bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical proof of concept for VivoVec, a lentiviral-based platform for in vivo CAR T-cell engineering
Authors: Michels Kathryn R , Sheih Alyssa , Hernandez Susana A , Brandes Alissa H , Parrilla Don , Irwin Blythe , Perez Anai M , Ting Hung-An , Nicolai Christopher J , Gervascio Timothy , Shin Seungjin , Pankau Mark D , Muhonen Mason , Freeman Jessica , Gould Sarah , Getto Rich , Larson Ryan P , Ryu Byoung Y , Scharenberg Andrew M , Sullivan Alessandra M , Green Shon
Published: March 2023

Background

Chimeric antigen receptor (CAR) T-cell therapies have demonstrated transformational outcomes in the treatment of B-cell malignancies, but their widespread use is hindered by technical and logistical challenges associated with ex vivo cell manufacturing. To overcome these challenges, we developed VivoVec, a lentiviral vector-based platform for in vivo engineering of T cells. UB-VV100, a VivoVec clinical candidate for the treatment of B-cell malignancies, displays an anti-CD3 single-chain variable fragment (scFv) on the surface and delivers a genetic payload that encodes a second-generation CD19-targeted CAR along with a rapamycin-activated cytokine receptor (RACR) system designed to overcome the need for lymphodepleting chemotherapy in supporting successful CAR T-cell expansion and persistence. In the presence of exogenous rapamycin, non-transduced immune cells are suppressed, while the RACR system in transduced cells converts rapamycin binding to an interleukin (IL)-2/IL-15 signal to promote proliferation.

Methods

UB-VV100 was administered to peripheral blood mononuclear cells (PBMCs) from healthy donors and from patients with B-cell malignancy without additional stimulation. Cultures were assessed for CAR T-cell transduction and function. Biodistribution was evaluated in CD34-humanized mice and in canines. In vivo efficacy was evaluated against normal B cells in CD34-humanized mice and against systemic tumor xenografts in PBMC-humanized mice.

Results

In vitro, administration of UB-VV100 resulted in dose-dependent and anti-CD3 scFv-dependent T-cell activation and CAR T-cell transduction. The resulting CAR T cells exhibited selective expansion in rapamycin and antigen-dependent activity against malignant B-cell targets. In humanized mouse and canine studies, UB-VV100 demonstrated a favorable biodistribution profile, with transduction events limited to the immune compartment after intranodal or intraperitoneal administration. Administration of UB-VV100 to humanized mice engrafted with B-cell tumors resulted in CAR T-cell transduction, expansion, and elimination of systemic malignancy.

Conclusions

These findings demonstrate that UB-VV100 generates functional CAR T cells in vivo, which could expand patient access to CAR T technology in both hematological and solid tumors without the need for ex vivo cell manufacturing.
Kantowski–Sachs cosmology in scalar-torsion theory
Authors: Paliathanasis Andronikos
Published: March 2023

In the context of scalar-torsion theory we investigate the evolution of the cosmological anisotropies for a Kantowski–Sachs background geometry. We study the phase-space of the gravitational field equations by determining the admitted stationary points and study their stability properties. For the potential function of the non-minimally coupled scalar field we assume the exponential and the power-law functions. Finally, we make use of Poincare variables in order to investigate the existence of stationary points at the infinity regime of the dynamics.
Linear Codes and Linear Complementary Pairs of Codes Over a Non-Chain Ring
Authors: Cheng Xiangdong , Cao Xiwang , Qian Liqin
Published: March 2023

Let [Formula: see text] be an odd prime number, [Formula: see text] for a positive integer [Formula: see text], let [Formula: see text] be the finite field with [Formula: see text] elements and [Formula: see text] be a primitive element of [Formula: see text]. We first give an orthogonal decomposition of the ring [Formula: see text], where [Formula: see text] and [Formula: see text] for a fixed integer [Formula: see text]. In addition, Galois dual of a linear code over [Formula: see text] is discussed. Meanwhile, constacyclic codes and cyclic codes over the ring [Formula: see text] are investigated as well. Remarkably, we obtain that if linear codes [Formula: see text] and [Formula: see text] are a complementary pair, then the code [Formula: see text] and the dual code [Formula: see text] of [Formula: see text] are equivalent to each other.
Real-time Pricing-based Resource Allocation in Open Market Environments
Authors: Mishra Pankaj , Moustafa Ahmed , Ito Takayuki
Published: March 2023

Open market environments consist of a set of participants (vendors and consumers) that dynamically leave or join the market. As a result, the arising dynamism leads to uncertainties in supply and demand of the resources in these open markets. In specific, in such uncertain markets, vendors attempt to maximise their revenue by dynamically changing their selling prices according to the market demand. In this regard, an optimal resource allocation approach becomes immensely needed to optimise the selling prices based on the supply and demand of the resources in the open market. Therefore, optimal selling prices should maximise the revenue of vendors while protecting the utility of buyers. In this context, we propose a real-time pricing approach for resource allocation in open market environments. The proposed approach introduces a priority-based fairness mechanism to allocate the available resources in a reverse-auction paradigm. Finally, we compare the proposed approach with two state-of-the-art resource allocation approaches. The experimental results show that the proposed approach outperforms the other two resource allocation approaches in its ability to maximise the vendors’ revenue.
FASTER: A Dynamic Fairness-assurance Strategy for Session-based Recommender Systems
Authors: Wu Yao , Cao Jian , Xu Guandong
Published: March 2023

When only users’ preferences and interests are considered by a recommendation algorithm, it will lead to the severe long-tail problem over items. Therefore, the unfair exposure phenomenon of recommended items caused by this problem has attracted widespread attention in recent years. For the first time, we reveal the fact that there is a more serious unfair exposure problem in session-based recommender systems (SRSs), which learn the short-term and dynamic preferences of users from anonymous sessions. Considering the fact that in SRSs, recommendations are provided multiple times and item exposures are accumulated over interactions in a session, we define new metrics both for the fairness of item exposure and recommendation quality among sessions. Moreover, we design a dynamic
F
airness-
A
ssurance
ST
rategy for s
E
ssion-based
R
ecommender systems (
FASTER
).
FASTER
is a post-processing strategy that tries to keep a balance between item exposure fairness and recommendation quality. It can also maintain the fairness of recommendation quality among sessions. The effectiveness of
FASTER
is verified on three real-world datasets and five original algorithms. The experiment results show that
FASTER
can generally reduce the unfair exposure of different session-based recommendation algorithms while still ensuring a high level of recommendation quality.
Lazy Load Scheduling for Mixed-criticality Applications in Heterogeneous MPSoCs
Authors: Kloda Tomasz , Gracioli Giovani , Tabish Rohan , Mirosanlou Reza , Mancuso Renato , Pellizzoni Rodolfo , Caccamo Marco
Published: March 2023

Newly emerging multiprocessor system-on-a-chip (MPSoC) platforms provide hard processing cores with programmable logic (PL) for high-performance computing applications. In this article, we take a deep look into these commercially available heterogeneous platforms and show how to design mixed-criticality applications such that different processing components can be isolated to avoid contention on the shared resources such as last-level cache and main memory.

Our approach involves software/hardware co-design to achieve isolation between the different criticality domains. At the hardware level, we use a scratchpad memory (SPM) with dedicated interfaces inside the PL to avoid conflicts in the main memory. At the software level, we employ a hypervisor to support cache-coloring such that conflicts at the shared L2 cache can be avoided. In order to move the tasks in/out of the SPM memory, we rely on a DMA engine and propose a new CPU-DMA co-scheduling policy, called 
Lazy Load
, for which we also derive the response time analysis. The results of a case study on image processing demonstrate that the contention on the shared memory subsystem can be avoided when running with our proposed architecture. Moreover, comprehensive schedulability evaluations show that the newly proposed
Lazy Load
policy outperforms the existing CPU-DMA scheduling approaches and is effective in mitigating the main memory interference in our proposed architecture.
Photochemically-Activated p-Type CuGaO2 Thin Films for Highly-Stable Room-Temperature Gas Sensors
Authors: Lin Pei-Te , Yu Chih-Ying , Ho Sin-Huei , Pan Shiuan-Wei , Jhang Jyun-Siang , Zhang Yi-Xun , Zhang Yo-Lun , Hsieh Tian-Tsz , Wang Hao-Chien , Hsueh Wen-Jeng , Huang Chun-Ying
Published: March 2023

The photochemical activation process is a promising way to operate metal oxide gas sensors at room temperature. However, this technique is only used in n-type semiconductors. In this study, we report a highly stable p-type copper gallium oxide (CuGaO2) gas sensor fabricated through the facile sol-gel process. The sensor is capable of detecting O3 gas at room temperature, and its gas response can be further enhanced by ultraviolet (UV) activation. The highest gas response of 7.12 to 5 ppm O3 gas at a UV intensity of 10 mW cm−2 is achieved at room-temperature. In addition, the CuGaO2 sensor shows excellent long-term stability, with a degradation of approximately 3% over 90 days. These results strongly support the solution-processed CuGaO2 as a good candidate for room-temperature gas sensors.
Development of a Core Set of Self-Management Support Needs of Esophageal Cancer Patients: Results from a Delphi Study among Healthcare Professionals
Authors: Adriaans Daniëlle J. M. , Heesakkers Fanny B. M. , Teijink Joep A. W. , Dierick-van Daele Angelique T. M. , Haveman Jan Willem , Sosef Meindert N. , van den Berg Jan Willem , van Det Marc J. , Hartgrink Henk H. , Jansen Walther J. B. M. , Rosman Camiel , Lagarde Sjoerd M. , van Esser Stijn , van der Harst Erwin , van Laarhoven Hanneke W. M. , Nieuwenhuijzen Grard A. P.
Published: March 2023

Objective. We aimed to gain consensus on HCPs’ perspectives on self-management support information needs of patients with esophageal cancer during the preoperative phase. Methods. Based on the literature, observations of clinical consultations, and hospital patient information leaflets, a survey was created. HCPs were surveyed twice about their opinion on importance of information, from “not essential” to “absolutely essential,” using Delphi methods. Topics were included in the second round if predetermined criteria were met. To be included in the final list, topics had to meet criteria for consensus and stability. Results. 64 information items and 6 sources of support were identified. Survey response rates were 59% (68 out of 116, first round) and 75% thereafter. The final list included 33 topics, including logistical information, expectations for future health condition, complications, follow-up care, nutrition during treatment, and nutrition during recovery as topics with 100% agreement. Consensus on the source of support was reached for face-to-face contact, written information, information video, and a case manager. Conclusion. This study provides a list of important topics, from the perspectives of HCPs, to guide the systematic provision of education to support EC patients’ self-management during the preoperative phase. Additionally, the most preferred sources of support were face-to-face contact and a case manager.
Ginsenoside Rg1 Improves Inflammation and Autophagy of the Pancreas and Spleen in Streptozotocin-Induced Type 1 Diabetic Mice
Authors: Zong Yi , Yu Weihua , Hong Hanghang , Zhu Zhiqiang , Xiao Wenbo , Wang Kewu , Xu Guoqiang
Published: March 2023

Background. Ginsenoside Rg1 (Rg1) is one of the key bioactive components of the precious Traditional Chinese Medicine that has been used to treat diabetes in China. Ginsenosides have been reported to protect diabetics from tissue damage, inflammation, and insulin resistance. Type 1 diabetes (T1D) is an organ-specific autoimmune disease that occurred frequently among adolescents over the world, its development was related to inflammation and β-cells immunodeficiency. The aim of this study is to explore the biological mechanism of Rg1 on inflammation and autophagy of β-cells in T1D and its therapeutic potential. Methods. The model of T1D mice was established by injecting Streptozotocin (STZ) (55 mg/kg) or citric acids once a day for 5 days and from the fourth day of injection, mice were administered with Rg1 (20 mg/kg) or saline by gavage once a day for 12 days. Hematoxylin-eosin staining, immunofluorescence, ELISA, quantitative real-time PCR, and Western blot were used to observe the histopathological changes, inflammatory factor levels, and autophagy markers after administration of ginsenoside Rg1. Results. Compared to the T1D mice, Rg1 improved the weight (

p
<
0.05

) and blood glucose (

p
<
0.01

) of mice, advanced the injury and apoptosis of β-cells in islets (

p
<
0.01

), and markedly inhibited the protein expression degrees of CD45, CXCL16, ox-LDL, and TF in the pancreas and spleens (

p
<
0.01

), also activated the degrees of insulin in serum (

p
<
0.01

). Besides, in T1D mice’ pancreas and spleen, Rg1 markedly repressed the IL-1β, TNF-α, and NOS2 mRNA levels (

p
<
0.05

or

p
<
0.01

), inhibited the CXCL16, NF-κB, and TF proteins (

p
<
0.05

or

p
<
0.01

), while elevating the ratio of LC3 II/I (

p
<
0.01

) and P62 (

p
<
0.05

) protein level. Conclusions. This study proved that Rg1 protected mice against T1D possibly by improving islet injury and tissue inflammation, raising serum insulin, and tissue autophagy marker.
The Identification of Immune-Related Biomarkers for Osteoarthritis Immunotherapy Based on Single-Cell RNA Sequencing Analysis
Authors: Tan Zhe , Chen Rong , Lin Hanyu , Wang Hong
Published: March 2023

Osteoarthritis (OA) is a chronic musculoskeletal disease affecting approximately 500 million people worldwide. Globally, OA is one of the most common and leading causes of disability. Several genetic factors are involved in OA, including inherited genes, genetic susceptibility, and genetic predisposition. As the pathogenesis of OA is unknown, there are almost no effective treatments available to prevent the onset or progression of the disease. In recent years, many researchers focused on bioinformatics analysis to explore new biomarkers for the diagnosis, treatment, and prognosis of human diseases. In this work, we obtain the traditional RNA sequencing data of OA patients from the GEO database. By performing the differentially expressed analysis, we successfully obtain the genes that are closely associated with the OA. In addition, the Venn diagram was applied to evaluate the genes that are involved in OA and immune-related genes. The protein-protein interaction analysis was further conducted to explore the hub genes. The single-cell RNA sequencing analysis was used to evaluate the expression distribution of the MMP, VEGFA, SPI1, and IRF8 in synovial tissues of patients with osteoarthritis. Finally, the GSVA enrichment analysis discovered the potential pathways involved in OA patients. Our analysis provides a new direction for the exploration of the process of OA patients. In addition, VEGFA may be considered a promising biomarker in OA.
Serum Bilirubin Levels and Disease Severity in Patients with Pneumoconiosis
Authors: Peng You-Fan , Deng Jun-Hua , Huang Xiao-Ying , Zhang Qing-Song
Published: March 2023

Aim. To investigate the association between serum bilirubin and disease severity in patients with pneumoconiosis. Methods. The study comprised 45 patients with pneumoconiosis retrospectively; all pneumoconiosis patients were classified into I, II, and III stage according to the radiological severity. Results. Serum direct bilirubin levels were significantly lower in III stage pneumoconiosis patients than those in I/II stage (p = 0.012) but not serum indirect bilirubin. Serum direct bilirubin was negatively correlated with radiological severity in patients with pneumoconiosis (r = −0.320; p = 0.032); by multiple linear-regression analysis, we observed that serum direct bilirubin levels had independent association with radiological severity in patients with pneumoconiosis (beta = −0.459; p = 0.005). Conclusions. Serum direct bilirubin levels are negatively associated with disease severity in patients with pneumoconiosis.
Houttuynia cordata Polysaccharide Ameliorates Chronic Inflammation-Induced Intestinal Impairment by Zonula Occludens-1 in Rats
Authors: Song Ye-Hao , You Hui-Ting , Sang Ting , Yao Yu-Fei , Chen Su-Mei , Wan Min , Li Wen-Juan
Published: March 2023

This study aimed to investigate the protective effects of Houttuynia cordata polysaccharide (HCP) against chronic intestinal inflammation in rats that were subjected to low-dose lipopolysaccharide once weekly for 6 weeks. Here, administration of HCP significantly restored morphological changes in the intestine along with enhancement of antioxidant enzymes including superoxide dismutase, catalase, and glutathione peroxidase activities, and reduction of malondialdehyde contents. HCP treatment was also found to attenuate the inflammatory mediators nitric oxide, inducible nitric oxide synthase, total nitric oxide synthase, and interleukin-1beta (IL-lβ) and enhanced the production of short-chain fatty acids. Correspondingly, a significant elevation of zonula occludens-1 (ZO-1) was displayed in the intestine of HCP-treated rats, indicating that the intestinal mechanical barrier could be repaired by HCP treatment. Therefore, these findings suggested that HCP performed protective effects against chronic inflammation-induced intestinal impairment through alleviating inflammation, modifying the redox system, and recovering the intestinal mechanical barrier, mediated by the control of ZO-1 in rats.
Image Classification Based on Light Convolutional Neural Network Using Pulse Couple Neural Network
Authors: Rafidison Maminiaina Alphonse , Ramafiarisona Hajasoa Malalatiana , Randriamitantsoa Paul Auguste , Rafanantenana Sabine Harisoa Jacques , Toky Faniriharisoa Maxime Rajaonarison , Rakotondrazaka Lovasoa Patrick , Rakotomihamina Andry Harivony
Published: March 2023

Recently, most image classification studies solicit the intervention of convolutional neural networks because these DL‐based classification methods generally outperform other methodologies with higher accuracy. However, this type of deep learning networks require many parameters and have a complex structure with multiple convolutional and pooling layers depending on the objective. These layers compute a large volume of data and it may impact the processing time and the performance. Therefore, this paper proposes a new method of image classification based on the light convolutional neural network. It consists of replacing the feature extraction layers of standard convolutional neural network with a single pulse coupled neural network by introducing the notion of foveation. This module provides the feature map of input image and the data compression using Discrete Wavelet Transform which is an optional step depending on the information quantity of this signature. The fully connected neural network, which has six hidden layers, classifies the image. With this technique, the computation time is reduced, and the network architecture is identical and simple independent of the type of dataset. The number of parameter is less than that in current research. The proposed method was validated with different dataset such as Caltech‐101, Caltech‐256, CIFAR‐10, CIFAR‐100, and ImageNet, and the accuracy reaches 92%, 90%, 99%, 94%, and 91%, respectively, which are better than the previous related works.
An Overview of Cancer Health Inequalities and the Relation to Diet
Authors: Carrillo-Alvarez Elena
Published: March 2023

Cancer health disparities remain stubbornly entrenched in the US health care system. The Affordable Care Act was legislation to target these disparities in health outcomes. Expanded access to health care, reduction in tobacco use, uptake of other preventive measures and cancer screening, and improved cancer therapies greatly reduced cancer mortality among women and men and underserved communities in this country. Yet, disparities in cancer outcomes remain. Underserved populations continue to experience an excessive cancer burden. This burden is largely explained by health care disparities, lifestyle factors, cultural barriers, and disparate exposures to carcinogens and pathogens, as exemplified by the COVID-19 epidemic. However, research also shows that comorbidities, social stress, ancestral and immunobiological factors, and the microbiome, may contribute to health disparities in cancer risk and survival. Recent studies revealed that comorbid conditions can induce an adverse tumor biology, leading to a more aggressive disease and decreased patient survival. In this review, we will discuss unanswered questions and new opportunities in cancer health disparity research related to comorbid chronic diseases, stress signaling, the immune response, and the microbiome, and what contribution these factors may have as causes of cancer health disparities.
Evaluating a Comprehensive Model of Euthymia
Authors: Vittengl Jeffrey R. , Jarrett Robin B. , Ro Eunyoe , Clark Lee Anna
Published: March 2023

Introduction: In research and treatment of mood disorders, “euthymia” traditionally denotes the absence of clinically significant mood disturbance. A newer, expanded definition of euthymia also includes positive affect and psychological well-being. Objective: We aimed to test this comprehensive model of euthymia and estimate the coherence and predictive power of each factor in the model. Methods: Community-dwelling adults (N = 601), including both mental health outpatients and non-patients at high risk for personality pathology, completed a battery of interviews and questionnaires at time 1. Most (n = 497) were reassessed on average 8 months later (time 2). We modeled euthymia using standard mood, personality, and psychosocial functioning assessments rather than measures designed specifically for euthymia. Results: The hypothesized model of euthymia was supported by confirmatory factor analysis: specific measures loaded on three lower order factors (mood disturbance, positive affect, and psychological well-being) that reflected general euthymia at time 1. Each factor (general euthymia plus lower order factors) demonstrated moderately strong concurrent (time 1) and predictive (time 1–2) correlations with outcomes, including employment status, income, mental health treatment consumption, and disability. Compared to positive affect and psychological well-being, mood disturbance had stronger incremental (i.e., nonoverlapping) relations with these outcomes. Conclusions: Support for a comprehensive model of euthymia reinforces efforts to improve assessment and treatment of mood and other disorders. Beyond dampening of psychological distress, euthymia-informed treatment goals encompass full recovery, including enjoyment and meaning in life.
Association of Four Types of Vascular Access Including Arterial Superficialization with Mortality in Maintenance Hemodialysis Patients: A Nationwide Cohort Study in Japan
Authors: Murakami Minoru , Fujii Naohiko , Kanda Eiichiro , Kikuchi Kan , Wada Atsushi , Hamano Takayuki , Masakane Ikuto
Published: March 2023

Introduction: Vascular access usage varies widely across countries. Previous studies have evaluated the association of clinical outcomes with the three types of vascular access, namely, arteriovenous fistula (AVF), arteriovenous graft (AVG), and tunneled and cuffed central venous catheter (TC-CVC). However, little is known regarding the association between arterial superficialization (AS) and the mortality of patients. Methods: A nationwide cohort study was conducted using data from the Japanese Society for Dialysis Therapy Renal Data Registry (2006–2007). We included patients aged ≥20 years undergoing hemodialysis with a dialysis vintage ≥6 months. The exposures of interest were the four types of vascular access: AVF, AVG, AS, and TC-CVC. Cox proportional hazard models were used to evaluate the associations of vascular access types with 1-year all-cause and cause-specific mortality. Results: A total of 183,490 maintenance hemodialysis patients were included: 90.7% with AVF, 6.9% with AVG, 2.0% with AS, and 0.4% with TC-CVC. During the 1-year follow-up period, 13,798 patients died. Compared to patients with AVF, those with AVG, AS, and TC-CVC had a significantly higher risk of all-cause mortality after adjustment for confounding factors: adjusted hazard ratios (95% confidence intervals) – 1.30 (1.20–1.41), 1.56 (1.39–1.76), and 2.15 (1.77–2.61), respectively. Similar results were obtained for infection-related and cardiovascular mortality. Conclusion: This nationwide cohort study conducted in Japan suggested that AVF usage may have the lowest risk of all-cause mortality. The study also suggested that the usage of AS may be associated with better survival rates compared to those of TC-CVC in patients who are not suitable for AVF or AVG.
Waldenström Macroglobulinemia and Non-IgM-Type Lymphoplasmacytic Lymphoma Are Genetically Similar
Authors: Awata-Shiraiwa Maaya , Yokohama Akihiko , Kanai Yukihiro , Gotoh Nanami , Kasamatsu Tetsuhiro , Handa Hiroshi , Saitoh Takayuki , Murakami Hirokazu , Hirato Junko , Ikota Hayato , Tsukamoto Norifumi
Published: March 2023

Introduction: Waldenström macroglobulinemia (WM) represents a subset of lymphoplasmacytic lymphoma (LPL) with the immunoglobulin (Ig)M paraprotein. MYD88 L265P and CXCR4 mutations are common mutations in WM patients, and mutations in ARID1A and KMT2D (MLL2) have also been reported. However, little information has been accumulated on genetic changes in LPL with other paraproteins like IgG. Methods: We therefore aimed to evaluate genetic differences between WM and LPL with non-IgM paraprotein (non-IgM-type LPL) using targeted next-generation sequencing (NGS) in 20 Japanese patients (10 with WM, 10 with non-IgM-type LPL). Results: Mutations were detected in ARID1A (10%), CXCR4 (20%), MYD88 (90%), and KMT2D (0%) for WM patients and in ARID1A (10%), CXCR4 (20%), MYD88 (70%), and KMT2D (10%) for non-IgM-type LPL patients. No significant differences were identified. No mutations were detected in NOTCH2, PRDM1, CD274 (PD-L1), PDCD1LG2 (PD-L2), RAG2, MYBBP1A, TP53, or CD79B. Discussion: Mutant allele frequency in MYD88 L265P did not differ significantly between WM and non-IgM-type LPL. Most mutations detected by NGS were subclonal following MYD88 L265P, although one non-IgM-type LPL patient harbored only CXCR4 S338X mutation. Our NGS analyses reveal genetic characteristics in LPL patients and suggest genetic similarities between these two subsets of LPL, WM and non-IgM-type.
Genetic variants in the endothelial protein C receptor gene: reaching significance
Authors: de Frutos Pablo García
Published: March 2023

Since the discovery of activated protein C (APC) resistance, mutations and genetic variants in the protein C pathway have been put into the spotlight of research in the pathophysiology of haemostasis. Although none of the more recently discovered mutations in the components of the natural anticoagulant pathways have equalled the clear-cut effect of factor V Leiden in thrombosis and its epidemiological importance, some recent work in several genes of the pathway have shown promising results in linking genotype and phenotype which could explain certain mechanisms in respective thrombosis associated pathologies. The discovery of a specific endothelial protein C receptor (EPCR) and the deciphering of its importance in the biology of protein C, opened up the possibility that genetic variants in the EPCR gene (PROCR) could play a role in the risk for thrombosis (1, 2). The EPCR functions to enhance the activation of anticoagulant protein C by the thrombin-thrombomodulin complex, and it is essential for the interaction of protein C with protease activated receptor 1. In this way, the EPCR acts in the anticoagulant, profibrinolytic and anti-inflammatory response (1, 3, 4). EPCR knock-out mice show early embryonic lethality (5), although a small amount of EPCR is sufficient to maintain the animals alive and fertile (6) …
Abstract 06: Discrimination Experiences and All-Cause and Cardiovascular Mortality: The Multi-Ethnic Study of Atherosclerosis
Authors: Lawrence Wayne R , Jones Gieira S , Johnson Jarrett A , Ferrell Koya P , Johnson Jacquita N , Shiels Meredith S , Diez Roux Ana V , Forde Allana T
Published: March 2023

Introduction:
Epidemiologic studies have documented the associations between experiences of discrimination and adverse health outcomes. However, the relationship between discrimination and mortality, and the factors that may moderate this relationship are not well understood. This study examined whether lifetime and everyday discrimination were associated with all-cause and cardiovascular mortality, and whether these associations differed by race/ethnicity, gender, and racial/ethnic residential segregation.

Hypothesis:
We hypothesized that greater exposure to lifetime and everyday discrimination would be associated with increased risk of cardiovascular mortality, and that these associations would be modified by race/ethnicity, gender, and racial/ethnic residential segregation.

Methods:
The study included 1,633 Black, 1,403 Hispanic/Latino, and 2,473 White participants aged 45 to 84 years from the Multi-Ethnic Study of Atherosclerosis, enrolled from 2000-2002 and followed across 5 exams (2002-2018). In addition to exams, follow-up for mortality involved phone calls and linkage with the National Death Index. Discrimination was measured using the lifetime discrimination (major experiences of unfair treatment) and everyday discrimination (day-to-day experiences of unfair treatment) scales. Racial/ethnic residential segregation was measured using the
Gi*
statistic. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs), adjusting for sociodemographic characteristics, health behaviors, and clinical risk factors.

Results:
Each increase in reports of lifetime discrimination was associated with increased all-cause (HR=1.06; 95%CI 1.00,1.11,) and cardiovascular (HR=1.15; 95%CI 1.04, 1.27) mortality, adjusting for sociodemographic factors, health behaviors, and clinical risk factors. Associations between lifetime discrimination and cardiovascular mortality were observed across all racial/ethnic groups but were strongest and only statistically significant among Black participants (HR=1.18; 95%CI 1.02, 1.37). Additionally, in the fully adjusted model, each increase in reports of everyday discrimination was marginally associated with increased all-cause mortality (HR=1.07; 95%CI 0.98-1.17) and strongly associated with increased cardiovascular mortality (HR=1.21; 95%CI 1.03, 1.43). Associations for lifetime and everyday discrimination with all-cause and cardiovascular mortality were not modified by race/ethnicity, gender, or racial/ethnic residential segregation.

Conclusion:
These findings suggest that experiences of discrimination are associated with increased all-cause and cardiovascular mortality. Our results underscore the need for interventions aimed at preventing and mitigating the adverse health effects of discrimination.
Abstract 40: Score Based on Immunoglobulin G N-glycans for Cardiovascular Risk Prediction: Secondary Analysis of Two Randomized Trials of Primary and Secondary Prevention
Authors: Hoshi Rosangela , Plavša Branimir , Liu Yanyan , Trbojevic-Akmacic Irena , Glynn Robert , Ridker Paul M , Cummings Richard , Lauc Gordan , Demler Olga , Mora Samia
Published: March 2023

Introduction:
Immunoglobulin G (IgG) are post-translationally modified proteins with the addition of complex carbohydrate molecules (glycans). These glycans can modulate IgG inflammatory capacity and determine the transition from healthy to diseased tissue.

Hypothesis:
A glycan score based on certain IgG glycosylation patterns is associated with CVD risk and can improve model prediction.

Methods:
IgG glycosylation profiles were measured on baseline plasma samples from nested CVD case-control participants from 2 studies: JUPITER (NCT00239681; Npairs=162; discovery) and the TNT (NCT00327691; Npairs=367, validation). Lasso regression was used to select IgG glycan peaks (GPs). The linear combination of selected IgG-GPs that significantly associated with CVD in a mutually adjusted conditional regression comprised the glycan score (IgG
GS
). CVD prediction using IgG
GS
was investigated controlling for clinical risk factors. Using a parametric approach, we calculated the area under the curve (AUC) with and without IgG
GS
.

Results:
From 24 IgG-GPs, Lasso selected 4 IgG-GPs that were also associated with incident CVD (P<.05) in a mutually adjusted conditional logistic regression. These 4 IgG-GPs (9, 12, 19, 20) composed the IgG glycan score (IgG
GS
; Fig1A), which was significantly associated with incident CVD in JUPITER after adjusting for clinical risk factors (model 2 hazard ratio [HR]: 2.1, 95% CI 1.55 - 2.84), with significant validation in TNT (HR = 1.2, 95% CI 1.03 - 1.4; Fig. 1B). The AUC was higher for the model with IgG
GS
(0.74, 95%CI = 0.69 - 0.81) than without (0.69, 95%CI = 0.67 - 0.71) in JUPITER; replicating in TNT: 0.72 [0.71 - 0.83] vs 0.64, [0.62 - 0.65]. The P-value for the likelihood ratio test comparing models with and without IgG
GS
was 5.9x10
-8
in JUPITER and .02 in TNT.

Conclusions:
An IgG glycan score with 4 IgG N-glycans was positively associated with incident CVD in the JUPITER primary prevention population, which replicated in TNT, a secondary prevention cohort, and improved model prediction performance.
Abstract 52: Using Smartphone-Based Digital Phenotyping to Understand Lifestyle and Behavioral Risks of Cardiometabolic Diseases: The Beiwe Smartphone Sub-Study of Nurses’ Health Study 3 and Growing Up Today Study
Authors: YI LI , Hart Jaime E , Wilt Grete , Hu Cindy , Laden Francine , Chavarro Jorge , James Peter
Published: March 2023

Background:
Emerging evidence has suggested lifestyle and behavioral factors such as physical activity, diet, and sleep may be associated with cardiometabolic health outcomes in US adults. However, these studies typically have limited temporal or spatial coverage. The current study aimed to fill in this gap by applying smartphone-based digital phenotyping to collect dynamic, high temporal resolution measures of lifestyle and behavioral factors.

Methods:
Participants (N = 2,127 as of Sep 7
th
, 2022) of the Beiwe Smartphone Sub-study of Nurses’ Health Study 3 (NHS3) and Growing Up Today Study (GUTS) completed microsurveys delivered by the Beiwe smartphone application for a year each. Starting July 2021, a microsurvey was delivered every 10 days, covering one of the 12 different topics, including emotions, stress, physical activity, green space, pets, diet, sleep, and sitting. These questionnaires aimed to measure various aspects of participants’ key health behaviors, to combine with objectively assessed high-resolution GPS and accelerometer data that participants provided during the same period.

Results:
Between July 28
th
, 2021, and Sep 7
th
, 2022, 2,127 participants completed 22,039 microsurveys delivered by the Beiwe application. The mean follow-up for participants was 116 days (SD=124, range=221). During this period, each participant on average submitted 10 microsurveys (SD=10, range=39). The topic completed most consistently (N=1,955 responses) was pets (the first microsurvey), and 43.3% of responses from participants reported a park visit in the past week. Additionally, 71.2% of responses from participants reported they spent at least a few minutes walking for exercise in the past week. Furthermore, during the same period, participants on average provided 177 days (SD=123, range=218) of GPS data and 181 days (SD=181, range=224) of accelerometer data.

Conclusions:
In this study, the smartphone-based digital phenotyping technology was implemented to collect intensive longitudinal data on lifestyle and behavioral factors in two well-established prospective cohorts. The efforts so far have resulted in a rich dataset on health behaviors, which can be linked to locations and future cardiometabolic health outcomes.
Abstract MP02: Gut Microbiome Alteration and Structural Brain Features Among Healthy Japanese Men
Authors: Ahmed Sabrina , Yano Yuichiro , Hexun Zhang , Okami Yukiko , Mohd Azahar Nazar Mohd Zabadi , Kondo Keiko , Arima Hisatomi , Torii Sayuki , Moniruzzaman Mohammad , Kadota Aya , Andoh Akira , Shiino Akihiko , Nozaki Kazuhiko , Ueshima Hirotsugu , Miura Katsuyuki
Published: March 2023

Introduction:
Growing evidence supports the bidirectional brain-gut microbiome interaction that contributes to brain health. However, no prior study has assessed the association between gut microbiomes and structural brain features in a healthy general population.

Hypothesis:
We assess the hypothesis that the gut microbiome composition is associated with structural brain features in healthy humans.

Methods:
Healthy Japanese men (n=623) aged 40-79 years participated in the examination of the Shiga Epidemiological Study of Subclinical Atherosclerosis II (SESSA II) between 2010 and 2014. Gut microbiota composition including diversity was assessed using 16S rRNA sequencing with DNA extracted from stool samples, and brain volumes (i.e., total brain volume, white matter, gray matter, and hippocampus) and white matter lesion volume (WMLV, reflecting Cerebral small vessel disease) were quantified using brain magnetic resonance imaging (MRI). We performed principal coordinate analysis (PCoA), multivariable-adjusted linear regression models, and linear discriminant analysis (LDA) by measuring effect size (Lefse).

Results:
Higher alpha diversity was associated with lower brain volumes of gray matter, white matter, and hippocampus (FDR adjusted Q <0.01). For beta diversity, weighted unifrac Bray-Curtis distances measured by PCoA showed lower and higher groups formed distinct clusters in white and gray matter volumes. Multivariable linear regression and LDA analysis suggested that higher amount of the genera Lachnospiraceae butyrate-producing bacteria were associated with greater gray and white matter volume (see Figure).

Conclusions:
In conclusion, the gut microbiome was associated with the brain gray and white matter structural alterations in healthy Japanese adult men. Persons with higher amount of Lachnospiraceae butyrate-producing bacteria had higher gray and white matter volumes compared to those with lower amount of the bacteria.
Abstract MP25: Circulating Odd-Chain Fatty Acids and Mortality Risk After Myocardial Infarction in the Alpha Omega Cohort
Authors: Cruijsen Esther , Pertiwi Kamalita , Geleijnse Johanna M
Published: March 2023

Background:
Circulating odd-chain fatty acids (OCFAs) 15:0 and 17:0, potential biomarkers of dairy (fat) intake, have been associated with cardiometabolic outcomes in population-based studies. Whether circulating OCFAs are related to mortality risk in patients who experienced a myocardial infarction (MI) is not yet clear.

Methods:
We included 4,741 Dutch patients aged 60-80 y (78% males) from the Alpha Omega Cohort, who experienced a myocardial infarction (MI) up to 10 years prior to study enrolment. At baseline (2002-2006), data were obtained on risk factors for cardiovascular disease (CVD), medication, lifestyle factors and dietary intakes (203-item FFQ). Fatty acids in serum cholesteryl esters (CE) were assessed using gas chromatography. Multivariable Cox models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CI) for total and CVD mortality in relation to 15:0 and 17:0 in CE (per 10
th
to 90
th
percentile range, P
10-90
). HRs were adjusted for age, sex, education, BMI, physical activity, diabetes, other CVD risk factors, medication, circulating linoleic acid, circulating EPA+DHA, and dietary factors. Missing data imputation was performed for confounders.

Findings:
Most patients used cardiovascular drugs (statins: 85%) and 979 patients (21%) had diabetes. During a median follow-up period of 12.4 years (total of 52,625 person-years), 2,233 patients died, of whom 984 from CVD. Circulating levels (% of total fatty acids) were low for 15:0 (median: 0.16; P
10-90
: 0.11-0.21) and 17:0 (median: 0.08; P
10-90
: 0.00-0.11). For 15:0, age and sex adjusted HRs per P
10-90
were 0.88 (95% CI: 0.81-0.95;
P
=0.001) for total mortality and 0.94 (0.83-1.06) for CVD mortality. In the most adjusted model, HRs for 15:0 were 0.92 (0.84-1.00;
P
=0.042) and 0.97 (0.85-1.11), respectively. For 17:0, HRs were 0.94 (0.85-1.05) for total mortality and 0.97 (0.83-1.13) for CVD mortality. Stratified analyses by sex showed inverse associations for 15:0 mainly in men (total mortality: HR of 0.90 [0.82-1.00];
P
=0.047). For 17:0, inverse but non-significant associations were mainly observed in women (total mortality: HR of 0.85 [0.68-1.05]). Associations for 17:0, but not for 15:0, were stronger in diabetic patients (total mortality: HR of 0.78 [0.64-0.96];
P
=0.019).

Conclusions:
Higher circulating OCFA levels may be related to a lower mortality risk after MI, which needs confirmation in other cohorts of CVD patients. The role of dairy fat intake in this relationship warrants further investigation.
Abstract MP36: Long-Term Dietary Lignan Intake and Weight Change: Results From Three Prospective Cohort Studies
Authors: Rai Sharan K , Hu Yang , Ding Ming , Hu Frank B , Wang Molin , Chavarro Jorge E , Sun Qi
Published: March 2023

Objectives:
Studies suggest that endogenous estrogen may be involved in regulating body weight. Dietary lignans can act as estrogen receptor agonists and may be beneficial for weight control. We prospectively examined the association between changes in dietary lignan intake with weight change.

Methods:
We analyzed data from 124,875 men and women in the Nurses’ Health Study (1986-2010), Nurses’ Health Study II (1991-2011), and the Health Professionals Follow-up Study (1986-2010). We calculated 4-year changes in total lignan intake as well as in four major individual lignans (matairesinol, secoisolariciresinol, pinoresinol, and lariciresinol) using data from a semi-quantitative food frequency questionnaire. Participants reported their height and weight at baseline and updated their current weight every 2 years thereafter, from which we calculated 4-year changes in weight as the primary study outcome. We used multivariable generalized linear regression models to examine the association between 4-year changes in lignan intake with 4-year weight changes over the same period, and these models were adjusted for age, baseline BMI in each period, and relevant lifestyle factors.

Results:
Each 1-standard deviation (SD) increase in total lignan intake was associated with a 4-year weight change of -0.36 lbs (95% confidence interval [CI] -0.40 to -0.33 lbs; P for trend <0.0001). This inverse association persisted among all four individual lignans, although the magnitude of this association was the strongest for lariciresinol (-0.63 lbs [95% CI, -0.67 to -0.59 lbs]; P for trend <0.0001)
(Figure)
. The observed associations were stronger among certain subgroups, including those with BMI ≥25 kg/m
2
, below-median diet quality, or below-median physical activity level.

Conclusions:
Increases in dietary lignan intake were associated with less weight gain over the same 4-year period. Our findings support existing dietary recommendations to consume a healthy plant-based diet.
Abstract MP72: Intrinsic Motivation is Associated With Greater Physical Activity and Less Sedentary Behavior During Early Pregnancy
Authors: Brown Susan D , Kiernan Michaela , Ehrlich Samantha F , Hedderson Monique , Daredia Saher , Millman Andrea , Buman Matthew P , Serrato Bandera Hillary , Quesenberry Charles P , Ferrara Assiamira
Published: March 2023

Background:
National guidelines recommend physical activity (PA) during pregnancy for optimal cardiovascular and overall health. Yet most individuals do not engage in sufficient PA and motivation for PA during pregnancy is poorly understood.

Methods:
We examined intrinsic motivation for PA (i.e., engaging in activity for enjoyment or satisfaction) and its cross-sectional associations with PA, by intensity level, in the first trimester of pregnancy. Data come from the Pregnancy, Lifestyle and Environment Study (PETALS), a population-based cohort study set in an integrated health system. Following recruitment at 10-13 weeks’ gestation, participants (
N
=472; 71% from racial/ethnic groups other than White) completed the validated Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2, intrinsic subscale); and Pregnancy Physical Activity Questionnaire (PPAQ) to estimate typical PA in the prior 2 months, as expressed in MET [metabolic equivalent] hours/week (by intensity and, for MVPA, by domain—i.e., limited to intentional activity such as sports, walking, aerobic exercise, etc.). Data were collected in 2017-18.

Results:
As hypothesized, intrinsic motivation was higher among those who met (
n
=192, 40.7%) vs. did not meet national guidelines for 150 minutes/week of moderate-to-vigorous intensity PA (MVPA; mean BREQ-2 scores [SD]: 2.84 [0.89] vs. 1.94 [1.02],
p
<0.0001). Likewise, intrinsic motivation was higher among those who scored at or above (
n
=131, 27.8%) vs. below the sample-specific 75
th
percentile for vigorous PA (2.86 [0.93] vs. 2.09 [1.03],
p
<0.0001); and lower among those who scored at or above (
n
=119, 25.2%) vs. below the 75
th
percentile for sedentary behavior (1.99 [1.14] vs. 2.41 [1.01],
p
=0.0005). Intrinsic motivation was not associated with reaching the 75
th
percentiles for total, light, or moderate PA. In modified Poisson regression models adjusted for age, pre-pregnancy body mass index, race/ethnicity, education, and parity, a 1-unit increase in BREQ-2 score was associated with an increased probability of meeting or exceeding MVPA guidelines (rate ratio [95% CI]: 1.66 [1.48, 1.86]) and scoring at or above the 75
th
percentile for vigorous PA (1.70 [1.44, 1.99]). A 1-unit increase in BREQ-2 score decreased the probability of scoring at or above the 75
th
percentile for sedentary behavior (0.79 [0.67, 0.92]).

Conclusions:
Only 4 in 10 participants met national guidelines for MVPA in the first trimester of pregnancy. Intrinsic motivation was associated with greater MVPA and vigorous PA, and less sedentary behavior, in this diverse sample. Intrinsic motivation is potentially modifiable and thus a promising target for new behavioral interventions to improve maternal cardiovascular health.