMC phenotypic switch and vascular remodelling after injury. METHODS AND RESULTS: Our results show that PRMT5 is the most abundantly expressed PRMT in human aortic SMCs, and its expression is up-regulated in platelet-derived growth factor (PDGF)-stimulated VSMCs, human atherosclerotic lesions, and rat carotid arteries after injury, as determined by western blot and immunohistochemical staining. PRMT5 overexpression inhibits the expression of SMC marker genes and promotes VSMC proliferation and migration, while silencing PRMT5 exerts the opposite effects. Mechanistically, we found that PRMT5 overexpression led to histone di-methylation of H3R8 and H4R3, which in turn attenuates acetylation of H3K9 and H4, thus limiting recruitment of the SRF/myocardin complexes to the CArG boxes of SMC marker genes. Furthermore, both SMC-specific deletion of PRMT5 in mice and local delivery of lentivirus expressing shPRMT5 to rat carotid arteries significantly attenuated neointimal formation after injury. Likewise, pharmacological inhibition of PRMT5 by EPZ015666 markedly inhibited carotid artery ligation-induced neointimal formation in mice. CONCLUSIONS: Our results identify PRMT5 as a novel regulator in VSMC phenotypic switch and suggest that inhibition of PRMT5 may represent an effective therapeutic strategy for proliferative vascular diseases.

Patterns of aeroallergen sensitization in asthma patients identified by latent class analysis: A cross-sectional study in China.

BACKGROUND: This cross-sectional study aimed to identify latent sensitization profiles of asthma patients in mainland China, unveiling the association between regional differences and sensitization patterns. METHODS: 1056 asthma participants from 10 medical centers divided into eastern and western cohorts were clustered into four individual sensitization patterns, respectively, by using an unsupervised statistical modeling method, latent class analysis (LCA), based on the levels of 12 aeroallergens specific IgE reactivities. Moreover, differences in clinical characteristics and environmental exposures were compared in different sensitization patterns. RESULTS: Four distinct sensitization patterns in the two cohorts were defined as follows, respectively. Eastern cohort: Class 1: "High weed pollen and house dust mites (HDMs) sensitization" (8.87%), Class 2: "HDMs dominated sensitization" (38.38%), Class 3: "High HDMs and animal dander sensitization" (6.95%), Class 4: "Low/no aeroallergen sensitization" (45.80%). Western cohort: Class 1: "High weed pollen sensitization" (26.14%), Class 2: "High multi-pollen sensitization" (15.02%), Class 3: "HDMs-dominated sensitization" (10.33%), Class 4: "Low/no aeroallergen sensitization" (48.51%). Of note, the significant statistical difference in age, asthma control test score (ACT) and comorbidities were observed within or between different sensitization patterns. Exposure factors in different sensitization patterns were pointed out. CONCLUSIONS: Asthmatic patients with distinct sensitization patterns were clustered and identified through the LCA method, disclosing the relationship between sensitization profiles of multiple aeroallergens and geographical differences, providing novel insights and potential strategies for atopic disease monitoring, management and prevention in clinical practice.

PIMT is a novel and potent suppressor of endothelial activation.

Proinflammatory agonists provoke the expression of cell surface adhesion molecules on endothelium in order to facilitate leukocyte infiltration into tissues. Rigorous control over this process is important to prevent unwanted inflammation and organ damage. Protein L-isoaspartyl O-methyltransferase (PIMT) converts isoaspartyl residues to conventional methylated forms in cells undergoing stress-induced protein damage. The purpose of this study was to determine the role of PIMT in vascular homeostasis. PIMT is abundantly expressed in mouse lung endothelium and PIMT deficiency in mice exacerbated pulmonary inflammation and vascular leakage to LPS(lipopolysaccharide). Furthermore, we found that PIMT inhibited LPS-induced toll-like receptor signaling through its interaction with TNF receptor-associated factor 6 (TRAF6) and its ability to methylate asparagine residues in the coiled-coil domain. This interaction was found to inhibit TRAF6 oligomerization and autoubiquitination, which prevented NF-κB transactivation and subsequent expression of endothelial adhesion molecules. Separately, PIMT also suppressed ICAM-1 expression by inhibiting its N-glycosylation, causing effects on protein stability that ultimately translated into reduced EC(endothelial cell)-leukocyte interactions. Our study has identified PIMT as a novel and potent suppressor of endothelial activation. Taken together, these findings suggest that therapeutic targeting of PIMT may be effective in limiting organ injury in inflammatory vascular diseases.

Application of machine learning in groundwater quality modeling - A comprehensive review.

Groundwater is a crucial resource across agricultural, civil, and industrial sectors. The prediction of groundwater pollution due to various chemical components is vital for planning, policymaking, and management of groundwater resources. In the last two decades, the application of machine learning (ML) techniques for groundwater quality (GWQ) modeling has grown exponentially. This review assesses all supervised, semi-supervised, unsupervised, and ensemble ML models implemented to predict any groundwater quality parameter, making this the most extensive modern review on this topic. Neural networks are the most used ML model in GWQ modeling. Their usage has declined in recent years, giving rise to more accurate or advanced techniques such as deep learning or unsupervised algorithms. Iran and the United States lead the world in areas modeled, with a wealth of historical data available. Nitrate has been modeled most exhaustively, targeted by nearly half of all studies. Advancements in future work will be made with further implementation of deep learning and explainable artificial intelligence or other cutting-edge techniques, application of these techniques for sparsely studied variables, the modeling of new or unique study areas, and the implementation of ML techniques for groundwater quality management.

Wet-spinning fluorescent alginate fibres achieved by doping PEI modified CPDs for multiple anti-counterfeiting.

Carbonized polymer dots (CPDs) with satisfactory excitation-dependent-emission and biocompatibility had great potential in anti-counterfeiting fibres field. However, it was difficult for CPDs to combined into the fibres due to the unstable interaction between CPDs and spinnable polymer matrix. Polyethyleneimine (PEI) was used to modify CPDs (namely PEI-CPDs) for achieving stable interactions with sodium alginate (SA) by a simple method, which including the physical interaction between the amino groups of PEI-CPDs and carboxyl groups of SA and the chain entanglement between two types of polymer chains. Then alginate fibres based on PEI-CPDs (PEI-CPDs/CaALG fibres) were successfully prepared by wet-spinning for the first time with less loss of PEI-CPDs. The high mechanical strength, excellent thermal stability and good biocompatibility achieved by PEI-CPDs/CaALG fibres. Furthermore, the fibres exhibited the excitation-dependent-emission property. Anti-counterfeiting of the fibres was conducted on both textile and papers, which showed higher security than the existing anti-counterfeiting fibres.

Mst1-mediated phosphorylation of Nur77 improves the endometrial receptivity in human and mice.

BACKGROUND: Successful embryo implantation requires the attachment of a blastocyst to the receptive endometrial epithelium, which was disturbed in the women with recurrent implantation failure (RIF). Endometrial ß3-integrin was the most important adhesion molecule contributing to endometrial receptivity in both humans and mice. Nur77 has been proven indispensable for fertility in mice, here we explore the role of Nur77 on embryo-epithelial adhesion and potential treatment to embryo implantation failure. METHODS: The expression and location of Mst1 and Nur77 in endometrium from fertile women and RIF patients were examined by IHC, qRT-PCR and Western blotting. In vitro kinase assay following with LC-MS/MS were used to identify the phosphorylation site of Nur77 activated by Mst1. The phosphorylated Nur77 was detected by phos-tag SDS-PAGE assay and specific antibody against phospho-Nur77-Thr366. The effect of embryo-epithelium interaction was determined in the BeWo spheroid or mouse embryo adhesion assay, and delayed implantation mouse model. RNA-seq was used to explore the mechanism by which Nur77 derived peptide promotes endometrial receptivity. FINDINGS: Endometrial Mammalian sterile 20 (STE20)-like kinase 1 (Mst1) expression level was decreased in the women with RIF than that in the fertile control group, while Mst1 activation in the epithelial cells promoted trophoblast-uterine epithelium adhesion. The effect of Nur77 mediated trophoblast-uterine epithelium adhesion was facilitated by active Mst1. Mechanistically, mst1 promotes the transcription activity of Nur77 by phosphorylating Nur77 at threonine 366 (T366), and consequently increased downstream target ß3-integrin expression. Furthermore, a Nur77-derived peptide containing phosphorylated T366 markedly promoted mouse embryo attachment to Ishikawa cells ([4 (2-4)] vs [3 (2-4)]) and increased the embryo implantation rate (4 vs 1.4) in a delayed implantation mouse model by regulating integrin signalling. Finally, it is observed that the endometrial phospho-Nur77 (T366) level is decreased by 80% in the women with RIF. INTERPRETATION: In addition to uncovering a potential regulatory mechanism of Mst1/Nur77/ß3-integrin signal axis involved in the regulation of embryo-epithelium interaction, our finding provides a novel marker of endometrial receptivity and a potential therapeutic agent for embryo implantation failure. FUNDING: National Key Research and Development Program of China (2018YFC1004400), the National Natural Science Foundation of China (82171653, 82271698, 82030040, 81971387 and 30900727), and National Institutes of Health grants (R01HL103869).

α-Asarone attenuates chronic sciatica by inhibiting peripheral sensitization and promoting neural repair.

This study explored the therapeutic effect of α-asarone on chronic sciatica. Thirty-two Sprague-Dawley (SD) rats were divided into four groups: the sham group, chronic constriction injury (CCI) group, pregabalin group, and α-asarone group. Hot hyperalgesia was induced after the CCI operation, and α-asarone was found to relieve chronic neuralgia. Furthermore, α-asarone reduced IL1ß, IL6, TNF-α, CRP, and LPS levels and increased IL10 levels in serum. α-Asarone decreased the protein levels of TRPA1, TRPM8, and TRPV1-4 and the mRNA levels of TRPA1, TRPM8, TRPV1-4, IL1ß, and TNF-α in dorsal root ganglion neurons. In the sciatic nerve, α-asarone treatment reduced the number of inflammatory cells and promoted the proliferation of Schwann cells, favouring recovery of the nerve structure. In cellular experiments, LPS induced Schwann cell apoptosis via TLR4/p38MAPK signalling; α-asarone attenuated LPS-induced Schwann cell apoptosis by decreasing TLR4, p-p38MAPK, cleaved-caspase3, and cleaved-caspase7 levels and increasing Bcl-2 and Bcl-xl expression. Overall, these findings suggest that α-asarone relieves chronic sciatica by decreasing the levels of inflammatory factors, inhibiting peripheral sensitization, and favouring the repair of damaged nerves.

NDRG1 Signaling Is Essential for Endothelial Inflammation and Vascular Remodeling.

BACKGROUND: NDRG-1 (N-myc downstream-regulated gene 1) is a member of NDRG family that plays essential roles in cell differentiation, proliferation, and stress responses. Although the expression of NDRG1 is regulated by fluid shear stress, its roles in vascular biology remain poorly understood. The purpose of the study is to determine the functional significance of NDRG1 in vascular inflammation and remodeling. METHODS AND RESULTS: By using quantitative polymerase chain reaction, western blot, and immunohistochemistry, we demonstrate that the expression of NDRG1 is markedly increased in cytokine-stimulated endothelial cells and in human and mouse atherosclerotic lesions. To determine the role of NDRG1 in endothelial activation, we performed loss-of-function studies using NDRG1 short hairpin RNA. Our results demonstrate that NDRG1 knockdown by lentivirus bearing NDRG1 short hairpin RNA substantially attenuates both IL-1ß (interleukin-1ß) and TNF-α (tumor necrosis factor-α)-induced expression of cytokines/chemokines and adhesion molecules. Intriguingly, inhibition of NDRG1 also significantly attenuates the expression of procoagulant molecules, such as PAI-1 (plasminogen activator inhibitor type 1) and TF (tissue factor), and increases the expression of TM (thrombomodulin) and t-PA (tissue-type plasminogen activator), thus exerting potent antithrombotic effects in endothelial cells. Mechanistically, we showed that NDRG1 interacts with orphan Nur77 (nuclear receptor) and functionally inhibits the transcriptional activity of Nur77 and NF-κB (nuclear factor Kappa B) in endothelial cells. Moreover, in NDRG1 knockdown cells, both cytokine-induced mitogen-activated protein kinase activation, c-Jun phosphorylation, and AP-1 (activator protein 1) transcriptional activity are substantially inhibited. Neointima and atherosclerosis formation induced by carotid artery ligation and arterial thrombosis were markedly attenuated in endothelial cell-specific NDRG1 knockout mice compared with their wild-type littermates. CONCLUSIONS: Our results for the first time identify NDRG1 as a critical mediator implicated in regulating endothelial inflammation, thrombotic responses, and vascular remodeling, and suggest that inhibition of NDRG1 may represent a novel therapeutic strategy for inflammatory vascular diseases, such as atherothrombosis and restenosis.

Experimental Study on the Effect of Micro-Texture on EHL Point-Contact Film Thickness Subject to Sliding Conditions.

Processing texture on contact surfaces can improve the friction performance of mechanical comments. In this research, micro-dimple textures with various parameter were processed on a steel ball's surface with a picosecond laser. Then, the EHL (elastohydrodynamic lubrication) oil film thickness was measured on an optical ball-on-disc tribometer subjected to pure sliding conditions. The effects of sliding velocity, load, dimple location and dimple depth on the film thickness were analyzed. The results showed that the dimple affected the pressure distribution in the contact area, which in turn changed the distribution of the local film thickness. An increase in the local film thickness occurred between the dimple and outlet of the contact region, while a decrease in the film thickness formed from the dimple to the entrance of the contact area and both sides of the dimple's edge. Velocity and applied loads affected the film thickness distribution as well. As the sliding velocity increased, the film thickness increasing region enlarged, while the film thickness-decreasing area shrank. The increase in load resulted in a negative effect on the increase in film thickness. This study will provide a reference for point-contact designs with low friction conditions.

A multicenter survey on the current status of chronic cough and its impact on quality of life in Guangdong, China.

Background: Chronic cough is a troublesome clinical problem with long-term impacts at the patient level. However, the burden of chronic cough in China is largely unknown. Thus, we performed a multicenter cross-sectional survey on the current status of chronic cough and its impact on quality of life in Guangdong, south China. Methods: Using a standardized questionnaire, we extracted and analyzed the relevant data on demographics, number of visits to a doctor, previous diagnosis, previous medications used and initial diagnosis. Cough-specific quality of life was measured by the Mandarin Chinese version of the Leicester Cough Questionnaire (LCQ-MC). Results: Of 933 patients from 13 tertiary medical centers in Guangdong, 52.2% were female, the median age was 40.0 [interquartile range (IQR), 31.0-52.0] years, and the median duration of chronic cough was 6.0 (IQR, 3.0-24.0) months. Over half (n=452, 54.0%) of the patients had visited physicians ≥3 times for cough. In terms of previous diagnosis, bronchitis (n=432, 46.5%) had been most frequently diagnosed, followed by pharyngitis (n=246, 26.5%) and asthmatic cough (n=98, 10.5%). A majority of patients with chronic cough had used antitussive agents (n=539, 58.5%), antibiotics (n=374, 40.6%) and traditional Chinese medicine (TCM) (n=294, 31.9%). Among the three subscales of the LCQ-MC, we observed lower scores in the mental health domain than in the physical and social domains (both P<0.001). Additionally, lower LCQ-MC scores were found in females and patients who saw the doctor >3 times for both the total and three subscale scores (all P<0.05). Conclusions: Misdiagnosis and inappropriate treatment are prevalent in patients with chronic cough and lead to considerable antibiotic abuse. Chronic cough markedly affects suffers' quality of life, especially for women.

Endothelial PRMT5 plays a crucial role in angiogenesis after acute ischemic injury.

Arginine methylation mediated by protein arginine methyltransferases (PRMTs) has been shown to be an important posttranslational mechanism involved in various biological processes. Herein, we sought to investigate whether PRMT5, a major type II enzyme, is involved in pathological angiogenesis and, if so, to elucidate the molecular mechanism involved. Our results show that PRMT5 expression is significantly upregulated in ischemic tissues and hypoxic endothelial cells (ECs). Endothelial-specific Prmt5-KO mice were generated to define the role of PRMT5 in hindlimb ischemia-induced angiogenesis. We found that these mice exhibited impaired recovery of blood perfusion and motor function of the lower limbs, an impairment that was accompanied by decreased vascular density and increased necrosis as compared with their WT littermates. Furthermore, both pharmacological and genetic inhibition of PRMT5 significantly attenuated EC proliferation, migration, tube formation, and aortic ring sprouting. Mechanistically, we showed that inhibition of PRMT5 markedly attenuated hypoxia-induced factor 1-α (HIF-1α) protein stability and vascular endothelial growth factor-induced (VEGF-induced) signaling pathways in ECs. Our results provide compelling evidence demonstrating a crucial role of PRMT5 in hypoxia-induced angiogenesis and suggest that inhibition of PRMT5 may provide novel therapeutic strategies for the treatment of abnormal angiogenesis-related diseases, such as cancer and diabetic retinopathy.

Potential quantitative effect of a laboratory-based approach to Lyme disease surveillance in high-incidence states.

Historically, public health surveillance for Lyme disease has required clinical follow-up on positive laboratory reports for the purpose of case classification. In areas with sustained high incidence of the disease, this resource-intensive activity yields a limited benefit to public health practice. A range of burden-reducing strategies have been implemented in many states, creating inconsistencies that limit the ability to decipher trends. Laboratory-based surveillance, or surveillance based solely on positive laboratory reports without follow-up for clinical information on positive laboratory reports, emerged as a feasible alternative to improve standardization in already high-incidence areas. To inform expectations of a laboratory-based surveillance model, we conducted a retrospective analysis of Lyme disease data collected during 2012-2018 from 10 high-incidence states. The number of individuals with laboratory evidence of infection ranged from 1302 to 20,994 per state and year. On average, 55% of those were ultimately classified as confirmed or probable cases (range: 29%-86%). Among all individuals with positive laboratory evidence, 18% (range: 2%-37%) were determined to be 'not a case' upon investigation and 23% (range: 2%-52%) were classified as suspect cases due to lack of associated clinical information and thus were not reported to the Centers for Disease Control and Prevention (CDC). The number of reported cases under a laboratory-based approach to surveillance in high-incidence states using recommended two-tier testing algorithms is likely to be, on average, 1.2 times higher (range: 0.6-1.8 times) than what was reported to CDC during 2012-2018. A laboratory-based surveillance approach for high-incidence states will improve standardization and reduce burden on public health systems, allowing public health resources to focus on prevention messaging, exploration of novel prevention strategies and alternative data sources to yield information on the epidemiology of Lyme disease.

Monocyte Adhesion Assays for Detecting Endothelial Cell Activation in Vascular Inflammation and Atherosclerosis.

Monocyte adhesion assay, a fluorescence-based method, enables the detection and quantification of monocyte adhesion to endothelial cell (EC) monolayers in vitro and measures EC activation. We describe in this chapter a monocyte adhesion assay based on two published papers from our laboratory that can be effectively used in studying the mechanisms of both pro- and anti-inflammatory cytokines in EC activation. Endothelial cell monolayers are cultured and treated with desired drug, cytokines, or other stimuli and incubated with fluorescently labeled monocytes.