bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Neurofilament Light Chain Levels Correlate With Skin Inflammation and Scratch Lesions in Patients With Pruritus
Authors: Mueller Simon M. , Zhu Jie , Brandt Oliver , Navarini Alexander A. , Yaldizli Oezguer , Papadopoulou Athina , Kuhle Jens 
Published: October 2024

Background: Neurofilament light chain (NfL) has been identified as a biomarker in neuroaxonal injury. Cutaneous nerve injury resulting from inflammation and/or forced scratching may also potentially affect serum NfL (sNfL) levels.Objectives: We aimed to explore the relationship between sNfL levels and the severity of skin inflammation and scratch lesions in patients with pruritus.Methods: In this cross‐sectional pilot study, we measured the sNfL levels of 10 patients with pruritus of different aetiologies, and calculated age‐ and BMI‐adjusted sNfL percentiles based on a normative database consisting of 4532 control individuals. Next, we investigated the relationship between the levels of sNfL and the severity of skin inflammation and scratching injuries in these patients using a newly‐created Skin Inflammation and Scratch Lesions (SISL) score.Results: A positive correlation was observed between sNfL levels and the severity of skin inflammation and scratch lesions as measured by the SISL score (Spearman’s rho = 0.70, p = 0.031). When correlated separately, both the “skin inflammation only” and “scratch lesions only” scores correlated positively with sNfL levels (Spearman’s rho = 0.68, p = 0.031; Spearman’s rho = 0.66, p = 0.041, respectively).Conclusions: sNfL may be a potential biomarker for cutaneous nerve injury associated with skin inflammation and/or scratching.
Abstract 22: Evaluation of the effects of CD8 knock-out on cognitive decline in the TAC-induced hypertension mouse model
Authors: Pacella Jacopo , Fardella Valentina , Migliaccio Agnese , Pallante Fabio , Carnevale Daniela , Lembo Giuseppe , Carnevale Lorenzo 
Published: October 2024

Hypertension is one of the main risk factors for cognitive impairment and dementia. We and others demonstrated the role of immunoinflammatory challenges in the establishment of cerebral injury following hypertension, highlighting a major role of inflammatory cytokines as interferon-gamma (IFN-γ) and finding increased parenchymal infiltration of CD8+ T cells.
To establish the mechanistic role of these cells in cognitive impairment we subjected mice lacking CD8 cells (CD8 KO) and matched controls to aortic coarctation (TAC) and performed advanced neuroimaging analyses with a dedicated 7T small animal MRI, evaluating perfusion, brain volumes, and white matter microstructural integrity. Cognitive performance was evaluated at 4 weeks using the Morris Water Maze (MWM) test.
Brain perfusion analyses shown protection from cerebral hypoperfusion in TAC CD8 KO mice compared to TAC WT mice (TAC WT vs TAC KO: 108 vs 148 ml/100g/min, p=0.0298) (Figure A). CD8 KO show preserved microstructural structure at DTI MRI, a typical trait of cerebral injury in clinical and experimental hypertension (Fimbria Fractional Anisotropy, TAC WT vs TAC KO: 0.45 vs 0.54, p=0.0210) , and show no a preserved cognition at MWM (Figure B), with a preserved learning curve at acquisition trial and a preserved memory retention capability evidenced at the probe trial (TAC WT vs TAC KO: 16,4 vs 32.2 seconds spent in platform quadrant, p=0.0014).
The rescue from cerebral injury evidenced at MRI and the absence of cognitive impairment in CD8 KO mice demonstrate the pivotal role of CD8+ lymphocytes in the pathogenesis of hypertension-induced cognitive impairment.
Abstract MP19: Hypertension Prevalence Among Youth aged 8–19 years in a National Survey — United States, 2017–2020
Authors: Sekkarie Ahlia , Zhou Wen , Lundeen Elizabeth , Imoisili Omoye , Jackson Sandra , Kumar Ashutosh , He Siran , Loustalot Fleetwood 
Published: October 2024

Hypertension in youth tracks into adulthood and has long-term negative health effects. In 2017, the American Academy of Pediatrics released new Clinical Practice Guidelines on pediatric hypertension. The guidelines updated blood pressure (BP) thresholds and age-sex-height percentile references for youth 1–17 years. Pediatric hypertension prevalence estimates since the new guideline are lacking.
This study aims to provide the latest nationally representative prevalence estimates of elevated BP and hypertension in youth aged 8–19 years, total and stratified by age group, sex, race and ethnicity, and body mass index (BMI) category. For adolescents aged 13–17 years, both percentile-based thresholds and adult BP thresholds are available in the guidelines. We therefore compared adult BP thresholds for elevated BP (120–129/<80 mmHg) and hypertension (≥130/≥80 mmHg) with percentile thresholds in adolescents.
We used data from 2017–March 2020 National Health and Nutrition Examination Survey to obtain a sample of 2600 youth after excluding those with no BMI or BP measures. Prevalence estimates of elevated BP and hypertension were 8.7% (95% CI: 6.9-10.6) and 5.4% (95% CI: 4.0-6.7), respectively. Estimates were higher among males and increased with age (Table). Youth with severe obesity had the highest prevalence of hypertension. Hispanic youth had the lowest prevalence of elevated BP. In adolescents, elevated BP prevalence was similar using percentile thresholds (11.9%, 95% CI: 9.3-15.1) and the adult threshold (10.8%, 95% CI: 8.5-13.7). Hypertension prevalence in adolescents was also similar for percentile thresholds (4.8%, 95% CI: 3.1-7.6) and the adult threshold (4.8%, 95% CI: 2.0-7.5).
Our findings suggest ongoing concern of elevated BP and hypertension among youth in the US. Either percentile or adult based thresholds for determining high BP could be used among adolescents by researchers. Knowledge of current national estimates can inform policies and interventions to support cardiovascular health in youth.
Abstract MP30: The Role of CD20+ B cells in Mediating Hypertension in Preeclampsia during Pregnancy
Authors: Campbell Nathan , Hankins Miriam , Zheng Baoying , Demesa Alexandra , Turner Ty , Deer Evangeline , Amaral Lorena , Morris Rachael , Lamarca Babbette 
Published: October 2024

Pre-eclampsia (PE), new-onset hypertension after the 20
th
week of pregnancy alongside other organ dysfunction, endothelial dysfunction, and immune activation. We have previously shown that CD19+ B cell adoptive transfer causes a PE phenotype in athymic nude rats. CD19 is present on all B cells including plasma cells. CD20 is absent from plasma cells but is present on mature B2 and memory B cells. The objective of this study was to determine if CD20+ B cells, excluding plasma cells, cause maternal hypertension, fetal growth restriction, and endothelial dysfunction.

Three hundred thousand placental CD20+ B Cells from normal pregnant (NP) or PE patients were isolated by magnetic separation and injected i.p. into nude athymic rats on gestational day (GD) 12. On GD18, carotid catheters were inserted. On GD19, mean arterial pressure (MAP) was measured and blood and tissues were collected. Preproendothelin (PPET) expression was quantified in kidney and placental tissues using RT-PCR. A student’s t-test was used for statistical analysis.
Participants whose placental B cells were used in this study had similar age, pre-pregnancy BMI, and diastolic BP on admission. PE participants had elevated systolic BP at admission (135±4 vs 120±4 mmHg) and delivery (139±6 vs 124±3 mmHg) as well as diastolic BP at delivery (79±4 vs 68±2 mmHg). PE participants also had trending decreases in fetal weight (2621±323 vs 3202±102 g) and gestational age (36±1 vs 39±0 weeks) at delivery.
MAP increased from 107±4 mmHg (n=8) in the NP recipient rats to 123±2 mmHg (n=8, p<0.01) in the PE recipient rats. Pup and placental weights were unchanged following adoptive transfer. Renal PPET expression increased by 2.595±0.61 fold (ΔΔct) in PE recipient rats (n=7, p<0.05) compared to NP recipient rats (n=7). Placental PPET expression was unchanged following adoptive transfer.
CD20+ B cells from women with PE contribute to hypertension and endothelial dysfunction during pregnancy. This data supports the important role of B cells in the development of PE and improves our understanding of the population of B cells responsible for contribution to the disease.
Abstract P223: Impact Of Dynamic Or Static Training On Flow-Mediated Dilatation Following Prolonged Head-Down Tilt Bedrest
Authors: Kloesges Lukas , Hoenemann Jan , Hoffmann Fabian , Bechler Sophie , Timmermans Finn , De Boni Laura , Gauger Peter , Mulder Edwin , Moestl Stefan , Heusser Karsten , Odainic Alexandru , Schmidt Susanne , Schmitz Marie-Therese , Heise Tim , Halbach Marcel , Baldus Stephan , Laurie Steve , Lee Stuart , Macias Brandon , Jordan Jens , Tank Jens 
Published: October 2024

Cardiovascular deconditioning, cephalad fluid shifts, and altered sympathetic activity in weightlessness may elicit changes in vascular structure and function akin to vascular ageing. Head-down tilt bedrest is an established terrestrial model for weightlessness and elicits similar cardiovascular responses. We hypothesized that 30 days head-down tilt bedrest (HDTBR) worsens flow mediated dilation (FMD), a non-invasive endothelial function marker, and that daily orthostatic stimuli or physical exercise attenuates the response.

Fourty-seven healthy individuals (20 women, age 35±9 years, BMI 23.7±2.6 kg/m
2
) were assigned to 30 days of strict HDTBR and divided into four groups: Daily 6 hours of upright sitting (positive control, n=11); 6 hours of -25 mmHg lower body negative pressure (n=12); 60 minutes of supine cycling followed by 6 hours of thigh cuff venous occlusion 6 days per week (n=12), or no countermeasure (negative control, n=12). We measured upper arm blood pressure and heart rate 5 days before and immediately after bedrest. We assessed plasma volume by carbon monoxide-rebreathing 2 days before and on day 28 of bedrest. We determined FMD of the brachial artery 5 days before, on day 28 of bedrest, and after 13-day recovery. We collected blood samples to measure pro- and anti-inflammatory cytokines.

Heart rate was elevated after bedrest (p<0.0001) but remained constant in seated and cycling groups (seated MD 5±2 /min, cycling MD 5±2, p=0.0051). Systolic blood pressure increased in all groups (MD 4±1 mmHg, p=0.0004). Diastolic blood pressure was higher post-bedrest in the control group (MD 8±2 mmHg, p=0.0002) but remained constant in the countermeasure groups. Plasma volume was reduced after bed rest (MD -400±37 ml, p<0.0001) but maintained in the cycling group (MD 147±72 ml, p=0.0001). FMD did not differ between groups, but was higher at bedrest (MD 1.9±0.8 %, p=0.0481), whereas recovery values did not differ from baseline. Resting brachial artery diameter tended to be higher at bedrest (p=0.0876). Cytokines revealed no clinically relevant inflammatory response.
Head-down tilt bedrest-induced cardiovascular deconditioning, which was not completely abolished by any countermeasure, paradoxically increased flow-mediated brachial vasodilation. Additional cardiovascular risk factors may be required to express endothelial dysfunction in the face of reduced physical activity.
Abstract P321: Team-Based Care: A Winning Strategy for Managing Hypertension
Authors: Sherpa Mingma , Anand Renata 
Published: October 2024

Hypertension is a serious health condition that can lead to heart disease. Despite available methods for managing hypertension, blood pressure (BP) control in the US is declining, highlighting a gap between expert recommendations and real-world practice. Our clinic initiative aimed to create a specialized workflow and team, which included resident physicians, pharmacists, and health counselors focused on underserved communities. We also provided blood pressure cuffs and encouraged patients to monitor their blood pressure at home. This approach, coupled with the 'Knowing Your Numbers' campaign, has significantly improved outcomes, promoted continuity of care, and built resilience within care communities for vulnerable populations.
110 patients with poorly controlled hypertension were provided with BP monitors to track their blood pressure. Demographic data and office BP readings before and after the monitors were distributed were collected from patient charts. The results were analyzed using descriptive statistics and paired t-tests.
The study included 58% female participants with an average age of 59. The racial distribution was 51% black, 35% white, 10% unreported/unknown, 2% Asian, and 2% American Indian/Alaska native. Most participants (70%) reported feeling empowered in their healthcare. Female participants who received a blood pressure cuff and engaged in shared decision-making experienced a significant reduction in their systolic BP by 17.6 mm Hg (P<0.05) and diastolic BP by 7.9 mm Hg (P<0.05). In comparison, males saw a reduction in their systolic BP by 10.6 mm Hg (P<0.05) and diastolic BP by 7.1 mm Hg (P<0.05). The average weight for both genders falls under the obese category, with females having an average BMI of 32.4 and males having an average BMI of 32.6.
Providing loan-free blood pressure monitoring cuffs for clinic patients or blood pressure machines through insurance can improve patient engagement and health outcomes. Removing cost barriers can significantly impact in-office blood pressure reduction, monitoring, and patient satisfaction. This initiative highlights the importance of implementing patient-centered approaches to healthcare that address the financial and logistical barriers that can hinder effective hypertension management. Future research is needed to confirm these findings, but this study supports implementing similar programs to improve patients' health and well-being.
Abstract P355: Multiomic Analyses Reveal Sex-specific Mechanisms Governing Cardiac Fibrosis.
Authors: Farrugia Gabriella , Harper Rebecca , Krstevski Crisdion , Lelliott Patrick , Hsu Ian , Dona Malathi , Harrison Thomas , Kiriazis Helen , Donner Daniel , Pinto Alexander 
Published: October 2024

Cardiac fibrosis—the deposition of excess extracellular matrix in the heart—occurs during pathological cardiac remodelling and precedes cardiac dysfunction and heart failure. Experimental and clinical data show that both cardiac fibrosis and heart failure exhibit sex-specific differences, particularly in the absence of ischemic injury. However, no study to date has systematically examined this, or the hormonal mechanisms driving these differences, using high-resolution single-cell and spatial omics.
To address this gap, we applied single-cell and spatial omics to map the quality and distribution of non-ischemic cardiac fibrosis in human and mouse hearts. Further, to query the impact of sex hormones on cardiac fibrosis development, we analysed hearts of castrated (CAST) and ovariectomized (OVX) mice, which were ectopically infused with angiotensin-II (AngII).
Using single cell transcriptomic data of hypertensive mouse hearts, we identified a fibroblast population driving cardiac fibrosis with a unique gene signature. We confirmed the presence of these cells in multiple mouse models and aged donor human hearts. Spatial mapping of fibrosis showed a sex-specific distribution of fibrosis, specifically in the development of perivascular fibrosis in the heart. Hypertensive male mice exhibited extensive perivascular fibrosis, and coronary artery adventitial hypertrophy, which was absent in females. However, OVX resulted in the development of perivascular fibrosis in hypertensive mice suggesting a cardioprotective role of estrogen. Confirming these observations, spatial transcriptomic analyses showed distinct fibrotic signatures driving perivascular and interstitial fibrosis, and transcriptomic differences between females and males. Our findings provide fundamental new insights towards the importance of biological sex in driving cardiac fibrosis, pointing to new mechanisms that may be manipulated to ameliorate development of heart failure.
Abstract P364: Chromatin Interactions Between Regulatory Elements Influence Gene Expression in Human iPSC-Derived Endothelial and Vascular Smooth Muscle Cells
Authors: Liu Pengyuan , Liu Yong , Pandey Rajan , Ray Atrayee , Huang Jing , Qiu Qiongzi , Greene Andrew , Cowley Allen , Geurts Aron , Rao Sridhar , Liang Mingyu 
Published: October 2024

Most SNPs associated with blood pressure (BP) are located in noncoding regions of the human genome, where they may regulate gene expression in BP-relevant cell types. However, the mechanisms by which these SNPs influence BP regulation are unclear. To address this, we developed comprehensive epigenomic landscapes in human induced pluripotent stem cell (iPSC)-derived endothelial cells (iECs) and vascular smooth muscle cells (iVSMCs), incorporating DNA methylation analysis (RRBS), transcriptome analysis (RNA-seq), chromatin state profiling (ATAC-seq), and chromatin interaction mapping (Micro-C).
We identified 5301, 8916, and 6046 chromatin loops in iECs and 5329, 7598, and 5228 loops in iVSMCs at 4, 8, and 16 kb resolutions (FDR < 0.05) respectively based on the Micro-C analysis. Remarkably, 82.4% and 83.8% of these chromatin contact regions in iECs and iVSMCs, respectively, harbored at least one known regulatory element such as an enhancer, promoter, or transcription factor binding site. Notably, 109 and 119 BP-associated SNPs were found within the chromatin contact regions of iECs and iVSMCs, respectively.
We further investigated chromatin contact regions that involved interactions of regulatory elements. In both iECs and iVSMCs, lower methylation levels were observed in chromatin contact regions involving promoter-promoter (PP) and enhancer-promoter (EP) interactions, compared to enhancer-enhancer (EE), enhancer-transcription factor binding site (ET), and promoter-transcription factor binding site (PT) interactions. Additionally, greater chromatin accessibility was observed in chromatin contact regions involving PP and EP interactions. BP-associated SNPs were significantly enriched in chromatin contact regions involving PP and EP interactions. Moreover, genes proximal to chromatin contact regions involving PP or EP interactions exhibited higher expression than those near EE or other regulatory element interactions.
These findings offer new insights into how chromatin interactions between regulatory elements define transcriptional states in human endothelial and vascular smooth muscle cells, providing a novel basis for understanding the genetic regulation of BP.
Abstract P367: Cross-Species Epigenomic Maps of Intergenic Loci for Hypertension and Blood Pressure
Authors: Tutaj Monika , Lin Chien-Wei , Ray Atrayee , Yang Chun , Stelloh Cary , Liu Pengyuan , Liu Yong , Widlansky Michael , Greene Andrew , Geurts Aron , Cowley Allen , Liang Mingyu , Rao Sridhar , Kwitek Anne 
Published: October 2024

Many non-coding SNPs identified in Genome-Wide Association Studies (GWAS) likely affect BP-related gene expression through epigenetic mechanisms. This study analyzes the comparative genomic and epigenomic landscapes in human and rat kidney tissues, including kidney proximal tubule (PT) and medullary thick ascending limb (mTAL), focusing on the major challenge of identifying conserved regulatory elements in intergenic regions. The purpose of our study is to identify BP gene regulatory elements in intergenic regions that are conserved from human to rat for
in vivo
validation and mechanistic studies. Our ultimate goal is to generate high-resolution, genome-wide epigenomic maps of key BP-relevant tissues, using ATAC-seq, Hi-C, CUT&Tag, DNA methylation profiling and RNA-seq.

We are creating visualization hubs for human and rat, integrating our data within the UCSC Genome Browser environment. UCSC contains extensive data for humans but very little for rats, particularly for the updated genome assemblies. To address this gap, we integrated our results with data from the Rat Genome Database (RGD). To date, we harmonized ATAC-seq data from human and rat PT and mTAL and displayed these data in RGD’s JBrowse2 genome browser for unique comparative genome views.
Based on our initial analysis of data density and intensity, we are developing a novel pattern recognition algorithm to identify epigenomic marks that are conserved across rat and human genomes. Existing algorithms predominantly focus on the conservation of coding genes, gene families, and genomic sequences. Here, average normalized peak intensities for ATAC-seq data across tissues were subject to canonical correlation between human and rat to identify conserved epigenomic patterns within the BP GWAS loci.

Here we present an example of a human BP locus in the intergenic region between
NPR3
and
TARS1
on chromosome 5 which has a region of conserved synteny with rat chromosome 2. Comparative analysis and visualization of this region show significant correlation between ATAC-seq peaks from rat and human PT and mTAL at this locus, with predicted conserved regulatory elements. These visualizations can uncover novel biological insights and identify potential regulatory targets for intervention. This work underscores the importance of advanced visualization techniques in understanding hypertension pathogenesis, facilitating cross-species comparisons, and enhancing the utility of genomic databases.
Abstract P402: The Impact of Preeclampsia Education in Rural Communities
Authors: Hurd-Jackson Ashley , Santillan Mark , Boeldt Kara , Faro Elissa , Santillan Donna 
Published: October 2024

Preeclampsia (PE) and other hypertensive disorders of pregnancy are the leading cause of maternal and perinatal morbidity and mortality. There are 4,000 PE cases/year in IA. Rural counties are at a significantly higher risk of pregnancy-related mortality. A lack of PE education regarding signs and symptoms may contribute to this risk. PE complications and mortality may be preventable with early implementation of patient education on preeclampsia during pregnancy. Our objective was to determine if implementing a magnet as an intervention increases patients' knowledge of the signs and symptoms of PE.
A magnet that includes common signs and symptoms of PE was designed to serve as an educational visual aid for patients. Pregnant patients ≥18 years old from two hospitals in Northwest IA were recruited. A pre-survey was given at a prenatal appointment prior to receiving the magnet. The post-magnet survey was administered during admission for delivery. The control group did not receive the magnet. Pre- and post-surveys asked about preeclampsia and current understanding, if they received a magnet, if it was referenced, number of healthcare visits, questions during visits about PE, and if they were diagnosed with PE.

Between 8/23-5/24, 62 pre- and 83 post-magnet surveys were collected. Statistical analyses were performed using a 95% confidence interval with p<0.05 considered significant. Ages ranged from 18-42 years old, with majority Caucasian patients (69% in pre-survey and 58% in post-survey). Levels of highest education obtained ranged from 4
th
grade to doctoral degree, with the majority completing high school as the highest level of education (29%).The magnet group rated their level of understanding of PE as good to excellent which was higher than both pre-intervention and control groups. Both control and magnet groups identified more symptoms and complications of PE on the post-survey compared to the pre-survey. Both control and magnet groups were noted to have increased discussions about preeclampsia with their physician. Lastly, both groups had increased knowledge on what to do if they developed symptoms on the post-survey compared to pre-survey responses. Of the magnet group, 71% thought receiving a magnet was helpful to increase awareness of PE.

Implementation of a magnet increased patient literacy regarding the signs, symptoms, and complications of PE, discussions with physicians, and knowledge of what to do if patients develop symptoms of PE.