bluuebunny/crossref_metadata_2025 huggingface dataset:
Intact HIV Reservoir in Monocytes Is Associated With Cognitive Function in Virally Suppressed Women With HIV
Authors: Rubin Leah H , Shirk Erin N , Pohlenz Lily , Romero Hayley , Roti Elizabeth , Dastgheyb Raha M , Santiuste Isabel , Coughlin Jennifer M , Brown Todd T , Clements Janice E , Veenhuis Rebecca T
Published: September 2024

Background

Monocytes are susceptible to human immunodeficiency virus (HIV) infection, form HIV reservoirs, and contribute to central nervous system complications (eg, cognitive impairment) in virally suppressed women with HIV (vsWWH). However, it remains unknown if the quality and/or quantity of the monocyte reservoir contributes to cognition in vsWWH.

Methods

Sixty-two vsWWH (mean age = 56.1 years, SD = 7.1; 93% Black, non-Hispanic; all HIV RNA <250 copies/mL) completed a cognitive test battery, blood draw, and whole-blood immunophenotyping. Monocytes and CD4 T cells were isolated from a subset of 53 participants and the HIV reservoir was assessed using cell-specific intact proviral DNA assays (IPDA). Demographically adjusted z-scores were calculated for each outcome using data from participants without HIV in the Women's Interagency HIV Study. Cognitive outcomes of interest included domain-specific and global z-scores.

Results

Thirty-Eight percent of vsWWH had detectable intact HIV genomes in monocytes (median = 21.5 copies/million). Higher levels of intact HIV genomes per million monocytes were associated with poorer verbal memory (delayed recall, r = 0.55, P = .01; recognition, r = 0.46, P = .04), fine motor skills (r = 0.50, P = .03), and global function (r = 0.47, P = .04). Higher levels of intact HIV genomes in monocytes were associated with percent intermediate monocytes (r = 0.60, P = .008), and the ratio of intact per intermediate monocyte was associated with worse memory (r = −0.59, P = .008). There were no associations between CD4 reservoir and cognition.

Conclusions

The number of intact HIV genomes per million monocytes was related to poorer cognition and the percentage of intermediate monocytes. These findings suggest that the presence of HIV genomes in general do not relate to cognitive complications, but intact, and therefore potentially replication-competent HIV, may contribute to cognitive complications in vsWWH.
Illiberal Jewish-Christian Encounters: Political Temporalities in Amish Country Tourism
Authors: Feldman Rachel , Fader Ayala
Published: September 2024

Increasing numbers of ultra-Orthodox Jews are flocking to Lancaster County, Pennsylvania, to participate in Amish country tourism and to consume kosher dairy products, sometimes produced through economic collaborations between Orthodox Jews and local Amish/Mennonite farmers. Through an ethnographic examination of these phenomena, we demonstrate how Amish tourism fosters illiberal interreligious encounters among the triangle of ultra-Orthodox Jewish tourists, Amish/Mennonite farmers, and Christian tour guide mediators. Whereas historically tourism to the Amish was driven by white nostalgic longings for a European peasant past and the American frontier, Orthodox Jews project a nostalgic vision of the Eastern European shtetl onto the Amish and their dairy products. We borrow the concept of political temporalities (Little 2022) to explore an illiberal political temporality formed by the encounter among illiberal religious groups in a recreational tourist setting. Despite different nostalgic projections, these religious groups converged over their visions of an American religious present and future.
Evaluation of circulating immune cells, analytes, and inflammatory markers in sows affected with postpartum dysgalactia syndrome
Authors: Studer Jamie M , Kiefer Zoë E , Koester Lucas R , Johnson Erika M , Schmitz-Esser Stephan , Farkas Attila , Galina Pantoja Lucina , Vonnahme Kimberly A , Greiner Laura L , Keating Aileen F , Baumgard Lance H , Ross Jason W
Published: September 2024

Postpartum dysgalactia syndrome (PDS) is a condition affecting periparturient sows, characterized by a reduction in milk and colostrum synthesis shortly after farrowing. Insufficient milk production results in substantial economic losses due to increased piglet morbidity/mortality and premature sow culling. Since PDS develops within a few days following farrowing, the study objectives were to determine if periparturient immune cell profiles and circulating biomarkers differ in sows affected by PDS. We hypothesized differences in immune cells, circulating analytes, and inflammatory markers would exist at farrowing in sows that subsequently developed PDS compared to healthy herd-mates. Thirty-six sows with PDS symptoms were matched by parity and day of lactation with 36 healthy control (CON) sows. Diagnosis of PDS (timepoint 2) occurred on average 9.25 ± 2.67 d after farrowing. Blood samples and litter weights were collected at farrowing (timepoint 1) and at the onset of clinical PDS (timepoint 2). Piglets from PDS sows had lower average daily gain and higher mortality than piglets from CON (P < 0.01). Aspartate aminotransferase was increased (20%; P ≤ 0.06) in PDS sows compared to CON at both timepoints. Additionally, blood urea nitrogen was increased in PDS sows at timepoint 1 and timepoint 2 (13%; P = 0.08 and 16%; P = 0.01, respectively). At timepoint 2, total protein, globulin, magnesium, and cholesterol were increased (P ≤ 0.03) while γ-glutamyl transferase and albumin were decreased (P ≤ 0.02) in PDS sows. Lipopolysaccharide-binding protein, an inflammatory biomarker, was increased (48%; P = 0.07) at timepoint 2 in PDS compared to CON sows. Collectively, these data indicate PDS sows have altered metabolism and appear immune activated compared to healthy herd-mates, and further investigation is needed to determine if PDS can be predicted at farrowing.
Navigating the Ethical Challenges of Clinical Decision-Making for Patients with Mental Illness Presenting with Self-Inflicted Burns
Authors: DePew Rebekka , Lal Ashima , Sivertsen Elizabeth , Smith Ashley , Johnson Laura S , Pinto Taylor Emily
Published: September 2024

Complex ethical considerations can arise when patients with severe, persistent mental illness (SPMI) present with critical illness resulting from self-injury. This article presents 2 clinical cases in which a patient with SPMI was admitted with severe injuries following self-inflicted burns, with a substantial impact on their anticipated quality of life and challenges directing their medical care. In both cases, the medical teams held discussions with surrogate decision-makers in order to evaluate the patient’s minimal acceptable quality of life and make medical decisions that best reflected the patient’s voice and goals. These cases underscore the importance of advance care planning in SPMI, particularly the appointment of a surrogate decision-maker, and highlight the moral distress that can arise among surgical teams and trainees while caring for patients with illness resulting from self-harm. This article offers a framework for approaching decision-making in critical illness resulting from self-harm for patients with SPMI.
Positive contribution of shoot apex to the growth and flooding tolerance of Hemarthria altissima upon complete submergence
Authors: Niu Hangang , Ayi Qiaoli , Xie Jiaojiao , Zhao Yujie , Luo Xian , Liu Xiangzheng , Wang Ting , Lin Feng , Zeng Bo
Published: September 2024

Flooding events tend to destroy the original flood-intolerant vegetation in riparian zones, but the flood-tolerant species can confront the stress, and contribute to the riparian ecosystem. Grass species, Hemarthria altissima, are usually dominant in the riparian zones. This species is considered as good forage which is usually grazed by livestock or mowed by local people. Therefore, the apical tissues of the plants are often removed, and the plants have to grow without stem apexes, during their life cycle. In this study, we aimed to examine the differences in growth performance of intact versus apex-cut individuals of H. altissima upon complete submergence. Two groups of H. altissima plants (with and without shoot apexes) were treated with dark non-submergence and dark complete submergence conditions for 200 days. During the experiment, we measured plant growth, biomass changes in plant organs, and the consumption of non-structural carbohydrates (NSC) by different tissues. During submergence, shoot elongation stopped, and around six lateral buds were developed averagely by each plant without apexes. This growth performance finally caused 60% decline of NSC in underground parts. The relatively intensive consumption of carbohydrates in submerged apex-removed plants induced the 21% stem length decreased under water, which indicated the decreasing submergence tolerance of plants with shoot apex removed. Therefore, we suggest that when using H. altissima for restoring degraded riparian ecosystems, the shoot apexes should be protected from grazing by livestock or harvesting by local people in order to maintain the submergence tolerance of H. altissima.
Midwives of Invention: Black Healers and Reconciling Worldviews of Wellness in American Emancipation
Authors: Cooper Abigail J
Published: September 2024

Of all the transformations that an enslaved woman hoped for in coming into a refugee camp during the American Civil War, foremost in her mind was surely the transformation of her reproductive labor. Her children could be her own. If we have characteristically viewed the Black Union soldier as serving his country and tugging his family with him into freedom, we should expand the paradigm to include the Black mothers who staked all to give birth out of slavery’s reach and the Black midwives who knew how to keep them all alive. More than an act of recovery, bringing Black wartime midwives’ perspective into view enriches the political emancipation narrative of soldier to citizen as well as the modern medicine narrative of primitive to professional. Midwives imparted intimate knowledge of Black women’s bodies as sites of vitality as well as subjection. Attending to their role brings not only Black female leadership to the fore but also spiritual practice as the locus of power and the location for making meaning of freedom’s birth.
CIDEC/FSP27 exacerbates obesity-related abdominal aortic aneurysm by promoting perivascular adipose tissue inflammation
Authors: Zhu Qing , Luo Da , Li Yining , Yu Liyang , Zhang Zixuan , Ouyang Feng , Li Liangkui , Lu Manxi , Hu Changyong , Dong Yinuo , Ma Chengxin , Liang Yan , Zhao Tong-Jin , Chen Feng-Jung , Li Peng , Yang Tian-Shu
Published: September 2024

Abdominal aortic aneurysm (AAA) is strongly correlated with obesity, partially due to the abnormal expansion of abdominal perivascular adipose tissue (PVAT). Cell death-inducing DNA fragmentation factor-like effector C (CIDEC), also known as fat-specific protein 27 (FSP27) in rodents, is specifically expressed in adipose tissue where it mediates lipid droplet fusion and adipose tissue expansion. Whether and how CIDEC/FSP27 plays a role in AAA pathology remains elusive. Here, we show that FSP27 exacerbates obesity and angiotensin Ⅱ (Ang Ⅱ)-induced AAA progression. FSP27 deficiency in mice inhibited high-fat diet-induced PVAT expansion and inflammation. Both global and adipose tissue-specific FSP27 ablation significantly decreased obesity-related AAA incidence. Deficiency of FSP27 in adipocytes abrogated matrix metalloproteinase-12 (MMP12) expression in aortic tissues. Infiltrated macrophages, which partially colocalize with MMP12, were significantly decreased in the FSP27-deficient aorta. Mechanistically, knockdown of Fsp27 in 3T3-L1 adipocytes inhibited C–C motif chemokine ligand 2 (CCL2) expression and secretion through a c-Jun N-terminal kinase (JNK)-dependent pathway, thereby leading to reduced induction of macrophage migration, while Cidec overexpression rescued this effect. Overall, our study demonstrates that CIDEC/FSP27 in adipose tissue contributes to obesity-related AAA formation, at least in part, by enhancing PVAT inflammation and macrophage infiltration, thus shedding light on its significance as a key regulator in the context of obesity-related AAA.
Reionization after JWST: a photon budget crisis?
Authors: Muñoz Julian B , Mirocha Jordan , Chisholm John , Furlanetto Steven R , Mason Charlotte
Published: September 2024

New JWST observations are revealing the first galaxies to be prolific producers of ionizing photons, which we argue gives rise to a tension between different probes of reionization. Over the last two decades, a consensus has emerged where star-forming galaxies are able to generate enough photons to drive reionization, given reasonable values for their number densities, ionizing efficiencies $\xi _{\rm ion}$ (per unit ultraviolet luminosity), and escape fractions $f_{\rm esc}$. However, some new JWST observations infer high values of $\xi _{\rm ion}$ during reionization and an enhanced abundance of earlier ($z\gtrsim 9$) galaxies, dramatically increasing the number of ionizing photons produced at high z. Simultaneously, recent low-z studies predict significant escape fractions for faint reionization-era galaxies. Put together, we show that the galaxies we have directly observed ($M_{\rm UV} < -15$) not only can drive reionization, but would end it too early. That is, our current galaxy observations, taken at face value, imply an excess of ionizing photons and thus a process of reionization in tension with the cosmic microwave background and Lyman-$\alpha$ forest. Considering galaxies down to $M_{\rm UV}\approx -11$, below current observational limits, only worsens this tension. We discuss possible avenues to resolve this photon budget crisis, including systematics in either theory or observations.
Real-world treatment patterns and outcomes of patients with advanced melanoma treated with nivolumab plus relatlimab
Authors: Thakker Sach , Belzberg Micah , Jang Sekwon , Al-Mondhiry Jafar
Published: September 2024

The use of programmed death-1 (PD-1) inhibitors has been a pivotal advancement in treating advanced melanoma, yet their efficacy is limited. The approval of relatlimab (RELA), a lymphocyte activation gene 3 protein (LAG-3) antibody, in combination with nivolumab (NIVO), a PD-1 inhibitor, marked a significant stride toward enhancing treatment efficacy for metastatic and unresectable stage 3 and 4 melanoma. This combination has been shown to synergistically improve antitumor activity and effector T-cell activity in the tumor microenvironment, despite limited data on real-world outcomes. Our retrospective review at a tertiary cancer center of patients with stage 3 and 4 melanoma treated with NIVO-RELA revealed an overall response rate (ORR) of 39%, with notable improvements in median PFS and ORR, especially in first-line treated patients. Our study highlights the superior efficacy of NIVO-RELA over previous reports, demonstrating its significant potential in the treatment landscape of advanced melanoma.
Evolutionary Systems Biology Identifies Genetic Trade-offs in Rice Defense against Aboveground and Belowground Attackers
Authors: Dunivant Taryn S , Godinez-Vidal Damaris , Perkins Craig , Lee Madelyn G , Ta Matthew , Groen Simon C
Published: September 2024

Like other plants, wild and domesticated rice species (Oryza nivara, O. rufipogon, and O. sativa) evolve in environments with various biotic and abiotic stresses that fluctuate in intensity through space and time. Microbial pathogens and invertebrate herbivores such as plant-parasitic nematodes and caterpillars show geographical and temporal variation in activity patterns and may respond differently to certain plant-defensive mechanisms. As such, plant interactions with multiple community members may result in conflicting selection pressures on genetic polymorphisms. Here, through assays with different aboveground and belowground herbivores, the fall armyworm (Spodoptera frugiperda) and the southern root-knot nematode (Meloidogyne incognita), and comparison with rice responses to microbial pathogens, we identify potential genetic trade-offs at the KSL8 and MG1 loci on chromosome 11. KSL8 encodes the first committed step toward the biosynthesis of either stemarane-type or stemodane-type diterpenoids through the japonica (KSL8-jap) or indica (KSL8-ind) allele. Knocking out KSL8-jap and CPS4, encoding an enzyme that acts upstream in diterpenoid synthesis, in japonica rice cultivars increased resistance to S. frugiperda and decreased resistance to M. incognita. Furthermore, MG1 resides in a haplotype that provided resistance to M. incognita, while alternative haplotypes are involved in mediating resistance to the rice blast fungus Magnaporthe oryzae and other pests and pathogens. Finally, KSL8 and MG1 alleles are located within trans-species polymorphic haplotypes and may be evolving under long-term balancing selection. Our data are consistent with a hypothesis that polymorphisms at KSL8 and MG1 may be maintained through complex and diffuse community interactions.
Combining in situ and ex situ plankton image data to reconstruct zooplankton (>1 mm) volume and mass distribution in the global ocean
Authors: Soviadan Yawouvi Dodji , Dugenne Mathilde , Drago Laetitia , Biard Tristan , Trudnowska Emilia , Lombard Fabien , Romagnan Jean-Baptiste , Jamet Jean-Louis , Kiko Rainer , Gorsky Gabriel , Stemmann Lars
Published: September 2024

Plankton size spectra are important indicators of the ecosystem state, yet such measurements are typically biased by the available sampling methods. Here, we combined individual size measurement from two zooplankton imaging approaches—in situ observation by the Underwater Vision Profiler5 and Multinet-collection supplemented by ex situ imaging via Zooscan—obtained in the global ocean, to calculate zooplankton normalized biovolume size spectra (NBSS) for all organisms larger than 1 mm. The reconstructed NBSS combining both datasets resulted in increased biomass estimates by adding organisms poorly sampled by either of the methods. The optimal values measured by both methods are used to reconstruct the zooplankton biovolume and biomass distributions. The reconstructed slopes appeared steeper and closer to those measured only by the UVP5 (+7.6%) and flatter than those obtained only from the Multinet (−20%), particularly in tropical and temperate latitudes. The main difference in tropical and temperate NBSS from the two devices is due to the fragile rhizarians that were not accounted for when using net data. When possible, we suggest using in situ and ex situ technologies together, and we provide potential indications on how to correct for missing components of the community when only one method is available.
Nuclear factor-Y–polycomb repressive complex2 dynamically orchestrates starch and seed storage protein biosynthesis in wheat
Authors: Chen Jinchao , Zhao Long , Li Haoran , Yang Changfeng , Lin Xuelei , Lin Yujing , Zhang Hao , Zhang Mengxia , Bie Xiaomin , Zhao Peng , Xu Shengbao , Seung David , Zhang Xiansheng , Zhang Xueyong , Yao Yingyin , Wang Dongzhi , Xiao Jun
Published: September 2024

The endosperm in cereal grains is instrumental in determining grain yield and seed quality, as it controls starch and seed storage protein (SSP) production. In this study, we identified a specific nuclear factor-Y (NF-Y) trimeric complex in wheat (Triticum aestivum L.), consisting of TaNF-YA3-D, TaNF-YB7-B, and TaNF-YC6-B, and exhibiting robust expression within the endosperm during grain filling. Knockdown of either TaNF-YA3 or TaNF-YC6 led to reduced starch but increased gluten protein levels. TaNF-Y indirectly boosted starch biosynthesis genes by repressing TaNAC019, a repressor of cytosolic small ADP-glucose pyrophosphorylase 1a (TacAGPS1a), sucrose synthase 2 (TaSuS2), and other genes involved in starch biosynthesis. Conversely, TaNF-Y directly inhibited the expression of Gliadin-γ-700 (TaGli-γ-700) and low molecular weight-400 (TaLMW-400). Furthermore, TaNF-Y components interacted with SWINGER (TaSWN), the histone methyltransferase subunit of Polycomb repressive complex 2 (PRC2), to repress TaNAC019, TaGli-γ-700, and TaLMW-400 expression through trimethylation of histone H3 at lysine 27 (H3K27me3) modifications. Notably, weak mutation of FERTILIZATION INDEPENDENT ENDOSPERM (TaFIE), a core PRC2 subunit, reduced starch but elevated gliadin and LMW-GS contents. Intriguingly, sequence variation within the TaNF-YB7-B coding region was linked to differences in starch and SSP content. Distinct TaNF-YB7-B haplotypes affect its interaction with TaSWN-B, influencing the repression of targets like TaNAC019 and TaGli-γ-700. Our findings illuminate the intricate molecular mechanisms governing TaNF-Y–PRC2-mediated epigenetic regulation for wheat endosperm development. Manipulating the TaNF-Y complex holds potential for optimizing grain yield and enhancing grain quality.
Comparing Regional and National Climate Policy Preferences: An Analysis of Political Parties in the Basque Country and Catalonia
Authors: Enguer Joan
Published: September 2024

Recent research has uncovered positive connections between parties’ center-periphery and climate policy preferences when they compete in regional elections, with pro-periphery parties using climate concerns to bolster their territorial claims. However, the particular significance of climate change at the regional level, due to its more direct impacts in this arena, raises questions about the extent to which these parties replicate similar behaviors in national elections. To address this gap, this article analyzes the manifestos of parties that secured representation during the 2016 and 2019 Spanish general elections, as well as in the regional elections held during overlapping periods in Catalonia (2017 and 2021) and the Basque Country (2016 and 2020). The empirical findings reveal that parties with stronger pro-decentralization and pro-independence stances allocate more content to climate change and adopt more favorable positions on this issue in their regional manifestos compared to their national counterparts.
Moral reconciling at career launch: politics, race, and occupational choice
Authors: Clair Matthew , Hunt Sophia
Published: September 2024

Recent research suggests that college-educated young adults, especially those who are politically liberal and/or racially marginalized, exhibit moral reservations about their intended occupations. How do they justify entering occupations that conflict with their morals, and with what consequences? This article examines the case of 74 mostly liberal prospective law school students from a range of racial backgrounds followed over 2 years. In interviews at career launch, respondents criticized the legal profession for its perceived perpetuation of inequality and violence. Despite their moral reservations, they articulated three occupational justification narratives for attending law school: lifting up (exceptional lawyering); leveraging out (legal education for nonlawyer aspirations); and leaning in (conscientious class mobility/maintenance). These narratives differentiate between morally ‘good’ and ‘bad’ occupational domains—a cultural-cognitive process we term moral reconciling. We theorize how moral reconciling at career launch charts young adults down different early career trajectories, with implications for occupational sorting and change.
Antibiotic Cold War and Ernst Chain’s Visit to China in 1961
Authors: Li Yanchang
Published: September 2024

The Cold War severely hindered the flow of antibiotic knowledge and medicines between different factions. With the continuous blockade by the USA and the deterioration of the Sino–Soviet relationship, China made some geopolitical efforts in its science diplomacy. British Nobel Laureate Ernst Chain’s month-long visit to China in 1961 was one such effort. During and after the visit to China, Chain gave the Chinese some sound advice and helped establish academic connections. Through reconstructing the wary contacts between the two sides—before, during and after the visit—this article illustrates the PRC’s predicament on antibiotics and its efforts to escape from it, elaborates Chain’s visit and the British response in the context of the antibiotic Cold War, analyses the reasons why Chain was invited and demonstrates the cooperation and confrontation between and within the factions over antibiotics during Cold War, as well as the porousness of the Iron Curtain.
The Intensity of Local Immigration Conflict: Variations across Space and Time
Authors: de Wilde Marieke
Published: September 2024

Many municipalities in the United States have experienced conflict over immigration, but the intensity of these conflicts varies. It is important to understand why one place experiences more conflict than another, because highly intense conflicts can have big impacts on local responses to immigration. This paper contributes to the immigration literature by constructing a measure of conflict intensity to assess what factors affect the intensity of local conflicts over immigration. A dataset on local conflict over day laborers in California in the period 1985–2020 is employed to assess how conflicts vary by time and space. This paper argues that demographics and politics do not play a major role when it comes to conflict intensity, while contact mediated by time and space is a decisive factor. Initial contact can boost conflict intensity as it may magnify differences and breed feelings of fear. However, endured encounters provide the opportunity to develop connections and allow communities to get familiar with immigrant day laborers.
O01 LISTEN TO YOUR HEART AND MIND: A FEASIBILITY STUDY ON COMBINED SCREENING OF RAISED BLOOD PRESSURE, ATRIAL FIBRILLATION, COGNITIVE IMPAIRMENT AND HEARING LOSS
Authors: Tan Isabella , Sharma Mridula , Morgan Catherine , Brodaty Henry , Gnanenthiran Sonali R , Numbers Katya , Liu Hueiming , Ouyang Menglu , Kitterick Padraig , Incerti Paola , Schutte Aletta E
Published: September 2024

Background and Objective.

Detection rates of hypertension continues to be suboptimal worldwide. The risk of hypertension increases substantially in older adults aged ≥65 years, a group also at increased risk of atrial fibrillation (AF), cognitive decline and hearing loss—all factors associated with hypertension. This pilot study aimed to 1) implement a combined screening strategy for these health conditions, and 2) assess feasibility and acceptability of the combined screening.

Methods.

Adults aged ≥65 years without a prior diagnosis of cognitive impairment and dementia were invited to attend a combined screening appointment through advertisements posted in university and community group newsletters and noticeboards. Participants underwent blood pressure (BP) and AF screening using an oscillometric BP monitor with AF detection (Microlife WatchBP Office 2G), cognitive assessment (General Practitioner Assessment of Cognition, GPCOG), and audiometric testing. A subset of participants was invited to participate in a post-study process evaluation interview.

Results.

Of the 35 participants (age 73±6 years, 51% females), 26 (74%) had hypertension (on antihypertensive medication: n=20; measured: n=6; unaware: n=2; uncontrolled: n=4). Possible AF was detected in two participants and seven had possible cognitive decline (GPCOG score <9). Hearing loss was detected in 13 participants. Interviews (n=16, 50% females) revealed that combined screening was acceptable and feasible as participants felt it was “convenient”, “saves time”, “a brilliant idea”, and that “… conditions are related and therefore appropriate to be together”. Most participants were already aware of their hypertension status, thus screening did not result in increased hypertension awareness except for one with uncontrolled hypertension who proceeded to purchase a home BP monitor. One participant with detected AF visited a cardiologist and confirmed non-AF arrhythmia. All interviewees found the appointment duration (approximately 60-75 minutes) was not too long nor too taxing.

Conclusions.

Combined screening in older adults with increased cardiovascular risk is feasible and acceptable and should be considered for future screening programs in older adults.
O19 CAUSAL INFERENCE FOR HYPERTENSION DETECTION WITH WEARABLE DEVICES
Authors: Ding Xiaorong
Published: September 2024

Background and Objective:

Hypertension is a leading cause of cardiovascular disease and premature death worldwide and it puts a heavy burden on the healthcare system. It is, therefore, very important to detect and evaluate hypertension and related cardiovascular events so as for early prevention, detection and management. Hypertension can be evaluated in real time with wearable noninvasive cardiac signals, such as electro-cardiogram (ECG) and photoplethysmography (PPG). Most previous studies predicted hypertension from ECG and PPG signals with extracted features that are correlated with hypertension. However, correlation is sometimes unreliable and may be affected by confounding factors. In this study, we explored the feasibility of predicting the risk of hypertension using causal inference methods. Additionally, we paid special attention to and verified the reliability and effectiveness of causality compared to correlation.

Methods:

Firstly, we constructed causal graphs by the Greedy Equivalence Search algorithm, and then applied causal strategies to obtain the optimal causal graph. Finally, we used machine learning classification algorithms to achieve hypertension prediction.

Results:

The machine learning classification models achieve great classification performance, with accuracy being 0.89, precision being 0.92, recall being 0.82, and F1-score being 0.87, which outperformed the correlation-based hypertension detection.

Conclusions:

The results indicate that the causal inference-based approach can potentially clarify the mechanism of hypertension detection with noninvasive signal and effectively detect hypertension. In addition, the results also re-veal that causality is more reliable and effective compared to correlation.
O20 CURRENT 24-HOUR AMBULATORY BLOOD PRESSURE TECHNOLOGIES SHOULD BE RECONSIDERED AS THE REFERENCE STANDARD FOR VALIDATION OF CUFFLESS BLOOD PRESSURE DEVICES
Authors: Bothe Tomas Lucca , Pilz Niklas , Patzak Andreas , Heinz Viktor , Sharman James E. , Picone Dean S.
Published: September 2024

Background and Objective:

Recommendations for the validation of cuffless blood pressure (BP) devices were recently released by the European Society of Hypertension (ESH). In this recommendation, 24-hour ambulatory BP monitoring (ABPM) is the reference standard for a newly proposed ‘awake-asleep’ accuracy test. However, this reference standard may be inappropriate because ABPM is subject to measurement insecurities, and it is unknown if it would pass the awake-asleep test. Therefore, the aim of this study was to determine if ABPM itself would pass the awake-asleep test recommended for validation of cuffless BP devices.

Methods:

Dual arm, simultaneous ABPM were recorded using two identical cuff-based devices (TM-2430, A&D, Japan) among 46 healthy adults (22±2.3 years; 54% female). The awake-asleep test was defined as the difference between the left arm ABPM minus right arm ABPM for assessing the change in BP between awake-asleep time (ESH recommendations: mean difference ± SD ≤5±8 mmHg, correlation r>0.7 for test and reference values; awake-asleep BP components calculated based on personalized sleeping times). Measurement artefacts were identified by analysis of the cuff deflation pressure curves and hydrostatic pressure differences (body position) between the cuffs.

Results:

ABPM did not pass the awake-asleep test due to higher than acceptable measurement variability for systolic BP, -0.1±8.6 mmHg, r=0.69 and partially met requirements for diastolic BP, -0.7±5.9 mmHg, r=0.63. After correction for measurement artefacts and hydrostatic pressure differences, ABPM passed the awake-asleep test for systolic BP (-1.7±5.0 mmHg, r=0.76) but still did not meet requirements for diastolic BP due to insufficient correlation (r=0.64).

Conclusion:

In this analysis, ABPM itself did not meet the awake-asleep test criteria recommended by the ESH. Using current ABPM technologies as a reference standard for cuffless BP validation protocols may need to be reconsidered and they need improvement before use for this purpose. Improving ABPM through better measurement artefact detection could be an initial solution which would also improve its value for clinical decision making.
O65 SARCOPLASMIC CALCIUM ATPASE (SERCA) PROTEOLYSIS BY MATRIX METALLOPROTEINASE (MMP)-2 CONTRIBUTES TO VASCULAR DYSFUNCTION IN EARLY HYPERTENSION
Authors: Castro Michele , Blascke de Mello Marcela , Parente Juliana , Pernomian Laena , de Oliveira Isadora , Pedersoli Carina , Awata Wanessa , Tirapelli Carlos , Arantes Eliane , Tostes Rita , Schulz Richard
Published: September 2024

Background and objective:

Hypertension-induced increased matrix metalloproteinase (MMP)-2 activity proteolyzes extra- and intracellular proteins in aortas and contributes to vascular dysfunction. MMP-2 proteolyzes sarcoplasmic reticulum calcium ATPase (SERCA) in the heart during ischemia and reperfusion injury, thus impairing cardiac function. SERCA activity is also impaired in the arteries of hypertensive animals. We investigated whether hypertension-induced increased MMP-2 activity in aorta contributes to SERCA proteolysis, vascular remodeling and dysfunction.

Methods:

Aortas from male Sprague-Dawley (SD) rats, incubated or not with angiotensin II (AngII) and MMP inhibitors, ONO-4817 or doxycycline (Doxy), were used for zymography and co-immunoprecipitation of SERCA with MMP-2. Male SD rats were also submitted to two kidney-one clip (2K-1C) or Sham surgery and treated with Doxy from third to seventh day post-surgery. Systolic blood pressure (SBP) was assessed basally and daily by tail-cuff plethysmography. After 7 days, aortas were collected for gel and in situ zymography, western blot to SERCA, ATPase activity assay, vascular reactivity to phenylephrine and acetylcholine, Ki-67 immunofluorescence and hematoxylin/eosin stain. A7r5 cells were incubated or not with AngII, in the presence or absence of SERCA inhibitor, tapsigargin, to assess intracellular calcium concentrations.

Results:

AngII increased MMP-2 activity in aortas and MMP-2 co-immunoprecipitated with SERCA. SBP was increased in 2K-1C rats and Doxy did not reduce it, but decreased MMP-2 activity and prevented SERCA proteolysis in aortas. Intracellular calcium concentrations were increased in A7r5 cells incubated with AngII and/or SERCA inhibitor, tapsigargin. Cross sectional area, media to lumen ratio and Ki-67 were all increased in the aortas of hypertensive rats and Doxy decreased Ki-67 cell proliferation. In 2K-1C rats, arterial contraction to phenylephrine was accentuated but Doxy ameliorated only the impaired relaxation to acetylcholine.

Conclusion:

Doxy reduced MMP-2 activity in the aortas of 2K-1C rats and prevented the ATPase activity impairment and MMP-2-induced SERCA proteolysis and vascular dysfunction.
O40 TELOMERE LENGTH AS A BIOMARKER FOR KIDNEY HEALTH: EVIDENCE FROM A MENDELIAN RANDOMISATION STUDY
Authors: Akinnibosun Olutope Arinola , Nguyen H. , Xu X. , Prestes P. R. , Eales J. , Samani N. J. , Tomaszewski M. , Charchar F. J.
Published: September 2024

Background and Objective:

Chronic kidney disease (CKD) is a significant public health challenge, often progressing undetected until advanced stages. Early detection through biomarkers can enhance CKD management and improve patient outcomes. Previous studies suggested a link between telomeres and kidney health, but these results were inconsistent. This study aims to clarify the association between telomere length, kidney function and disease, and assess its causality using Mendelian randomisation (MR).

Methods:

Using the UK Biobank data, we examined the relationship between leukocyte telomere length (LTL) and kidney health. We performed multiple linear and logistic regression analyses using estimated glomerular filtration rate (eGFR) measures and reported kidney disease diagnoses, adjusting for age, sex, white blood cell count, body mass index, and hypertension. The causality of associations was tested using MR with established genetic instruments.

Results:

338,143 participants were included in our analysis. The cohort had an average age of 56.52 years, with 54.41% being females. LTL was associated with eGFR from serum creatinine (eGFRcrea, beta = 0.001, p <0.01), serum cystatin C (eGFRcys, beta = 0.004, p <0.0001), and their combination (eGFRcreacys, beta = 0.003, p <0.0001). Additionally, longer LTL was associated with reduced odds of CKD (OR = 0.94 [95% CI 0.93-0.96], p <0.0001). Significant associations were also observed between LTL and acute renal failure (OR = 0.95 [95% CI 0.93-0.97], p <0.0001), and hypertensive kidney disease (OR = 0.91 [95% CI 0.86-0.96], p <0.001). MR analysis supported a causal effect of LTL on eGFRcrea (Effect size = 0.006, Bonferroni corrected p = 0.04). However, no causal effect was observed between LTL and CKD or other kidney diseases. Bi-directional MR analysis revealed that the relationship between LTL and kidney function is unidirectional.

Conclusions:

Longer LTL correlates with better kidney function and reduced kidney disease risk. MR findings suggest a potential causal relationship between LTL and kidney function, highlighting telomeres as promising biomarkers for early detection of CKD.
O53 RENOMETABOLIC DISORDER IN EXPERIMENTAL RAT MODEL OF PCOS IS REVERSED VIA INHIBITION OF PYRUVATE DEHYDROGENASE KINASE 4
Authors: Areloegbe Stephanie Esosa Joy , Fafure Adedamola , Olaniyi Kehinde
Published: September 2024

Background and Objective:

Chronic Kidney disorders is a global public health problem, including in women with polycystic ovarian syndrome (PCOS), and is characterized by renal fibrosis, nephrotoxicity and glomerulonephritis, which increases the possibility of renal failure and organ transplant. Pyruvate dehydrogenase kinase 4 (PDK4) has been implicated in mitochondria dysfunction, contributing to metabolic dysregulation in different organs, including kidney. Studies have shown the metabolic regulatory impact of probiotics in human and experimental models. Hence, the present study investigated the therapeutic potential of probiotics on renometabolic disorders associated with experimental PCOS model. The study in addition elucidates the probable involvement of PDK4 in PCOS-associated renometabolic disorders.

Methods:

Eight-week-old nulliparous female Wistar rats were randomly allotted into four groups (n=6). Letrozole (1 mg/kg) was used to induce PCOS for 3 weeks. Thereafter, probiotics (2 x 107 CFU) was administered for 6 weeks, uninterruptedly. Biochemical parameters, histological analysis, immunohistochemistry and gene expression were carried out with appropriate methods.

Results

Experimental PCOS rats were characterized with elevated circulating testosterone and the presence of multiple ovarian cysts. In addition, rat with PCOS also manifested insulin resistance, increased plasma urea and creatinine levels, increased renal Gamma glutamyltransferase (GGT), MDA, NF-kappa B, TNF-alpha, TGF-beta 1, caspase-6, HDAC2, while a decrease in G6PD, GSH, renal NO and eNOS, when compared with animals in the control rats. These were associated with elevated level of PDK4 in the renal tissue. However, administration of probiotics ameliorates these renal/metabolic abnormalities.

Conclusion:

Altogether, the results from the present study revealed that probiotics ameliorates renal dysfunction in PCOS via downregulation of PDK4.
O56 NIGHTTIME BLOOD PRESSURE REFERENCE VALUES FOR AMBULATORY BLOOD PRESSURE MONITORING AND THEIR RELATIONSHIP WITH AGE
Authors: Álvarez-Montoya Diego , Gallo-Villegas Jaime , Aristizábal-Ocampo Dagnovar
Published: September 2024

Background and Objective:

Nocturnal hypertension is characterized by elevated blood pressure (BP) levels during sleep (systolic blood pressure [SBP]>120 mmHg or diastolic blood pressure [DBP]>70 mmHg) as measured by 24-hour ambulatory blood pressure monitoring (24-h ABPM) (ESH 2023 guidelines). With aging, there is a gradual decline in renal function and vascular health, leading to changes in BP patterns. This study seeks to evaluate the necessity of age-specific cutoff points in defining hypertension, particularly during nocturnal hours.

Methods:

A cross-sectional study was conducted, involving 3,220 patients without hypertension, defined by 24-hour BP values, who were not using any antihypertensive medications and were referred for 24-h ABPM. Patients with a body mass index (BMI) ≥30 kg/m2 were excluded. The sleep period was defined as spanning from midnight to 6 am. Reference percentiles were established and juxtaposed with standard references. To determine the significance of age-specific cutoff points for defining nocturnal hypertension, the ESH 2023 reference was compared with the 95th percentile (P95) for age.

Results:

Among the participants, 64.6% were female, with an average age of 51.0±15.0 years, BMI of 25.0±2.7 kg/m2, nocturnal SBP of 106.4±9.0 mmHg (P95=121.8 mmHg), and nocturnal DBP of 66.0±5.0 mmHg (P95=74.3 mmHg). Normal distribution was observed for both SBP and DBP (Jarque Bera test). Nocturnal SBP exhibited a “J” shaped curve concerning age, whereas the average DBP remained relatively stable. Significant differences were noted for SBP across different age groups (P value <0.00001). Proposed cutoff points for mean nocturnal SBP were suggested as follows: i) P95 <60 years=120 mmHg; ii) P95 60-70 years=125 mmHg; and iii) P95 >70 years=130 mmHg (Figure). A reference of 75 mmHg was proposed as the cutoff point for mean nocturnal DBP.

Conclusions:

The study highlights age-related variations in the P95 of mean nocturnal SBP, while DBP remains relatively stable across age groups. Consequently, we propose new cutoff points for defining these parameters.
O33 ARE METABOLICALLY HEALTHY OBESE INDIVIDUALS REALLY A BENIGN CARDIOVASCULAR GROUP? AN ANALYSIS OF 162,590 PARTICIPANTS WITH MEASURES OF ARTERIAL STIFFNESS IN UK BIOBANK
Authors: Ananda Roshan , Solomon Bethelemen , Ray Kausik
Published: September 2024

Background and Objective:

There is conflicting evidence as to whether so called metabolically healthy but overweight and obese individuals are at increased cardiovascular risk or mortality. We assessed whether metabolic health correlates with vascular health among these individuals using arterial stiffness as a proxy for vascular health and cardiovascular risk.

Methods:

Participants in UK Biobank with body-mass index (BMI) and arterial stiffness index (ASI) recorded between 2006 and 2010, and free from cardiovascular diseases and not underweight (BMI<18.5 kg/m2) were included. Participants were stratified by BMI and metabolic abnormalities (hypertension, diabetes, dyslipidaemia). The primary outcome was the severity of ASI analysed using multivariate-adjusted linear regression.

Results:

Of 162,590 participants, 55.0% were female, their mean age was 57 years (SD 8), 42.5% were overweight and 24.4% were obese. Within the normal BMI strata, 50.7% had ≥1 metabolic abnormality. Compared to individuals with normal BMI and no metabolic abnormalities (reference group), increased BMI or metabolic abnormalities were similarly associated with higher ASI: normal BMI with metabolic abnormalities (adjusted β-coefficient 0.35;95%CI 0.30 to 0.40), overweight without metabolic abnormalities (β 0.32; 95%CI 0.26 to 0.37). Obese individuals with no metabolic abnormalities had higher ASI (β 0.65; 95%CI 0.57 to 0.74) but was lower than overweight participants with metabolic abnormalities (β 0.80; 95%CI 0.75 to 0.84). Obese participants with metabolic abnormalities had the highest ASI (β 1.07; 95%CI 1.02 to 1.12) among all six metabolic combinations, p<0.001 for each vs ref group. Sensitivity analysis suggested higher ASI with increasing number of metabolic abnormalities within BMI categories.

Conclusions:

Excess weight and metabolic abnormalities, are independently associated with adverse measures of vascular health to a similar degree, suggesting that the so called metabolically health overweight and obese are not benign groups. Primary prevention strategies should be considered in overweight, or obese individuals even if metabolic abnormalities are absent.
O80 A HIGH 24-HOUR URINE SODIUM-TO-POTASSIUM RATIO IS ASSOCIATED WITH WORSE RENAL OUTCOME
Authors: Olde Engberink Rik , Zwager Charlotte , Kwok Kevin , Slagmolen Famke , Vogt Liffert , van Vliet Myrthe
Published: September 2024

Background and Objective:

Low sodium and high potassium intake are advised to control blood pressure and may improve long term cardiorenal outcomes. The optimal potassium intake for patients with chronic kidney disease remains to be defined and. We investigated whether the 24-hour urine sodium-to-potassium ratio (Na/K-ratio), which incorporates estimates of both sodium and potassium intake, could predict long-term renal outcome.

Methods:

We selected adult outpatients of a Dutch tertiary hospital who collected at least one 24-hour urine collection between 1998-2023. Patients with a history of dialysis or kidney transplantation were excluded. We examined the need for persistent renal replacement therapy (RRT), defined as dialysis or kidney transplantation, using Cox-regression. The association between the 24-hour urine Na/K-ratio and the estimated glomerular filtration rate (eGFR) slope was assessed using linear regression in patients who had ≥3 eGFR measurements available in ≥3 years, adjusted for age, sex, baseline eGFR, diabetes mellitus and hypertension. In the Cox-regression analysis, we additionally adjusted for the interaction between the 24-hour urine Na/K-ratio and baseline eGFR. Hypertension was defined as a clinical diagnosis or an office blood pressure ≥140/90 mmHg.

Results: We included 720 patients aged 50±15 years, of whom 52% were male, 58% had hypertension and 31% diabetes mellitus. The baseline eGFR was 64±34 ml/min/1.73m2. The 24-hour urine Na/K ratio was 2.5±1.2 in a median number of 1 (IQR=1-2) urine collection. During a median follow-up of 11.2±14.0 years, 29% of patients needed RRT. The median annual eGFR decline was 1.51 (IQR=0.49-3.98) ml/min/1.73m2. Every unit increase in 24-hour urine Na/K-ratio was associated with a 19% higher risk for RRT (HR 1.19, 95% CI 1.03-1.39; p=0.02) and an additional 0.44 ml/min/1.73m2 (95% CI -0.83, -0.04; p=0.03) annual eGFR decline.

Conclusions:

This study suggests that higher 24-hour urine Na/K-ratio is associated with faster kidney function decline and the need for RRT, independent of hypertension, in a selected group of outpatients with available 24-hour urine measurements.