Histologic subtypes of non-muscle invasive bladder cancer

The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characterization of histologic subtypes(HS)in UC in BC have mainly been described in muscle in-vasive bladder cancer(MIBC).However,the currently used classification is ap-plied for invasive urothelial neoplasm and therefore,also valid for a subset of NMIBC.The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known.HS in NMIBC are associated with an aggressive phenotype.Conse-quently,clinical guidelines categorize HS of NMIBC as“(very)high-risk”tumors and recommend offering radical cystectomy to these patients.Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials.Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively invest-igated in the context of HS in NMIBC.Further evaluation prior to implementation into clinical practice is needed.

Comparative transcriptome analysis between rhesus macaques(Macaca mulatta) and crab-eating macaques(M. fascicularis)

Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques(Macaca mulatta, MMU)and crab-eating macaques(M. fascicularis, MFA) serve as crucial nonhuman primate biomedical models with different phenotypes. To date, however, large-scale comparative transcriptome research between these two species has not yet been fully explored. Here, we conducted systematic comparisons utilizing newly sequenced RNA-seq data from84 samples(41 MFA samples and 43 MMU samples)encompassing 14 common tissues. Our findings revealed a small fraction of genes(3.7%) with differential expression between the two species, as well as 36.5% of genes with tissue-specific expression in both macaques. Comparison of gene expression between macaques and humans indicated that 22.6% of orthologous genes displayed differential expression in at least two tissues. Moreover,19.41% of genes that overlapped with macaque-specific structural variants showed differential expression between humans and macaques. Of these, the FAM220A gene exhibited elevated expression in humans compared to macaques due to lineage-specific duplication. In summary,this study presents a large-scale transcriptomic comparison between MMU and MFA and between macaques and humans. The discovery of gene expression variations not only enhances the biomedical utility of macaque models but also contributes to the wider field of primate genomics.

The relationship between compartment models and their stochastic counterparts:A comparative study with examples of the COVID-19 epidemic modeling

Deterministic compartment models(CMs)and stochastic models,including stochastic CMs and agent-based models,are widely utilized in epidemic modeling.However,the relationship between CMs and their corresponding stochastic models is not well understood.The present study aimed to address this gap by conducting a comparative study using the susceptible,exposed,infectious,and recovered(SEIR)model and its extended CMs from the coronavirus disease 2019 modeling literature.We demonstrated the equivalence of the numerical solution of CMs using the Euler scheme and their stochastic counterparts through theoretical analysis and simulations.Based on this equivalence,we proposed an efficient model calibration method that could replicate the exact solution of CMs in the corresponding stochastic models through parameter adjustment.The advancement in calibration techniques enhanced the accuracy of stochastic modeling in capturing the dynamics of epidemics.However,it should be noted that discrete-time stochastic models cannot perfectly reproduce the exact solution of continuous-time CMs.Additionally,we proposed a new stochastic compartment and agent mixed model as an alternative to agent-based models for large-scale population simulations with a limited number of agents.This model offered a balance between computational efficiency and accuracy.The results of this research contributed to the comparison and unification of deterministic CMs and stochastic models in epidemic modeling.Furthermore,the results had implications for the development of hybrid models that integrated the strengths of both frameworks.Overall,the present study has provided valuable epidemic modeling techniques and their practical applications for understanding and controlling the spread of infectious diseases.

Comparative efficacy of proximal femoral nail vs dynamic condylar screw in treating unstable intertrochanteric fractures

BACKGROUND Among the most frequent hip fractures are trochanteric fractures,which usually occur from low-energy trauma like minor falls,especially in older people with osteoporotic bones.AIM To evaluate the treatment efficacy of dynamic condylar screws(DCS)and proximal femoral nails(PFN)for unstable intertrochanteric fractures.METHODS To find pertinent randomized controlled trials and retrospective observational studies comparing PFN with DCS for the management of unstable femoral intertrochanteric fractures,a thorough search was carried out.For research studies published between January 1996 and April 2024,PubMed,EMBASE,Scopus,Web of Science,Cochrane Library,and Google Scholar were all searched.The complete texts of the papers were retrieved,vetted,and independently examined by two investigators.Disputes were settled by consensus,and any disagreements that persisted were arbitrated by a third author.RESULTS This study included six articles,comprising a total of 173 patients.Compared to the DCS,the PFN had a shorter operation time[mean difference(MD):-41.7 min,95%confidence interval(95%CI):-63.04 to-20.35,P=0.0001],higher success rates with closed reduction techniques[risk ratio(RR):34.05,95%CI:11.12-104.31,P<0.00001],and required less intraoperative blood transfusion(MD:-1.4 units,95%CI:-1.80 to-1.00,P<0.00001).Additionally,the PFN showed shorter fracture union time(MD:-6.92 wk,95%CI:-10.27 to-3.57,P<0.0001)and a lower incidence of reoperation(RR:0.37,95%CI:0.17-0.82,P=0.01).However,there was no discernible variation regarding hospital stay,implant-related complications,and infections.CONCLUSION Compared to DCS,PFN offers shorter operative times,reduces the blood transfusions requirements,achieves higher closed reduction success,enables faster fracture healing,and lowers reoperation incidence.

Common Artifacts and Remedies in Histological Preparations

The importance of the accuracy of preparing biological specimen as histological sections that can be examined under a microscope lies in reflecting a true image of the tissue that includes all its components, which are used in scientific research or for the purpose of diagnosing various diseases of the body. Despite this, some cellular structures within the tissue may suffer from some alterations that result from the appearance of defects during any stage of preparing these microscopic sections, which alter or interfere with the precise cellular structures and morphology that constitute the tissue and thus give a different image for tissue features and cause confusion in the work histopathologist in the diagnosis. There are several reasons that can cause a misdiagnosis of the sample that occurs during the surgical separation process or after separation during the stages of microscopic preparation techniques from fixation stage, tissue processing, embedding or microtomy, staining until mounting procedures. The constant need to identify these defects and their causes in addition to try to reduce them is one of the biggest challenges evident in pathology laboratories. Therefore, this study aims to review the most common defects that occur in any stage of tissue processing, with an explanation of their causes and appropriate ways to avoid them.

A long-term histological research on human frontalis muscle flap specimens from recurrent blepharoptosis patients

Dear Editor,We present two patients with recurrent severe blepharoptosis after frontalis muscle(FM)flap suspension.Here we describe long-term histological changes of the FM flaps observed in revision surgeries.FM flap suspension is widely applied in treating severe ptosis with poor levator function(<4 mm),and its effect is relatively stable and lasting[1].FM flap suspension is reliable and recurrent cases are observed only occasionally.Since longterm research about FM flap is rare,we investigated tissue samples of revision surgery flaps which could reflect trends of morphological changes within the functioning FM flaps to some extent.

Descriptive and Comparative Histology of the Urinary System of the Hematophagous Bats Desmodus rotundus and Diphylla ecaudata

Desmodus rotundus and Diphylla ecaudata, both of which are mammals of the order Chiroptera, Desmodontidae family, their diet consisting exclusively of blood. D. rotundus is the main vector and transmitter of the rabies virus, which affects human beings as well as several livestock species so the study of this bat species is of high importance within the fields of animal agriculture and public health. The present study describes and compares the histologic characteristics of the urinary system of two hematophagous bat species. A total of 5 bats from each species were captured in the municipalities of Progreso de Obregón, Hidalgo (D. rotundus), and Huayacocotla, Veracruz (D. ecaudata). Organs belonging to the urinary system were extracted: kidneys, ureters, urinary bladder, and urethra;samples were fixed using 10% formalin and processed by the paraffin embedding technique, obtaining sections of 5 µm thickness, which in turn were stained using hematoxylin-eosin (H-E) and Gomori trichrome (GT) stains. From the obtained histologic preparations, a descriptive and comparative analysis of the structural organography of the urinary system of both species was made, and no noteworthy histological differences between samples were noted. The present research is intended to provide a framework for future studies of these species’ currently understudied microscopic anatomy.

Comparative Orotomy of the Archean Superior,North China,and Phanerozoic Altaid Orogenic Systems Architecture

Geological maps encode vast amounts of data about rock types,ages,chemistry,orogenic architecture and deep-time history or different tectonic units,yet these are often difficult to extract because of the way different geologists portray their results at various scales.To understand orogenesis in 4D,it is essential to uniformly integrate map data,together with geophysical data and deep geochemical mapping(Wang et al.,2023).

Rice-wheat comparative genomics:Gains and gaps

Rice and wheat provide nearly 40%of human calorie and protein requirements.They share a common ancestor and belong to the Poaceae(grass)family.Characterizing their genetic homology is crucial for developing new cultivars with enhanced traits.Several wheat genes and gene families have been characterized based on their rice orthologs.Rice–wheat orthology can identify genetic regions that regulate similar traits in both crops.Rice–wheat comparative genomics can identify candidate wheat genes in a genomic region identified by association or QTL mapping,deduce their putative functions and biochemical pathways,and develop molecular markers for marker-assisted breeding.A knowledge of gene homology facilitates the transfer between crops of genes or genomic regions associated with desirable traits by genetic engineering,gene editing,or wide crossing.

Comparative genomic analysis revealed that dietary habits affected the adaptation of Bifidobacterium bifidum to the intestinal tract in different geographic populations

Recent research on the genome of Bifidobacterium bifidum has mainly focused on the isolation sources(intestinal tract niche)recently,but reports on the isolation region are limited.This study analyzed the differences in the genome of B.bifidum isolated from different geographical populations by comparative genomic analysis.Results at the genome level indicated that the GC content of American isolates was significantly higher than that of Chinese and Russian isolates.The phylogenetic tree,based on 919 core genes showed that B.bifidum might be related to the geographical characteristics of isolation region.Furthermore,functional annotation analysis demonstrated that copy numbers of carbohydrate-active enzymes(CAZys)involved in the degradation of polysaccharide from plant and host sources in B.bifidum were high,and 18 CAZys showed significant differences across different geographical populations,indicating that B.bifidum had adapted to the human intestinal environment,especially in the groups with diets rich in fiber.Dietary habits were one of the main reasons for the differences of B.bifidum across different geographical populations.Additionally,B.bifidum exhibited high diversity,evident in glycoside hydrolases,the CRISPR-Cas system,and prophages.This study provides a genetic basis for further research and development of B.bifidum.

Comparative and Phylogenetic Analysis of the Complete Chloroplast Genomes of 19 Species in Rosaceae Family

Rosaceae represents a vast and complex group of species,with its classification being intricate and contentious.The taxonomic placement of many species within this family has been a subject of ongoing debate.The study utilized the Illumina platform to sequence 19 plant species from 10 genera in the Rosaceae.The cp genomes,vary-ing in size from 153,366 to 159,895 bp,followed the typical quadripartite organization consisting of a large single-copy(LSC)region(84,545 to 87,883 bp),a small single-copy(SSC)region(18,174 to 19,259 bp),and a pair of inverted repeat(IR)regions(25,310 to 26,396 bp).These genomes contained 132–138 annotated genes,including 87 to 93 protein-coding genes(PCGs),37 tRNA genes,and 8 rRNA genes using MISA software,52 to 121 simple sequence repeat(SSR)loci were identified.D.arbuscular contained the least of SSRs and did not have hexanotides,A.lineata contained the richest SSRs.Long terminal repeats(LTRs)were primarily composed of palindromic and forward repeat sequences,meanwhile,The richest LTRs were found in Argentina lineata.Except for Argentina lineata,Fragariastrum eriocarpum,and Prunus trichostoma,which varied in gene type and position on both sides of the boundary,the remaining species were found to be mostly conserved according to IR boundary analysis.The examination of the Ka/Ks ratio revealed that only the infA gene had a value greater than 1,indicating that this gene was primarily subjected to positive selection during evolution.Additionally,9 hotspots of variation were identified in the LSC and SSC regions.Phylogenetic analysis confirmed the scientific validity of the genus Prunus L.sensu lato(s.l.)within the Rosaceae family.The separation of the three genera Argentina Hill,Fragariastrum Heist.ex Fabr.and Dasiphora Raf.from Potentilla L.may be a more scientific classification.These results offer fresh perspectives on the taxonomy of the Rosaceae.

Exploring Nominalization in English Abstracts of Applied Linguistics Research Articles:A Comparative Study Between Chinese and International Journals

Researchers around the world strive to communicate new knowledge,primarily via publication,with the abstract being crucial in conveying core insights.Previous research has generally analyzed the discourse features of abstracts from a macro perspective and often employed either outdated texts,such as those over a decade old,or papers written by authors with lower English academic writing proficiency as research material.In this study,we analyzed forty abstracts from leading journals in applied linguistics,evenly split between Chinese and international journals.It revealed that the use of nominalization in abstracts by Chinese and international scholars showed similarities due to the universal academic requirement for conciseness.However,due to cultural and educational differences,each group differed in their respective language choices and nominalization usage.By analyzing the application of nominalization in different cultural contexts,the results of our study offered practical suggestions for crafting abstracts that effectively convey information,thereby,contributing to the broader academic community.

Comparative proteomics analysis reveals the domesticated Lepista sordida primordium differentiation regulation mechanism and the subsequent different development patterns in the pileus and stipe

The wild Lepista sordida is a kind of precious and rare edible fungus.An excellent strain of it by artificial domestication was obtained,which was high-yield and high in iron content.In this study,high-throughput comparative proteomics was used to reveal the regulatory mechanism of its primordium differentiation in the early fruiting body formation.The mycelium before the primordium differentiation mainly expressed high levels of mitochondrial functional proteins and carbon dioxide concentration regulatory proteins.In young mushrooms,the highly expressed proteins were mainly involved in cell component generation,cell proliferation,nitrogen compound metabolism,nucleotide metabolism,glutathione metabolism,and purine metabolism.The differential regulation patterns of pileus and stipe growth to maturity were also revealed.The highly expressed proteins related to transcription,RNA splicing,the production of various organelles,DNA conformational change,nucleosome organization,protein processing,maturation and transport,and cell detoxification regulated the pileus development and maturity.The proteins related to carbohydrate and energy metabolism,large amounts of obsolete cytoplasmic parts,nutrient deprivation,and external stimuli regulated the stipe development and maturity.Multiple CAZymes regulated nutrient absorption,morphogenesis,spore production,stress response,and other life activities at different growth and development stages.

GAN-DIRNet:A Novel Deformable Image Registration Approach for Multimodal Histological Images

Multi-modal histological image registration tasks pose significant challenges due to tissue staining operations causing partial loss and folding of tissue.Convolutional neural network(CNN)and generative adversarial network(GAN)are pivotal inmedical image registration.However,existing methods often struggle with severe interference and deformation,as seen in histological images of conditions like Cushing’s disease.We argue that the failure of current approaches lies in underutilizing the feature extraction capability of the discriminator inGAN.In this study,we propose a novel multi-modal registration approach GAN-DIRNet based on GAN for deformable histological image registration.To begin with,the discriminators of two GANs are embedded as a new dual parallel feature extraction module into the unsupervised registration networks,characterized by implicitly extracting feature descriptors of specific modalities.Additionally,modal feature description layers and registration layers collaborate in unsupervised optimization,facilitating faster convergence and more precise results.Lastly,experiments and evaluations were conducted on the registration of the Mixed National Institute of Standards and Technology database(MNIST),eight publicly available datasets of histological sections and the Clustering-Registration-Classification-Segmentation(CRCS)dataset on the Cushing’s disease.Experimental results demonstrate that our proposed GAN-DIRNet method surpasses existing approaches like DIRNet in terms of both registration accuracy and time efficiency,while also exhibiting robustness across different image types.

Decoding rural connections:A comparative insight into social network analysis in rural communities of China and beyond

Social Network Theory and methods have emerged as pivotal tools for dissecting intricate interdisciplinary issues in rural communities.This study aims to systematically delineate the application characteristics and trends of Social Network Analysis(SNA)in rural community research.Using a twofold approach,we integrate a traditional literature review and CiteSpace bibliometric analysis to assess the application status and evolutionary trends of SNA methods in this context.The key findings include the following:①Chinese research trends:scholars predominantly concentrate on the“three rural”issues(related to agriculture,rural areas,and small-scale farmers)and social support mechanisms for vulnerable rural populations.With policy shifts,rural revitalization,tourism,governance,social trust,and multi-dimensional poverty are poised to emerge as hot topics for the future.For further refinement,we suggest that the application of SNA in rural community research could benefit from content expansion,long-term studies,and innovative modelling techniques.②Research by international scholars has been primarily directed toward the physical and mental health of rural residents,as well as socioeconomic issues.Despite these studies covering a range of typical cases across various nations,a conspicuous lack of thorough,systematic,and prolonged efforts focused on rural community development in specific regions remains.Additionally,health issues affecting rural residents are expected to sustain long-standing and focused international academic attention.This study contributes to a more nuanced understanding of the current applications and potential future directions of SNA in rural community studies,both in China and internationally.

A Comparative Study on Factors Influencing Food Security in China and India

This paper analyzes and compares the key factors influencing food security in two populous countries(China and India),and cate-gorizes them into three types:agricultural production,economic development and income level,and income distribution.Using the prevalence of undernourishment as an indicator of food security,the paper empirically tests the degree of impact of various factors on food security in both countries using Tobit regression and Newey regression methods.The study finds that improving the level of economic development can significantly enhance food security in both countriesꎻreducing the Gini coefficient has a significant impact on India,but not on Chinaꎻincreasing the agricultural production per capita has a much greater effect on China than on India.Therefore,both countries should take measures that are both similar and different according to their national conditions to improve their food security level.

Clinicopathological features and medium-term outcomes of histologic variants of primary focal segmental glomerulosclerosis in adults:A retrospective study

BACKGROUND The Columbia classification identified five histological variants of focal segmental glomerulosclerosis(FSGS).The prognostic significance of these variants remains controversial.AIM To evaluate the relative frequency,clinicopathologic characteristics,and medium-term outcomes of FSGS variants at a single center in Pakistan.METHODS This retrospective study was conducted at the Department of Nephrology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan on all consecutive adults(≥16 years)with biopsy-proven primary FSGS from January 1995 to December 2017.Studied subjects were treated with steroids as a first-line therapy.The response rates,doubling of serum creatinine,and kidney failure(KF)with replacement therapy were compared between histological variants using ANOVA or Kruskal Wallis,and Chi-square tests as appropriate.Data were analyzed by SPSS version 22.0.P-value≤0.05 was considered significant.RESULTS A total of 401 patients were diagnosed with primary FSGS during the study period.Among these,352(87.7%)had a designated histological variant.The not otherwise specified(NOS)variant was the commonest,being found in 185(53.9%)patients,followed by the tip variant in 100(29.1%)patients.Collapsing(COL),cellular(CEL),and perihilar(PHI)variants were seen in 58(16.9%),6(1.5%),and 3(0.7%)patients,respectively.CEL and PHI variants were excluded from further analysis due to small patient numbers.The mean follow-up period was 36.5±29.2 months.Regarding response rates of variants,patients with TIP lesions achieved remission more frequently(59.5%)than patients with NOS(41.8%)and COL(24.52%)variants(P<0.001).The hazard ratio of complete response among patients with the COL variant was 0.163[95%confidence interval(CI):0.039-0.67]as compared to patients with NOS.The TIP variant showed a hazard ratio of 2.5(95%CI:1.61-3.89)for complete remission compared to the NOS variant.Overall,progressive KF was observed more frequently in patients with the COL variant,43.4%(P<0.001).Among these,24.53%of patients required kidney replacement therapy(P<0.001).The hazard ratio of doubling of serum creatinine among patients with the COL variant was 14.57(95%CI:1.87-113.49)as compared to patients with the TIP variant.CONCLUSION In conclusion,histological variants of FSGS are predictive of response to treatment with immunosuppressants and progressive KF in adults in our setup.

Comparative Analysis of Ki-67 Protein as a Proliferative Expression Index in Cutaneous Basal and Squamous Cell Carcinoma in Federal Medical Centre Umuahia, Nigeria

Background: Evaluating the tumor proliferative index helps predict clinical behavior and provides prognostic insights for cutaneous basal cell carcinoma (cBCC) and squamous cell carcinoma (cSCC). Objective: This study aimed to identify differences in the proliferative indices among variants of cBCC and cSCC diagnosed at a tertiary healthcare center. Method: Skin biopsies histologically diagnosed as cBCC and cSCC between 2012 and 2018 at the Federal Medical Centre (FMC) Umuahia, Abia State, Nigeria, were analyzed. Archival formalin-fixed, paraffin-embedded (FFPE) tissue blocks were retrieved along with clinical data, and were prepared on charged microscope slides and the immunohistochemical staining was carried out. The primary antibody used in this study was clone BioCare CRM325C (RM) and adenotonsillar tissue blocks/slides served as positive controls. Ki-67 immunohistochemistry was performed on fresh 4µm sections of the tumor specimens. Results: The application of Ki-67 immunoperoxidase on both BCC and SCC cohort, yielded an intense observable brownish nuclear stain in areas of dense proliferating tumour cells on both cutaneous tumours. The average Ki-67 index for all cSCC cases was 24.7%, with a range of 2.3% - 80%, while the mean for cBCC was 15.8%, ranging from 1.2% - 45.6%. Variants with high proliferative indices were observed in 11.9% of cBCC cases and 29.1% of cSCC cases. Among the low proliferative index category, cSCC accounted for 5.4%, while cBCC represented 14.3%. For mild proliferative indices, cSCC cases made up 7.3% and cBCC, 11.9%. The majority of cases showed moderate proliferative indices, with 61.9% for cBCC and 58.2% for cSCC. Overall, there was a significant difference in proliferative indices between cSCC, cBCC, and their variants. Conclusion: The study found a significantly higher rate of cell proliferation, measured by Ki-67 immunostaining, in cSCC and its variants compared to cBCC. However, certain variants of cBCC also exhibited high Ki-67 expression, indicating they can be as aggressive as some cSCC variants.

Comparative Study of the Reliability and Complexity of Symmetrical and Asymmetrical Cryptosystems for the Protection of Academic Data in the Democratic Republic of Congo

In the digital age, the data exchanged within a company is a wealth of knowledge. The survival, growth and influence of a company in the short, medium and long term depend on it. Indeed, it is the lifeblood of any modern company. A companys operational and historical data contains strategic and operational knowledge of ever-increasing added value. The emergence of a new paradigm: big data. Today, the value of the data scattered throughout this mother of knowledge is calculated in billions of dollars, depending on its size, scope and area of intervention. With the rise of computer networks and distributed systems, the threats to these sensitive resources have steadily increased, jeopardizing the existence of the company itself by drying up production and losing the interest of customers and suppliers. These threats range from sabotage to bankruptcy. For several decades now, most companies have been using encryption algorithms to protect and secure their information systems against the threats and dangers posed by the inherent vulnerabilities of their infrastructure and the current economic climate. This vulnerability requires companies to make the right choice of algorithms to implement in their management systems. For this reason, the present work aims to carry out a comparative study of the reliability and effectiveness of symmetrical and asymmetrical cryptosystems, in order to identify one or more suitable for securing academic data in the DRC. The analysis of the robustness of commonly used symmetric and asymmetric cryptosystems will be the subject of simulations in this article.

Integrated Machine Learning and Deep Learning Models for Cardiovascular Disease Risk Prediction: A Comprehensive Comparative Study

Cardiovascular Diseases (CVDs) pose a significant global health challenge, necessitating accurate risk prediction for effective preventive measures. This comprehensive comparative study explores the performance of traditional Machine Learning (ML) and Deep Learning (DL) models in predicting CVD risk, utilizing a meticulously curated dataset derived from health records. Rigorous preprocessing, including normalization and outlier removal, enhances model robustness. Diverse ML models (Logistic Regression, Random Forest, Support Vector Machine, K-Nearest Neighbor, Decision Tree, and Gradient Boosting) are compared with a Long Short-Term Memory (LSTM) neural network for DL. Evaluation metrics include accuracy, ROC AUC, computation time, and memory usage. Results identify the Gradient Boosting Classifier and LSTM as top performers, demonstrating high accuracy and ROC AUC scores. Comparative analyses highlight model strengths and limitations, contributing valuable insights for optimizing predictive strategies. This study advances predictive analytics for cardiovascular health, with implications for personalized medicine. The findings underscore the versatility of intelligent systems in addressing health challenges, emphasizing the broader applications of ML and DL in disease identification beyond cardiovascular health.