Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel targets of therapy in asthma

Purpose of review The use of inhaled corticosteroids, short and long acting β2-adrenoceptor agonists and inhibitors of leukotrienes provide most asthmatic patients with good disease control. However, none of these therapies are specifically directed to the underlying causal pathways of asthma. In this review the role of selective inhibitors of the inflammatory cascade are presented with a particular emphasis on biologics. Recent findings Apart from antihuman immunoglobulin E, biologics have had little impact on this disease. However, with the definition of critical pathways in driving ongoing inflammation and airway remodelling, the situation is about to change with several exciting new approaches being on the horizon. Specific cytokines that are considered central to the Th2 inflammatory response as therapeutic targets are discussed along with some entirely new approaches such as restoration of mucosal innate immunity and epithelial barrier function and the application of radiofrequency ablation of airway smooth muscle or thermal bronchoplasty. Summary What is becoming clear in filling the pipeline with new asthma therapies that treat the underlying disease causes is the need for closer working between clinical academics and industry to ensure that there is a rapid and sustained transfer of knowledge on novel targets through to their validation, proof of concept studies and clinical trials.
Cholesteryl ester acyl oxidation and remodeling in murine macrophages: formation of oxidized phosphatidylcholine[S]

Cholesterol is an essential component of eukaryotic cell membranes, regulating fluidity and permeability of the bilayer. Outside the membrane, cholesterol is esterified to fatty acids forming cholesterol esters (CEs). Metabolism of CEs is characterized by recurrent hydrolysis and esterification as part of the CE cycle; however, since recombinant 15-lipoxygenase (15-LO) was shown to oxidize cholesteryl linoleate of LDL, there has been interest in CE oxidation, particularly in the context atherogenesis. Studies of oxidized CE (oxCE) metabolism have focused on hydrolysis and subsequent reverse cholesterol transport with little emphasis on the fate the newly released oxidized fatty acyl component. Here, using mass spectrometry to analyze lipid oxidation products, CE metabolism in murine peritoneal macrophages was investigated. Ex vivo macrophage incubations revealed that cellular 15-LO directly oxidized multiple CE substrates from intracellular stores and from extracellular sources. Freshly harvested murine macrophages also contained 15-LO-specific oxCEs, suggesting the enzyme may act as a CE-oxidase in vivo. The metabolic fate of oxCEs, particularly the hydrolysis and remodeling of oxidized fatty acyl chains, was also examined in the macrophage. Metabolism of deuterated CE resulted in the genesis of deuterated, oxidized phosphatidylcholine (oxPC). Further experiments revealed these oxPC species were formed chiefly from the hydrolysis of oxidized CE and subsequent reacylation of the oxidized acyl components into PC.
Patient preferences for diabetes-related complications in Taiwan

Abstract Background: As the prevalence of diabetes mellitus (DM) continues to increase rapidly, there has been a rising need not only to assess the clinical outcomes but also the impact of DM on the health-related quality of life (HRQoL) of affected individuals. Most previous studies have found that having complications is strongly associated with decreased HRQoL in DM patients. As such, it is crucial to measure individuals’ preferences for DM-related complications in order to assess the magnitude of complications’ effect on overall HRQoL. In addition, preference scores are an essential component of cost–utility analyses (CUAs), which studies can incorporate healthcare costs, HRQoL and clinical outcomes of DM into one analysis. Objective: The aims of this study were to assess the preference scores of DM-related complications using both the standard gamble (SG), a choice-based method, and visual analogue scale (VAS), a scaling method. We also aimed to assess several possible factors that might be associated with the preference scores of the complications. Methods: This is a cross-sectional interview-administered survey, and 213 patients with type 2 DM were interviewed. The respondents’ preference scores of eleven DM-related complications were obtained using VAS and SG techniques. Demographic information, clinical characteristics and risk attitudes were also collected to explore factors that may affect patients’ preference scores. Results: Nearly one quarter of participants in Taiwan ranked at least one of the complications worse than death. The mean VAS scores ranged from 0.004 (amputation) to 0.47 (nocturnal hypoglycemia) while the mean adjusted SG scores ranged from 0.30 (blindness) to 0.66 (nocturnal hypoglycemia). There were significant differences in all of the complications’ preference scores depending on risk attitudes. Conclusion: Both the VAS and SG methods were used to elicit the preference scores of DM-related complications, and the preference scores derived could be useful for future cost utility analyses.
Effects of lornoxicam, piroxicam, and meloxicam in a model of thermal hindpaw hyperalgesia induced by formalin injection in rat tail.

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used as analgesics. Although the results of clinical studies indicate considerable disparity in the analgesic efficacy of NSAIDs, the pre-clinical models generally used for the study of nociception do not allow a clear distinction to be made between the analgesic properties of agents belonging to this family. As clinical pain is characterized by hyperalgesia, we evaluated the effects of NSAIDs with similar chemical structures but different selectivities for cyclo-oxygenase (COX)-1 and COX-2 in a new behavioural model of central hyperalgesia in rats. We assessed the effects of lornoxicam, piroxicam, and meloxicam on the reduction of hindpaw nociceptive thresholds to thermal stimulation produced by a 10% formaldehyde (formalin) injection into rat tail. Each drug was administered intraperitoneally (i.p.) at its ED(50)for the anti-inflammatory effect (namely the inhibition of carrageenan-induced hindpaw oedema). At this dose (1.3 mg kg(-1), 1.0 mg kg(-1), and 5.8 mg kg(-1), respectively), lornoxicam, piroxicam, and meloxicam produced the same anti-inflammatory effect, did not modify thermal nociceptive thresholds, and significantly reduced the hyperalgesia. However, only lornoxicam was fully effective for prevention of hyperalgesia. Our results indicate a dissociation between the anti-inflammatory and the anti-hyperalgesic activity of NSAIDs, where the latter seems to be more evident after the block of both COX-1 and COX-2. Finally, they suggest that our experimental model of thermal hindpaw hyperalgesia can be effectively utilized to assess the ability of different drugs to reduce central sensitization, and thus hyperalgesia.
Enoxaparin and fondaparinux attenuates endothelial damage in endotoxemic rats

Background: Prophylactic use of anticoagulants for septic patients in intensive care unit is a standard therapy for the prevention of venous thrombosis. Moreover, recent studies have demonstrated the anti-inflammatory effects of anticoagulants such as Factor Xa inhibitors and heparins. However, there have been no studies to examine the effects of fondaparinux and enoxaparin when applied in a sepsis model. Therefore, we examined the anti-inflammatory effects and bleeding events when these agents are applied in a lipopolysaccharide challenge model. Methods: Wistar rats received lipopolysaccharides followed by a bolus infusion of fondaparinux, enoxaparin, or placebo. Microscopic observation of the mesenteric microcirculation for endothelial damage and measurement of bleeding area after vascular puncture was performed (n = 6 in each group). In another series, blood samples were taken, and blood cell counts, coagulation markers, and organ damage markers were measured (n = 6 in each). Results: Both leukocyte adherence to vascular endothelium and endothelial damage were reduced in fondaparinux and enoxaparin groups. The bleeding area was markedly increased in the fondaparinux group. Coagulation markers were maintained better in the enoxaparin group. Levels of organ damage markers were significantly suppressed in both fondaparinux and enoxaparin groups (p < 0.01, compared with control, each). Conclusions: Fondaparinux and enoxaparin reduce organ dysfunction by decreasing endothelial damage. However, bleeding was more prominent in the fondaparinux group compared with the enoxaparin group at an equipotent dose for anti-Xa activity. Because the setting of this experiment is different from the clinical use, further study is required for the comparison of both pharmaceuticals.
Exhaled breath condensate: lessons learned from veterinary medicine

Exhaled breath condensate (EBC) describes any sample collected by cooling exhaled breath. Because the method of condensate collection is simple, non-invasive, repeatable and does not necessarily require patient cooperation, EBC is not only an interesting, but also challenging, biological sample. Despite a period of EBC research lasting for more than 15 years, there are still many open questions with respect to EBC collection and analysis, and many biomarkers are still awaiting careful validation. In veterinary research, EBC collection has been described in conscious animals including calves, pigs, horses, cats and dogs. Numerous studies performed in these domestic animals not only contributed substantially to the current knowledge about the potentials of EBC-based diagnoses but also demonstrated pitfalls in EBC collection, analysis and interpretation. This review summarizes information about the collection of EBC and the interpretation of EBC results, particularly with respect to proteins, leukotrienes, hydrogen peroxide, urea, ammonia and pH. Published data emphasize the need to standardize approaches to produce reproducible EBC data. Quantifying the concentration of the EBC component of interest exhaled in a defined volume of exhaled breath (instead of comparing concentrations of this component analysed in liquid EBC) is an important step of standardization that might help to overcome methodological limitations deriving from the EBC collection process. Although information is based on domestic animal studies, it contributes to the general understanding in EBC research—independent of any particular mammalian species—and opens new perspectives for further studies.
Additive survival least square support vector machines and feature selection on health data in Indonesia

Survival analysis is widely applied in many areas such as medicine, public health, engineering, economics, demography, and others. The initial approach has been employed for survival analysis is parametric model. Next, the semi parametric approach so-called Cox Proportional Hazard model (Cox-PHM) was developed. The parameters estimation in Cox PHM use partial likelihood function. The drawback of the Cox PHM is that it requires proportional condition in its hazard function between categories. In addition, it assumes linearity on its covariate pattern. This work employs nonparametric model so-called Additive Survival Least Square Support Vector Machines (A-SURLSSVM). The Cox PHM is used as a benchmark. The first data used in this study are generated from simulation. The second data are three health datasets in Indonesia. The performance of the proposed approach is compared with the benchmark based on the Concordance index (C-index) criterion. The higher C-index indicates better performance. In this study, application on three health datasets produce empirical results that conclude A-SURLSSVM perform better than Cox PHM for both with and without feature selection. In addition, the results of simulation study using 100 replications inform that feature selection can increase the C-index significantly. Moreover, the interaction between covariates yields the main confounder variable (the greatest probability to persist in the model) and the sub-main confounder (the most frequently excluded covariates from the model).
Chemical reactions and morphological stability at the Cu/Al2O3 interface

The microstructures of diffusion‐bonded Cu/(0001)Al2O3 bicrystals annealed at 1000 °C at oxygen partial pressures of 0.02 or 32 Pa have been studied with various microscopy techniques ranging from optical microscopy to high‐resolution transmission electron microscopy. The studies revealed that for both oxygen partial pressures a 20–35 nm thick interfacial CuAlO2 layer formed, which crystallises in the rhombohedral structure. However, the CuAlO2 layer is not continuous, but interrupted by many pores. In the samples annealed in the higher oxygen partial pressure an additional reaction phase with a needle‐like structure was observed. The needles are several millimetres long, ∼10 µm wide and ∼1 µm thick. They consist of CuAlO2 with alternating rhombohedral and hexagonal structures. Solid‐state contact angle measurements were performed to derive values for the work of adhesion. The results show that the adhesion is twice as good for the annealed specimen compared to the as‐bonded sample.
Family history, age, and risk of breast cancer. Prospective data from the Nurses' Health Study.

OBJECTIVE To examine prospectively the risk of breast cancer as influenced by a maternal history of breast cancer, the mother's age at diagnosis, or a sister's history of breast cancer. DESIGN Prospective cohort study with biennial follow-up. SETTING/PARTICIPANTS 117,988 women in the Nurses' Health Study aged 30 to 55 years in 1976, followed up through 1988 (1.3 million person-years of follow-up). RESULTS We identified 2389 incident cases of invasive breast cancer. Compared with women without a maternal history of breast cancer, the age-adjusted relative risk (RR) of breast cancer was highest among women whose mother was diagnosed before the age of 40 years (RR, 2.1 [95% confidence interval, 1.6 to 2.8]). The RR decreased with advancing maternal age at time of diagnosis to 1.5 (95% confidence interval, 1.1 to 2.2) for maternal diagnosis after the age of 70 years. Having a sister with a history of breast cancer also was related to increased risk; for women with one sister with breast cancer compared with those with one sister without such a history, the age-adjusted RR was 2.3 (95% confidence interval, 1.6 to 3.4). Women whose mother and sister both had a history of breast cancer had an RR of 2.5 (95% confidence interval, 1.5 to 4.2) compared with those without a family history. These associations did not differ appreciably when stratified by age; menopausal status; history of benign breast disease; body mass index; age at menarche; or parity or age at first birth of the women at risk. The results remained unchanged when we controlled for these risk factors in multivariate models. Despite slightly greater mammography surveillance and earlier detection of tumors among women with a family history of breast cancer, detection bias is unlikely to account for more than a small part of the observed association. CONCLUSIONS Risk of breast cancer is approximately doubled among women whose mother had breast cancer diagnosed before the age of 40 years or who have a sister with breast cancer, and remains elevated even for those whose mothers were diagnosed with breast cancer at the age of 70 years or older. However, the risk associated with a mother or sister history of breast cancer is smaller than suggested by earlier retrospective studies. Overall, within this population of middle-aged women, only 2.5% of breast cancer cases are attributable to a positive family history.
Integrating collaboration engineering with software process modeling: a visual approach

The way as a team interact is determinant for increasing the software organization capability. So, recognize the best interaction mechanisms is a key strategy in order to improve performance in software development teams. Since a growing number of available SPEM 2.0 process models, we propose use this kind of the models as a tool, coAVISPA, in order to identify collaboration aspects to be potentially incorporated as improvement strategies for software development teams. coAVISPA follows a visual strategy and collaboration patterns applied to tasks and roles blueprints. A case study indicates that coAVISPA is an effective analysis tool.
Genetics of Inflammatory Bowel Disease: A Reappraisal

The advent of advanced molecular biological techniques in the last two decades has allowed the study of genetic factors in inflammatory bowel disease (IBD). A variety of techniques have been employed to elucidate the effects of genes, starting with the clinical observations that IBD is more common in the relatives of patients than the general population, and the consistency of clinical features within families. The situation is likely to be much more complicated than single gene disorders, and it is estimated that between 10 and 20 genes may be involved. Genome scanning techniques using microsatellite markers have been employed to highlight areas of chromosomes linked to disease such as those on chromosomes 12 and 16. In addition association studies of specific genes such as HLA and cytokine genes have been carried out on functional or positional grounds. It is likely that a combination of these techniques will be required to elucidate the role of individual genes. Recently much work has been focused on genes that may determine clinical phenotype such as disease extent or severity or the response to treatment. Identification of these genes may lead to better targeting of therapy and prognostication, and they are likely to be easier to identify than disease susceptibility genes.
Superfamily phenomena and motifs of networks induced from time series

We introduce a transformation from time series to complex networks and then study the relative frequency of different subgraphs within that network. The distribution of subgraphs can be used to distinguish between and to characterize different types of continuous dynamics: periodic, chaotic, and periodic with noise. Moreover, although the general types of dynamics generate networks belonging to the same superfamily of networks, specific dynamical systems generate characteristic dynamics. When applied to discrete (map-like) data this technique distinguishes chaotic maps, hyperchaotic maps, and noise data.
Maternal Diabetes and Retarded Preimplantation Development of Mice

The streptozocin-induced diabetic (STZ-D) mouse was found to be a suitable model for studying the effects of maternal diabetes on the preimplantation embryo. This study looked at the effects of maternal diabetes on embryonic growth. Female Quakenbush mice were made diabetic (plasma glucose levels >20 mM) by injection of 190 mg/kg i.p. STZ and were superovulated by standard methods. The blastocysts collected on day 4 from diabetic mothers had 8.5% fewer cells and a 35% lower protein synthetic rate than control embryos. Their cellular protein synthetic rate was 19% less than that in controls. Morulae from diabetic mothers also displayed a reduced protein synthetic rate, but this reduction was not seen in the two-cell embryo. Furthermore, blastocysts cultured in vitro from two-cell embryos from diabetic and control mothers displayed similar protein synthetic rates. This infers that the two-cell embryos from diabetic mothers are normal, and the retardation seen in later development in vivo occurs after the two-cell stage while the embryo is still free in the oviductal and uterine environment. Treatment of the diabetic mice with ultralente insulin every 12 h raised the protein synthetic rate of those blastocysts toward control levels, whereas treatment with lente insulin every 8 h recovered the embryo to the same rate as the control embryos. Because insulin has been shown to be mitogenic and stimulates protein synthesis of morulae and blastocysts in vitro, the absence of insulin in the diabetic mothers may be the cause of the retardation observed in their preimplantation embryos.
An Ultra-Low Power ECG Acquisition and Monitoring ASIC System for WBAN Applications

This paper proposes a power and area efficient electrocardiogram (ECG) acquisition and signal processing application sensor node for wireless body area networks (WBAN). This sensor node can accurately record and detect the QRS peaks of ECG waveform with high-frequency noise suppression. The proposed system is implemented in 0.18-μm complementary metal-oxide-semiconductor technology with two chips: analog front end integrated circuit (IC) and digital application specific integrated circuit (ASIC), where the analog IC consumes only 79.6 μW with area of 4.25 mm2 and digital ASIC consumes 9 μW at 32 kHz with 1.2 mm2. Therefore, this ECG sensor node is convenient for long-term monitoring of cardiovascular condition of patients, and is very suitable for on-body WBAN applications.
The guanylate cyclase/receptor family of proteins

Guanylate cyclase, which catalyzes the formation of cGMP from GTP, exists in both the soluble and particulate fractions of cells. At least two different cellular compartments for the particulate enzyme exist: the plasma membrane and cytoskeleton. The enzyme form found in the soluble fraction is a heterodimer that can be regulated by free radicals and nitrovasodilators, whereas the membrane form exists as a single‐chain polypeptide that can be regulated by various peptides. These peptides include resact and speract obtained from eggs and atrial natriuretic peptides (ANP). The species of guanylate cyclase present in cytoskeletal fractions resists solubilization with non‐ionic detergents; its structural properties are not yet known. cDNAs encoding the membrane form of guanylate cyclase have been isolated from different tissues and species, and in all cases the DNA sequences predict a protein containing a single transmembrane domain. The carboxyl (intracellular) domain is highly conserved from sea urchins through mammals, whereas the extracellular domain (amino terminus) varies considerably. The predicted amino acid sequences demonstrate that the membrane form of guanylate cyclase is a member of a diverse and complex family of proteins that includes a low molecular weight ANP receptor, protein kinases, and the cytoplasmic form of guanylate cyclase. cDNA encoding a membrane form of the enzyme from mammalian tissues has been expressed in cultured cells, and the expressed guanylate cyclase specifically binds ANP and is activated by ANP. The membrane form of guanylate cyclase, then, serves as a cell surface receptor, representing the first recognized protein to directly catalyze formation of a low molecular weight second messenger in response to ligand binding. —Schulz, S. ; Chinkers, M. ; Garbers, D. L. The guanylate cyclase/receptor family of proteins. FASEB J. 3: 2026‐2035; 1989.
The pluripotency homeobox gene NANOG is expressed in human germ cell tumors

The NANOG gene, a member of the homeobox family of DNA binding transcription factors, was recently identified in a screen for pluripotency‐promoting genes. NANOG overexpression in murine embryonic stem cells is sufficient to maintain self‐renewal and to block differentiation. The NANOG gene is located on human chromosome 12p13, a region frequently duplicated in human tumors of germ cell origin and in cultured human embryonic stem cells. Here we investigate the expression and gene copy number of NANOG in human germ cells and tumors of germ cell origin.