bluuebunny/crossref_metadata_2025_split huggingface dataset:
Willingness and preferences for long-acting injectable PrEP among US men who have sex with men: a discrete choice experiment
Authors: Cole Sam Wilson , Glick Jennifer L , Campoamor Nicola B , Sanchez Travis H , Sarkar Supriya , Vannappagari Vani , Rinehart Alex , Rawlings Keith , Sullivan Patrick S , Bridges John F P 
Published: April 2024

IntroductionCabotegravir long-acting injectable HIV pre-exposure prophylaxis (LA-PrEP) was shown to be safe and effective in multiple clinical trials. Increasing uptake and persistence among populations with elevated risk for HIV acquisition, especially among men who have sex with men (MSM), is critical to HIV prevention.ObjectiveThis analysis aims to understand potential users’ preferences for LA-PrEP, with audience segmentation.DesignWillingness to use and preferences for LA-PrEP were measured in HIV-negative, sexually active MSM in the 2020 American Men’s Internet Survey. Respondents answered a discrete choice experiment with paired profiles of hypothetical LA-PrEP characteristics with an opt-out option (no LA-PrEP). Conditional and mixed logit models were run; the final model was a dummy-coded mixed logit that interacted with the opt-out.SettingUS national online sample.ResultsAmong 2506 MSM respondents, most (75%) indicated a willingness to use LA-PrEP versus daily oral PrEP versus no PrEP. Respondents were averse to side effects and increasing costs and preferred increasing levels of protection. Respondents preferred a 2-hour time to obtain LA-PrEP vs 1 hour, with a strong aversion to 3 hours. Overall, there was an aversion to opting out of LA-PrEP, with variations: those with only one partner, no/other insurance or who were Black, Indigenous or People of Colour were significantly less likely to prefer LA-PrEP, while those who were Hispanic/Latino, college educated and <40 years significantly preferred LA-PrEP.ConclusionsA large proportion of MSM expressed a preference for LA-PrEP over daily oral pills. Most respondents chose LA-PrEP regardless of cost, clinic time, side effects or protection level; however, preferences varied by sociodemographics. These varied groups likely require tailored intervention strategies to achieve maximum LA-PrEP uptake and persistence.
Keratoconus disease classification with multimodel fusion and vision transformer: a pretrained model approach
Authors: Yaraghi Shokufeh , Khatibi Toktam 
Published: April 2024

ObjectiveOur objective is to develop a novel keratoconus image classification system that leverages multiple pretrained models and a transformer architecture to achieve state-of-the-art performance in detecting keratoconus.Methods and analysisThree pretrained models were used to extract features from the input images. These models have been trained on large datasets and have demonstrated strong performance in various computer vision tasks.The extracted features from the three pretrained models were fused using a feature fusion technique. This fusion aimed to combine the strengths of each model and capture a more comprehensive representation of the input images. The fused features were then used as input to a vision transformer, a powerful architecture that has shown excellent performance in image classification tasks. The vision transformer learnt to classify the input images as either indicative of keratoconus or not.The proposed method was applied to the Shahroud Cohort Eye collection and keratoconus detection dataset. The performance of the model was evaluated using standard evaluation metrics such as accuracy, precision, recall and F1 score.ResultsThe research results demonstrated that the proposed model achieved higher accuracy compared with using each model individually.ConclusionThe findings of this study suggest that the proposed approach can significantly improve the accuracy of image classification models for keratoconus detection. This approach can serve as an effective decision support system alongside physicians, aiding in the diagnosis of keratoconus and potentially reducing the need for invasive procedures such as corneal transplantation in severe cases.
Associations of Early-Life and Adult Anthropometric Measures with the Expression of Stem Cell Markers CD44, CD24, and ALDH1A1 in Women with Benign Breast Biopsies
Authors: Oh Hannah , Yaghjyan Lusine , Heng Yujing J. , Rosner Bernard , Mahoney Matt B. , Murthy Divya , Baker Gabrielle M. , Tamimi Rulla M. 
Published: April 2024

Abstract

Background:
According to the stem cell hypothesis, breast carcinogenesis may be related to the breast stem cell pool size. However, little is known about associations of breast cancer risk factors, such as anthropometric measures, with the expression of stem cell markers in noncancerous breast tissue.

Methods:
The analysis included 414 women with biopsy-confirmed benign breast disease in the Nurses’ Health Study and Nurses’ Health Study II. Birthweight, weight at age 18, current weight, and current height were reported via self-administered questionnaires. IHC staining of stem cell markers (CD44, CD24, and aldehyde dehydrogenase family 1 member A1) in histopathologically normal epithelial and stromal breast tissue was quantified using an automated computational image analysis system. Linear regression was used to examine the associations of early-life and adult anthropometric measures with log-transformed stem cell marker expression, adjusting for potential confounders.

Results:
Birthweight [≥10.0 vs. &lt;5.5 lbs: β (95% confidence interval) = 4.29 (1.02, 7.56); P trend = 0.001 in the stroma] and adult height [≥67.0 vs. &lt;63.0 inch: 0.86 (0.14, 1.58); P trend = 0.02 in the epithelium and stroma combined] were positively associated with CD44 expression. Childhood body fatness was inversely associated (P trend = 0.03) whereas adult height was positively associated with CD24 expression in combined stroma and epithelium (P trend = 0.03).

Conclusions:
Our data suggest that anthropometric measures, such as birthweight, adult height, and childhood body fatness, may be associated with the stem cell expression among women with benign breast disease.

Impact:
Anthropometric measures, such as birthweight, height, and childhood body fatness, may have long-term impacts on stem cell population in the breast.
Abstract 4859: Genetic Polymorphism T45G on Adiponectin Gene Affects Cardiovascular Risk by Regulating Adiponectin Levels in Arterial Hypertension
Authors: Antonopoulos Alexis S , Tousoulis Dimitris , Antoniades Charalambos , Miliou Antigoni , Koumallos Nikolaos , Hatzis George , Demosthenous Michalis , Bakogiannis Constantinos , Stefanadi Elli , Tsioufis Costas , Papageorgiou Nikolaos , Siasos Gerasimos , Ntarladimas Ioannis , Stefanadis Christodoulos 
Published: April 2024

Background: Evidence suggests that adiponectin, an adipokine facilitating insulin action, has antiatherogenic effects, while it is inversely associated with obesity and the development of arterial hypertension. We examined the impact of T45G polymorphism on adiponectin gene, on the risk for coronary artery disease (CAD) and the expression of adipokines in heathy individuals and patients with CAD. We also examined its possible impact on the development of arterial hypertension.
Methods: We studied 214 pts with CAD and 147 healthy controls. Genetic polymorphism T45G was determined by PCR, while circulating adiponectin, resistin and leptin were determined by ELISA, under stable clinical conditions.
Results: The genotype distribution was different between CAD patients (GG: 5(2.3%) GT: 65(30.4%), TT:144(67.3%)) and controls (GG:2(1.4%), GT: 31(21.1%), TT:114(77.6%), p<0.05). The risk for CAD was OR[95%CI]:0.595[0.368 – 0.964], p=0.03 for 45TT vs 45GT+GG. Importantly, The 45TT homozygotes had lower risk of arterial hypertension (OR[95%CI]:0.439[0.270 – 0.713], p=0.001). The 45TT genotype was associated with higher adiponectin levels (13.1±1.14pg/ml) compared to 45GT+GG (8.30±2.17pg/ml, p<0.05) among healthy individuals, but not in CAD patients (13.67±0.97 vs 15.20±1.6pg/ml respectively, p=NS). Circulating resistin and leptin were not different between genotypes in the control group (6.88±0.40 and 13.6±0.85 in TT vs 6.16±0.65 pg/ml and 14.04±2.23 pg/ml in GT+GG, p=NS for both). In the CAD group, leptin levels were also similar between 45TT (15.2±1.8pg/ml) and 45GT+GG (14.1±3.2pg/ml, p=NS). Similarly, the 45TT genotype had similar resistin (5.9±0.3pg/ml) compared to 45GT+GG (7.69±0.81pg/ml, p=NS), in the CAD group.
Conclusions: The 45TT genotype of adiponectin gene is associated with lower risk of arterial hypertension and decreased cardiovascular risk. This genotype has a striking effect on adiponectin expression in healthy individuals, but not in CAD patients. Therefore, homozygosity for the 45T allele decreases the risk for CAD by increasing circulating levels of adiponectin in healthy individuals, while its functional effect is masked after the establishment of coronary atherosclerosis.
Abstract 5009: Prothrombotic Effect After Aspirin Discontinuation is Cox 2-dependent
Authors: Doutremepuich Christian , Aguejouf Omar M , Desplat Vanessa L , Eizayaga Francisco X 
Published: April 2024

Aspirin (ASA) discontinuation for surgery or non-compliance increases the risk of a thrombotic accident or stent thrombosis, especially after the second week. Previous papers have shown that 8 to 10 days after a single high dose of ASA in the rat, a pro-thrombotic state develops. We hypothesized that insignificant amounts of ASA may remain after discontinuation and cause a prothrombotic COX 2-mediated effect.
Mehtods: Wistar rats (1000) were separated into 100 groups. Induced hemorrhagic time in seconds (IHT) and Laser-induced thrombosis, expressed as number of emboli (NE), were used. ASA was injected in 100 mg/kg, 1 mg/kg or 1/100 dilutions (Dil) 5, 9 or 15, subcutaneously, in a final volume of 1 ml/kg. Sterilized water was used as placebo. Selective inhibitors of COX 1 (SC-560) or COX 2 (NS-398) were used at 2.5, 5, 7.5 and 10 mg/kg, intragastrically. Carboxy-methyl-cellulose, the vehicle of COX inhibitors, was used as control. Each group was compared with its control with the t-test, p<0.05 was considered significant.
Results: (only highest or lowest doses shown) the highest dose of ASA prolonged IHT and decreased thrombosis. A clear opposite trend was observed with the highest dilution, which generated a shortened IHT and an increased NE. SC-560 produced an effect similar to the higher doses of ASA, prolonged IHT and decreased NE, proportional to dose increase. This effect of COX 1 inhibition was antagonized by the highest ASA dilutions. NS-398 created a pro-thrombotic effect that was antagonized by ASA at higher doses. There was no further effect of the highest dilution of ASA after NS-398.
Conclusion: There is a clear prothrombotic effect of ASA Dil 15 that is opposed to COX 1 inhibition and which is inhibited by COX 2 inhibition. COX 2 inhibition and Dil 15 of ASA have similar effects. The prothrombotic effect of the highest dilution of ASA is achieved through COX 2 inhibition and may be blamed for the thrombotic accidents and stent thrombosis described after ASA discontinuation.
Abstract 5116: Stable Arteriogenesis of Ischemic Hind Limbs by a Conditionally Silenced AAV9 Gene Therapy Vector Expressing Human VEGF
Authors: Boden Jeffrey , Webster Keith A 
Published: April 2024

INTRODUCTION: Therapeutic angiogenesis to treat coronary and peripheral artery disease with genes or cells has not been successful.
RATIONALE: Previous protocols focused on angiogenesis with two major flaws

Inadequate delivery vehicles

Use of unregulated genes with no directional cues for new vessel growth.

HYPOTHESIS: VEGF gene delivery in a semipermanent muscle-tropic AAV9 vector with tight hypoxia-regulation supports directional angiogenesis, arteriogenesis and stable reperfusion.

METHODS: The human (h)VEGF gene driven by a PGK promoter containing tandem arrays of HIF-1
α
and NSF (silencer) binding sites was cloned into AAV9. Gene expression and regulation were quantified in myocytes and ischemic hind limbs of normal and atherosclerosis-prone mice. Arteriogenesis was evaluated in ischemic hind limbs with intramuscular delivery.

RESULTS: Systemic delivery of AAV9-HR-VEGF to mice showed high tropism for muscle with a 3-fold greater preference for cardiac over skeletal muscle. VEGF expression from AAV9-HR-hVEGF was negligible in aerobic myocytes or normally perfused hind limb and displayed 50 –100-fold induction by hypoxia. Concurrent atherosclerosis muted transgene expression. Delivery of AAV9-HR-hVEGF to ischemic hind limbs supported a progressive increase of limb perfusion that reached 87% of the contra lateral limb after 12 weeks and was sustained at 40 weeks. Limps treated with PBS or adenoviral-hVEGF auto-amputated at 12 weeks. Immunohistology of hind limbs at 2, 4, 12, 16 and 30 weeks revealed significantly larger vessels containing smooth muscle actin in limbs treated with AAV9-HR-VEGF compared with an unregulated vector. DiI imaging combined with scanning confocal microscopy revealed a progressive longitudinal (hip to foot) growth of vessels with the appearance of arteries at 16-weeks. HVEGF expression peaked at 12 weeks and declined thereafter, confirming regulation by ischemia.
CONCLUSION: Sustained, ischemia-regulated VEGF expression supports early angiogenesis that evolves into arteriogenesis with the generation of stable vessels, muscle perfusion and limb salvage. Down-regulation of the transgene coincident with therapy provides a safety switch that will allow the clinical translation of this strategy.
Abstract 18300: Myocardial Ischemia Induces Telomerase Activity in the Mouse Heart
Authors: Werner Christian , Arendt Christophe , Bakogiannis Constantinos , Schirmer Stephan H , Mueller Andreas , Boehm Michael , Laufs Ulrich 
Published: April 2024

Introduction: The incidence of cardiovascular disease rises with age. Ischemia and oxidative stress-induced DNA damage and telomere erosion may accelerate cardiac senescence. The enzyme telomerase has been shown to protect cardiovascular cells from mitochondrial oxidative stress independent of telomere elongation. We examined whether myocardial ischemia impacts on telomere biology and cellular aging in the infarcted mouse heart.
Methods and results: C57Bl/6 mice (10 weeks old, n=6-8 per group) were subjected to anterior myocardial ischemia induced by proximal ligation of the left anterior descendant coronary artery or sham operation. Cardiac MRI was used to verify infarct localization and measure LV function, showing that ejection fraction was reduced in MI mice (47±5% vs. 68±3% in sham, p<0.01). Sham and MI mice were compared 3 days, 7 days, or 4 weeks after LAD ligation and myocardial infarct zone (IZ) and remote zone (RZ) were analyzed. Telomerase activity as measured by TRAP assays was elevated in the infarct zone 3 days after LAD ligation (187±9% vs. sham mice, p<0.01), but not in the remote zone (113±35%). Seven days after myocardial infarction, telomerase was up-regulated both, in the infarct zone (177±31%) and the remote zone (154±26%). This effect was even more pronounced 4 weeks after LAD ligation (IZ: 271±14%; RZ 223±28%). In concert with telomerase activation, telomere repeat binding factor (TRF) 2 protein expression was up-regulated in the infarct zone after three days (337±25%) and in both areas after 7 days (IZ: 431±48%; RZ: 380±31%) and less strongly after 4 weeks (IZ: 170±23%; RZ: 141±27%). In parallel to telomerase activity and TRF2 expression, the apoptosis and senescence markers p53 (189±11%), Chk2 (167±32%), bax/bcl2-ratio (278±27%) and p16 (518±42%) were up-regulated in the myocardium of MI mice after 4 weeks (all shown values p<0.05 vs. myocardial tissue of sham-operated mice).

Conclusion:
Myocardial telomerase and telomere-associated factors are up-regulated in a time- and region-specific manner in the infarcted mouse heart in concert with apoptosis and cell-cycle regulators. This regulatory process may be of relevance for myocardial survival, inflammation, and remodelling after ischemia.
Abstract 18388: Is Pregnancy Associated with an Increased Risk of Arrhythmias and Disease Progression in Arrhythmogenic Right Ventricular Cardiomyopathy?
Authors: Rigato Ilaria , Rigato Sara , Steriotis Alexandros Klavdios , Zorzi Alessandro , Basso Cristina , Thiene Gateano , Iliceto Sabino , Corrado Domenico , Bauce Barbara 
Published: April 2024

BACKGROUND:The risk of pregnancy in women with ARVC is an important clinical issue for which systematic data have not been reported so far.
OBJECTIVES: to assess the morbidity and mortality in nulliparous and multiparous women affected by Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC).
METHODS: The study cohort included 27 women affected by ARVC with one or more live births, for a total of 47 live births. Maternal mortality and morbidity related to ARVC during pregnancy was evaluated with a follow-up programme, consisting of personal and family history, ECG, signal-averaged ECG, 24-h Holter and echocardiogram within three years of their pregnancy. The symptoms considered were dyspnoea, asthenia and palpitations. Moreover in 15 patients with >1 pregrancies, clinical and instrumental findings detected at the time of the first and the second pregnancy were compared. Finally, data of 13 nulliparous ARVC patients (mean age 32,3±5yrs) were correlated to those of 10 multiparous patients with the same age (34,9± 3,3 yrs).
RESULTS: No pregnancy-related death occurred. In the 27 patients evaluated within close proximity of their first pregnancy, 4 (14%) showed worsening of arrhythmias during pregnancy. All 4 patients had severe form of the disease. One patient experienced a sustained ventricular tachycardia 50 days after delivery. No patient complained of worsening symptoms. In the 15 patients who had more than one pregnancy, the comparison between the first and the second pregnancy demonstrated worsening of symptoms (P=0,05) and arrhythmias (P=0,03) after the second delivery. Similarly, the comparison between nulliparous and mutiparous ARVC patients demonstrated a significant dilatation of the Right Ventricular Outflow Tract (RVOT1= 21mm/m2; p=0,03) as well as worsening of symptoms (P=0,05) and arrhythmias (p=0,03) after the second pregnancy.
CONCLUSIONS: Maternal mortality is not increased in patients with ARVC compared with the general population. During gestation a worsening of arrhythmic pattern is more common in subjects with a severe form of the disease. A second pregnancy seems to be associated with worsening of clinical and instrumental features of the disease. Pre-conception planning and risk assessment are essential.
Abstract 18531: Impact of MicroRNA-145 to Prevent Vein Graft Disease in Rabbit by Regulation of Smooth Muscle Cell Phenotype
Authors: Ohnaka Motoaki , Marui Akira , Yamahara Kenichi , Minakata Kenji , Yamazaki Kazuhiro , Kumagai Motoyuki , Masumoto Hidetoshi , Ikeda Tadashi , Sakata Ryuzo 
Published: April 2024

Backgrounds Intimal hyperplasia is the major cause of vein graft disease. Smooth muscle cell (SMCs) proliferation and migration into the intima are key mechanism in this process. Recent studies have reported that microRNA-145(miR-145) is a specific mediator in the regulation of proliferation, differentiation, and phenotype of SMCs. In this study, we sought to investigate the impact of miR-145 to intimal hyperplasia in rabbit model of vein graft disease using electropolation mediated gene transfer.
Methods and Results Right jugular vein of male Japanese white rabbit was harvested (15mm) and endothelial cells of the graft were injured by balloon catheter. The graft was interposed in ipsilateral jugular artery in reversed fashion (Control group). Alternatively, harvested jugular vein was transduced with miR-145 encoding plasmids by electroporator after balloon injury, and then interposed in ipsilateral jugular artery in the same fashion (miR-145 group). Two weeks after surgery, venous graft was explanted. Four sections were obtained and each section was stained with both hematoxylin and eosin, and the elastica van Gieson method for elastic fiber staining. Neointima formation was quantified on cross sections of vein graft and reendothelialization and intima/media area ratio were evaluated. Optimal condition of the electroporator (Figure 1a) was confirmed by DsRed immunostaining (Figure 1b: positive red fluorescence on inner surface of the graft 1c: DsRed monoclonal antibody staining). Reendothelialization was significantly reduced in miR-145 transduced grafts at 2 weeks (Figure 1d, 1e). Arrowheads indicate the internal lamina. Intima/media area ratio was significantly lower in the miR-145 group compared to the control group (0.062±0.011 vs. 0.365±0.281, p=0.03) .
Conclusion Transduction of miR-145, which specifically regulates smooth muscle cell phenotype, into the bypass graft may be a novel option to prevent intimal hyperplasia in vein graft disease.
Abstract 18628: Aortic Arch Dissection: Does it Matter in the Current Management of Type B?
Authors: Tolenaar Jip , Tsai Thomas T , Evangelista Arturo , O'Gara Patrick , Pape Linda , Fattori Rossella , Braverman Alan C , Desai Nimesh D , Appoo Jehangir , Bossone Eduardo , Montgomery Daniel G , Isselbacher Eric M , Nienaber Christoph A , Eagle Kim A , Trimarchi Santi 
Published: April 2024

Introduction: Current guidelines report that arch involvement in aortic dissection requires open surgical repair. However, arch dissections are frequently managed with less invasive treatment when ascending aorta involvement is absent. The aim of this project is to clarify the importance of aortic arch involvement in such conditions,
Methods: Patients with aortic arch dissection enrolled in IRAD from January 1, 1996 to May 1, 2012 were included in this analysis. Patient groups were defined based on the location of the entry tear and aortic extension: entry tear in the aortic arch with extension confined to the arch (group 1; n = 8), entry tear in the aortic arch with antegrade extension (group 2; n = 55) and entry tear in de descending or abdominal aorta with retrograde extension into the arch (group 3; n = 55). For this abstract, we analyzed the difference in therapies and outcome for these groups.
Results: Compared with the other groups, isolated arch patients presented more frequent with syncope, an abrupt onset of pain and less frequent with posterior pain. Treatment differed among groups and most of the isolated arch patients were treated medically. One third of the Group 3 patients was managed endovascular, with excellent outcomes, with a total in-hospital mortality of 7.3% (p = .062). No differences in mortality were observed during follow-up. (p = .193)
Conclusion: Aortic arch involvement in aortic dissection is diverse and our observations emphasize that open surgical repair may be not always indicated in all patients. Selective patients, based on entry tear and aortic extension, might benefit from less invasive treatment options, such as endovascular repair and medical therapy