Predictive and Prognostic Relevance of Tumor-Infiltrating Immune Cells: Tailoring Personalized Treatments against Different Cancer Types.

TIICs are critical components of the TME and are used to estimate prognostic and treatment responses in many malignancies. TIICs in the tumor microenvironment are assessed and quantified by categorizing immune cells into three subtypes: CD66b+ tumor-associated neutrophils (TANs), FoxP3+ regulatory T cells (Tregs), and CD163+ tumor-associated macrophages (TAMs). In addition, many cancers have tumor-infiltrating M1 and M2 macrophages, neutrophils (Neu), CD4+ T cells (T-helper), CD8+ T cells (T-cytotoxic), eosinophils, and mast cells. A variety of clinical treatments have linked tumor immune cell infiltration (ICI) to immunotherapy receptivity and prognosis. To improve the therapeutic effectiveness of immune-modulating drugs in a wider cancer patient population, immune cells and their interactions in the TME must be better understood. This study examines the clinicopathological effects of TIICs in overcoming tumor-mediated immunosuppression to boost antitumor immune responses and improve cancer prognosis. We successfully analyzed the predictive and prognostic usefulness of TIICs alongside TMB and ICI scores to identify cancer's varied immune landscapes. Traditionally, immune cell infiltration was quantified using flow cytometry, immunohistochemistry, gene set enrichment analysis (GSEA), CIBERSORT, ESTIMATE, and other platforms that use integrated immune gene sets from previously published studies. We have also thoroughly examined traditional limitations and newly created unsupervised clustering and deconvolution techniques (SpatialVizScore and ProTICS). These methods predict patient outcomes and treatment responses better. These models may also identify individuals who may benefit more from adjuvant or neoadjuvant treatment. Overall, we think that the significant contribution of TIICs in cancer will greatly benefit postoperative follow-up, therapy, interventions, and informed choices on customized cancer medicines.

Unveiling the ion sensing capabailities of 'click' derived chalcone-tailored 1,2,3-triazolic isomers for Pb(ii) and Cu(ii) ions: DFT analysis.

In this study, two novel chalcone-derived 1,2,3-triazole-appended positional isomers (probe 6 and probe 9) were synthesized via the 'CuAAC' (Cu(i) - catalysed alkyne azide cycloaddition) methodology for the purpose of metal ion detection. The synthesized probes underwent characterization utilizing standard spectroscopic methodologies including FTIR, NMR (1H and 13C), and mass spectrometry. Subsequently, the sensing capabilities of these probes were explored using UV-Vis and fluorescence spectroscopy, wherein their selective recognition potential was established for Pb(ii) and Cu(ii), both of which can pose serious health hazards when prevalent in the environment above permissible limits. Both the probes exhibited fairly low limits of detection (LoD), determined as 5.69 µM and 6.55 µM in the case of probe 6 for Pb(ii) and Cu(ii) respectively; whereas the probe 9 exhibited an LoD of 5.06 µM and 7.52 µM for Pb(ii) and Cu(ii), respectively. The job's plot for the probe demonstrates the formation of a 1 : 1 complex between the metal and ligand. Furthermore, the interaction of the free probes with the metal ions in the metal-ligand complex was elucidated through 1H NMR analysis and validated theoretically using Density Functional Theory (DFT) simulations with the B3LYP/6-311G++(d,p) and B3LYP/LANL2DZ basis sets for geometry optimization of the probes and their corresponding metal complexes. These findings offer a reliable approach to Cu(ii) and Pb(ii) ion detection and can be further used for the potential applications in environmental monitoring and analytical chemistry.

Stilbenes: a journey from folklore to pharmaceutical innovation.

In modern times, medicine is predominantly based on evidence-based practices, whereas in ancient times, indigenous people relied on plant-based medicines with factual evidence documented in ancient books or folklore that demonstrated their effectiveness against specific infections. Plants and microbes account for 70% of drugs approved by the USFDA (U.S. Food and Drug Administration). Stilbenes, polyphenolic compounds synthesized by plants under stress conditions, have garnered significant attention for their therapeutic potential, bridging ancient wisdom with modern healthcare. Resveratrol, the most studied stilbene, initially discovered in grapes, red wine, peanuts, and blueberries, exhibits diverse pharmacological properties, including cardiovascular protection, antioxidant effects, anticancer activity, and neuroprotection. Traditional remedies, documented in ancient texts like the Ayurvedic Charak Samhita, foreshadowed the medicinal properties of stilbenes long before their modern scientific validation. Today, stilbenes are integral to the booming wellness and health supplement market, with resveratrol alone projected to reach a market value of 90 million US$ by 2025. However, challenges in stilbene production persist due to limited natural sources and costly extraction methods. Bioprospecting efforts reveal promising candidates for stilbene production, particularly endophytic fungi, which demonstrate high-yield capabilities and genetic modifiability. However, the identification of optimal strains and fermentation processes remains a critical consideration. The current review emphasizes the knowledge of the medicinal properties of Stilbenes (i.e., cardiovascular, antioxidant, anticancer, anti-inflammatory, etc.) isolated from plant and microbial sources, while also discussing strategies for their commercial production and future research directions. This also includes examples of novel stilbenes compounds reported from plant and endophytic fungi.

Expression Atlas update: insights from sequencing data at both bulk and single cell level.

Expression Atlas (www.ebi.ac.uk/gxa) and its newest counterpart the Single Cell Expression Atlas (www.ebi.ac.uk/gxa/sc) are EMBL-EBI's knowledgebases for gene and protein expression and localisation in bulk and at single cell level. These resources aim to allow users to investigate their expression in normal tissue (baseline) or in response to perturbations such as disease or changes to genotype (differential) across multiple species. Users are invited to search for genes or metadata terms across species or biological conditions in a standardised consistent interface. Alongside these data, new features in Single Cell Expression Atlas allow users to query metadata through our new cell type wheel search. At the experiment level data can be explored through two types of dimensionality reduction plots, t-distributed Stochastic Neighbor Embedding (tSNE) and Uniform Manifold Approximation and Projection (UMAP), overlaid with either clustering or metadata information to assist users' understanding. Data are also visualised as marker gene heatmaps identifying genes that help confer cluster identity. For some data, additional visualisations are available as interactive cell level anatomograms and cell type gene expression heatmaps.

Cu(i)-catalysed 1,2,3-triazole stitched chalcomer assembly as Pb(ii) and Cu(ii) ion sensor: DFT and docking scrutiny.

Herein, a 1,2,3-triazole derivative (CBT), synthesized using the Copper(i) catalyzed Alkyne Azide Cycloaddition (CuAAC) procedure, based on a chalcone skeleton has been reported, that was implemented as an effective sensor for Pb(ii) and Cu(ii) ions. The synthesized CBT was characterized using spectroscopic techniques such as FTIR, NMR (1H and 13C), and mass spectrometry. The sensing behaviour of CBT was analyzed using UV-Vis spectroscopy, demonstrating selective sensing for Pb(ii) and Cu(ii) ions, competitively. The correlation plot revealed the detection limit for Pb(ii) and Cu(ii) ions to be 100 µM and 110 µM respectively. In addition, DFT simulations and molecular electrostatic potential (MEP) studies scrutinized the binding strategy of the free CBT and its orientation towards the metal ions in the metal-ligand complex. The probe CBT was predicted via the online platform Way2drug for its pharmacological properties, investigating the possibility to inhibit early atherosclerosis. CBT was subsequently docked to the TRIB1 protein using AutoDock Vina and demonstrated a high binding affinity with a value of -6.2 kcal mol-1.

Ampyrone appended 1,2,3-triazole as selective fluorescent Cu(II) ion sensor: DFT and docking findings.

The present report describes the application of the 'Click Chemistry' pathway to synthesize a fluorescent probe (APT) based on ampyrone (4-aminoantipyrine), entailing two benzyl groups as the fluorophores coupled to the antipyrine structure through 1,2,3-triazole moieties. Infrared spectroscopy (IR), nuclear magnetic resonance (1H and 13C), and mass spectrometry were the standard spectroscopic methods used to characterize APT. The ion recognition potential of the probe was analyzed through absorption and emission spectroscopy employing a 4:1 combination of CH3CN and H2O, which demonstrated APT to be an efficient sensing agent for Cu(II) ions, wherein the absorption spectrum of the probe displayed a hypsochromic shift with a hyperchromic shift on gradually adding the metal ion solution of Cu(II), whereas quenching of the probe's fluorescence emission on Cu(II) addition was attributed to the chelation-enhanced fluorescence quenching (CHEQ), induced by the d9 electronic configuration of Cu(II). The stoichiometry of the complexation of APT with Cu(II) is indicative of a 1:1 ratio, while the detection limit (LOD) and quantification limit (LOQ) as estimated from the fluorescence titration results were 3.11 µM and 10.35 µM respectively. Furthermore, DFT analysis was also undertaken to yield the energy-optimized structures and HOMO-LUMO density plots of APT and its corresponding Cu(II) complex via the B3LYP/631G+(d,p) level of theory for APT, and LANL2DZ basis set for the APT-Cu(II) complex. Docking analysis of the probe with the synaptic vesicle protein (SV2A) gave glimpses about its anticonvulsant properties.

Emergence of toxic trace elements in plant environment: Insights into potential of silica nanoparticles for mitigation of metal toxicity in plants.

Emergence of trace elements at potentially toxic concentrations in the environment has become a global issue in recent times. Owing to the rapid population growth, unregulated industrialisation, intensive farming practices and excessive mining activities, these elements are accumulating in environment at high toxic concentrations. The exposure of plants to metal-contaminated environments severely influences their reproductive and vegetative growth, eventually affecting crop performance and production. Hence, it is crucial to find alternatives to mitigate the stress caused by toxic elements, in plants of agricultural importance. In this context, silicon (Si) has been widely recognized to alleviate metal toxicity and promote plant growth during various stress conditions. Amending soil with silicates has shown to ameliorate the lethal effects of metals and stimulates crop development. However, in comparison to silicon in bulk form, nano-sized silica particles (SiNPs) have been demonstrated to be more efficient in their beneficial roles. SiNPs can be used for various technological applications, viz. Improving soil fertility, agricultural yield, and remediating heavy metal-polluted soil. The research outcomes of studies focussing on role of silica nanoparticles to specifically mitigate the metal toxicity in plants have not been reviewed earlier in depth. The aim of this review is to explore the potential of SiNPs in alleviating metal stress and improving plant growth. The benefits of nano-silica over bulk-Si fertilizers in farming, their performance in diverse plant varieties, and the possible mechanisms to mitigate metal toxicity in plants have been discussed in detail. Further, research gaps are identified and future prospects are envisioned for advanced investigations in this field. The growing interest towards nano-silica related research will facilitate exploration of the true prospective of these nanoparticles for mitigation of metal stress in crops and in other fields of agriculture as well.

Purification of ursolic acid and ß-sitosterol from endophytic Alternaria alternata for their alpha-amylase inhibitory activity.

Fungal endophytes are a known warehouse of bioactive compounds with multifarious applications. In the present investigation two compounds, ß-Sitosterol (1) and ursolic acid (2), were isolated from Alternaria alternata, an endophytic fungus associated with Morus alba Linn for the first time. The structure of the compounds was elucidated on the basis of comprehensive spectral analysis (UV, IR, 1 H-, 13 C- and 2D-NMR, as well as HRESI-MS). In the in vitro alpha amylase inhibitory assay both compounds (1) and (2) show potent antidiabetic activity. In support, Docking studies indicate significant binding affinity of the isolated compounds. Hence from the present study, it can be concluded that endophytic fungi in Morus alba Linn can find use in antidiabetic drug development in the medicinal industry.Communicated by Ramaswamy H. Sarma.

CuAAC ensembled 1,2,3-triazole linked nanogels for targeted drug delivery: a review.

Copper(i) catalyzed alkyne azide cycloaddition (CuAAC), the quintessential example of 'click chemistry', provides an adaptable and adequate platform for the synthesis of nanogels for sustained drug release at targeted sites because of their better biocompatibility. The coupling of drugs, carried out via various synthetic routes including CuAAC, into long-chain polymeric forms like nanogels has exhibited considerable assurance in therapeutic advancements and intracellular drug delivery due to the progression of water solubility, evacuation of precocious drug release, and improved upthrust of the pharmacokinetics of the nanogels, thereby rendering them as better and efficient drug carriers. The inefficiency of drug transmission to the target areas due to the resistance of complex biological barriers in vivo is a major hurdle that impedes the therapeutic translation of nanogels. This review compiles the data of nanogels synthesized specifically via CuAAC 'click' methodology, as scaffolds for targeted drug delivery and their assimilation into nanomedicine. In addition, it elaborates the ability of CuAAC to graft specific moieties and conjugating biomolecules like proteins and growth factors, onto orthogonally functionalized polymer chains with various chemical groups resulting in nanogels that are not only more appealing but also more effective at delivering drugs, thereby enhancing their site-specific target approach and initiating selective therapies.

Integrated View of Baseline Protein Expression in Human Tissues.

The availability of proteomics datasets in the public domain, and in the PRIDE database, in particular, has increased dramatically in recent years. This unprecedented large-scale availability of data provides an opportunity for combined analyses of datasets to get organism-wide protein abundance data in a consistent manner. We have reanalyzed 24 public proteomics datasets from healthy human individuals to assess baseline protein abundance in 31 organs. We defined tissue as a distinct functional or structural region within an organ. Overall, the aggregated dataset contains 67 healthy tissues, corresponding to 3,119 mass spectrometry runs covering 498 samples from 489 individuals. We compared protein abundances between different organs and studied the distribution of proteins across these organs. We also compared the results with data generated in analogous studies. Additionally, we performed gene ontology and pathway-enrichment analyses to identify organ-specific enriched biological processes and pathways. As a key point, we have integrated the protein abundance results into the resource Expression Atlas, where they can be accessed and visualized either individually or together with gene expression data coming from transcriptomics datasets. We believe this is a good mechanism to make proteomics data more accessible for life scientists.

Response Surface Optimization for Investigating Antioxidant Potential of Camellia Sinensis and Withania Somnifera in Synergistic Manner.

The paper highlights the synergistic potential of the novel combination of Camellia sinensis (Kangra green tea) and Withania somnifera (Ashwagandha). One variable at a time approach was used to find antioxidant potential of C. sinensis and W. somnifera alone and in combination. Optimization of antioxidant potential was done by using different plant concentrations of C. sinensis and W. somnifera using a statistical approach of central composite design (CCD) of RSM (response surface methodology). Initial antioxidant activity during optimization of the solvent system was observed in methanol for C. sinensis with DPPH, superoxide radical scavenging assay and hydrogen peroxide scavenging assay (44.9 ± 0.62, 43.77 ± 0.10, 43.88 ± 0.10% scavenging) and for W. somnifera (40.22 ± 0.39, 43.29 ± 1.12, 41.88 ± 0.11% scavenging), respectively. Initially, IC50 has been calculated for C. sinensis (235.26 ± 0.012 µg/mL) and W. somnifera (256.39 ± 0.43 µg/mL) in methanol. Before statistical optimization, the maximum synergistic antioxidant potential of C. sinensis (200 µg/mL) and W. somnifera (150 µg/mL) with DPPH assay, superoxide radical scavenging and hydrogen peroxide scavenging assay was found to be 56.57 ± 0.62, 56.99 ± 0.42, 55.44 ± 0.53% scavenging, respectively. IC50 value has been calculated for C. sinensis + W. somnifera (IC50 = 215.47 ± 0.06 µg/mL). Optimization of plant concentration using CCD of RSM resulted in enhancement of antioxidant potential of C. sinensis (200.5 µg/mL) and W. somnifera (200.5 µg/mL) was found to be 78.01 ± 0.01% scavenging when compared to the initial antioxidant potential, i.e., 56.57 ± 0.62% scavenging shows a 1.37-fold increase from initial antioxidant potential. Research unveils that using various combination of C. sinensis and W. somnifera enhance the antioxidant potential in vitro. Supplementary Information: The online version contains supplementary material available at 10.1007/s40011-022-01423-6.

CuAAC-Derived Selective Fluorescent Probe as a Recognition Agent for Pb(II) and Hg(II): DFT and Docking Studies.

Copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) is a resourceful and stereospecific methodology that has considerably yielded promising 1,2,3-triazole-appended "click" scaffolds with the potential for selective metal ion recognition. Based on "click" methodology, this report presents a chemosensor probe (TCT) based on 4-tert-butylcatechol architecture, via the CuAAC pathway, as a selective and efficient sensor for Pb(II) and Hg(II) ions, categorized as the most toxic and alarming environmental contaminants among the heavy metal ions. The synthesized probe was successfully characterized by spectroscopy [IR and NMR (1H and 13C)] and mass spectrometry. The chemosensing study performed in acetonitrile/water (4:1) solvent media, via UV-vis and fluorescence spectroscopy, established its selective sensitivity for Pb(II) and Hg(II) species among the list of explored metal ions with the limits of detection being 8.6 and 11 µM, respectively. Additionally, the 1H NMR and IR spectra of the synthesized TCT-metal complex also confirmed the metal-ligand binding. Besides, the effect of time and temperature on the binding ability of TCT with Pb(II) and Hg(II) was also studied via UV-vis spectroscopy. Furthermore, density functional theory studies put forward the structural comprehension of the sensor by availing the hybrid density functional (B3LYP)/6311G++(d,p) basis set of theory which was subsequently utilized for investigating its anti-inflammatory potential by performing docking analysis with human leukotriene b4 protein.

Integrated view and comparative analysis of baseline protein expression in mouse and rat tissues.

The increasingly large amount of proteomics data in the public domain enables, among other applications, the combined analyses of datasets to create comparative protein expression maps covering different organisms and different biological conditions. Here we have reanalysed public proteomics datasets from mouse and rat tissues (14 and 9 datasets, respectively), to assess baseline protein abundance. Overall, the aggregated dataset contained 23 individual datasets, including a total of 211 samples coming from 34 different tissues across 14 organs, comprising 9 mouse and 3 rat strains, respectively. In all cases, we studied the distribution of canonical proteins between the different organs. The number of canonical proteins per dataset ranged from 273 (tendon) and 9,715 (liver) in mouse, and from 101 (tendon) and 6,130 (kidney) in rat. Then, we studied how protein abundances compared across different datasets and organs for both species. As a key point we carried out a comparative analysis of protein expression between mouse, rat and human tissues. We observed a high level of correlation of protein expression among orthologs between all three species in brain, kidney, heart and liver samples, whereas the correlation of protein expression was generally slightly lower between organs within the same species. Protein expression results have been integrated into the resource Expression Atlas for widespread dissemination.

Implementing the reuse of public DIA proteomics datasets: from the PRIDE database to Expression Atlas.

The number of mass spectrometry (MS)-based proteomics datasets in the public domain keeps increasing, particularly those generated by Data Independent Acquisition (DIA) approaches such as SWATH-MS. Unlike Data Dependent Acquisition datasets, the re-use of DIA datasets has been rather limited to date, despite its high potential, due to the technical challenges involved. We introduce a (re-)analysis pipeline for public SWATH-MS datasets which includes a combination of metadata annotation protocols, automated workflows for MS data analysis, statistical analysis, and the integration of the results into the Expression Atlas resource. Automation is orchestrated with Nextflow, using containerised open analysis software tools, rendering the pipeline readily available and reproducible. To demonstrate its utility, we reanalysed 10 public DIA datasets from the PRIDE database, comprising 1,278 SWATH-MS runs. The robustness of the analysis was evaluated, and the results compared to those obtained in the original publications. The final expression values were integrated into Expression Atlas, making SWATH-MS experiments more widely available and combining them with expression data originating from other proteomics and transcriptomics datasets.

DNA dyes: toxicity, remediation strategies and alternatives.

Release of untreated effluent from processing or manufacturing industries and other commercial premises into water bodies is a major threat to environment and human health. In this regard, the effluent generated from laboratories and other research facilities is of great concern. Among other harmful chemicals, the effluent is rich in toxic organic dyes, which get exposed to the environment and pose serious health risk. The dyes used in nucleic acid analysis specially the DNA dyes are known for their teratogenicity and mutagenic potential, which mainly depends upon the organism and circumstances under which it is exposed. Among animals and humans, exposure to theses dyes may lead to irritation in mouth, eyes and respiratory tract and many other possible effects which are yet to be explored. To overcome these problems, dyes present in the effluents from laboratories must be degraded to non-toxic forms. Various strategies have been proposed and investigated for degradation and remediation of contaminated laboratory effluent. As a modern and cost-effective technique, biodegradation using microbes and plants is potentially eco-friendly and sustainable technique for detoxifying these dyes. In this article, we have discussed and reviewed the structure, properties and toxicity profile of prominent nucleic acid dyes, along with the strategies of remediation of laboratory effluents contaminated with these dyes. In addition, we have also discussed the feasibility and limitations of these remediation strategies and identified research gaps that can help researchers to explore more effective solutions to manage this area of great concern. We have also reviewed various less toxic alternatives of these common as safer options of these dyes.

Expression Atlas update: gene and protein expression in multiple species.

The EMBL-EBI Expression Atlas is an added value knowledge base that enables researchers to answer the question of where (tissue, organism part, developmental stage, cell type) and under which conditions (disease, treatment, gender, etc) a gene or protein of interest is expressed. Expression Atlas brings together data from >4500 expression studies from >65 different species, across different conditions and tissues. It makes these data freely available in an easy to visualise form, after expert curation to accurately represent the intended experimental design, re-analysed via standardised pipelines that rely on open-source community developed tools. Each study's metadata are annotated using ontologies. The data are re-analyzed with the aim of reproducing the original conclusions of the underlying experiments. Expression Atlas is currently divided into Bulk Expression Atlas and Single Cell Expression Atlas. Expression Atlas contains data from differential studies (microarray and bulk RNA-Seq) and baseline studies (bulk RNA-Seq and proteomics), whereas Single Cell Expression Atlas is currently dedicated to Single Cell RNA-Sequencing (scRNA-Seq) studies. The resource has been in continuous development since 2009 and it is available at https://www.ebi.ac.uk/gxa.

A proteomics sample metadata representation for multiomics integration and big data analysis.

The amount of public proteomics data is rapidly increasing but there is no standardized format to describe the sample metadata and their relationship with the dataset files in a way that fully supports their understanding or reanalysis. Here we propose to develop the transcriptomics data format MAGE-TAB into a standard representation for proteomics sample metadata. We implement MAGE-TAB-Proteomics in a crowdsourcing project to manually curate over 200 public datasets. We also describe tools and libraries to validate and submit sample metadata-related information to the PRIDE repository. We expect that these developments will improve the reproducibility and facilitate the reanalysis and integration of public proteomics datasets.

Single-Cell Analysis Reveals the Immune Characteristics of Myeloid Cells and Memory T Cells in Recovered COVID-19 Patients With Different Severities.

Despite many studies on the immune characteristics of Coronavirus disease 2019 (COVID-19) patients in the progression stage, a detailed understanding of pertinent immune cells in recovered patients is lacking. We performed single-cell RNA sequencing on samples from recovered COVID-19 patients and healthy controls. We created a comprehensive immune landscape with more than 260,000 peripheral blood mononuclear cells (PBMCs) from 41 samples by integrating our dataset with previously reported datasets, which included samples collected between 27 and 47 days after symptom onset. According to our large-scale single-cell analysis, recovered patients, who had severe symptoms (severe/critical recovered), still exhibited peripheral immune disorders 1-2 months after symptom onset. Specifically, in these severe/critical recovered patients, human leukocyte antigen (HLA) class II and antigen processing pathways were downregulated in both CD14 monocytes and dendritic cells compared to healthy controls, while the proportion of CD14 monocytes increased. These may lead to the downregulation of T-cell differentiation pathways in memory T cells. However, in the mild/moderate recovered patients, the proportion of plasmacytoid dendritic cells increased compared to healthy controls, accompanied by the upregulation of HLA-DRA and HLA-DRB1 in both CD14 monocytes and dendritic cells. In addition, T-cell differentiation regulation and memory T cell-related genes FOS, JUN, CD69, CXCR4, and CD83 were upregulated in the mild/moderate recovered patients. Further, the immunoglobulin heavy chain V3-21 (IGHV3-21) gene segment was preferred in B-cell immune repertoires in severe/critical recovered patients. Collectively, we provide a large-scale single-cell atlas of the peripheral immune response in recovered COVID-19 patients.

Faith Community Nursing: Faith Element Enhances Cardiovascular Risk Reduction Program Outcomes.

The high prevalence of hypertension among African Americans makes faith-based education programs culturally appropriate. Faith-enhanced health education is a way to reach these often healthcare-disenfranchised populations. With Every Heartbeat is Life (WEHL), a community-based heart health program, was enhanced with Scripture and prayer for this project. The program took place in an African American nondenominational church. The Scripture-enhanced WEHL program emphasized biblical teachings of self-care with standard lessons on nutrition, exercise, smoking cessation, and disease management interventions that increased knowledge of hypertension and associated cardiovascular risks.