bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Cost-Effectiveness of Antibiotic Prophylaxis for Patients at Risk of Infective Endocarditis
Authors: Franklin Matthew , Wailoo Allan , Dayer Mark J. , Jones Simon , Prendergast Bernard , Baddour Larry M. , Lockhart Peter B. , Thornhill Martin H. 
Published: November 2016

Background:
In March 2008, the National Institute for Health and Care Excellence recommended stopping antibiotic prophylaxis (AP) for those at risk of infective endocarditis (IE) undergoing dental procedures in the United Kingdom, citing a lack of evidence of efficacy and cost-effectiveness. We have performed a new economic evaluation of AP on the basis of contemporary estimates of efficacy, adverse events, and resource implications.

Methods:
A decision analytic cost-effectiveness model was used. Health service costs and benefits (measured as quality-adjusted life-years) were estimated. Rates of IE before and after the National Institute for Health and Care Excellence guidance were available to estimate prophylactic efficacy. AP adverse event rates were derived from recent UK data, and resource implications were based on English Hospital Episode Statistics.

Results:
AP was less costly and more effective than no AP for all patients at risk of IE. The results are sensitive to AP efficacy, but efficacy would have to be substantially lower for AP not to be cost-effective. AP was even more cost-effective in patients at high risk of IE. Only a marginal reduction in annual IE rates (1.44 cases in high-risk and 33 cases in all at-risk patients) would be required for AP to be considered cost-effective at £20 000 ($26 600) per quality-adjusted life-year. Annual cost savings of £5.5 to £8.2 million ($7.3–$10.9 million) and health gains >2600 quality-adjusted life-years could be achieved from reinstating AP in England.

Conclusions:
AP is cost-effective for preventing IE, particularly in those at high risk. These findings support the cost-effectiveness of guidelines recommending AP use in high-risk individuals.
Chemical Enhancement of In Vitro and In Vivo Direct Cardiac Reprogramming
Authors: Mohamed Tamer M. A. , Stone Nicole R. , Berry Emily C. , Radzinsky Ethan , Huang Yu , Pratt Karishma , Ang Yen-Sin , Yu Pengzhi , Wang Haixia , Tang Shibing , Magnitsky Sergey , Ding Sheng , Ivey Kathryn N. , Srivastava Deepak 
Published: November 2016

Background:
Reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells in situ represents a promising strategy for cardiac regeneration. A combination of 3 cardiac transcription factors, Gata4, Mef2c, and Tbx5 (GMT), can convert fibroblasts into induced cardiomyocyte-like cells, albeit with low efficiency in vitro.

Methods:
We screened 5500 compounds in primary cardiac fibroblasts to identify the pathways that can be modulated to enhance cardiomyocyte reprogramming.

Results:
We found that a combination of the transforming growth factor-β inhibitor SB431542 and the WNT inhibitor XAV939 increased reprogramming efficiency 8-fold when added to GMT-overexpressing cardiac fibroblasts. The small molecules also enhanced the speed and quality of cell conversion; we observed beating cells as early as 1 week after reprogramming compared with 6 to 8 weeks with GMT alone. In vivo, mice exposed to GMT, SB431542, and XAV939 for 2 weeks after myocardial infarction showed significantly improved reprogramming and cardiac function compared with those exposed to only GMT. Human cardiac reprogramming was similarly enhanced on transforming growth factor-β and WNT inhibition and was achieved most efficiently with GMT plus myocardin.

Conclusions:
Transforming growth factor-β and WNT inhibitors jointly enhance GMT-induced direct cardiac reprogramming from cardiac fibroblasts in vitro and in vivo and provide a more robust platform for cardiac regeneration.
Premature Cardiac Aging in South Asian Compared to Afro‐Caribbean Subjects in a Community‐Based Screening Study
Authors: Shantsila Eduard , Shantsila Alena , Gill Paramjit S. , Lip Gregory Y.H. 
Published: November 2016

Background
People of South Asian (SAs) and African Caribbean (AC) origin have increased cardiovascular morbidity, but underlying mechanisms are poorly understood. Aging is the key predictor of deterioration in diastolic function, which can be assessed by echocardiography using E/e′ ratio as a surrogate of left ventricular (LV) filling pressure. The study aimed to assess a possibility of premature cardiac aging in SA and AC subjects.

Methods and Results

We studied 4540 subjects: 2880 SA and 1660 AC subjects. All participants underwent detailed echocardiography, including LV ejection fraction, average septal‐lateral E/e′, and LV mass index (LVMI). When compared to ACs, SAs were younger, with lower mean LVMI, systolic blood pressure (BP), diastolic BP, and body mass index (BMI), as well as a lower prevalence of hypertension and smoking (
P
≤0.001 for all). In a multivariate linear regression model including age, sex, ethnicity, BP, heart rate, BMI, waist circumference, LVMI, history of smoking, hypertension, coronary artery disease, diabetes mellitus, medications, SA origin was independently associated with higher E/e′ (regression coefficient±standard error, −0.66±0.10;
P
<0.001, adjusted
R
2
for the model 0.21;
P
<0.001). Furthermore, SAs had significantly accelerated age‐dependent increase in E/e′ compared to ACs. On multivariable Cox regression analysis without adjustment for E/e′, SA ethnicity was independently predictive of mortality (
P
=0.04). After additional adjustment for E/e′, the ethnicity lost its significance value, whereas E/e′ was independently predictive of higher risk of death (
P
=0.008).

Conclusions
Premature cardiac aging is evident in SAs and may contribute to high cardiovascular morbidity in this ethnic group, compared to ACs.
Stroke Thrombolysis in a Centralized and a Decentralized System (Helsinki and Telemedical Project for Integrative Stroke Care Network)
Authors: Hubert Gordian J. , Meretoja Atte , Audebert Heinrich J. , Tatlisumak Turgut , Zeman Florian , Boy Sandra , Haberl Roman L. , Kaste Markku , Müller-Barna Peter 
Published: November 2016

Background and Purpose—
Intravenous thrombolysis with tissue-type plasminogen activator (tPA) for acute ischemic stroke is more effective when delivered early. Timely delivery is challenging particularly in rural areas with long distances. We compared delays and treatment rates of a large, decentralized telemedicine-based system and a well-organized, large, centralized single-hospital system.

Methods—

We analyzed the centralized system of the Helsinki University Central Hospital (Helsinki and Province of Uusimaa, Finland, 1.56 million inhabitants, 9096 km
2
) and the decentralized TeleStroke Unit network in a predominantly rural area (Telemedical Project for Integrative Stroke Care [TEMPiS], South-East Bavaria, Germany, 1.94 million inhabitants, 14 992 km
2
). All consecutive tPA treatments were prospectively registered. We compared tPA rates per total ischemic stroke admissions in the Helsinki and TEMPiS catchment areas. For delay comparisons, we excluded patients with basilar artery occlusions, in-hospital strokes, and those being treated after 270 minutes.

Results—

From January 1, 2011, to December 31, 2013, 912 patients received tPA in Helsinki University Central Hospital and 1779 in TEMPiS hospitals. Area-based tPA rates were equal (13.0% of 7017 ischemic strokes in the Helsinki University Central Hospital area versus 13.3% of 14 637 ischemic strokes in the TEMPiS area;
P
=0.078). Median prehospital delays were longer (88; interquartile range, 60–135 versus 65; 48–101 minutes;
P
<0.001) but in-hospital delays were shorter (18; interquartile range, 13–30 versus 39; 26–56 minutes;
P
<0.001) in Helsinki University Central Hospital compared with TEMPiS with no difference in overall delays (117; interquartile range, 81–168 versus 115; 87–155 minutes;
P
=0.45).

Conclusions—
A decentralized telestroke thrombolysis service can achieve similar treatment rates and time delays for a rural population as a centralized system can achieve for an urban population.
Early Magnetic Resonance Imaging and Cognitive Markers of Hereditary Cerebral Amyloid Angiopathy
Authors: van Rooden Sanneke , van Opstal Anna M. , Labadie Gerda , Terwindt Gisela M. , Wermer Marieke J.H. , Webb Andrew G. , Middelkoop Huub A.M. , Greenberg Steven M. , van der Grond Jeroen , van Buchem Mark A. 
Published: November 2016

Background and Purpose—
Early markers for cerebral amyloid angiopathy are largely unknown. We aimed to identify which magnetic resonance imaging (MRI) (performed at 7 and 3T) and cognitive markers are an early sign in (pre) symptomatic subjects with hereditary cerebral hemorrhage with amyloidosis-Dutch type.

Methods—
Twenty-seven DNA-proven Dutch-type mutation carriers (15 symptomatic and 12 presymptomatic) (mean age of 45.9 years) and 33 controls (mean age of 45.6 years) were included. 7T and 3T MRI was performed, cerebral amyloid angiopathy and small-vessel disease type MRI markers were estimated, and cognitive performance was assessed. Univariate general linear modeling analysis was used to assess the association between MRI markers and cognitive performance on the one hand and on the other, mutation status, adjusted for age, sex, and education.

Results—

In symptomatic patients, all established cerebral amyloid angiopathy MRI markers (microbleeds, intracerebral hemorrhages, subarachnoid hemorrhages, superficial siderosis, microinfarcts, volume of white matter hyperintensities, and dilated perivascular spaces in centrum semiovale) were increased compared with controls (
P
<0.05). In presymptomatic subjects, the prevalence of microinfarcts and median volume of white matter hyperintensities were increased in comparison to controls (
P
<0.05). Symptomatic patients performed worse on all cognitive domains, whereas presymptomatic subjects did not show differences in comparison with controls (
P
<0.05).

Conclusions—
White matter hyperintensities and microinfarcts are more prevalent among presymptomatic subjects and precede cognitive and neuropsychiatric symptoms and intracerebral hemorrhages.
Impaired Collateral Flow Compensation During Chronic Cerebral Hypoperfusion in the Type 2 Diabetic Mice
Authors: Nishijima Yasuo , Akamatsu Yosuke , Yang Shih Yen , Lee Chih Cheng , Baran Utku , Song Shaozhen , Wang Ruikang K. , Tominaga Teiji , Liu Jialing 
Published: November 2016

Background and Purpose—
The presence of collaterals is associated with a reduced risk of stroke and transient ischemic attack in patients with steno-occlusive carotid artery disease. Although metabolic syndrome negatively impacts collateral status, it is unclear whether and to what extent type 2 diabetes mellitus affects cerebral collateral flow regulation during hypoperfusion.

Methods—

We examined the spatial and temporal changes of the leptomeningeal collateral flow and the flow dynamics of the penetrating arterioles in the distal middle cerebral artery and anterior cerebral artery branches over 2 weeks after unilateral common carotid artery occlusion (CCAO) using optical coherent tomography in
db/+
and
db/db
mice. We also assessed the temporal adaptation of the circle of Willis after CCAO by measuring circle of Willis vessel diameters.

Results—

After unilateral CCAO,
db/db
mice exhibited diminished leptomeningeal collateral flow compensation compared with
db
/+ mice, which coincided with a reduced dilation of distal anterior cerebral artery branches, leading to reduced flow not only in pial vessels but also in penetrating arterioles bordering the distal middle cerebral artery and anterior cerebral artery. However, no apparent cell death was detected in either strain of mice during the first week after CCAO.
db/db
mice also experienced a more severe early reduction in the vessel diameters of several ipsilateral main feeding arteries in the circle of Willis, in addition to a delayed post-CCAO adaptive response by 1 to 2 weeks, compared with
db/+
mice.

Conclusions—
Type 2 diabetes mellitus is an additional risk factor for hemodynamic compromise during cerebral hypoperfusion, which may increase the severity and the risk of stroke or transient ischemic attack.
Cyclooxygenase-2-Derived Prostaglandins Mediate Cerebral Microcirculation in a Juvenile Ischemic Rat Model
Authors: Leger Pierre-Louis , Pansiot Julien , Besson Valerie , Palmier Bruno , Renolleau Sylvain , Baud Olivier , Cauli Bruno , Charriaut-Marlangue Christiane 
Published: November 2016

Background and Purpose—
We previously showed that the selective neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) increases cerebral microcirculation in a juvenile ischemic rat model. We address the roles of cyclooxygenase (COX)-elaborated prostaglandins in collateral recruitment and blood supply.

Methods—

Fourteen-day-old rats were subjected to ischemia–reperfusion and treated with either PBS or 7-NI (25 mg/kg) at the reperfusion onset. Six-keto-prostaglandin F
1α
was measured using ELISA. COX-1 and COX-2 and prostaglandin terminal synthesizing enzymes were evaluated using reverse-transcriptase polymerase chain reaction and immunofluorescence. Microvascular blood flow indexes (artery diameter and capillaries number) were measured using sidestream dark-field videomicroscopy in PBS- and 7-NI-treated ischemic rats in the absence or presence of the COX-2 inhibitor NS-398 (5 mg/kg). Cell death was measured with the TUNEL (terminal transferase dUTP nick end labeling) assay and cleaved-caspase-3 immunostaining.

Results—

Six-keto-prostaglandin F
1α
and COX-2, associated with a prostaglandin E synthase, were significantly increased in PBS- and 7-NI-treated animals 15 minutes and 1 hour after ischemia–reperfusion, respectively. In contrast and as compared with PBS, 7-NI significantly decreased prostacyclin synthase and cytosolic prostaglandins E synthase mRNA. Selective COX-2 inhibition significantly decreased blood flow indexes and significantly reversed the effects of 7-NI, including the number of TUNEL
+
- and cleaved-caspase-3
+
-nuclei.

Conclusions—
These results show that the juvenile rat brains mostly respond to ischemia by a COX-2-dependent prostaglandins production and suggest that the transcriptional responses observed under 7-NI facilitate and reorient COX-2-dependent prostaglandins production.
20-Hydroxyeicosatetraenoic Acid as a Predictor of Neurological Deterioration in Acute Minor Ischemic Stroke
Authors: Yi Xingyang , Han Zhao , Zhou Qiang , Lin Jing , Liu Ping 
Published: November 2016

Background and Purpose—
The relationship between high plasma 20-hydroxyeicosatetraenoic acid (20-HETE) levels and neurological deterioration (ND) has not been investigated in patients with acute minor ischemic stroke.

Method—
We conducted a prospective, multicenter observational study in patients with acute minor ischemic stroke. Plasma levels of 20-HETE were measured at admission in all patients. The primary end point of the study was ND within 10 days after admission. The degree of disability was assessed using modified Rankin scale at 3 months after admission.

Results—
A total of 322 patients were enrolled, of which 85 patients (26.4%) developed ND. Mean 20-HETE level was 1687±158 pmol/L. On multivariate analyses, high level (>1675 pmol/L) of 20-HETE was an independent predictor of ND (third and fourth quartiles). Neurological deterioration was associated with a higher risk of poor outcome (modified Rankin scale scores 3–6) at 3 months.

Conclusions—
ND is fairly common in acute minor ischemic stroke and is associated with poor prognosis. Elevated plasma level of 20-HETE may be a predictor for ND in acute minor ischemic stroke.
The Importance of Critical Layer in Differentiating Developing from Nondeveloping Easterly Waves
Authors: Asaadi Ali , Brunet Gilbert , Yau M. K. 
Published: November 2016

Abstract
Recently Asaadi et al. found that an easterly wave (EW) train over the Atlantic and eastern Pacific is oriented in a southeast–northwest direction because of the observed tilt in the easterly jet. This tilt results in only one out of four (~25%) waves to be located at the cyclonic critical layer south of the jet axis in a comoving frame, and they subsequently developed into named storms. Asaadi et al. suggested a geometrical view for developing disturbances, which is the coexistence of a nonlinear critical layer and a region of weak meridional potential vorticity (PV) gradient over several days. Asaadi et al. focused on the developing waves and did not investigate the nondeveloping ones.
To determine whether the nondeveloping EWs are not associated with a critical layer, a simple objective tracking technique is used to identify EWs. Composite views of the large-scale structure and characteristics of nondeveloping EWs show that ~91% of nondeveloping waves are not located on a critical layer, while the remaining ~9% indicate characteristics similar to the developing waves. Examination of the composite Okubo–Weiss parameter indicates that the nondeveloping waves are characterized by larger negative values, implying that they are dominated by deformation, unlike developing waves, which tend to be more immune from the deformation.
Recurrent somatic mutations affecting B-cell receptor signaling pathway genes in follicular lymphoma
Authors: Krysiak Kilannin , Gomez Felicia , White Brian S. , Matlock Matthew , Miller Christopher A. , Trani Lee , Fronick Catrina C. , Fulton Robert S. , Kreisel Friederike , Cashen Amanda F. , Carson Kenneth R. , Berrien-Elliott Melissa M. , Bartlett Nancy L. , Griffith Malachi , Griffith Obi L. , Fehniger Todd A. 
Published: November 2016

Key Points
FLs harbor more recurrent mutations in the BCR signaling pathway, SWI/SNF complex, and histone genes than previously known. Novel recurrent mutations affecting BTK, SYK, and HVCN1 may have therapeutic and prognostic implications for FL.
Rapamycin regulates autophagy and cell adhesion in induced pluripotent stem cells
Authors: Sotthibundhu Areechun , McDonagh Katya , von Kriegsheim Alexander , Garcia-Munoz Amaya , Klawiter Agnieszka , Thompson Kerry , Chauhan Kapil Dev , Krawczyk Janusz , McInerney Veronica , Dockery Peter , Devine Michael J. , Kunath Tilo , Barry Frank , O’Brien Timothy , Shen Sanbing 
Published: November 2016

Abstract
Background
Cellular reprogramming is a stressful process, which requires cells to engulf somatic features and produce and maintain stemness machineries. Autophagy is a process to degrade unwanted proteins and is required for the derivation of induced pluripotent stem cells (iPSCs). However, the role of autophagy during iPSC maintenance remains undefined.

Methods
Human iPSCs were investigated by microscopy, immunofluorescence, and immunoblotting to detect autophagy machinery. Cells were treated with rapamycin to activate autophagy and with bafilomycin to block autophagy during iPSC maintenance. High concentrations of rapamycin treatment unexpectedly resulted in spontaneous formation of round floating spheres of uniform size, which were analyzed for differentiation into three germ layers. Mass spectrometry was deployed to reveal altered protein expression and pathways associated with rapamycin treatment.

Results
We demonstrate that human iPSCs express high basal levels of autophagy, including key components of APMKα, ULK1/2, BECLIN-1, ATG13, ATG101, ATG12, ATG3, ATG5, and LC3B. Block of autophagy by bafilomycin induces iPSC death and rapamycin attenuates the bafilomycin effect. Rapamycin treatment upregulates autophagy in iPSCs in a dose/time-dependent manner. High concentration of rapamycin reduces NANOG expression and induces spontaneous formation of round and uniformly sized embryoid bodies (EBs) with accelerated differentiation into three germ layers. Mass spectrometry analysis identifies actin cytoskeleton and adherens junctions as the major targets of rapamycin in mediating iPSC detachment and differentiation.

Conclusions
High levels of basal autophagy activity are present during iPSC derivation and maintenance. Rapamycin alters expression of actin cytoskeleton and adherens junctions, induces uniform EB formation, and accelerates differentiation. IPSCs are sensitive to enzyme dissociation and require a lengthy differentiation time. The shape and size of EBs also play a role in the heterogeneity of end cell products. This research therefore highlights the potential of rapamycin in producing uniform EBs and in shortening iPSC differentiation duration.
Vascular Disease Is Associated With the Expression of Genes for Intestinal Cholesterol Transport and Metabolism
Authors: Widdowson William M. , McGowan Anne , Phelan James , Boran Gerard , Reynolds John , Gibney James 
Published: November 2016

AbstractContext:Intestinal cholesterol metabolism is important in influencing postprandial lipoprotein concentrations, and might be important in the development of vascular disease.Objective:This study evaluated associations between expression of intestinal cholesterol metabolism genes, postprandial lipid metabolism, and endothelial function/early vascular disease in human subjects.Design/Patients:One hundred patients undergoing routine oesophago-gastro-duodenoscopy were recruited. mRNA levels of Nieman-Pick C1-like 1 protein (NPC1L1), ABC-G5, ABC-G8, ABC-A1, microsomal tissue transport protein (MTTP), and sterol-regulatory element-binding protein (SREBP)-2 were measured in duodenal biopsies using quantitative reverse transcription polymerase chain reaction. Postprandially, serum lipid and glycemic profiles were measured, endothelial function was assessed using fasting, and postprandial flow-mediated dilatation (FMD) and carotid intima-media thickness (IMT). Subjects were divided into those above and below the median value of relative expression of each gene, and results were compared between the groups.Results:There were no between-group differences in demographic variables or classical cardiovascular risks. For all genes, the postprandial triglyceride incremental area under the curve was greater (P &lt; 0.05) in the group with greater expression. Postprandial apolipoprotein B48 (ApoB48) levels were greater (P &lt; 0.05) in groups with greater expression of NPC1L1, ABC-G8, and SREBP-2. For all genes, postprandial but not fasting FMD was lower (P &lt; 0.01) in the group with greater expression. Triglyceride and ApoB48 levels correlated significantly with postprandial FMD. Carotid artery IMT was greater (P &lt; 0.05) in groups with greater expression of MTTP, ABC-A1, and SREBP-2.Conclusion:Intestinal cholesterol metabolism gene expression is significantly associated with postprandial increment in triglycerides, intestinal ApoB48, and reduced postprandial FMD. Some genes were also associated with increased IMT. These findings suggest a role of intestinal cholesterol metabolism in development of early vascular disease.
Wheel steel strengthening with fiber lasers
Authors: Мурзаков Максим , Murzakov Maksim , Шмелев Сергей , Shmelyov Sergey , Грезев Николай , Grezev Nikolay , Богданов Александр , Bogdanov Aleksandr , Маркушов Юрий , Markushov Yuriy 
Published: November 2016

At present time in Russia under conditions of a stable industrial growth the effectiveness of railway transport work obtains importance. One of the basic expense items of “RR” Co. (“Russian Railways” Company) is connected with the intensive wear problem of contact surfaces in wheel pairs at the interaction with a railway surface. In the railway system of Russia there are used many ways for the solution of this problem such as friction constant decrease – lubrication, wear-resistance increase in wheel pairs at the expense of various methods use for surface strengthening and other methods.
The authors offer for the strengthening problem solution to use fiber lasers the application of which gives a number of incontestable advantages in comparison with common methods of material processing: a controllability of a strengthened layer depth, a possibility of surface local working and others. Today the demand for laser techniques grows actively because, in the opinion of authors, fiber lasers give a considerably higher result in comparison with common methods of processing.