bluuebunny/crossref_metadata_2025_split huggingface dataset:
N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats
Authors: Chaumais Marie-Camille , Ranchoux Benoît , Montani David , Dorfmüller Peter , Tu Ly , Lecerf Florence , Raymond Nicolas , Guignabert Christophe , Price Laura , Simonneau Gérald , Cohen-Kaminsky Sylvia , Humbert Marc , Perros Frédéric 
Published: June 2014

Abstract

Background
The outcome of patients suffering from pulmonary arterial hypertension (PAH) are predominantly determined by the response of the right ventricle to the increase afterload secondary to high vascular pulmonary resistance. However, little is known about the effects of the current available or experimental PAH treatments on the heart. Recently, inflammation has been implicated in the pathophysiology of PAH. N-acetylcysteine (NAC), a well-known safe anti-oxidant drug, has immuno-modulatory and cardioprotective properties. We therefore hypothesized that NAC could reduce the severity of pulmonary hypertension (PH) in rats exposed to monocrotaline (MCT), lowering inflammation and preserving pulmonary vascular system and right heart function.

Methods
Saline-treated control, MCT-exposed, MCT-exposed and NAC treated rats (day 14–28) were evaluated at day 28 following MCT for hemodynamic parameters (right ventricular systolic pressure, mean pulmonary arterial pressure and cardiac output), right ventricular hypertrophy, pulmonary vascular morphometry, lung inflammatory cells immunohistochemistry (monocyte/macrophages and dendritic cells), IL-6 expression, cardiomyocyte hypertrophy and cardiac fibrosis.

Results
The treatment with NAC significantly decreased pulmonary vascular remodeling, lung inflammation, and improved total pulmonary resistance (from 0.71 ± 0.05 for MCT group to 0.50 ± 0.06 for MCT + NAC group, p < 0.05). Right ventricular function was also improved with NAC treatment associated with a significant decrease in cardiomyocyte hypertrophy (625 ± 69 vs. 439 ± 21 μm2 for MCT and MCT + NAC group respectively, p < 0.001) and heart fibrosis (14.1 ± 0.8 vs. 8.8 ± 0.1% for MCT and MCT + NAC group respectively, p < 0.001).

Conclusions
Through its immuno-modulatory and cardioprotective properties, NAC has beneficial effect on pulmonary vascular and right heart function in experimental PH.
Determination of sample size for a multi-class classifier based on single-nucleotide polymorphisms: a volume under the surface approach
Authors: Liu Xinyu , Wang Yupeng , Sriram TN 
Published: June 2014

Abstract

Background
Data on single-nucleotide polymorphisms (SNPs) have been found to be useful in predicting phenotypes ranging from an individual’s class membership to his/her risk of developing a disease. In multi-class classification scenarios, clinical samples are often limited due to cost constraints, making it necessary to determine the sample size needed to build an accurate classifier based on SNPs. The performance of such classifiers can be assessed using the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) for two classes and the Volume Under the ROC hyper-Surface (VUS) for three or more classes. Sample size determination based on AUC or VUS would not only guarantee an overall correct classification rate, but also make studies more cost-effective.

Results
For coded SNP data from D(≥2) classes, we derive an optimal Bayes classifier and a linear classifier, and obtain a normal approximation to the probability of correct classification for each classifier. These approximations are then used to evaluate the associated AUCs or VUSs, whose accuracies are validated using Monte Carlo simulations. We give a sample size determination method, which ensures that the difference between the two approximate AUCs (or VUSs) is below a pre-specified threshold. The performance of our sample size determination method is then illustrated via simulations. For the HapMap data with three and four populations, a linear classifier is built using 92 independent SNPs and the required total sample sizes are determined for a continuum of threshold values. In all, four different sample size determination studies are conducted with the HapMap data, covering cases involving well-separated populations to poorly-separated ones.

Conclusion
For multi-classes, we have developed a sample size determination methodology and illustrated its usefulness in obtaining a required sample size from the estimated learning curve. For classification scenarios, this methodology will help scientists determine whether a sample at hand is adequate or more samples are required to achieve a pre-specified accuracy. A PDF manual for R package “SampleSizeSNP” is given in Additional file 1, and a ZIP file of the R package “SampleSizeSNP” is given in Additional file 2.
Serum TFF3 may be a pharamcodynamic marker of responses to chemotherapy in gastrointestinal cancers
Authors: Xiao Li , Liu Yun-Peng , Xiao Chuan-Xing , Ren Jian-Lin , Guleng Bayasi 
Published: June 2014

Abstract

Background
As a secreted protein, serum trefoil factor 3 (TFF3) has been reported to be a biomarker of several malignancies. We further investigated whether TFF3 can be applied as a biomarker for and predictor of responses to chemotherapy in gastrointestinal cancer.

Methods
Serum and urine samples were collected from 90 patients with gastric cancer, 128 patients with colorectal cancer and 91 healthy individuals. Serum and urine TFF3 levels were measured using an ELISA.

Results
Serum and urine TFF3 levels were significantly higher in the patients with gastric and colorectal cancer compared with the healthy individuals (P < 0.05). Higher serum levels of TFF3 were significantly correlated with distant metastasis and an advanced stage in the two types of cancer (P < 0.05). Age and the number of lymph node metastases were significantly correlated with serum TFF3 levels in colorectal cancer, and decreased serum TFF3 levels were significantly correlated with responses to chemotherapy in both the gastric and the colorectal cancer partial response (PR) groups. A combination of serum and urine data did not significantly improve the detection of either cancer, although urine levels have shown a significant negative relationship with the glomerular filtration rate (GFR).

Conclusions
Our data indicate that TFF3 may be an effective biomarker of tumor stage and the presence of distant metastasis, and may be a pharmacodynamic marker of response to chemotherapy in gastrointestinal cancer.
A simple block diagonal precoding for multi-user MIMO broadcast channels
Authors: Khan Md Hashem Ali , Cho K M , Lee Moon Ho , Chung Jin-Gyun 
Published: June 2014

Abstract
The block diagonalization (BD) is a linear precoding technique for multi-user multi-input multi-output (MIMO) broadcast channels, which is able to completely eliminate the multi-user interference (MUI), but it is not computationally efficient. In this paper, we propose the block diagonal Jacket matrix decomposition, which is able not only to extend the conventional block diagonal channel decomposition but also to achieve the MIMO broadcast channel capacity. We also prove that the QR algorithm achieves the same sum rate as that of the conventional BD scheme. The complexity analysis shows that our proposal is more efficient than the conventional BD method in terms of the number of the required computation.
Gain and Loss of Function of P2X7 Receptors: Mechanisms, Pharmacology and Relevance to Diabetic Neuropathic Pain
Authors: Ursu Daniel , Ebert Philip , Langron Emily , Ruble Cara , Munsie Leanne , Zou Wei , Fijal Bonnie , Qian Yue-Wei , McNearney Terry A , Mogg Adrian , Grubisha Olivera , Merchant Kalpana , Sher Emanuele 
Published: June 2014

Background: Genetic causes of exaggerated or reduced pain sensitivity in humans are well known. Recently, single nucleotide polymorphisms (SNPs) in the gene P2RX7, coding for the ATP-gated ion channel P2X7, have been described that cause gain-of-function (GOF) and loss-of-function (LOF), respectively of this channel. Importantly, P2RX7 SNPs have been associated with more or less severe pain scores in patient suffering of post-mastectomy pain and osteoarthritis. Results: The functional consequences of some P2RX7 SNPs (rs208294 (His155Tyr), rs1718119 (Ala348Thr) and rs3751143 (Glu496Ala)) were studied in recombinant cells in vitro. Our findings suggest a correlation between GOF and LOF of P2X7 and actual channel protein expression. Both channel and pore function for these mutant P2X7 receptors changed in parallel to protein levels. On the other hand, the mutant receptors did not differ in their sensitivity to known P2X7 agonists and antagonists. We further demonstrated that in patients with diabetic peripheral neuropathic pain (DPNP), the presence of the GOF SNPs rs208294 (His155Tyr) and rs1718119 (Ala348Thr) is associated, in females, with higher pain intensity scores. Conclusions: Our present results confirm the physiological relevance of some of the SNPs in the P2RX7 gene and show that the presence of these genetic variants correlates with pain sensitivity also in a diabetic neuropathic pain patient population.
Age related changes to the dynamics of contralateral DPOAE suppression in human subjects
Authors: Konomi Ujimoto , Kanotra Sohit , James Adrian L , Harrison Robert V 
Published: June 2014

Background The two ears are linked with a neural pathway such that stimulation of one ear has a modulating effect on the contralateral cochlea. This is mediated by cochlear afferent neurons connecting with olivo-cochlear efferents. The monitoring of this pathway is easily achieved by measuring contralateral suppression of otoacoustic emissions, and there is some clinical value in the ability to assess the integrity of this pathway. An important step in an evaluation of clinical utility is to assess any age-related changes. Accordingly, in the present study we measure the dynamics of contralateral DPOAE suppression in a population of normal hearing subjects of different ages. Methods Using a real-time DPOAE recording method we assessed contralateral DPOAE suppression in 95 ears from 51 subjects (age range 2–52 years). DPOAE (2f1-f2; f2 = 4.4 kHz; f2/f1 = 1.22) input–output functions were measured. In response to contralateral broadband noise, dynamic aspects of DPOAE suppression were measured, specifically suppression onset latency and time constants. Results An age-related reduction in DPOAE amplitudes was observed. Both the detectability and the degree of contralateral DPOAE suppression were decreased in older age groups. We find an age-related increase in the latency of onset of DPOAE suppression to contralateral stimulation, but no significant change in suppression time-constants. Conclusion Olivo-cochlear function as revealed by contralateral suppression of DPOAEs shows some important age-related changes. In addition to reduced emissions (outer haircell suppression) we find an increased latency that may reflect deterioration in auditory brainstem function. Regarding clinical utility, it is possible that the changes observed may reflect an aspect of age-related hearing loss that has not been previously considered.
Applying compressed sensing to genome-wide association studies
Authors: Vattikuti Shashaank , Lee James J , Chang Christopher C , Hsu Stephen D H , Chow Carson C 
Published: June 2014

Abstract

Background
The aim of a genome-wide association study (GWAS) is to isolate DNA markers for variants affecting phenotypes of interest. This is constrained by the fact that the number of markers often far exceeds the number of samples. Compressed sensing (CS) is a body of theory regarding signal recovery when the number of predictor variables (i.e., genotyped markers) exceeds the sample size. Its applicability to GWAS has not been investigated.

Results
Using CS theory, we show that all markers with nonzero coefficients can be identified (selected) using an efficient algorithm, provided that they are sufficiently few in number (sparse) relative to sample size. For heritability equal to one (h2 = 1), there is a sharp phase transition from poor performance to complete selection as the sample size is increased. For heritability below one, complete selection still occurs, but the transition is smoothed. We find for h2 ~ 0.5 that a sample size of approximately thirty times the number of markers with nonzero coefficients is sufficient for full selection. This boundary is only weakly dependent on the number of genotyped markers.

Conclusion
Practical measures of signal recovery are robust to linkage disequilibrium between a true causal variant and markers residing in the same genomic region. Given a limited sample size, it is possible to discover a phase transition by increasing the penalization; in this case a subset of the support may be recovered. Applying this approach to the GWAS analysis of height, we show that 70-100% of the selected markers are strongly correlated with height-associated markers identified by the GIANT Consortium.
Serum HDL-C level of Iranian adults: results from sixth national Surveillance of Risk Factors of Non-Communicable Disease
Authors: Hosseini Mostafa , Navidi Iman , Yousefifard Mahmoud , Heshmat Ramin , Koohpayehzadeh Jalil , Asgari Fereshteh , Etemad Koorosh , Rafei Ali , Gouya Mohammad Mehdi 
Published: June 2014

Abstract
Background
Reduced level of high-density lipoprotein-cholesterol (HDL-C) is shown to be in association with the risk of coronary artery disease (CAD), metabolic syndrome, and chronic renal disease. Lack of a national representative research for assessing the level of HDL-C among Iranian adults, which is essential for health policy makers, was the motivation for this study.

Methods
HDL-C levels of 4,803 Iranian adults aged 25–64 years old were measured by sixth national Surveillance of Risk Factors of Non-Communicable Disease (SuRFNCD) in 2011. Data were entered into STATA 12 software and were analyzed using fractional polynomial model and other statistical methods.

Results
In average, Iranian adult women had 5.8 ± 0.3 mg/dL higher HDL-C level than men. The analysis showed that the HDL-C levels will be changed at most 3 mg/dL from the age of 25 to 64 years. Furthermore, it was shown that approximately half of the men and one third of the women had HDL-C level less than 40 mg/DL. Also HDL-C level of more than 60% of the women was less than 50 mg/dL.

Conclusions
High level of HDL-C among Iranian adults was shown in this study which can be a major reason of increasing incidence of heart diseases in Iran. Hence, formulating policy regulations and interventions in Iranian lifestyle to reduce HDL-C levels should be among top priorities for health politicians.
Incidence and predictors of morphometric vertebral fractures in patients with ankylosing spondylitis
Authors: Kang Kwi Young , Kim In Je , Jung Seung Min , Kwok Seung-Ki , Ju Ji Hyeon , Park Kyung-Su , Hong Yeon Sik , Park Sung-Hwan 
Published: June 2014

Abstract
Introduction
Ankylosing spondylitis (AS) is associated with an increased incidence of vertebral fractures (VFs); however the actual incidence and predictors of morphometric VFs are unknown. The present study examined the incidence and predictors of new VFs in a large AS cohort.

Methods
In total, 298 AS patients who fulfilled the modified New York criteria were enrolled and spinal radiographs were evaluated biennially. Clinical and laboratory data and radiographic progression were assessed according to the Bath AS Disease Activity Index, erythrocyte sedimentation rate, C-reactive protein (CRP), and the Stoke AS spine score (SASSS). VF was defined according to the Genant criteria. The incidence of VFs at 2 and 4 years was evaluated using the Kaplan-Meier method. The age-specific standardized prevalence ratio (SPR) for AS patients in comparison with the general population was calculated.

Results
Of 298 patients, 31 (10.8%) had previous VFs at baseline. A total of 30 new VFs occurred in 26 patients over 4 years. The incidence of morphometric VFs was 4.7% at 2 years and 13.6% at 4 years. Multivariate logistic regression analysis showed that previous VFs at baseline and increased CRP levels at 2 years were predictors of new VFs (odds ratio (OR) =12.8, 95% confidence interval (CI) = 3.6-45.3 and OR = 5.4, 95% CI = 1.4–15.9). The age-specific specific standardized prevalence ratio of morphometric VFs in AS was 3.3 (95% CI 2.1–4.5).

Conclusions
The incidence of morphometric VFs increased in AS. Previous VFs and increased CRP levels predicted future VFs. Further studies are needed to identify the effects of treatment interventions on the prevention of new VFs.
Novel serum protein biomarker panel revealed by mass spectrometry and its prognostic value in breast cancer
Authors: Chung Liping , Moore Katrina , Phillips Leo , Boyle Frances M , Marsh Deborah J , Baxter Robert C 
Published: June 2014

Abstract
Introduction
Serum profiling using proteomic techniques has great potential to detect biomarkers that might improve diagnosis and predict outcome for breast cancer patients (BC). This study used surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS) to identify differentially expressed proteins in sera from BC and healthy volunteers (HV), with the goal of developing a new prognostic biomarker panel.

Methods
Training set serum samples from 99 BC and 51 HV subjects were applied to four adsorptive chip surfaces (anion-exchange, cation-exchange, hydrophobic, and metal affinity) and analyzed by time-of-flight MS. For validation, 100 independent BC serum samples and 70 HV samples were analyzed similarly. Cluster analysis of protein spectra was performed to identify protein patterns related to BC and HV groups. Univariate and multivariate statistical analyses were used to develop a protein panel to distinguish breast cancer sera from healthy sera, and its prognostic potential was evaluated.

Results
From 51 protein peaks that were significantly up- or downregulated in BC patients by univariate analysis, binary logistic regression yielded five protein peaks that together classified BC and HV with a receiver operating characteristic (ROC) area-under-the-curve value of 0.961. Validation on an independent patient cohort confirmed the five-protein parameter (ROC value 0.939). The five-protein parameter showed positive association with large tumor size (P = 0.018) and lymph node involvement (P = 0.016). By matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS, immunoprecipitation and western blotting the proteins were identified as a fragment of apolipoprotein H (ApoH), ApoCI, complement C3a, transthyretin, and ApoAI. Kaplan-Meier analysis on 181 subjects after median follow-up of >5 years demonstrated that the panel significantly predicted disease-free survival (P = 0.005), its efficacy apparently greater in women with estrogen receptor (ER)-negative tumors (n = 50, P = 0.003) compared to ER-positive (n = 131, P = 0.161), although the influence of ER status needs to be confirmed after longer follow-up.

Conclusions
Protein mass profiling by MS has revealed five serum proteins which, in combination, can distinguish between serum from women with breast cancer and healthy control subjects with high sensitivity and specificity. The five-protein panel significantly predicts recurrence-free survival in women with ER-negative tumors and may have value in the management of these patients.
Midazolam and propofol used alone or sequentially for long-term sedation in critically ill, mechanically ventilated patients: a prospective, randomized study
Authors: Zhou Yongfang , Jin Xiaodong , Kang Yan , Liang Guopeng , Liu Tingting , Deng Ni 
Published: June 2014

Abstract
Introduction
Midazolam and propofol used alone for long-term sedation are associated with adverse effects. Sequential use may reduce the adverse effects, and lead to faster recovery, earlier extubation and lower costs. This study evaluates the effects, safety, and cost of midazolam, propofol, and their sequential use for long-term sedation in critically ill mechanically ventilated patients.

Methods
A total of 135 patients who required mechanical ventilation for >3 days were randomly assigned to receive midazolam (group M), propofol (group P), or sequential use of both (group M-P). In group M-P, midazolam was switched to propofol until the patients passed the spontaneous breathing trial (SBT) safety screen. The primary endpoints included recovery time, extubation time and mechanical ventilation time. The secondary endpoints were pharmaceutical cost, total cost of ICU stay, and recollection to mechanical ventilation-related events.

Results
The incidence of agitation following cessation of sedation in group M-P was lower than group M (19.4% versus 48.7%, P = 0.01). The mean percentage of adequate sedation and duration of sedation were similar in the three groups. The recovery time, extubation time and mechanical ventilation time of group M were 58.0 (interquartile range (IQR), 39.0) hours, 45.0 (IQR, 24.5) hours, and 192.0 (IQR, 124.0) hours, respectively; these were significantly longer than the other groups, while they were similar between the other two groups. In the treatment-received analysis, ICU duration was longer in group M than group M-P (P = 0.016). Using an intention-to-treat analysis and a treatment-received analysis, respectively, the pharmaceutical cost of group M-P was lower than group P (P <0.01) and its ICU cost was lower than group M (P <0.01; P = 0.015). The proportion of group M-P with unbearable memory of the uncomfortable events was lower than in group M (11.7% versus 25.0%, P <0.01), while the proportion with no memory was similar (P >0.05). The incidence of hypotension in group M-P was lower than group (P = 0.01).

Conclusion
Sequential use of midazolam and propofol was a safe and effective sedation protocol, with higher clinical effectiveness and better cost-benefit ratio than midazolam or propofol used alone, for long-term sedation of critically ill mechanically ventilated patients.

Trial registration
Current Controlled Trials ISRCTN01173443. Registered 25 February 2014.
Adrenomedullin: a vasodilator to treat sepsis?
Authors: Pugin Jérôme 
Published: June 2014

AbstractAdrenomedullin is a vasodilatory polypeptide with pleiotropic effects secreted by various organs. Adrenomedullin is produced first as a prepropeptide, and then cleaved into mature adrenomedullin and mid-regional proadrenomedullin. Whereas levels of the latter have been shown to correlate with severity of sepsis and carry prognostic value, adrenomedullin plays a role in vascular tone homeostasis. In the previous issue of Critical Care, the infusion of exogenous adrenomedullin is suggested to protect against increased lung endothelial permeability and end-organ dysfunction in a model of pneumococcal pneumonia in mechanically ventilated mice, possibly by stabilizing vascular endothelia. Since adrenomedullin is a strong vasodilatory molecule, further studies are needed to evaluate its potential as a future treatment of sepsis.