bluuebunny/crossref_metadata_2025_split huggingface dataset:
АКАДЕМІЧНЕ ПИСЬМО: СТРУКТУРА І ЗАВДАННЯ
Authors: Вихрущ А. В. 
Published: June 2021

При вирішенні актуальних питань методики викладання важливо чітко визначити головні пріоритети, оскільки існує загроза хаотичного нагромадження інформації, що ускладнить вирішення головних завдань. У статті аналізуються особливості вивчення академічного письма в медичних університетах, узагальнюються перспективні напрямки підвищення допрофесійної підготовки студентів, удосконалення системи науково-методичного забезпечення навчального процесу. Академічне письмо розглядається як процес створення і оприлюднення наукового тексту. Підкреслено, що написання наукового тексту передбачає насамперед вибір теми дослідження, доведення актуальності, новизни, значимості результатів, відповідної структури і належних методів. Оприлюднення результатів передбачає раціональне використання можливостей сучасних інформаційних технологій, а також безпосереднє ознайомлення наукової спільноти з новими фактами. Виокремлено також перспективні форми і методи навчального процесу.
Abstract 143: Enrichment of Dimethylation of Lysine 4 on Histone 3 and Resident Vascular Stem Cell Transition to Vascular Smooth Muscle Cells
Authors: Hakimjavadi Roya , Burtenshaw Denise , Fitzpatrick Emma , Di Luca Mariana , Casey Gillian , Redmond Eileen M , Cahill Paul A 
Published: June 2021

Data support a role for stem cell-derived vascular smooth muscle cells (SMC) in arteriosclerosis. Epigenetics play a critical role in SMC differentiation where histone proteins associated with the myosin heavy chain (Myh11) promoter are post-translationally modified by dimethylation of lysine 4 on histone 3 (H3K4me2). Studies report that ‘de-differentiated’ SMC do not exhibit loss of H3K4me2 at the Myh11 promoter even when mRNA levels decrease thereby allowing this modification to be used to track differentiated SMC.
Our aim was to determine the level of H3K4me2 and H3K27me3 methylation of differentiated SMCs and compare to resident vascular stem cells and stem cell-derived SMC.

Murine adventitial Sca1
+
stem cells (APCs), rat medial Sox10
+
multipotent vascular stem cells (MVSCs) and CD44
+
bone-marrow derived mesenchymal stem cells (MSCs) were all examined for methylation of lysine 4 (H3K4me2) and lysine 27 (H3K27me3) on histone 3 associated with the Myh11 promoter, before and after SMC differentiation and compared to fresh aortic differentiated SMC and sub-cultured de-differentiated SMC
in vitro
by Chromatin Immunoprecipitation (ChIP) assay. Cells were also examined for Myh11 expression, stemness (telomerase activity) and multipotentcy.

Differentiated rat and murine SMC were enriched for H3K4Me2 at the Myh11 promoter, compared to H3K27me3. Phenotypically de-differentiated sub-cutured rat and murine SMC were enriched for H3K4Me2 when compared to H3K27me3, but to a much lesser extent when compared to differentiated aortic SMC. In contrast, resident APCs and MVSCs, and bone-marrow derived MSCs, were all enriched for H3K27me3, concomitant with significant telomerase activity and multipotent differentiation capacity. The levels of enrichment of H3K27me3 dropped significantly after SMC differentiation with TGF-βeta1 concomitant with a significant enrichment of H3K4me2 to levels that mimicked the level of enrichment in de-differentiated SMC when compared to aortic differentiated SMC.
De-differentiated SMC exhibit reduced enrichment of H3K4me2 at the Myh11 promoter region when compared to differentiated aortic SMCs, but mimic the level of enrichment of H3K4me2 observed following resident vascular stem cell differentiation to SMCs.
Abstract 206: Randomized Double Blind Clinical Trial on the Effect of Oral Alpha-cyclodextrin on Serum Lipids
Authors: Amar Marcelo , Kaler Maryann , Mokhtari Vida B , Shamburek Robert D , Sampson Maureen , Levine Stewart J , Remaley Alan T 
Published: June 2021

Despite numerous therapeutic advances, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in developed countries. Statins, currently the most effective therapeutic agents for reducing CVD risk, only reduce cardiovascular events by approximately 30%. One possible complementary approach for lowering LDL-C involves the use of oral agents that complex or associate with dietary fats, preventing their intestinal absorption. Bile acid sequestrants are among the oldest lipid-altering drugs and have been known for decades to improve lipid levels and also improve glucose control. Alpha-cyclodextrin (a-CD), a cyclical polymer containing 6 glucose sub-units, is found in many foods, drinks and is sold as an over the counter food supplement. a-CD has a hydrophobic central cavity that binds lipids; one gram of a-CD binds as much as 9 grams of dietary fat and animal studies as well as clinical trials showed that it reduces dietary lipid absorption.
This is the first study that evaluated the effect of a-CD in healthy subjects and was designed as a single center, double-blinded, cross-over, placebo controlled clinical pilot study. We screened 103 subjects, males and females, and obtained 75 completed studies (42% male, 58% female, mean age 34 ±12 y.o., BMI 25±4 kg/m2). Eligible subjects were randomized into two arms and received placebo or a-CD (6 grams P.O. a day; two 1 gram tablets per meal) for 12-14 weeks with a one week of wash out period between arms. Several biochemistry and lipid parameters were analyzed and statistics were performed using paired t-test. a-CD was well tolerated and no serious adverse events related to a-CD were observed. Minor GI symptoms were the most common complaint but occurred in less than 7% of subjects on a-CD (vs 3% in placebo). No significant differences were detected on serum lipid and other lipid values but fasting serum glucose (-13% a-CD vs placebo), insulin (-7% a-CD vs placebo), HbA1C (-6% a-CD vs placebo) were decreased. Further positive alterations were present in individuals with higher glucose levels. In conclusion, in healthy subjects, a dose of 6 grams a day of a-CD was able to improve plasma glucose related indexes, in the population studied, but had no significant effect in lipid or lipoprotein plasma levels.
Abstract 268: Vascular Dysfunction in High BMI Black College Football Players
Authors: Powers Edward M , Fudim Murat , Silver Heidi J , Fitch Robert W , Niswender Kevin D 
Published: June 2021

Background:
Former football players (FP) who competed with BMI > 30 have high rates of atherosclerosis and early mortality (28% by age 50). FP are disproportionately black, a group predisposed to hypertension and atherosclerosis.

Hypothesis:
Positive energy balance and oxidative stress lead to vascular dysfunction in black FP.

Methods:
High BMI college FP (n=33) underwent metabolic and vascular testing at the Vanderbilt Medical Center during the offseason training program. Endothelial function was tested using flow-mediated dilation (FMD) of the brachial artery. Arterial elasticity and vascular resistance were tested using a calibrated tonometer. Regression was performed using least squares on Stat, version 12.

Results:
Elevated blood pressure (EBP) (SBP > 130) was common in both black (n = 14) and white (n = 19) athletes (78% vs 63%, p = .34). Black players had significantly higher systemic vascular resistance and lower arterial elasticity. However, they had significantly better lipid profiles and body composition, and comparable insulin resistance assessed by HOMA.

In black FP, EBP was associated with positive energy balance (4.3 kg gained during six weeks from enrollment to clinic visit vs. 0.7 kg, p = .05). Daily caloric intake predicted endothelial function as measured by flow mediated vasodilation (FMD) (r=.76, p=.001). Caloric intake and oxidative stress (F2-isoprostanes) trended to inversely correlate with larger artery elasticity (r=.40, p=.09 and r=.41, p=.09, respectively). HOMA did not predict FMD (r < .01, p = .56).
Respiratory quotient (RQ) correlated with f2-isoprostanes (r=.53, p=.02), suggesting a link between mitochondrial dysfunction and oxidative stress.

Conclusion:
High BMI black FP suffer from vascular dysfunction, possibly due to oxidative stress from overfeeding. This correlates with studies of non-athlete adult population, but differs notably in being independent of insulin resistance. A larger, longitudinal study is needed to establish a link between overfeeding, vascular dysfunction and early cardiovascular morbidity and mortality in high BMI black athletes. The role of oxidative stress and selective use of nitric oxide donor drugs in black athletes should be explored.
Abstract 578: Na/K-ATPase Forms a Signaling Complex with CD36 and Toll-like Receptor 4 to Mediate NF-kappaB Activation in Macrophages
Authors: Chen Yiliang , Huang Wenxin , Yang Moua , Silverstein Roy 
Published: June 2021

Cardiotonic steroids such as ouabain, digoxin, and marinobufagenin are known ligands for the plasma membrane receptor, Na/K-ATPase (NKA). These ligands stimulate complex formation of NKA with other membrane and cytosolic proteins leading to cellular events such as activation of kinase cascades and gene transcription independent of the ion transporting function. Endogenous cardiotonic steroids have been detected within human circulation and their levels are elevated in patients with diseases associated with chronic systemic inflammation. However, the role of cardiotonic steroids and NKA-mediated signaling in inflammation has not been well studied.
We now report that ouabain activates the NF-κB pathway in human monocyte-derived macrophages, leading to pro-inflammatory responses. Using Western blot and densitometry analysis, we found that physiological concentrations of ouabain stimulated IκBα degradation (n=3). Using quantitative RT-PCR (n=4), we found that ouabain increased mRNA levels of pro-inflammatory genes MCP-1 (3.2±1.1 fold), TNF-α (59.7±35.6 fold), CXCL-10 (2.8±1.6 fold), ICAM1 (2.9±0.5 fold), and PTGS2 (3.1±0.1 fold). Consistent with the increase in mRNA level, MCP-1 protein levels in post-culture media assessed by ELISA were elevated by 1.4±0.1 fold (n=4).
Mechanistically, when macrophages were incubated with ouabain for 20 min and then subjected to IP, we found that antibodies to NKA co-precipitated more TLR4 (2.2±0.8 fold) compared to unstimulated cells. Additionally, antibodies to CD36 co-precipitated more NKA (1.8±0.6 fold) and more TLR4 (2.2±0.5 fold) (n=3). Blockade of TLR4 signaling using a specific inhibitor, CLI-095, abolished ouabain-induced MCP-1 production as assessed by ELISA (n=4). Next, we used siRNA to specifically knock down either NKA α1, CD36, TLR4 or MyD88 (the adaptor protein downstream of TLR4) in THP-1 cells stably transfected with a NF-κB reporter construct. After siRNA transfection for 48h, cells were treated with ouabain for additional 24h. Knockdown of any one of these proteins fully suppressed ouabain-induced NF-κB activation by NF-κB reporter assay (n=4). In conclusion, ouabain activates NF-κB through an NKA/CD36/TLR4 complex leading to pro-inflammatory responses in human macrophages.
Abstract 605: Bone Morphogenetic Protein Inhibitors Play Important Roles in Brown and White Adipogenesis
Authors: Blazquez-Medela Ana M , Jumabay Medet , Bostrom Kristina I 
Published: June 2021

Adipose tissue is intimately connected to the development of metabolic syndrome, type 2 diabetes and cardiovascular disease. The near pandemic increase in incidence and prevalence of obesity makes it necessary to understand adipose regulation in order to develop strategies against obesity and its comorbidities.
Adipose tissue performs a variety of functions. White adipose tissue (WAT) is responsible for energy storage, hormone production and organ protection, whereas brown adipose tissue (BAT) has a key role in thermogenesis.
Previous studies have shown the importance of Bone Morphogenetic Proteins (BMPs) in the differentiation of brown and white adipocytes. BMP4 has been linked to both brown and white adipogenesis and BMP7 is essential for brown adipogenesis. Nevertheless, the role of the BMP inhibitors, which modulate the actions of BMPs, has not yet been elucidated. Our hypothesis is that the BMP inhibitors play important roles in the adipogenic process.
Using two different mice models -Matrix Gla Protein (Mgp) KO and Noggin fat-specific KO- we found that the absence of Mgp resulted in dramatic adipose changes, suggesting a critical role in the separation of white and brown adipocytes. Adipocyte-specific deletion of Noggin, however, suggested a role in modulating the size and lipid accumulation in fully differentiated adipocytes. The absence of Mgp led to a reduction in body fat and body weight (3-12 animals per group and time point) whereas the absence of Noggin caused an increase in body fat and body weight (4-18 animals per time point and body weight).
Tissue culture experiments using white and brown adipocyte progenitor cells showed specific temporal patterns of the BMPs and BMP-inhibitors that were consistent with the mouse findings.
In conclusion, BMP inhibitors are essential in distinguishing brown and white adipogenic differentiation. We hypothesize that MGP is critical in the initial separation, whereas Noggin regulates cell size and lipid accumulation.
Abstract 621: Reduced Dietary Cholesterol Availability in Infancy Programs Cholesterol Absorption in Adult Mice
Authors: Dimova Lidiya G , de Boer Jan F , Verkade Henkjan J , Tietge Uwe J 
Published: June 2021

Epidemiological research showed that feeding breast milk, which is rich in cholesterol, translates into reduced cardiovascular risk in adulthood compared to feeding formula, which is cholesterol free. The mechanisms underlying these observations are unclear. Therefore, the present study aimed to investigate the impact of reduced dietary cholesterol availability during the suckling period on cholesterol metabolism in adult life in mice.
To achieve reduced dietary cholesterol exposure from breast milk LDLR knockout offspring were given the cholesterol absorption inhibitor ezetimibe for 3 weeks during the suckling period. Ezetimibe was added to the food of nursing dams and reached the offspring’s intestine via excretion into breast milk. Low cholesterol exposure (LC) mice were compared to normal cholesterol (NC) controls with respect to all relevant parameters of cholesterol metabolism including biliary and fecal cholesterol excretion, intestinal absorption and endogenous synthesis using stable isotope kinetics.
At 24 weeks intestinal cholesterol absorption was decreased in LC mice (-30%, p<0.001) due to decreased Npc1l1 expression, the main intestinal cholesterol uptake transporter (-50%, p<0.05). Methylation analysis of the NPC1L1 promoter revealed substantial differences between jejunum and colon (p<0.001), but not between LC and NC. Plasma cholesterol levels were not different between NC and LC due to increased endogenous synthesis in the LC group (p<0.05). Food intake, biliary and fecal cholesterol excretion did not differ between groups.
In summary, our results demonstrate that early life reduction of dietary cholesterol exposure programs the murine intestine in adulthood towards decreased cholesterol absorption via reduced Npc1l1 expression. These results support a key role of the intestine as sensor and integrator of cholesterol metabolism with high relevance for cardio-metabolic disease.
Chronic Inhibition of Toll‐Like Receptor 9 Ameliorates Pulmonary Hypertension in Rats
Authors: Ishikawa Tomohito , Abe Kohtaro , Takana‐Ishikawa Mariko , Yoshida Keimei , Watanabe Takanori , Imakiire Satomi , Hosokawa Kazuya , Hirano Mayumi , Hirano Katsuya , Tsutsui Hiroyuki 
Published: June 2021

Background
Recent accumulating evidence suggests that toll‐like receptor 9 (TLR9) is involved in the pathogenesis of cardiovascular diseases. However, its role in pulmonary hypertension remains uncertain. We hypothesized that TLR9 is involved in the development of pulmonary hypertension.

Methods and Results

A rat model of monocrotaline‐induced pulmonary hypertension was used to investigate the effects of TLR9 on hemodynamic parameters, vascular remodeling, and survival. Monocrotaline‐exposed rats significantly showed increases in plasma levels of mitochondrial DNA markers, which are recognized by TLR9, TLR9 activation in the lung, and
interleukin‐6
mRNA level in the lung on day 14 after monocrotaline injection. Meanwhile, monocrotaline‐exposed rats showed elevated right ventricular systolic pressure, total pulmonary vascular resistance index and vascular remodeling, together with macrophage accumulation on day 21. In the preventive protocol, administration (days −3 to 21 after monocrotaline injection) of selective (E6446) or nonselective TLR9 inhibitor (chloroquine) significantly ameliorated the elevations of right ventricular systolic pressure and total pulmonary vascular resistance index as well as vascular remodeling and macrophage accumulation on day 21. These inhibitors also significantly reduced NF‐κB activation and
interleukin‐6
mRNA levels to a similar extent. In the short‐term reversal protocol, E646 treatment (days 14–17 after monocrotaline injection) almost normalized NF‐κB activation and
interleukin‐6
mRNA level, and reduced macrophage accumulation. In the prolonged reversal protocol, E6446 treatment (days 14–24 after monocrotaline injection) reversed total pulmonary vascular resistance index and vascular remodeling, and improved survival in monocrotaline‐exposed rats.

Conclusions
TLR9 is involved in the development of pulmonary hypertension concomitant via activation of the NF‐κB‒IL‐6 pathway. Inhibition of TLR9 may be a novel therapeutic strategy for pulmonary hypertension.
Hospital Variation in 30‐Day Readmissions Following Transcatheter Aortic Valve Replacement
Authors: Kolte Dhaval , Kennedy Kevin , Wasfy Jason H. , Jena Anupam B. , Elmariah Sammy 
Published: June 2021

Background
Data on hospital variation in 30‐day readmission rates after transcatheter aortic valve replacement (TAVR) are limited. Further, whether such variation is explained by differences in hospital characteristics and hospital practice patterns remains unknown.

Methods and Results

We used the 2017 Nationwide Readmissions Database to identify hospitals that performed at least 5 TAVRs. Hierarchical logistic regression models were used to examine between‐hospital variation in 30‐day all‐cause risk‐standardized readmission rate (RSRR) after TAVR and to explore reasons underlying hospital variation in 30‐day RSRR. The study included 27 091 index TAVRs performed across 325 hospitals. The median (interquartile range) hospital‐level 30‐day RSRR was 11.9% (11.1%–12.8%) ranging from 8.8% to 16.5%. After adjusting for differences in patient characteristics, there was significant between‐hospital variation in 30‐day RSRR (hospital odds ratio, 1.59; 95% CI, 1.39–1.77). Differences in length of stay and discharge disposition accounted for 15% of the between‐hospital variance in RSRRs. There was no significant association between hospital characteristics and 30‐day readmission rates after TAVR. There was statistically significant but weak correlation between 30‐day RSRR after TAVR and that after surgical aortic valve replacement, percutaneous coronary intervention, acute myocardial infarction, heart failure, and pneumonia (
r
=0.132–0.298;
P
<0.001 for all). Causes of 30‐day readmission varied across hospitals, with noncardiac readmissions being more common at the bottom 5% hospitals (ie, those with the highest RSRRs).

Conclusions
There is significant variation in 30‐day RSRR after TAVR across hospitals that is not entirely explained by differences in patient or hospital characteristics as well as hospital‐wide practice patterns. Noncardiac readmissions are more common in hospitals with the highest RSRRs.
Abstract TP368: Improving In-House Stroke Code Imaging and Treatment Times
Authors: Ward Erin L , Lighthizer Gail , Uppal Avneesh 
Published: June 2021

Background:
In acute ischemic stroke, a blood vessel in the brain is blocked and brain cells die within

minutes; therefore rapid recognition and treatment to restore circulation to the brain is essential.
National guidelines call for a CT scan of the brain to be done within 25 minutes of hospital arrival in
patients presenting with acute stroke to rule out bleeding in the brain. Findings of a hemorrhage would
be a contraindication for thrombolytic therapy. Additional guidelines call for intravenous t-PA (alteplase)
to be administered within 60 minutes of arrival and rapid triage to endovascular therapy in appropriate
patients. Similar goals for rapid treatment should be followed for patients experiencing a stroke while in
the hospital. Urgent treatment with a clot busting medication (alteplase) or with special endovascular
techniques to mechanically remove a clot have been shown to improve outcomes.

Purpose:
A performance improvement plan was developed and initiated in January 2015 to improve the

time to CT, time to t-PA administration, and time to endovascular therapy for patients having a stroke
while hospitalized for other diagnoses (In-House Stroke).

Method
s: The following revisions were made to current practice: Mock Stroke Code Drills for In-House

Stroke Code responders; creation of an In-House Stroke Code algorithm; addition of CT & MRI screening
forms to In-house Stroke Code packet; development of a Stroke Code criteria checklist to assist floor
nurses; implementation of a feedback loop to Stroke Code team reporting imaging and treatment times
along with patient outcomes; addition of a radiology supervisor to the Stroke Code response team.

Results:
“Stroke Code called” to “CT initiated“< 25 minutes improved from 32% in 2013, 30% in 2014, to

60% in 2015. “Stroke Code called” to “IV t-PA (alteplase) administered” < 60 minutes improved from 0%
in 2013, 25% in 2014, to 100% in 2015. “Stroke Code called” to “groin puncture for endovascular
therapy” < 2 hours, 40% for 2013, 43% in 2014 to 50% in 2015.

Conclusion:
These interventions resulted in faster CT imaging and treatment times, thereby providing

the patient with the highest quality patient care.
Abstract TP393: Information Technology to Measure and Drive Outcomes for Acute Ischemic Stroke Patients
Authors: Brendle Kellie , Zhang Hao , Turner Michelle , Holder Derek , Ng Kwan 
Published: June 2021

Background:
The stroke program did not have a formal system to gather data elements needed for driving processes and measuring outcomes. Abstracting data was done by manually auditing every stroke electronic medical record.

Purpose:
The purpose was to use technology:

To collect data for baseline and benchmarking patient demographics and outcomes.
To communicate and educate healthcare professionals and improve processes.

Methods:
Based on the AHA/ASA Get with the Guidelines (GWTG). We identified and abstracted data from discrete fields in the electronic medical record (EMR). Using Clarity the Information Technology (IT) department built discrete fields in EMR to capture 23 missing fields for GWTG. Manual concurrent review and monthly clarity reports were completed. This data was used retrospectively for benchmarking and prospectively for telemedicine and transition of care follow-up.

Results:
To keep in alignment with AHA/ASA guidelines for GWTG data collection on the 48 GWTG discrete fields 43 are now automated. Random chart review is completed to validate data abstraction. We now have completed demographic and outcomes data on over 600 patients.

Conclusions:
In conclusion, the use of IT is a reliable and valid way of abstracting GWTG AIS data to provide benchmarking and process improvement. This IT process facilitates clinical data collection, transmission and communication between providers, enabling modification of treatment regimens and transitions of care.