LLukas22/scidocs huggingface dataset:
Resveratrol Mediated Modulation of Sirt-1/Runx2 Promotes Osteogenic Differentiation of Mesenchymal Stem Cells: Potential Role of Runx2 Deacetylation

OBJECTIVE
Osteogenic repair in response to bone injury is characterized by activation and differentiation of mesenchymal stem cells (MSCs) to osteoblasts. This study determined whether activation of Sirt-1 (a NAD(+)-dependent histone deacetylase) by the phytoestrogen resveratrol affects osteogenic differentiation.


METHODS
Monolayer and high-density cultures of MSCs and pre-osteoblastic cells were treated with an osteogenic induction medium with/without the Sirt-1 inhibitor nicotinamide or/and resveratrol in a concentration dependent manner.


RESULTS
MSCs and pre-osteoblastic cells differentiated to osteoblasts when exposed to osteogenic-induction medium. The osteogenic response was blocked by nicotinamide, resulting in adipogenic differentiation and expression of the adipose transcription regulator PPAR-γ (peroxisome proliferator-activated receptor). However, in nicotinamide-treated cultures, pre-treatment with resveratrol significantly enhanced osteogenesis by increasing expression of Runx2 (bone specific transcription factor) and decreasing expression of PPAR-γ. Activation of Sirt-1 by resveratrol in MSCs increased its binding to PPAR-γ and repressed PPAR-γ activity by involving its cofactor NCoR (nuclear receptor co-repressor). The modulatory effects of resveratrol on nicotinamide-induced expression of PPAR-γ and its cofactor NCoR were found to be mediated, at least in part, by Sirt-1/Runx2 association and deacetylation of Runx2. Finally, knockdown of Sirt-1 by using antisense oligonucleotides downregulated the expression of Sirt-1 protein and abolished the inhibitory effects of resveratrol, namely nicotinamide-induced Sirt-1 suppression and Runx2 acetylation, suggesting that the acetylated content of Runx2 is related to downregulated Sirt-1 expression.


CONCLUSION
These data support a critical role for Runx2 acetylation/deacetylation during osteogenic differentiation in MSCs in vitro. (242 words in abstract).
Amphibian-killing fungus loses genetic diversity as it spreads across the New World

Emergent infectious diseases are a severe threat to global biodiversity, thus conservation biologists need to understand the emergence, spread, and evolution of pathogens to identify factors driving disease outbreaks. Amphibian chytridiomycosis is a recently emerged amphibian disease caused by the fungus Batrachochytrium dendrobatidis (Bd) that has led to species extinctions and declines worldwide. The spatio-temporal dynamics of pathogen occurrence and disease outbreaks, and comparative genomic analyses of global Bd strains, support the spreading pathogen hypothesis (SPH) with pandemics occurring after introduction of Bd into naïve host populations. Here we used population genetics of the amphibian-killing fungus to test for genetic consequences of pathogen spread. Our population genetic analyses are consistent with the spread of Bd from North to Central America, based on low genetic diversity, reduction in heterozygosity, and increased allele fixation in Bd from recently infected populations. Our findings confirm the spread of Bd in the New World, and indicate that future conservation efforts should focus on: (i) functional consequences (such as changes in pathogenicity) of these genetic changes, and (ii) public education and restrictions on wildlife trade to help slow spread of the pathogen at the invasion front. 2011 Elsevier Ltd. All rights reserved.
Monitoring diastolic dysfunction using a simplified algorithm in patients undergoing off-pump coronary artery bypass grafting surgery

CONTEXT
Left ventricle diastolic dysfunction (LVDD) is gaining importance as useful marker of mortality and morbidity in cardiac surgical patients. Different algorithms have been proposed for the intraoperative grading of DD. Knowledge of the particular grade of DD has clinical implications with the potential to modify therapy, but there is a paucity of literature on the role of diastolic function evaluation during off-pump coronary artery bypass grafting (OPCABG) surgery.


AIMS
The aim of this study was to monitor changes in LVDD using simplified algorithm proposed by Swaminathan et al. in patients undergoing OPCABG.


SETTINGS AND DESIGN
The study was conducted in a tertiary care level hospital; this was a prospective, observational study.


SUBJECTS AND METHODS
Fifty consecutive patients undergoing OPCABG were enrolled. Hemodynamic and echocardiographic parameters were measured at 6 stages in every patient namely after anesthetic induction (baseline), during left internal mammary artery (LIMA) to left anterior descending (LAD) grafting (LIMA → LAD), saphenous vein graft (SVG) to obtuse marginal (OM) grafting (SVG → OM), SVG to posterior descending artery (PDA) grafting (SVG → PDA), during proximal anastomosis of SVG to aorta, and postprotamine. The patients were classified in grades of LVDD as per simplified algorithm proposed by Swaminathan et al. using only intraoperatively measured E and E'.


RESULTS
The success rate of measurement and classification of LVDD was 98.92% (277 out of 280 measurements). The grades of LVDD varied significantly as per surgical steps with maximum downgrading occurring during OM and LAD grafting. During OM grafting, none of the patients had normal diastolic function while 29% of patients exhibited restrictive pattern (Grade 3 LVDD). Patients with normal baseline LV diastolic function also exhibited downgrading during OM and LAD grafting. Postprotamine, 37% of patients with normal baseline diastolic function continued to exhibit some degree of DD.


CONCLUSIONS
The LVDD changes dynamically during various stages of OPCABG, which can be successfully monitored with simplified algorithm.
Association of coffee and caffeine intake with the risk of Parkinson disease.

CONTEXT
The projected expansion in the next several decades of the elderly population at highest risk for Parkinson disease (PD) makes identification of factors that promote or prevent the disease an important goal.


OBJECTIVE
To explore the association of coffee and dietary caffeine intake with risk of PD.


DESIGN, SETTING, AND PARTICIPANTS
Data were analyzed from 30 years of follow-up of 8004 Japanese-American men (aged 45-68 years) enrolled in the prospective longitudinal Honolulu Heart Program between 1965 and 1968.


MAIN OUTCOME MEASURE
Incident PD, by amount of coffee intake (measured at study enrollment and 6-year follow-up) and by total dietary caffeine intake (measured at enrollment).


RESULTS
During follow-up, 102 men were identified as having PD. Age-adjusted incidence of PD declined consistently with increased amounts of coffee intake, from 10.4 per 10,000 person-years in men who drank no coffee to 1.9 per 10,000 person-years in men who drank at least 28 oz/d (P<.001 for trend). Similar relationships were observed with total caffeine intake (P<.001 for trend) and caffeine from non-coffee sources (P=.03 for trend). Consumption of increasing amounts of coffee was also associated with lower risk of PD in men who were never, past, and current smokers at baseline (P=.049, P=.22, and P=.02, respectively, for trend). Other nutrients in coffee, including niacin, were unrelated to PD incidence. The relationship between caffeine and PD was unaltered by intake of milk and sugar.


CONCLUSIONS
Our findings indicate that higher coffee and caffeine intake is associated with a significantly lower incidence of PD. This effect appears to be independent of smoking. The data suggest that the mechanism is related to caffeine intake and not to other nutrients contained in coffee. JAMA. 2000;283:2674-2679.
Connecting and Serving the Software Engineering Community

Presents an editorial discusses the current status and activities supported by this publication.
The Grand Cooperative Driving Challenge 2016: boosting the introduction of cooperative automated vehicles

The Grand Cooperative Driving Challenge (GCDC), with the aim to boost the introduction of cooperative automated vehicles by means of wireless communication, is presented. Experiences from the previous edition of GCDC, which was held in Helmond in the Netherlands in 2011, are summarized, and an overview and expectations of the challenges in the 2016 edition are discussed. Two challenge scenarios, cooperative platoon merge and cooperative intersection passing, are specified and presented. One demonstration scenario for emergency vehicles is designed to showcase the benefits of cooperative driving. Communications closely follow the newly published cooperative intelligent transport system standards, while interaction protocols are designed for each of the scenarios. For the purpose of interoperability testing, an interactive testing tool is designed and presented. A general summary of the requirements on teams for participating in the challenge is also presented.
Robust rank aggregation for gene list integration and meta-analysis

MOTIVATION
The continued progress in developing technological platforms, availability of many published experimental datasets, as well as different statistical methods to analyze those data have allowed approaching the same research question using various methods simultaneously. To get the best out of all these alternatives, we need to integrate their results in an unbiased manner. Prioritized gene lists are a common result presentation method in genomic data analysis applications. Thus, the rank aggregation methods can become a useful and general solution for the integration task.


RESULTS
Standard rank aggregation methods are often ill-suited for biological settings where the gene lists are inherently noisy. As a remedy, we propose a novel robust rank aggregation (RRA) method. Our method detects genes that are ranked consistently better than expected under null hypothesis of uncorrelated inputs and assigns a significance score for each gene. The underlying probabilistic model makes the algorithm parameter free and robust to outliers, noise and errors. Significance scores also provide a rigorous way to keep only the statistically relevant genes in the final list. These properties make our approach robust and compelling for many settings.


AVAILABILITY
All the methods are implemented as a GNU R package RobustRankAggreg, freely available at the Comprehensive R Archive Network http://cran.r-project.org/.
Effects of heat stress and plane of nutrition on lactating Holstein cows: I. Production, metabolism, and aspects of circulating somatotropin.

Heat stress is detrimental to dairy production and affects numerous variables including feed intake and milk production. It is unclear, however, whether decreased milk yield is primarily due to the associated reduction in feed intake or the cumulative effects of heat stress on feed intake, metabolism, and physiology of dairy cattle. To distinguish between direct (not mediated by feed intake) and indirect (mediated by feed intake) effects of heat stress on physiological and metabolic indices, Holstein cows (n = 6) housed in thermal neutral conditions were pair-fed (PF) to match the nutrient intake of heat-stressed cows (HS; n = 6). All cows were subjected to 2 experimental periods: 1) thermal neutral and ad libitum intake for 9 d (P1) and 2) HS or PF for 9 d (P2). Heat-stress conditions were cyclical with daily temperatures ranging from 29.7 to 39.2 degrees C. During P1 and P2 all cows received i.v. challenges of epinephrine (d 6 of each period), and growth hormone releasing factor (GRF; d 7 of each period), and had circulating somatotropin (ST) profiles characterized (every 15 min for 6 h on d 8 of each period). During P2, HS cows were hyperthermic for the entire day and peak differences in rectal temperatures and respiration rates occurred in the afternoon (38.7 to 40.2 degrees C and 46 to 82 breaths/min, respectively). Heat stress decreased dry matter intake by greater than 35% and, by design, PF cows had similar reduced intakes. Heat stress and PF decreased milk yield, although the pattern and magnitude (40 and 21%, respectively) differed between treatments. The reduction in dry matter intake caused by HS accounted for only approximately 35% of the decrease in milk production. Both HS and PF cows entered into negative energy balance, but only PF cows had increased (approximately 120%) basal nonesterified fatty acid (NEFA) concentrations. Both PF and HS cows had decreased (7%) plasma glucose levels. The NEFA response to epinephrine did not differ between treatments but was increased (greater than 50%) in all cows during P2. During P2, HS (but not PF) cows had a modest reduction (16%) in plasma insulin-like growth factor-I. Neither treatment nor period had an effect on the ST response to GRF and there was little or no treatment effect on mean ST levels or pulsatility characteristics, but both HS and PF cows had reduced mean ST concentrations during P2. In summary, reduced nutrient intake accounted for just 35% of the HS-induced decrease in milk yield, and modest changes in the somatotropic axis may have contributed to a portion of the remainder. Differences in basal NEFA between PF and HS cows suggest a shift in postabsorptive metabolism and nutrient partitioning that may explain the additional reduction in milk yield in cows experiencing a thermal load.
Multiclinic Evaluation of Timoiol in the Treatment of Mild-to-Moderate Essential Hypertension

In a double-blind (DB), multicenter, clinical trial, 355 patients with mild-to-moderate essential hypertension, characterized by a diastoiic blood pressure (DBP) of 95-115 mm Hg, received either timoiol (T) 10-30 mg twice-a-day, or placebo (P). After 12 weeks of treatment, the mean supine BP for the T group was 145/94 mm Hg (baseline [BL] = 154/103), and for the P group, 155/102 (BL = 156/103). Fifty-seven percent (74/129) of the patients receiving T and 13% (15/114) of the patients receiving P had a reduction in supine DBP (SDBP) to 90 mm Hg or less or had a reduction greater than 10 mm Hg but not to 90 mm Hg. The reduction in SDBP for the T group was significantly greater than the reduction for the P group. After Week 12, patients responding to T continued to receive T (T/T group), while patients receiving P who did not respond were then treated with T (P/T group). Results obtained after 24 weeks of timoiol treatment for the T/T group and after 12 weeks of timoiol treatment for the P/T group were similar to those observed for the T group at 12 weeks. During the 12-week DB study, the incidence of adverse experiences was not significantly different between the T and P groups. Safety evaluations, including complete ophthalmologic exams, have not revealed any toxic effects for T. Withdrawal of timoiol for 2 weeks after 24 weeks of treatment for the T/T group and after 12 weeks of treatment for the P/T group was not associated with any rebound phenomena. (Hypertension 2: 643-648, 1980)
Randomized controlled equivalence trial comparing videoconference and in person delivery of cognitive processing therapy for PTSD.

INTRODUCTION
In an effort to improve access to and utilization of health care, the Veterans Health Administration (VHA) continues to investigate the effectiveness of video-teleconferencing (VTC) technologies for service delivery. While previous research focused on the efficacy of VTC treatment for post-traumatic stress disorder (PTSD) in Vietnam era veterans, few studies have evaluated the efficacy of this modality and treatment for the Iraq/Afghanistan era veterans. The aim of this randomized clinical trial was to evaluate equivalence between in person and VTC psychotherapy for PTSD in this newer cohort.


METHODS
Veterans of the Iraq/Afghanistan conflict from two VHA hospitals in the United States were recruited and randomized to receive cognitive processing therapy (CPT) for PTSD either in person (IP) or over VTC. Clinician-administered and self-report measures were collected before, during, and after treatment.


RESULTS
A trend was observed which suggested that CPT over VTC may be equivalent to the treatment delivered in person, as suggested by previous studies. Regardless of treatment, veterans who received the intervention in both conditions reported significant decreases on post-treatment measures.


DISCUSSION
This study highlighted research and clinical challenges in providing services to the newest veteran generation in general as well as unique challenges with VTC. One complicating factor to the statistical power of this study was a treatment dropout rate twice the original estimate. Factors that could have influenced this high dropout rate are explored.
Fructose-1, 6-bisphosphatase opposes renal carcinoma progression

Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is characterized by elevated glycogen levels and fat deposition. These consistent metabolic alterations are associated with normoxic stabilization of hypoxia-inducible factors (HIFs) secondary to von Hippel–Lindau (VHL) mutations that occur in over 90% of ccRCC tumours. However, kidney-specific VHL deletion in mice fails to elicit ccRCC-specific metabolic phenotypes and tumour formation, suggesting that additional mechanisms are essential. Recent large-scale sequencing analyses revealed the loss of several chromatin remodelling enzymes in a subset of ccRCC (these included polybromo-1, SET domain containing 2 and BRCA1-associated protein-1, among others), indicating that epigenetic perturbations are probably important contributors to the natural history of this disease. Here we used an integrative approach comprising pan-metabolomic profiling and metabolic gene set analysis and determined that the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) is uniformly depleted in over six hundred ccRCC tumours examined. Notably, the human FBP1 locus resides on chromosome 9q22, the loss of which is associated with poor prognosis for ccRCC patients. Our data further indicate that FBP1 inhibits ccRCC progression through two distinct mechanisms. First, FBP1 antagonizes glycolytic flux in renal tubular epithelial cells, the presumptive ccRCC cell of origin, thereby inhibiting a potential Warburg effect. Second, in pVHL (the protein encoded by the VHL gene)-deficient ccRCC cells, FBP1 restrains cell proliferation, glycolysis and the pentose phosphate pathway in a catalytic-activity-independent manner, by inhibiting nuclear HIF function via direct interaction with the HIF inhibitory domain. This unique dual function of the FBP1 protein explains its ubiquitous loss in ccRCC, distinguishing FBP1 from previously identified tumour suppressors that are not consistently mutated in all tumours.
Structural Health Monitoring System for the Shandong Binzhou Yellow River Highway Bridge

Structural health monitoring (SHM) provides a useful tool for ensuring safety and detecting the evolution of damage and performance deterioration of civil infrastructures. A great number of civil infrastructures under construction can be used as test beds for SHM systems. The Binzhou Yellow River Highway Bridge is a cable-stayed bridge in Shandong Province, China. An SHM system has been implemented on this bridge during its construction for monitoring its health status and assessing its safety for long-term services. The system includes a sensor module, a data acquisition module, a wired and wireless data transmit module, a structural analysis module, a database module, and a warning module. It is integrated by using LabVIEW software and can be remotely operated via Internet. The database is available freely to all scientists and engineers in the SHM research area. This article introduces the deployment and functions of this system, and presents the measured responses of the bridge subjected to moving vehicle loads.
Neural network protocols and model performance

The benchmark performance of neural network models in exchange rate forecasting has been established in a number of recent papers. In this paper, we drop a number of customary features that are used in neural modeling to improve performance yet are able to predict daily returns for the four main exchange rates with accuracy above levels previously reported for comparable data sets. Signi-cant outperformance relative to a random walk without drift and against the mean value predictor is reported, indicating that the transparent neural network used in the study is -nding new and potentially pro-table information. c © 2003 Elsevier B.V. All rights reserved.
'Hospital at home' care model as an effective alternative in the management of decompensated chronic heart failure.

AIMS
The 'Hospital at home' (HaH) model avoids hospital admission by transferring healthcare and treatment to the patient's home. We aimed to compare the effectiveness and direct healthcare costs of treating elderly patients with decompensated heart failure (HF) using HaH care vs. inpatient hospital care (IHC) in a cardiology unit.


METHODS AND RESULTS
Eighty patients aged over 65 years who presented at the emergency department with decompensated HF were randomly assigned to IHC or HaH. All patients were studied for 1 year. Seventy-one patients completed the study, of these 34 were admitted to cardiology and 37 received HaH care. No significant differences were found in baseline characteristics, including comorbidity, functional status, and health-related quality of life. Clinical outcomes were similar after initial admission and also after the 12 months of follow-up. Death or re-admission due to HF or another cardiovascular event occurred in 19 patients in IHC and 20 in HaH (P = 0.88). Changes in functional status and health-related quality of life over the follow-up period were not significantly different. The average cost of the initial admission was 4502 +/- 2153 euro in IHC and 2541 +/- 1334 euro in HaH (P < 0.001). During 12 months of follow-up, the average expenditure was 4619 +/- 7679 euro and 3425 +/- 4948 euro (P = 0.83) respectively.


CONCLUSION
Hospital at home care allows an important reduction in the costs during the index episode compared with hospital care, whilst maintaining similar outcomes with respect to cardiovascular mortality and morbidity and quality of life at 1 year follow-up.
Physician orders for life-sustaining treatment (POLST): lessons learned from analysis of the Oregon POLST Registry.

BACKGROUND
Physician Orders for Life-Sustaining Treatment (POLST) has become a common means of documenting patient treatment preferences. In addition to orders either for Attempt Resuscitation or Do Not Attempt Resuscitation, for patients not in cardiopulmonary arrest, POLST provides three levels of treatment: Full Treatment, Limited Interventions, and Comfort Measures Only. Oregon has an electronic registry for POLST forms completed in the state. We used registry data to examine the different combinations of treatment orders.


METHODS AND RESULTS
We analyzed data from forms signed and entered into the Oregon POLST Registry in 2012. The analysis included 31,294 POLST forms. The mean Registrant age was 76.7 years. 21,396 (68.4%) had Do Not Attempt Resuscitation (DNR) orders and 9900 (31.6%) had orders for "Attempt Resuscitation". The 6 order combinations were: Do Not Resuscitate (DNR)/Comfort Measures Only 10,769 (34.4%), DNR/Limited Interventions 9306 (29.7%), DNR/Full Treatment 1211 (3.9%), Attempt Cardiopulmonary Resuscitation (CPR)/Comfort Measures Only 11 (0.04%), Attempt CPR/Limited Interventions 2281 (7.3%), and Attempt CPR/Full Treatment 7473 (23.9%).


CONCLUSIONS
The most common order combinations were DNR/Comfort Measures Only, DNR/Limited Interventions and Attempt Resuscitation/Full Treatment. These three makes sense to health professionals. However, other order combinations that require interpretation at the time of a crisis were completed for about 10% of Registrants. These combinations need further investigation.