Miracle-dz/UniFAR-FTUs huggingface dataset:
SGK1 Mediates Hypoxic Pulmonary Hypertension through Promoting Macrophage Infiltration and Activation

Inflammation plays a pivotal role in the development of pulmonary arterial hypertension (PAH). Meanwhile, serum glucocorticoid-regulated kinase-1 (SGK1) has been considered to be an important factor in the regulation of inflammation in some vascular disease. However, the role of SGK1 in hypoxia-induced inflammation and PAH is still unknown. WT and SGK1−/− mice were exposed to chronic hypoxia to induce PAH. The quantitative PCR and immunohistochemistry were used to determine the expression of SGK1. The right ventricular hypertrophy index (RVHI), RV/BW ratio, right ventricle systolic pressure (RVSP), and percentage of muscularised vessels and medical wall thickness were measured to evaluate PAH development. The infiltration of macrophages and localization of SGK1 on cells were examined by histological analysis. The effects of SGK1 on macrophage function and cytokine expression were assessed by comparing WT and SGK1−/− macrophages in vitro. SGK1 has high expression in hypoxia-induced PAH. Deficiency of SGK1 prevented the development of hypoxia-induced PAH and inhibited macrophage infiltration in the lung. In addition, SGK1 knockout inhibited the expression of proinflammatory cytokines in macrophages. SGK1-induced macrophage activation and proinflammatory response contributes to the development of PAH in hypoxia-treated mice. Thus, SGK1 might be considered a promising target for PAH treatment.
Multi-frequency bioimpedance and myofascial release therapy: An equine “AtlasOrange1” validation study

Background: Measurable sources of muscle tension include viscoelastic tone, physiological contracture, voluntary contraction, and muscle spasm, and if left untreated, they can over a period of time result in clinical pain as a direct result of increased myofascia tension. Typically, physiotherapy is used to stretch affected muscles, thereby reducing motor neuron excitability, and as a consequence give the patient a sensation of correct posture and movement, thereby facilitating normal movement patterns. However, cases of documented therapy effectiveness are rare. Methods: A total of 6 horses with myofascial tension/imbalance issues were selected for this trial. The horses were assessed manually by a qualified Veterinarian and note was taken of regions with high resting myofascial tension as well as movement restrictions. The horses were then measured using a multi-frequency BioImpedance Analysis unit (SFB7) by a technician blinded to the manual assessment. AtlasOrange1, a new form of mechanical physiotherapy massage was used to treat all 6 horses. Treatment was applied directly to two anatomically identifiable myo-fascial regions for a total period of two minutes. Subsequently, the effects of treatment were followed using multi-frequency bioimpedance at an interval of 1, 24 and 48 hours. Results: Regions of increased myofascial tonus/stiffness were detected manually and noted for all 6 horses. The bioimpedance data was analyzed for centre frequency (fc) and extracellular resistance (Re) and delta values between the right- and left-hand sides of each horse were calculated. Treatment induced a 39% decrease for Re (NS) and a 58% decrease for fc ( P =0.003) over 48 hours post-treatment. The mfBIA values were subsequently compared with the findings of the manual evaluation revealing a 94.4% overall agreement. Conclusion: We suggest that a high level of resting myofascial tension/stiffness is measureable using mf-BIA, and that it can be relieved with massage forms of treatment like AtlasOrange1.
An innovative support group for parents with intellectual disabilities whose children have been removed

Parents who have had children removed constitute a vulnerable group of adults, who have been determined for a variety of reasons as not providing adequate care for their children. Parents with intellectual disability are at high risk of having their children removed from their care. Studies in Australia and internationally have found that up to one in three children of parents with intellectual disabilities will be placed in alternate care (Booth and Booth, 2005; McConnell, Llewellyn, and Ferronato, 2002; Mirfin-Veitch, Bray, Williams, Clarkson, and Belton, 1999). Despite these large numbers, little is known about the support needs of parents with intellectual disability in this situation. This paper reports on an innovative group program Parents on the Outside for mothers with intellectual disabilities who have lost custody of their children.
Pharmacokinetics in children with liver disease : can ex vivo obtained population-specific CYP450 characteristics bridge the knowledge gap?

For the determination of the in vitro cytochrome P450 activity in microsomes, a quantification method for the probe metabolites, formed during incubation, is required. Due to insufficient sensitivity of a previously developed high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for some of the metabolites, a fast and easy derivatization method with pyridine-3-sulfonyl chloride (PS) is described. Acetaminophen (CYP1A2), dextrorphan (CYP2D6), hydroxy-chlorzoxazone (CYP2E1) and hydroxy-mephenytoin (CYP2C19) can be derivatized because of the presence of a phenolic OH, whereas hydroxy-midazolam (CYP3A4) and hydroxytolbutamide (CYP2C9) remain unchanged. As PS improves the ionization efficiency in the positive electrospray ionization (ESI) mode, the sensitivity of the detection is improved significantly and meets requirements for the activity determination. Native negative electrospray type molecules, moreover, become positive ESI candidates. The direct derivatization in the aqueous incubation medium, without any other sample pretreatment steps, such as evaporation or extraction, makes this procedure easy to perform. The method using 20 s microwave irradiation was shown to equal a 10 minute reaction in a 60°C heating block, consequently simplifying and shortening the process. Collision induced fragmentation of the derivatives resulted in at least one native compound, rather than derivative, specific product ion, thereby improving the selectivity of the method in the multiple reaction monitoring mode. The HPLC-MS/MS method was validated, and was demonstrated to be sensitive, selective, precise and accurate. The absence of a relative matrix effect was established, notwithstanding that an absolute matrix effect was observed. The analysis of a sample after (human) microsomal incubation, from which some of the metabolites could not be quantified using the method without derivatization, proved the usefulness of the method. CHAPTER 1 – DERIVATIZATION-HPLC-MS/MS ANALYSIS OF SIX PROBE METABOLITES
Cytokine levels in severe trauma injury

Objectives: It is well known that trauma induces a generalized inflammatory reaction involving a huge number of different mediators. The pro-inflammatory cytokines: tumour necrosis factor α (TNF-α), interleukin-1 (IL-1), IL-6 and anti-inflammatory cytokine IL-10 play pivotal roles. Their serum levels have been reported to be associated with clinical outcomes in trauma patients.The aim of this research was to assess the kinetics of above mentioned cytokines during seven days follow up and to compare their serum levels between trauma survivors and non-survivors. Methods: This prospective study recruited 47 patients treated for severe injuries at surgical intensive care units. All patients met the inclusion criteria, which included an Injury Severity Score ≥18 (severe injury), age range 16-65 years, admission to the hospital within the first 24 hours after injury and survival longer than 48 hours. Blood samples for serum TNF-α, IL-1, IL-6 and IL-10 measurements were drawn at the baseline and at 24, 48, 72 hours and day 7th of hospitalization. Results: A significant decrease in serum IL-6 levels during the follow-up was observed in non-survivors (p=0.010) and survivors (p=0.000). Serum IL-6 level was significantly higher in non-survivors compared to survivors at 72h [140.3 (28.86-981.8) pg/mL vs. 62.4 (24.8-262.4) pg/mL; p=0.033] and at day 7th upon admission [102.6 (36.4-718.5) pg/mL vs. 29.87 (11.4-344.2) pg/mL; p<0.001]. Conclusion: IL-6 is potentially associated with survival outcome in severely injured patients, although larger prospective studies are needed. Keywords: cytokines, severe injury, outcome prediction
Evolutionary algorithms for the optimization of reliability in parallel/series redundant systems

The allocation of redundancy and availability in parallel/series system is known to be an intractable problem for which no deterministic algorithm is expected to succeed. The difficulties come from the constraints put on the problem and the mixed variable types. This paper presents two problem-specific evolutionary algorithms for solving the cost minimization and the availability maximization versions of this problem. For the first case, the proposed algorithm makes use of evolutionary operators that map feasible points into other feasible points. Specialized operators for boundary search allows an optimal utilization of available resources, since the search is restricted to solutions corresponding to a full utilization of these resources. In the second case, boundary search operators can not be explicitly stated. The proposed alternative is a repair algorithm that maps infeasible solutions to feasible ones as close as possible to the boundary of feasibility, if not exactly on it.
Prospects for Detecting X-Ray Polarization in Blazar Jets

X-ray polarization should provide new probes of magnetic field geometry and acceleration physics near the base of blazar jets, but near-future missions will have limited sensitivity. We thus use existing lower energy data and X-ray variability measurements in the context of a basic synchro-Compton model to predict the X-ray polarization level and the probability of detection success for individual sources, listing the most attractive candidates for an Imaging X-ray Polarimetry Explorer campaign. We find that, as expected, several high-peak blazars such as Mrk 421 can be easily measured in 100 ks exposures. Most low-peak sources should only be accessible to triggered campaigns during bright flares. Surprisingly, a few intermediate peak sources can have anomalously high X-ray polarization and thus are attractive targets.
Empirical Risk Minimization under Random Censorship: Theory and Practice

We consider the classic supervised learning problem, where a continuous non-negative random label $Y$ (i.e. a random duration) is to be predicted based upon observing a random vector $X$ valued in $\mathbb{R}^d$ with $d\geq 1$ by means of a regression rule with minimum least square error. In various applications, ranging from industrial quality control to public health through credit risk analysis for instance, training observations can be right censored, meaning that, rather than on independent copies of $(X,Y)$, statistical learning relies on a collection of $n\geq 1$ independent realizations of the triplet $(X, \; \min\{Y,\; C\},\; \delta)$, where $C$ is a nonnegative r.v. with unknown distribution, modeling censorship and $\delta=\mathbb{I}\{Y\leq C\}$ indicates whether the duration is right censored or not. As ignoring censorship in the risk computation may clearly lead to a severe underestimation of the target duration and jeopardize prediction, we propose to consider a plug-in estimate of the true risk based on a Kaplan-Meier estimator of the conditional survival function of the censorship $C$ given $X$, referred to as Kaplan-Meier risk, in order to perform empirical risk minimization. It is established, under mild conditions, that the learning rate of minimizers of this biased/weighted empirical risk functional is of order $O_{\mathbb{P}}(\sqrt{\log(n)/n})$ when ignoring model bias issues inherent to plug-in estimation, as can be attained in absence of censorship. Beyond theoretical results, numerical experiments are presented in order to illustrate the relevance of the approach developed.
THE FACTORS RELEVANT TO THE ONSET OF VASCULAR COMPLICATIONS AFTER CORONARY INTERVENTION IN SHAHID RAJAEI CARDIOVASCULAR CENTER IN TEHRAN, IRAN

Background: Vascular complications, as the most common complications of diagnostic catheterization and percutaneous coronary intervention (PCI) , are important factors in the morbidity of patients undergoing such procedures; thus, this study was done to evaluate the prevalence of these complications and their related factors. Methods: This is a descriptive study composed of 2097 consecutive patients who underwent percutaneous coronary intervention in Shahid Rajaei Cardiovascular Center in Tehran, Iran from January 2008 to January 2009 . Occurrence of vascular complications in course of hospitalization and the related factors leading to the complications were investigated. Results: Out of 2097 patients, 1544 (73.6%) were male and 553 (26.4%) were female, and the mean age of the participants was 57  10 years. Vascular complications from the time of PCI to the time discharge were observed in 19 (0.9%) patients. The other complications included: hematoma in 10 cases (52.6%) , pseudoaneurysm in five cases (26.3%) , retroperitoneal hemorrhage and arteriovenous fistula in 2 (10.5%) patients each. The complications were significantly more common in female patients (P=0.003) , in patients with a history of hypertension (P=0.02) , people of shorter stature (P=0.004) , and being on gp III a/ II b inhibitors (P=0.003) . Conclusion: The rate of vascular complications post-percutaneous coronary interventions is low and it is considered to be a good treatment option for patients with coronary stenosis; provided that sufficient compression is applied on the vascular access point in the right time after removal of the arterial sheath. PCI is of fewer vascular complications, especially in female patients, history of hypertension, and higher anticoagulant complication.
Keeping patients safe: The relationship between patient safety climate and patient outcomes

Author(s): O'Brien, Roxannne Louise | Advisor(s): Blegen, Mary A | Abstract: KEEPING PATIENTS SAFE: THE RELATIONSHIP BETWEEN PATIENT SAFETY CLIMATE AND PATIENT OUTCOMESRoxanne Louise O'BrienIncreasing complexity and use of technology in health care has provided life-saving advances in patient care and also increased risks of medical error. Developing a culture of safety and assessing the safety climate or measurable attitudes of staff, in hospitals has been recommended as approaches to enhancing the safety of hospitalized patients. This study used a cross-sectional, descriptive, model testing design to evaluate the relationship between patient safety climate, patient outcomes, staffing, and hospital performance measures. The sample consisted of multiple patient care units and ancillary departments in 10 hospitals. Secondary databases used in this research included responses to a patient safety attitudes survey, unit level patient falls and hospital acquired pressure ulcers, unit staffing data, and hospital level performance measures. Bivariate correlations, descriptive statistics, ANOVA, and hierarchical linear modeling were used to describe unit and hospital level safety attitudes. Patient safety climate was found to vary significantly across units and among hospitals. There were no relationships found between patient safety climate, falls and hospital acquired pressure ulcers. Higher staffing hours in ICU were a confounder in the analysis of a significant relationship between patient safety climate and nurse staffing. A reduction in the failure rate for the community acquired pneumonia hospital performance measure was associated with staff perception of support from unit managers. Understanding how patient safety climate influences the safety of hospitalized patients is currently evolving. Continuing research in this area is warranted to explore this relationship.
Changes in growth, digestibility and gut anatomy by broilers fed diets containing ethanol-treated castor oil seed (Ricinus communis L.) meal.

Eight weeks feeding trial was conducted to investigate the chemical composition, growth response, apparent nutrient digestibility, gut characteristics and morphology of broiler chickens fed four diets containing ethanol-treated castor oil seed meal (ECAM). Two hundred day-old Anak 2000 broiler chicks were then allotted to the four experimental diets containing ECAM at 0, 100, 150 and 200 g/kg, respectively. Each treatment was replicated five times with 10 birds per replicate. The final live weight, weight gain and feed intake reduced (P < 0.01) with increasing dietary inclusion of ECAM. Control fed broilers and those fed diets containing 100 g/kg and 150 g/kg ECAM had similar feed to gain ratio. Broilers fed diets containing 200 g/kg ECAM recorded the least (Linear and quadratic contrast, P < 0.05) crude protein and crude fibre digestibility, and the poorest (Linear contrast, P < 0.05) feed to gain ratio. Similar improved feed to gain ratio, apparent crude fibre, fat and ash digestibility were noticed with birds fed the control diet, diets containing 100 g/kg and 150 g/kg ECAM, respectively. Relative gizzard weight increased (P < 0.05) with increasing dietary inclusion levels of ECAM. Broilers fed with 200 g/kg ECAM recorded the heaviest (P < 0.05) relative gizzard, pancreas, duodenum weight and the longest (P < 0.05) relative jejunum and ileum length. Villi length and crypt depth of the duodenum reduced (P < 0.05) with increasing dietary inclusion of ECAM. In conclusion, ethanol-treated castor seed oil meal can be included up to 150 g/kg diet in broiler ration without impairing growth and nutrient digestibility.
Configuration-Dependent Fault Localization

In a buggy configurable system, configuration-dependent bugs cause the failures in only certain configurations due to unexpected interactions among features. Manually localizing configuration-dependent faults in configurable systems could be highly time-consuming due to their complexity. However, the cause of configuration-dependent bugs is not considered by existing automated fault localization techniques, which are designed to localize bugs in non-configurable code. Thus, their capacity for efficient configuration-dependent localization is limited. In this work, we propose COFL, a novel approach to localize configuration-dependent bugs by identifying and analyzing suspicious feature interactions that potentially cause the failures in buggy configurable systems. We evaluated the efficiency of COFL in fault localization of artificial configuration-dependent faults in a highly-configurable system. We found that COFL significantly improves the baseline spectrum-based approaches. With COFL, on average, the correctness in ranking the buggy statements increases more than 7 times, and the search space is significantly narrowed down, about 15 times.
Inducible expression of NOS and COX-2 in evaluating the effects of Ruyi-Jinhuang Gao on somatic pain - Associated inflammation

Ruyi-Jinhuang Gao (RJG) is an ointment prepared from Ruyi-Jinhuang San (RJS), a traditional formula of powder-type Chinese medicine, usually used in anti-inflammatory analgesic care in China. The present study is aimed to detect the anti-inflammatory signaling of RJG exposed by an experimental model of lipopolysaccharides (LPS)-induced pro-inflammatory expression of inducible nitric oxide synthase (iNOS) and prostaglandin endoperoxide synthase (PGH synthase-2, COX-2). LPS-induced activation of iNOS and COX-2 has been recognized to increase cytokines and nitric oxide (NO), which play predominant roles in inflammation. In the culture of RAW264.7 cells, RJG concentration-dependently inhibited LPS-induced iNOS and COX-2 expression. However, the herbal components of RJG displayed different results, including increase and decrease of both protein expressions. Among them, inhibition by Curcuma Zedorarica Rhizoma (Cu), Atractylodis Lancea Rhizoma (At), and Glycyrrhizae Radix (Gl) are more potent than that by others. Inhibition by Cu and At are associated with their cytotoxicity. Glycyrrhizae Radix (Gl), with lower cytotoxicity in comparison with Cu and At, is the most potent component of RJG on inhibiting LPS-induced iNOS and COX-2 expression. In comparison with LPS-induced tumor necrosis factor-α (TNF-α), croton oil-induced formation of TNF-α and interleukin-4 (IL4), RJG did not increase the pro-inflammatory cytokines. These facts indicated that RJG could not significantly sensitize an immunologic response during the treatment of non-wounded inflammation on body surface. Ruyi-Jinhuang Patch (RJP), a pharmaceutical preparation of RJG, has proven to have significant relief of cutaneous inflammation-associated somatic pain in clinical use.
cis-Regulatory control of three cell fate-specific genes in vulval organogenesis of C. elegans and C. briggsae

The great-grandprogeny of the Caenorhabditis elegans vulval precursor cells (VPCs) adopt one of the final vulA, B1, B2, C, D, E and F cell types in a precise spatial pattern. Formation of the pattern of vulval cell types is likely to depend upon the cis-regulatory regions of the transcriptional targets of these intercellular signals in vulval development. The outcome of such differential activation will result in individual cell types. egl-17, zmp-1, cdh-3 are expressed differentially in the developing vulva cells, providing a potential readout for different signaling pathways. To understand how different signaling pathways interact to specify unique vulval cell types in a precise pattern, I have identified upstream cis-regulatory regions that are sufficient for their ability to confer vulval cell type-specific regulation when fused in cis to the basal pes-10 promoter. In the egl-17 promoter, I have identified a 143 base pair (bp) region that drives vulC and vulD expression, and a 102 bp region that is sufficient to drive the early expression in presumptive vulE and vulF cells. In the zmp-1 promoter, I have identified a 300 bp region that is sufficient to drive expression in vulE, vulA and the anchor cell. In the cdh-3 promoter, I have identified a 689 bp region sufficient to drive expression in the anchor cell and vulE, vulF, vulD and vulC, a 155 bp region sufficient to drive only anchor cell expression, and a separate 563 bp region that was also sufficient to drive expression in these vulval cells. I have identified the C. briggsae homologs of these three genes, and the corresponding control regions, and tested these regions in both C. elegans and C. briggsae. I find that these regions of similarity in C. elegans and C. briggsae upstream of egl-17, zmp-1, and cdh-3 promote expression in vulval cells and the anchor cell. Using the regions defined by the sufficiency analysis and phylogenetic footprinting, I have been able to isolate over-represented sequences that may play important roles in conferring vulval and anchor cell expression.