bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated Homocysteine Concentrations Decrease the Antihypertensive Effect of Angiotensin-Converting Enzyme Inhibitors in Hypertensive Patients
Authors: Qin Xianhui , Li Youbao , Sun Ningling , Wang Hong , Zhang Yan , Wang Jiguang , Li Jianping , Xu Xin , Liang Min , Nie Jing , Wang Binyan , Cheng Xiaoshu , Li Nanfang , Sun Yingxian , Zhao Lianyou , Wang Xiaobin , Hou Fan Fan , Huo Yong 
Published: November 2016

Objective—
We aimed to examine whether baseline homocysteine (Hcy) concentrations affect antihypertensive responses to enalapril treatment among previously untreated hypertensive patients (n=10 783) in the CSPPT (China Stroke Primary Prevention Trial).

Approach and Results—

After a 3-week run-in treatment with a daily dose of 10 mg enalapril, eligible hypertensive patients were randomly assigned to a double-blind daily treatment of a tablet of either enalapril (10 mg) and folic acid (0.8 mg) or enalapril (10 mg) alone for a median of 4.5 years. After the 3-week treatment period with enalapril alone, the systolic blood pressure–lowering effect was significantly reduced by 1.39 (95% confidence interval 0.40–2.37) and 3.25 (95% confidence interval 1.98–4.52) mm Hg, respectively, in those with baseline Hcy concentrations of 10 to 15 and ≥15 μmol/L (
P
for trend <0.001) as compared with those with Hcy concentration of <10 μmol/L. Similar results were observed after a 15-week treatment period with enalapril alone. After a median 4.5-year enalapril-based antihypertensive treatment period, compared with those with Hcy concentration of <10 μmol/L, the systolic blood pressure–lowering effect was still significantly reduced by 0.77 (95% confidence interval 0.01–1.53) and 1.70 (95% confidence interval 0.72–2.68) mm Hg, respectively, in those with Hcy concentrations of 10 to 15 and ≥15 μmol/L (
P
for trend <0.001). In addition, participants with higher baseline Hcy concentrations had persistently higher systolic blood pressure levels across the entire study treatment period. Similarly, baseline Hcy concentrations were inversely associated with diastolic blood pressure reduction during the short-term enalapril alone treatment. However, the inverse association between baseline Hcy and diastolic blood pressure reduction was attenuated and became insignificant after the long-term enalapril-based treatment period.

Conclusions—
Elevated Hcy concentrations significantly decreased the antihypertensive effect of the short-term and long-term enalapril-based antihypertensive treatment in previously untreated hypertensive patients.
Greater Volume but not Higher Density of Abdominal Aortic Calcium Is Associated With Increased Cardiovascular Disease Risk
Authors: Forbang Nketi I. , Michos Erin D. , McClelland Robyn L. , Remigio-Baker Rosemay A. , Allison Matthew A. , Sandfort Veit , Ix Joachim H. , Thomas Isac , Rifkin Dena E. , Criqui Michael H. 
Published: November 2016

Background—
Abdominal aortic calcium (AAC) and coronary artery calcium (CAC) independently and similarly predict cardiovascular disease (CVD) events. The standard AAC and CAC score, the Agatston method, upweights for greater calcium density, thereby modeling higher calcium density as a CVD hazard.

Methods and Results—

Computed tomography scans were used to measure AAC and CAC volume and density in a multiethnic cohort of community-dwelling individuals, and Cox proportional hazard was used to determine their independent association with incident coronary heart disease (CHD, defined as myocardial infarction, resuscitated cardiac arrest, or CHD death), cardiovascular disease (CVD, defined as CHD plus stroke and stroke death), and all-cause mortality. In 997 participants with Agatston AAC and CAC scores >0, the mean age was 66±9 years, and 58% were men. During an average follow-up of 9 years, there were 77 CHD, 118 CVD, and 169 all-cause mortality events. In mutually adjusted models, additionally adjusted for CVD risk factors, an increase in ln(AAC volume) per standard deviation was significantly associated with increased all-cause mortality (hazard ratio=1.20; 95% confidence interval, 1.08–1.33;
P
<0.01) and an increased ln(CAC volume) per standard deviation was significantly associated with CHD (hazard ratio=1.17; 95% confidence interval, 1.04–1.59;
P
=0.02) and CVD (hazard ratio=1.20; 95% confidence interval, 1.05–1.36;
P
<0.01). In contrast, both AAC and CAC density were not significantly associated with CVD events.

Conclusions—
The Agatston method of upweighting calcium scores for greater density may be inappropriate for CVD risk prediction in both the abdominal aorta and coronary arteries.
Discordance Between Resting and Hyperemic Indices of Coronary Stenosis Severity
Authors: Hennigan Barry , Oldroyd Keith G. , Berry Colin , Johnson Nils , McClure John , McCartney Peter , McEntegart Margaret B. , Eteiba Hany , Petrie Mark C. , Rocchiccioli Paul , Good Richard , Lindsay Martin M. , Hood Stuart , Watkins Stuart 
Published: November 2016

Background—
Distal coronary to aortic pressure ratio (Pd/Pa) and instantaneous wave-free ratio (iFR) are indices of functional significance of a coronary stenosis measured without hyperemia. It has been suggested that iFR has superior diagnostic accuracy to Pd/Pa when compared with fractional flow reserve (FFR).
We hypothesized that in comparison with FFR, revascularization decisions based on either binary cutoff values for iFR and Pd/Pa or hybrid strategies incorporating iFR or Pd/Pa will result in similar levels of disagreement.

Methods and Results—

This is a prospective study in consecutive patients undergoing FFR for clinical indications using proprietary software to calculate iFR. We measured Pd/Pa, iFR, FFR, and hyperemic iFR. Diagnostic accuracy versus FFR ≤0.80 was calculated using binary cutoff values of ≤0.90 for iFR and ≤0.92 for Pd/Pa, and adenosine zones for iFR of 0.86 to 0.93 and Pd/Pa of 0.87 to 0.94 in the hybrid strategy. One hundred ninety-seven patients with 257 stenoses (mean diameter stenosis 48%) were studied. Using binary cutoffs, diagnostic accuracy was similar for iFR and resting Pd/Pa with misclassification rates of 21% versus 20.2% (
P
=0.85). In the hybrid analysis, 54% of iFR cases and 53% of Pd/Pa cases were outside the adenosine zone and rates of misclassification were 9.4% versus 11.9% (
P
=0.55).

Conclusions—
Binary cutoff values for iFR and Pd/Pa result in misclassification of 1 in 5 lesions. Using a hybrid strategy, approximately half of the patients do not receive adenosine, but 1 in 10 lesions are still misclassified. The use of nonhyperemic indices of stenosis severity cannot be recommended for decision making in the catheterization laboratory.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02377310.
MiR‐590 Promotes Transdifferentiation of Porcine and Human Fibroblasts Toward a Cardiomyocyte‐Like Fate by Directly Repressing Specificity Protein 1
Authors: Singh Vivek P. , Mathison Megumi , Patel Vivekkumar , Sanagasetti Deepthi , Gibson Brian W. , Yang Jianchang , Rosengart Todd K. 
Published: November 2016

Background
Reprogramming of cardiac fibroblasts into induced cardiomyocyte‐like cells represents a promising potential new therapy for treating heart disease, inducing significant improvements in postinfarct ventricular function in rodent models. Because reprogramming factors effective in transdifferentiating rodent cells are not sufficient to reprogram human cells, we sought to identify reprogramming factors potentially applicable to human studies.

Methods and Results

Lentivirus vectors expressing Gata4, Mef2c, and Tbx5 (
GMT
); Hand2 (H), Myocardin (My), or microRNA (miR)‐590 were administered to rat, porcine, and human cardiac fibroblasts in vitro. induced cardiomyocyte‐like cell production was then evaluated by assessing expression of the cardiomyocyte marker, cardiac troponin T (
cTnT
), whereas signaling pathway studies were performed to identify reprogramming factor targets.
GMT
administration induced
cTnT
expression in ≈6% of rat fibroblasts, but failed to induce
cTnT
expression in porcine or human cardiac fibroblasts. Addition of H/My and/or miR‐590 to
GMT
administration resulted in
cTNT
expression in ≈5% of porcine and human fibroblasts and also upregulated the expression of the cardiac genes,
MYH
6 and
TNNT
2. When cocultured with murine cardiomyocytes,
cTnT
‐expressing porcine cardiac fibroblasts exhibited spontaneous contractions. Administration of
GMT
plus either H/My or miR‐590 alone also downregulated fibroblast genes
COL
1A1 and
COL
3A1. miR‐590 was shown to directly suppress the zinc finger protein, specificity protein 1 (Sp1), which was able to substitute for miR‐590 in inducing cellular reprogramming.

Conclusions
These data support porcine studies as a surrogate for testing human cardiac reprogramming, and suggest that miR‐590‐mediated repression of Sp1 represents an alternative pathway for enhancing human cardiac cellular reprogramming.
Effect of High (200 μg/kg per Minute) Adenosine Dose Infusion on Fractional Flow Reserve Variability
Authors: Alexopoulos Dimitrios , Xanthopoulou Ioanna , Tsigkas Grigorios , Koutsogiannis Nikolaos , Salata Paraskevi , Armylagos Stylianos , Moulias Athanasios , Davlouros Periklis 
Published: November 2016

Background
Variations in distal coronary pressure (Pd)/aortic pressure (Pa) ratio during steady‐state hyperemia with standard (140 μg/kg per minute) adenosine dose may hamper accurate fractional flow reserve assessment. This study investigated to what extent an increased adenosine dose can overcome Pd/Pa variation.

Methods and Results

In a prospective, single‐arm study, out of 95 prospectively screened patients, 38 (40.0%) exhibited significant (≥0.05 difference of max Pd/Pa minus min Pd/Pa) variations in Pd/Pa from 15 s post Pd/Pa dip and until the end of a 3‐minute adenosine (140 μg/kg per minute) infusion. Thirty patients agreed to participate in a post 5‐minute repeat fractional flow reserve assessment using 200 μg/kg per minute 3‐minute adenosine infusion. The study's co‐primary end point of Pd/Pa coefficient of dispersion was lower for the high versus standard adenosine dose: 1.31 (1.13–2.72) versus 2.76 (2.38–5.60),
P
=0.002. The study's co‐primary end point of ΔPd/Pa was also lower for the high versus standard adenosine dose: 0.065 (0.038–0.10) versus 0.08 (0.06–0.11),
P
=0.002. This difference was mainly driven by the lowering effect of the high adenosine dose on the maximum Pd/Pa compared to the standard dose: 0.84 (0.81–0.93) versus 0.90 (0.83–0.95),
P
=0.007, while minimum Pd/Pa remained unaffected. High adenosine dose was adequately tolerated by all patients, without requiring infusion discontinuation in any case.

Conclusions
Pd/Pa variability is frequently observed during standard adenosine infusion and is significantly decreased following a high (200 μg/kg per minute) adenosine dose. This is achieved without a significant difference in the minimum Pd/Pa.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov
. Unique identifier:
NCT
02350439.
Histological Findings and Predictors of Cerebral Debris From Transcatheter Aortic Valve Replacement: The ALSTER Experience
Authors: Schmidt Tobias , Akdag Ozan , Wohlmuth Peter , Thielsen Thomas , Schewel Dimitry , Schewel Jury , Alessandrini Hannes , Kreidel Felix , Bader Ralf , Romero Maria , Ladich Elena , Virmani Renu , Schäfer Ulrich , Kuck Karl‐Heinz , Frerker Christian 
Published: November 2016

Background
Histopathological analyses of debris captured by a cerebral protection system during transcatheter aortic valve replacement have been reported, but the origin of the captured debris was not determined and risk factors were not defined.

Methods and Results

Embolic debris was analyzed from 322 filters used in a dual‐cerebral‐filter protection system implemented during transcatheter aortic valve replacement for 161 patients (mean age 81 years, 82 male [51%], logistic EuroSCORE 19% [interquartile range 12–31%]). The debris capture rate was high, with debris from 97% of all patients (156 of 161). No differences by filter location were found (brachiocephalic trunk 86% [139 of 161], left carotid artery 91% [147 of 161]; adjusted
P
=0.999). Five prevalent types of debris were identified: thrombus (91%), arterial wall tissue (68%), valve tissue (53%), calcification (46%), and foreign material (30%). Female sex (
P
=0.0287, odds ratio 1.364, 95% CI 1.032–1.812) and diabetes mellitus (
P
=0.0116, odds ratio 1.474, 95% CI 1.089–2.001) were significant risk factors for embolic debris. Additional analysis showed significantly more valve tissue in patients with predilation (
P
=0.0294). Stroke and transient ischemic attack rates were 0.6% each (1 of 161).

Conclusion
This study showed a high rate of embolic debris consisting of typical anatomic structures known to be altered in patients with aortic stenosis undergoing transcatheter aortic valve replacement. Female patients with diabetes mellitus have increased risk of embolic debris and should be protected by a cerebral protection system during transcatheter aortic valve replacement. Because valve tissue embolizes more often in patients with predilation, procedural planning should consider this finding. Both cerebral arteries (brachiocephalic trunk, left carotid artery) should be protected in the same way.
Baseline Predictors of Poor Outcome in Patients Too Good to Treat With Intravenous Thrombolysis
Authors: Ali Syed F. , Siddiqui Khawja , Ay Hakan , Silverman Scott , Singhal Aneesh , Viswanathan Anand , Rost Natalia , Lev Michael , Schwamm Lee H. 
Published: November 2016

Background and Purpose—
Several studies have reported poor outcomes in patients too good to treat with intravenous thrombolysis because of mild or rapidly improving symptoms. We sought to determine baseline clinical and imaging predictors of poor outcome in these patients.

Methods—
Among 3950 consecutive stroke admissions (2009–2015) in our local Get With the Guidelines–Stroke database, 632 patients presented ≤4.5 hours and did not receive tissue-type plasminogen activator, with 380 of 632 (60.1%) being too good to treat. Univariate and multivariable analyses explored the clinical and imaging features associated with poor outcome (defined as not being discharged to home) in these 380 cases.

Results—
Among these 380 cases, only 68% were discharged home; the other 25% to inpatient rehabilitation, 4% to a skilled nursing facility, and 3% expired or were discharged to hospice. Patients with poor outcome were older, were more often Hispanic, had more vascular risk factors, and had higher median National Institutes of Health Stroke Scale. Imaging characteristics associated with poor outcomes included large or multifocal infarction and poor collaterals. In multivariable analysis, only age, initial National Institutes of Health Stroke Scale, and infarct location were independently associated with poor outcome.

Conclusions—
Approximately one third of patients deemed too good for intravenous tissue-type plasminogen activator are unable to be discharged directly to home. Given the current safety profile of intravenous tissue-type plasminogen activator, our results suggest that the concept of being too good to treat should be re-examined with an emphasis on the features associated with poor outcome identified in our study. If replicated, these findings could be incorporated into tissue-type plasminogen activator decision-making algorithms.
Mapping Flash Flood Severity in the United States
Authors: Saharia Manabendra , Kirstetter Pierre-Emmanuel , Vergara Humberto , Gourley Jonathan J. , Hong Yang , Giroud Marine 
Published: November 2016

Abstract
Flash floods, a subset of floods, are a particularly damaging natural hazard worldwide because of their multidisciplinary nature, difficulty in forecasting, and fast onset that limits emergency responses. In this study, a new variable called “flashiness” is introduced as a measure of flood severity. This work utilizes a representative and long archive of flooding events spanning 78 years to map flash flood severity, as quantified by the flashiness variable. Flood severity is then modeled as a function of a large number of geomorphological and climatological variables, which is then used to extend and regionalize the flashiness variable from gauged basins to a high-resolution grid covering the conterminous United States. Six flash flood “hotspots” are identified and additional analysis is presented on the seasonality of flash flooding. The findings from this study are then compared to other related datasets in the United States, including National Weather Service storm reports and a historical flood fatalities database.
Storie di piccola borghesia nelle pagine iniziali del Cristo
Authors: Guaragnella Pasquale 
Published: November 2016

Il confino al quale Carlo Levi fu condannato nei territori della Lucania, in particolare ad Aliano, gli diede occasione di conoscere molto da vicino le mentalità e i costumi della piccola borghesia meridionale del Ventennio fascista. Attraverso la descrizione dei personaggi più rilevanti del Cristo si è fermato a Eboli, come per esempio il podestà Don Luigi, il dottor Gibilisco e il dottor Milillo per citarne alcuni, Levi opererà una denuncia acre del ruolo della piccola borghesia, una denuncia che si protrarrà con l’ Orologio e susciterà scandalo nella cultura comunista del secondo dopoguerra. L’orientamento di Levi affonda le sue radici nella posizione in particolare di Gaetano Salvemini e di Piero Gobetti. Il contributo critico che si propone affronta queste tematiche attraversando le pagine iniziali del Cristo.
Using Population-Size Estimation and Cross-sectional Survey Methods to Evaluate HIV Service Coverage Among Key Populations in Burkina Faso and Togo
Authors: Holland Claire E. , Kouanda Seni , Lougué Marcel , Pitche Vincent Palokinam , Schwartz Sheree , Anato Simplice , Ouedraogo Henri Gautier , Tchalla Jules , Yah Clarence S. , Kapesa Laurent , Ketende Sosthenes , Beyrer Chris , Baral Stefan 
Published: November 2016

Objectives: The objective of our study was to measure progress toward the UNAIDS 90-90-90 HIV care targets among key populations in urban areas of 2 countries in West Africa: Burkina Faso and Togo. Methods: We recruited female sex workers (FSWs) and men who have sex with men (MSM) through respondent-driven sampling. From January to July 2013, 2738 participants were enrolled, tested for HIV, and completed interviewer-administered surveys. We used population-size estimation methods to calculate the number of people who were engaged in the HIV continuum of care. Results: HIV prevalence ranged from 0.6% (2 of 329) of MSM in Kara, Togo, to 32.9% (115 of 350) of FSWs in Bobo Dioulasso, Burkina Faso. Of those confirmed to be HIV infected, a range of 0.0% (0 of 2) of MSM in Kara to 55.7% (64 of 115) of FSWs in Bobo Dioulasso were using ART. Based on population estimates, the percentage gap between HIV-infected people who should be using ART (per the 90-90-90 targets) and those who reported using ART ranged from 31.5% among FSWs in Bobo Dioulasso to 100.0% among MSM in Kara. Conclusions: HIV service coverage among MSM and FSWs in Burkina Faso and Togo was low in 2013. Interventions for improving engagement of these at-risk populations in the HIV continuum of care should include frequent, routine HIV testing and linkage to evidence-based HIV treatment services. Population-size estimates can be used to inform governments, policy makers, and funding agencies about where elements of HIV service coverage are most needed.
Heme oxygenase-1-transduced bone marrow mesenchymal stem cells in reducing acute rejection and improving small bowel transplantation outcomes in rats
Authors: Yang Yang , Song Hong Li , Zhang Wen , Wu Ben Juan , Fu Nan Nan , Dong Chong , Shen Zhong Yang 
Published: November 2016

Abstract
Background
We determined whether bone marrow mesenchymal stem cells (BMMSCs) transduced with heme oxygenase-1 (HO-1), a cytoprotective and immune-protective factor, could improve outcomes for small bowel transplantation (SBTx) in rats.

Methods
We performed heterotopic SBTx from Brown Norway rats to Lewis rats, before infusing Ad/HO-1-transduced BMMSCs (Ad/HO-1/BMMSCs) through the superficial dorsal veins of the penis. Respective infusions with Ad/BMMSCs, BMMSCs, and normal saline served as controls. The animals were sacrificed after 1, 5, 7, or 10 days. At each time point, we measured small bowel histology and apoptosis, HO-1 protein and mRNA expression, natural killer (NK) cell activity, cytokine concentrations in serum and intestinal graft, and levels of regulatory T (Treg) cells.

Results
The saline-treated control group showed aggravated acute cellular rejection over time, with mucosal destruction, increased apoptosis, NK cell activation, and upregulation of proinflammatory and immune-related mediators. Both the Ad/BMMSC-treated group and the BMMSC-treated group exhibited attenuated acute cellular rejection at an early stage, but the effects receded 7 days after transplantation. Strikingly, the Ad/HO-1/BMMSC-treated group demonstrated significantly attenuated acute cellular rejection, reduced apoptosis and NK cell activity, and suppressed concentrations of inflammation and immune-related cytokines, and upregulated expression of anti-inflammatory cytokine mediators and increased Treg cell levels.

Conclusion
Our data suggest that Ad/HO-1-transduced BMMSCs have a reinforced effect on reducing acute rejection and protecting the outcome of SBTx in rats.
MicroRNA-29 facilitates transplantation of bone marrow-derived mesenchymal stem cells to alleviate pelvic floor dysfunction by repressing elastin
Authors: Jin Minfei , Wu Yuelin , Wang Jun , Ye Weiping , Wang Lei , Yin Peipei , Liu Wei , Pan Chenhao , Hua Xiaolin 
Published: November 2016

Abstract
Background
Pelvic floor dysfunction (PFD) is a condition affecting many women worldwide, with symptoms including stress urinary incontinence (SUI) and pelvic organ prolapse (POP). We have previously demonstrated stable elastin-expressing bone marrow-derived mesenchymal stem cells (BMSCs) attenuated PFD in rats, and aim to further study the effect of microRNA-29a-3p regulation on elastin expression and efficacy of BMSC transplantation therapy.

Methods
We inhibited endogenous microRNA-29a-3p in BMSCs and investigated its effect on elastin expression by RT-PCR and Western blot. MicroRNA-29-inhibited BMSCs were then transplanted into PFD rats, accompanied by sustained release of bFGF using formulated bFGF in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP), followed by evaluation of urodynamic tests.

Results
MicroRNA-29a-3p inhibition resulted in upregulated expression and secretion of elastin in in vitro culture of BMSCs. After co-injection with PLGA-loaded bFGF NP into the PFD rats in vivo, microRNA-29a-3p-inhibited BMSCs significantly improved the urodynamic test results.

Conclusions
Our multidisciplinary study, combining microRNA biology, genetically engineered BMSCs, and nanoparticle technology, provides an excellent stem cell-based therapy for repairing connective tissues and treating PFD.