bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome sequence of
Novirhabdovirus
isolated from white bass (
Morone chrysops
), Ohio/North Carolina, USA
Authors: Warg Janet , Killian Mary Lea , Clayton Richard , Cruz Angela 
Published: April 2024

ABSTRACT

We sequenced the genome of a hirame novirhabdovirus isolate recovered from a white bass (
Morone chrysops
). Hirame novirhabdoviruses are in the genus
Novirhabdovirus
, along with infectious hematopoietic necrosis virus and viral hemorrhagic septicemia virus. This detection highlights that the full host range of rhabdoviruses in fish is not fully understood.
Association of the Controlling Nutritional Status (CONUT) score with all-cause and cause-specific mortality in patients with diabetic kidney disease: evidence from the NHANES 2009–2018
Authors: Zhang Huifeng , Liu Na , Dang Huaixin 
Published: April 2024

ObjectiveTo investigate the association between the Controlling Nutritional Status (CONUT) score and all-cause and cause-specific mortality in patients with diabetic kidney disease (DKD).DesignA retrospective cohort study.Setting and participantsData on patients with DKD from the National Health and Nutrition Examination Survey 2009–2018.Primary and secondary outcome measuresAll-cause mortality, cardiovascular disease (CVD)-related mortality, diabetes-related mortality and nephropathy-related mortality.ResultsA total of 1714 patients were included, with 1119 (65.29%) in normal nutrition group (a score of 0–1), 553 (32.26%) in mild malnutrition group (a score of 2–4) and 42 (2.45%) in moderate and severe malnutrition group (a score of 5–12), according to the CONUT score. After controlling for age, race, marital status, smoking, hypertension, CVD, diabetic retinopathy, poverty income ratio, antidiabetics, diuretics, urinary albumin to creatinine ratio, uric acid, energy, protein, total fat, sodium and estimated glomerular filtration rate, a higher CONUT score was associated with a significantly greater risk of all-cause death (HR 1.30, 95% CI 1.15 to 1.46, p<0.001). In contrast to patients with a CONUT score of 0–1, those who scored 5–12 had significantly increased risks of all-cause death (HR 2.80, 95% CI 1.42 to 5.51, p=0.003), diabetes-related death (HR 1.78, 95% CI 1.02 to 3.11, p=0.041) and nephropathy-related death (HR 1.84, 95% CI 1.04 to 3.24, p=0.036).ConclusionModerate and severe malnutrition was associated with greater risks of all-cause death, diabetes-related death and nephropathy-related death than normal nutritional status in DKD. Close monitoring of immuno-nutritional status in patients with DKD may help prognosis management and improvement.
Estimating the incidence of COVID-19, influenza and respiratory syncytial virus infection in three regions of Queensland, Australia, winter 2022: findings from a novel longitudinal testing-based sentinel surveillance programme
Authors: May Fiona , Ginige Shamila , Firman Elise , Li Yee Sum , Soonarane Yudish Kumar , Smoll Nicolas , Hunter Ian , Pery Brielle , Macfarlane Bonnie , Bladen Tracy , Allen Terresa , Green Trevor , Walker Jacina , Slinko Vicki , Stickley Mark , Khandaker Gulam , Anuradha Satyamurthy , Wattiaux Andre 
Published: April 2024

ObjectiveThe 2022 Australian winter was the first time that COVID-19, influenza and respiratory syncytial virus (RSV) were circulating in the population together, after two winters of physical distancing, quarantine and borders closed to international travellers. We developed a novel surveillance system to estimate the incidence of COVID-19, influenza and RSV in three regions of Queensland, Australia.DesignWe implemented a longitudinal testing-based sentinel surveillance programme. Participants were provided with self-collection nasal swabs to be dropped off at a safe location at their workplace each week. Swabs were tested for SARS-CoV-2 by PCR. Symptomatic participants attended COVID-19 respiratory clinics to be tested by multiplex PCR for SARS-CoV-2, influenza A and B and RSV. Rapid antigen test (RAT) results reported by participants were included in the analysis.Setting and participantsBetween 4 April 2022 and 3 October 2022, 578 adults were recruited via their workplace. Due to rolling recruitment, withdrawals and completion due to positive COVID-19 results, the maximum number enrolled in any week was 423 people.ResultsA total of 4290 tests were included. Participation rates varied across the period ranging from 25.9% to 72.1% of enrolled participants. The total positivity of COVID-19 was 3.3%, with few influenza or RSV cases detected. Widespread use of RAT may have resulted in few symptomatic participants attending respiratory clinics. The weekly positivity rate of SARS-CoV-2 detected during the programme correlated with the incidence of notified cases in the corresponding communities.ConclusionThis testing-based surveillance programme could estimate disease trends and be a useful tool in settings where testing is less common or accessible. Difficulties with recruitment meant the study was underpowered. The frontline sentinel nature of workplaces meant participants were not representative of the general population but were high-risk groups providing early warning of disease.
CuPBoP: Making CUDA a Portable Language
Authors: Han Ruobing , Chen Jun , Garg Bhanu , Zhou Xule , Lu John , Young Jeffrey , Sim Jaewoong , Kim Hyesoon 
Published: April 2024

CUDA is designed specifically for NVIDIA GPUs and is not compatible with non-NVIDIA devices. Enabling CUDA execution on alternative backends could greatly benefit the hardware community by fostering a more diverse software ecosystem.
To address the need for portability, our objective is to develop a framework that meets key requirements, such as extensive coverage, comprehensive end-to-end support, superior performance, and hardware scalability. Existing solutions that translate CUDA source code into other high-level languages, however, fall short of these goals.
In contrast to these source-to-source approaches, we present a novel framework, CuPBoP , which treats CUDA as a portable language in its own right. Compared to two commercial source-to-source solutions, CuPBoP offers a broader coverage and superior performance for the CUDA-to-CPU migration. Additionally, we evaluate the performance of CuPBoP against manually optimized CPU programs, highlighting the differences between CPU programs derived from CUDA and those that are manually optimized.
Furthermore, we demonstrate the hardware scalability of CuPBoP by showcasing its successful migration of CUDA to AMD GPUs.
To promote further research in this field, we have released CuPBoP as an open-source resource.
Fraction Dose Escalation of Hypofractionated Radiotherapy with Concurrent Chemotherapy and Subsequent Consolidation Immunotherapy in Locally Advanced Non–Small Cell Lung Cancer: A Phase I Study
Authors: Zhou Rui , Liu FangJie , Zhang HongMei , Wang DaQuan , Zhang PengXin , Zheng ShiYang , Liu YiMei , Chen Li , Guo JinYu , Zou YingYi , Rong Yu-Ming , Liu Hui , Qiu Bo 
Published: April 2024

Abstract

Purpose:
This phase I trial aimed to determine the maximum tolerated fraction dose (MTFD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non–small cell lung cancer.

Patients and Methods:
Split-course hypo-RT and hypoboost combined with concurrent chemotherapy was administered at three dose levels (DL), using a stepwise dose-escalation protocol. The sophisticated esophagus-sparing technique was implemented to restrict the dose to the esophagus. Patients who did not experience disease progression or unresolved ≥grade 2 (G2+) toxicities after RT received cICI. Each DL aimed to treat six patients. The MTFD was defined as the highest DL at which ≤2 patients of the six who were treated experienced treatment-related G3+ toxicity and ≤1 patient experienced G4+ toxicity within 12 months post-RT.

Results:
Eighteen patients were enrolled, with six patients in each DL. All patients completed hypo-RT and concurrent chemotherapy, and 16 (88.9%) received at least one infusion of cICI, with a median of 10 infusions. Within the 12-month assessment period, one patient in DL1 experienced G3 pneumonitis, and one patient in DL3 developed G3 tracheobronchitis. The MTFD was not reached. The objective response rate was 100%. With a median follow-up of 20.9 months, the 1-year overall survival and progression-free survival rates were 94.4% and 83.3%, respectively.

Conclusions:
Utilizing the split-course hypo-RT and hypoboost approach, a fraction dose of 5 Gy to a total dose of 60 Gy, combined with concurrent chemotherapy and subsequent cICI, was well tolerated and yielded a promising objective response rate and survival outcomes.
Abstract 593: A Novel PGE2 Receptor 4-Selective Agonist Suppresses Acute Rejection via Inflammatory Factor Regulation in Murine Cardiac Allografts
Authors: Ogawa Masahito , Suzuki Jun-ichi , Takayama Kiyoshi , Isobe Mitsuaki 
Published: April 2024

Background: PGE2 exerts an anti-inflammatory action by ligation of the PGE2 receptor subtype EP4 among the four of the receptor subtypes in inflammatory diseases. Because little is known about the effect of EP4R in transplantation, we examined the anti-inflammatory effect of EP4 using the murine cardiac transplantation model.
Methods and Results: We developed a novel EP4 selective agonist, EP4RAG, and performed subcutaneous injection of EP4RAG (3mg/kg) into recipient mice. We demonstrated that EP4RAG treatment prolonged graft survival (13.5+/−1.4 days, P<0.05, n=7) compared to that of the vehicle treated group (7.3+/−0.2 days, n=7). Allografts were harvested on day 7 for pathological and molecular examination. While the vehicle treated group showed severe myocardial cell infiltrations (38.4+/−2.5 %, n=10), the EP4RAG treated group attenuated the development (16.7+/−3.4 %, P<0.05, n=8). EP4RAG suppressed various inflammatory factors such as cytokines (e.g. IFN-g, IL-6), chemokines (e.g. IP-10, MIP-1) and adhesion molecules (e.g. ICAM-1) compared to the vehicle treated group in mRNA and protein levels. In vitro assay, we demonstrated that EP4RAG suppressed T lymphocyte proliferation (0.067+/−0.001 OD, P<0.05) compared to the control group (0.105+/−0.003 OD) by MLR. We also showed that EP4 mainly attenuated the activation of macrophages by co-culture. EP4RAG inhibited the activation of NF-kB compared to the control group in macrophages with IL-1beta stimulation.
Conclusions: An EP4R agonist, EP4RAG is potent for the suppression of acute rejection through proinflammatory factor regulation.
Abstract 4957: Robust Transfection of Vascular Endothelium for siRNA Knockdown of Vascular Cell Adhesion Molecule-1 Through a Novel Nanoparticle-Lipid Raft Pathway
Authors: Kaneda Megan M , Lanza Gregory M , Wickline Samuel A 
Published: April 2024

Controlling adhesion molecule expression as an antiatherosclerotic therapy is a heretofore untested concept that could modify disease progression and/or interdict acute coronary syndromes.

Methods: To design a synthetic vehicle to deliver vascular cell adhesion molecule-1 (VCAM-1) siRNA to endothelial cells, perfluorocarbon nanoparticles (PFC-NP) were loaded with the cationic lipid 1,2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP) in the lipid monolayer to form transfection complexes (10 pM PFC-NP + 5 nM siRNA) with VCAM-1 specific siRNA. Mouse 2F2B endothelial cells were treated with TNF
α
(10 ng/ml) to induce VCAM-1 expression and after 48h, mRNA and protein levels were measured. For endocytosis colabeling studies, transfection complexes were produced with fluorescently labled siRNA (red) and incubated with endothelial cells in the presence of fluorescently labeled pathway specific markers (green, macropinocytosis: dextran, clathrin: transferrin, lipid raft: cholera toxin-B).

Results: PFC-NP mediated siRNA transfection led to a significant decrease in both VCAM-1 mRNA and protein levels(A) . siRNA exhibited little intracellular colocalization with common markers of both macropinocytosis (B) and clathrin mediated endocytosis (C), while abundant membrane colocalization with lipid rafts was observed(D).
Conclusion: Because endothelial cells harbor an excess of lipid rafts in their plasma membranes, the development of an effective targeted nanoparticle carrier for siRNA that utilizes lipid raft transport rather than traditional endocytotic pathways could represent a valuable strategy for controlling vascular inflammation in atherosclerosis.

This research has received full or partial funding support from the American Heart Association, Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).
Abstract 5095: The Role of Circulating Transforming Growth Factor-β in Vascular Ehlers-Danlos Syndrome: Implications for Drug Therapy
Authors: Schoenhoff Florian S , Griswold Benjamin F , Matt Peter , Sloper Leslie J , Yamazaki Michiyo , Carlson Olga D , Dietz Harry C , Van Eyk Jennifer E , McDonnell Nazli B 
Published: April 2024

Objective: TGFβ signaling has been shown to play a major role in the pathogenesis of Marfan syndrome (MFS), leading to a novel treatment strategy through TGFβ inhibition using losartan. We hypothesized that circulating TGFβ levels may be elevated in disorders that disrupt arterial wall extracellular matrix, such as the vascular form of Ehlers-Danlos syndrome (VEDS).
Patients and Methods: Circulating levels of TGFβ-1 were measured in EDTA plasma of 141 patients with MFS (n=21, mean age 43±16y), VEDS (n=41, 37±13y) and controls (n=79, 48±13y) using an electrochemoluminescence platform (LLOQ 4±2.6pg/ml).
Results: In keeping with prior work, this study revealed increased circulating TGFβ in patients with MFS compared to control patients (9.2±1.2ng/ml vs. 2.5±0.4ng/ml, p<0.0001). Remarkably, the levels seen in patients with VEDS were also significantly higher than controls (8.0±1.0ng/ml vs. 2.5±0.4ng/ml, p<0.0001) and statistically indistinguishable from those seen in MFS (9.2±1.2ng/ml vs. 8.0±1.0ng/ml, p=0.5). In a bivariate logistic regression model, the odds ratio was 7.5 (p=0.02, CI 1.3– 43.3) when comparing quartiles of TGFβ values in VEDS patients with age, sex and BMI matched controls. There was a non-statistically significant trend for higher TGFβ levels in patients without cardiovascular medication (MFS, 11.4±3.0ng/ml; VEDS, 8.5±1.3ng/ml) compared to patients treated with ARBs and/or ACE-Is (MFS, 6.1±1.0ng/ml; VEDS, 4.6±0.8ng/ml), whereas β-blockers appeared to have some impact on TGFβ levels in MFS (9.0±1.7ng/ml) but not in VEDS patients (8.3±1.8ng/ml). The influence of age on TGFβ levels in the controls is statistically significant but weak (r=0.3, p=0.007). In the disease groups, TGFβ is inversely related to age (MFS, r=−0.7, p<0.0001; VEDS, r=−0.1, p=0.6), which is most likely due to ascertainment bias towards a less severe phenotype in the older patients and longer duration of medical therapy, especially in the MFS population.
Conclusion: Further investigation is warranted to establish the role of TGFβ signaling in the pathogenesis of VEDS. The current results may help to provide a rationale for the use of TGFβ lowering drug therapy in this patient population as it is emerging in the MFS patient population.
Abstract 5311: Proteolysis-resistant Collagen Drives Vascular Smooth Muscle Cell Senescence
Authors: Vafaie Faran , O’Neil Caroline , Watson Alanna , Holdsworth David , Pickering J. Geoffrey 
Published: April 2024

Senescence of vascular smooth muscle cells (SMCs) has recently been identified as a feature of atherosclerosis. However, the factors that lead to premature SMC senescence are not well understood. Plaque SMCs reside within a milieu of type I collagen fibrils that, over time, can undergo progressive intermolecular cross-linking rendering the collagen resistant to proteol-ysis. We hypothesized that vascular SMC longevity depends on the extent to which the surrounding type I collagen can be proteolytically edited. To test this, we studied mice with a targeted mutation of the 3/4 −1/4 collagenase cleavage site in type I collagen (Col1a1r/r). Mice harboring the Col1a1r/r mutation appeared normal up to 5 months of age but subsequently developed features of premature aging, including shortened lifespan (p<0.01), impaired weight gain (p<0.01), decreased adipose tissue content (p<0.01), and increased kyphosis (p<0.05), the latter two attributes quantified by micro CT imaging. Furthermore, SMCs in the aortic wall of aged, Col1a1r/r mice showed increased accumulation of reactive oxygen species, as assessed by hydroethidine incubation and nuclear fluorescence. To determine if collagenase-resistant collagen directly impacted SMC lifespan, primary human SMCs were cultured on collagen harvested from the tails of wild-type or Col1a1r/r mice. SMCs on mutant collagen displayed a 67% decrease in cumulative population doublings (p<0.01), which was associated with increased senescence-associated beta-galactosidase (SA-β-gal) activity (p<0.05) and increased p21 expression (p<0.05). Furthermore, stress-induced premature senescence, initiated by serum-deprivation and assessed by SA-β-gal activity and p21 expression, was also amplified in cells cultured on collagenase-resistant collagen.
Conclusions: Collagenase-resistant type I collagen induces a premature aging-like syndrome in mice and accelerates both replicative and stress-induced senescence of vascular SMCs. These findings identify a novel, extracellular driver of vascular cell senescence that may underlie plaque instability in aging arteries.
Abstract 5417: Peripheral Blood Monocytes Are Activated in Patients With Well Controlled Hypertension: Implications for the Understanding of the Residual Cardiovascular Risk
Authors: Czesnikiewicz-Guzik Marta , Bzowska Malgorzata , Jasiewicz-Honkisz Barbara , Korbut Richard , Naruszewicz Marek , Pryjma Juliusz , Guzik Tomasz J 
Published: April 2024

Hypertension is associated with significant risk of cardiovascular events which remains increased even in the setting of well controlled hypertension. This residual risk may be related to inflammation persisting in spite of sufficient blood pressure control. We have recently reported that monocytes show pro-inflammatory and pro-atherosclerotic phenotype (co-expression of the Fc-gamma receptor-CD16+ and LPS receptor-CD14+) in relation to atherosclerosis risk factors and that hypertension is the strongest independent predictor of CD16+CD14+ monocytes. It is thus possible that monocytes remain activated in spite of appropriate blood pressure control and thus may be in part responsible for residual risk. We studied 112 hypertensive subjects and 25 control non-hypertensive individuals matched for major risk factors. Hypertension was well controlled (<140/90) in 52 and poorly controlled in 60 pts. Cytokine production was assessed by ELISA.
Results: The prevalence of CD14+CD16+ monocytes was significantly positively correlated with systolic and diastolic blood pressure (R=0.3; p<0.01). Both subpopulations CD14(high)CD16+ (R=0.4; p<0.01) and to the lesser extent CD14(dim)CD16+ (R=0.2; p<0.05) showed relationships to systolic but only the CD14(high)CD16+ to diastolic blood pressure. The percentage of total CD14+CD16+ and CD14(high)CD16+ monocytes were highest in subjects whose blood pressure was poorly controlled. A significant difference was also observed between normotensives and hypertensive subjects with well controlled blood pressure. Further analysis of monocyte subpopulations showed that levels of pro-atherosclerotic CD14(high)CD16+ monocytes, revealed a strong relationship to hypertension and greatest difference between well controlled hypertension and normotensives (6±0.2 vs 9±0.4 p<0.01). These monocytes showed significantly higher expression of activation markers HLA-DR and CD45RA and TNF-a production in patients with hypertension, even in the absence of high blood pressure at the time of the study. These results provide a novel marker of inflammation in hypertension which remains increased even in the setting of well controlled disease providing an inflammatory mechanism for the residual risk.
Abstract 5483: The Inflammatory Protein Complement C3 is a Novel Substrate for Factor XIII and Impairs Fibrin Clot Lysis
Authors: Carter Angela M , Schroeder Verena , Polkinghorne Victoria R , Smith Kerrie A , Somani Riyaz , Standeven Kristina F , Grant Peter J 
Published: April 2024

Introduction: Inflammation is fundamentally important in the pathogenesis of cardiovascular disease (CVD) and increasing evidence supports a functional role for complement C3. Using a functional proteomics approach we have identified zymogen and activated C3 in perfused solubilized clots, suggesting C3 influences thrombus formation.
Hypothesis: In this study we assessed the hypothesis that complement C3 interacts with coagulation and fibrinolytic factors to influence thrombosis.
Methods and Results: Analysis of 123 paired plasma and serum samples revealed that 24.8% (SD 7.6) of plasma C3 was incorporated into the clot. To explore the mechanism of incorporation we investigated binding interactions between C3, fibrin and FXIII using ELISA based binding assays and surface plasmon resonance and found that C3 bound to immobilized fibrinogen and FXIII in a concentration dependent manner. Further analysis of the interactions between C3 and FXIII demonstrated that activated FXIII (FXIIIa) incorporated a known FXIIIa substrate, 5-(biotinamido)pentylamine, into immobilized C3 in a concentration dependent manner and FXIIIa also induced the formation of high-molecular weight C3 polymers, indicating that C3 is a FXIII substrate. Furthermore, FXIIIa incorporated plasma C3 into immobilized fibrin and Western blot analysis of clots formed from purified fibrinogen and C3 indicated high molecular weight bands that cross-reacted with specific antibodies against C3 and fibrinogen, suggesting that C3 is cross-linked to fibrin alpha chains. In turbidimetric assays using purified proteins C3 prolonged fibrin clot lysis times in a concentration dependent manner and Western blot analysis of lysed clots indicated that C3 was cleaved by plasmin, suggesting impaired fibrinolysis is due to substrate competition for plasmin. Increased plasma C3 concentration was significantly associated with increased ex vivo plasma clot density and prolonged fibrinolysis times, after adjusting for fibrinogen concentrations, to support our in vitro results. In conclusion, taken together these data indicate that complement C3 influences key processes involved in fibrin formation and fibrinolysis supporting a role for C3 in cardiovascular thrombosis.