Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: Further evidence for an etiologic association

This study aims to determine the presence of the components of the metabolic syndrome in primary nonalcoholic steatohepatitis (NASH) and to assess the role of liver disease in the genesis of peripheral hyperinsulinemia. Nineteen patients (18 men and 1 woman; mean age, ± SD, 38 ± 10 years; body mass index [BMI], 26 ± 2 kg/m2) with histologic evidence of NASH were enrolled; 19 age‐ and sex‐matched normal subjects were investigated as controls. Plasma glucose, insulin, and C‐peptide levels were measured during an oral glucose tolerance test, and a frequently sampled intravenous glucose tolerance test (FSIGT), analyzed by minimal modeling technique, was performed. Compared with controls, the NASH group had lower insulin sensitivity (3.84 ± 2.44 vs. 7.48 ± 3.01 10−4 × min−1/μU/mL; P = .0003) and higher total insulin secretion (21 ± 13 vs. 10 ± 3 nmol/L in 240 minutes; P = .001). Hepatic insulin extraction was similar in both groups (69.8% ± 16.1% vs. 70.2% ± 18.3%; P = .854). According to the results of the oral glucose tolerance test, no patient was classified as diabetic, 5 were classified as glucose intolerant, and 1 was classified as having impaired fasting glycemia. Nine patients (47%) had at least the 2 minimum criteria required to define the metabolic syndrome according to the European Group for the Study of Insulin Resistance (EGIR). In conclusion, hyperinsulinemia and insulin resistance occur frequently in patients with NASH; these conditions do not stem from a reduced hepatic insulin extraction but from an enhanced pancreatic insulin secretion compensatory to reduced insulin sensitivity. The derangement of insulin regulation, often associated with the metabolic syndrome, may play a causal role in the pathogenesis of NASH.
Frequency and path length scaling of rain attenuation from 38 GHz, 58 GHz and 93 GHz data obtained on terrestrial paths

The frequency band 48 GHz is allocated for backhaul links between high altitude platforms (HAPs) operated in the troposphere and Earth base-stations. The cumulative distributions of attenuation due to hydrometeors at 48 GHz band are needed for the assessment of availability performance of HAPs links. Some experimental results obtained at other frequencies on either terrestrial paths of different lengths or satellite paths can be used for frequency and path length scaling. A suitable method was chosen, tested and applied for calculation of cumulative distribution of rain attenuation at 47.7 GHz for the path length equivalent to the path between HAPs and Earth base-stations. The results obtained are discussed.
Bayesian Degradation Analysis With Inverse Gaussian Process Models Under Time-Varying Degradation Rates

Degradation observations of modern engineering systems, such as manufacturing systems, turbine engines, and high-speed trains, often demonstrate various patterns of time-varying degradation rates. General degradation process models are mainly introduced for constant degradation rates, which cannot be used for time-varying situations. Moreover, the issue of sparse degradation observations and the problem of evolving degradation observations both are practical challenges for the degradation analysis of modern engineering systems. In this paper, parametric inverse Gaussian process models are proposed to model degradation processes with constant, monotonic, and S-shaped degradation rates, where physical meaning of model parameters for time-varying degradation rates is highlighted. Random effects are incorporated into the degradation process models to model the unit-to-unit variability within product population. A general Bayesian framework is extended to deal with the degradation analysis of sparse degradation observations and evolving observations. An illustrative example derived from the reliability analysis of a heavy-duty machine tool's spindle system is presented, which is characterized as the degradation analysis of sparse degradation observations and evolving observations under time-varying degradation rates.
Clinical Practice Guidelines for the Treatment of Obstructive Sleep Apnea and Snoring with Oral Appliance Therapy : An Update for 2015

s from these articles were assessed by 2 reviewers to determine whether they met inclusion criteria. However, if there were any questions on whether the abstract met the inclusion criteria, the article was reviewed in detail to determine whether to accept or reject. Articles were included for evaluation if they focused on treatment of snoring and/or OSA with OAs, and included only adult subjects. Included articles also had to address at least one of the eleven “PICO” questions identified ahead of the review process. Articles were accepted if they used either the apnea hypopnea index (AHI) or the respiratory disturbance index (RDI) as determined by an overnight polysomnogram (PSG) or the respiratory event index (REI) as determined by a home sleep apnea test. However, there were 3 articles that did not necessarily meet the above criteria, but were still included in our analysis. [16-18] In two studies by Gauthier et al. RDI was defined as the combination of apneas, hypopneas and arousals per hour of sleep, [16] [17] while Gotsopoulos et al. defined AHI as the combination of apneas, hypopneas, and arousals per hour of sleep. [18] Articles were excluded if they focused on diagnosis, described the use of OAs to treat central or complex sleep apnea, or if they were studies on pediatric patients. A total of 51 articles met these criteria and were used for data extraction, meta-analysis, and grading.
MCP-1 Is Induced by Receptor Activator of Nuclear Factor-κB Ligand, Promotes Human Osteoclast Fusion, and Rescues Granulocyte Macrophage Colony-stimulating Factor Suppression of Osteoclast Formation*

Human osteoclast formation from monocyte precursors under the action of receptor activator of nuclear factor-κB ligand (RANKL) was suppressed by granulocyte macrophage colony-stimulating factor (GM-CSF), with down-regulation of critical osteoclast-related nuclear factors. GM-CSF in the presence of RANKL and macrophage colony-stimulating factor resulted in mononuclear cells that were negative for tartrate-resistant acid phosphatase (TRAP) and negative for bone resorption. CD1a, a dendritic cell marker, was expressed in GM-CSF, RANKL, and macrophage colony-stimulating factor-treated cells and absent in osteoclasts. Microarray showed that the CC chemokine, monocyte chemotactic protein 1 (MCP-1), was profoundly repressed by GM-CSF. Addition of MCP-1 reversed GM-CSF suppression of osteoclast formation, recovering the bone resorption phenotype. MCP-1 and chemokine RANTES (regulated on activation normal T cell expressed and secreted) permitted formation of TRAP-positive multinuclear cells in the absence of RANKL. However, these cells were negative for bone resorption. In the presence of RANKL, MCP-1 significantly increased the number of TRAP-positive multinuclear bone-resorbing osteoclasts (p = 0.008). When RANKL signaling through NFATc1 was blocked with cyclosporin A, both MCP-1 and RANTES expression was down-regulated. Furthermore, addition of MCP-1 and RANTES reversed the effects of cyclosporin A and recovered the TRAP-positive multinuclear cell phenotype. Our model suggests that RANKL-induced chemokines are involved in osteoclast differentiation at the stage of multinucleation of osteoclast precursors and provides a rationale for increased osteoclast activity in inflammatory conditions where chemokines are abundant.
Preclinical stroke research – advantages and disadvantages of the most common rodent models of focal ischaemia

This review describes the most commonly used rodent models and outcome measures in preclinical stroke research and discusses their strengths and limitations. Most models involve permanent or transient middle cerebral artery occlusion with therapeutic agents tested for their ability to reduce stroke‐induced infarcts and improve neurological deficits. Many drugs have demonstrated preclinical efficacy but, other than thrombolytics, which restore blood flow, none have demonstrated efficacy in clinical trials. This failure to translate efficacy from bench to bedside is discussed alongside achievable steps to improve the ability of preclinical research to predict clinical efficacy: (i) Improvements in study quality and reporting. Study design must include randomization, blinding and predefined inclusion/exclusion criteria, and journal editors have the power to ensure statements on these and mortality data are included in preclinical publications. (ii) Negative and neutral studies must be published to enable preclinical meta‐analyses and systematic reviews to more accurately predict drug efficacy in man. (iii) Preclinical groups should work within networks and agree on standardized procedures for assessing final infarct and functional outcome. This will improve research quality, timeliness and translational capacity. (iv) Greater uptake and improvements in non‐invasive diagnostic imaging to detect and study potentially salvageable penumbral tissue, the target for acute neuroprotection. Drug effects on penumbra lifespan studied serially, followed by assessment of behavioural outcome and infarct within in the same animal group, will increase the power to detect drug efficacy preclinically. Similar progress in detecting drug efficacy clinically will follow from patient recruitment into acute stroke trials based on evidence of remaining penumbra.
Mouse muscle identity: The position‐dependent and fast fiber‐specific expression of a transgene in limb muscles is methylation‐independent and cell‐autonomous

We previously characterised transgenic mice in which fast‐muscle‐specific regulatory sequences from the human aldolase A pM promoter drive the chloramphenicol acetyltransferase gene expression. Mutation of a NF1/MEF2 binding site (M2 motif) in this promoter does not affect fibre‐type specificity of the transgene but modifies its expression in a subset of fast‐twitch fibres at the limb level, preferentially affecting distal limb muscles. We investigated the molecular and cellular bases of this peculiar expression pattern that provided an adequate model to characterise the mechanisms responsible for muscle positional information. By direct electrotransfer of mutated M2 construct in adult muscle, we demonstrate that positional differences in mutated M2 transgene expression are not observed when the transgene is not integrated into chromatin. Also, this transgene expression pattern does not seem to be correlated with the extent of CpG methylation in its promoter sequence. Finally, we show that positional values reflected by CAT levels are maintained in primary cultures established from different adult limb muscles, as well as in heterotopically transplanted muscles. Our results suggest that mutation of the M2 site contributes to reveal a molecular memory of fibre fate that would be set up on pM promoter during development and persist into adulthood possibly through a chromatin imprint maintained in satellite cells associated with various limb muscles. Developmental Dynamics 228:594–605, 2003. © 2003 Wiley‐Liss, Inc.
RULES-F: A fuzzy inductive learning algorithm

Abstract Current inductive learning algorithms have difficulties handling attributes with numerical values. This paper presents RULES-F, a new fuzzy inductive learning algorithm in the RULES family, which integrates the capabilities and performance of a good inductive learning algorithm for classification applications with the ability to create accurate and compact fuzzy models for the generation of numerical outputs. The performance of RULES-F in two simulated control applications involving numerical output parameters is demonstrated and compared with that of the well-known fuzzy rule induction algorithm by Wang and Mendel.
The Role of Bisphosphonates in the Management of Advanced Cancer with a Focus on Non-Small-Cell Lung Cancer

Newer-generation intravenous bisphosphonates have resulted in the reduction of skeletal-related complications, i.e. skeletal-related events (SREs) such as pain, hypercalcemia, pathologic fractures and spinal cord and nerve compression, as well as improvements in the quality of life in patients with metastatic bone disease who are likely to have a prolonged clinical course. Highly potent, nitrogen-containing bisphosphonates such as zoledronic acid reduce SREs in patients with bone metastases from other solid tumors (including lung cancer). Part one of our review discussed the mechanisms of action by bisphosphonates as well as potential roles for bone markers and imaging in lung cancer. In this article, part two of our review, we examine the economic and clinical impact of bisphosphonates in lung cancer, with a focus on the potential role of newer-generation bisphosphonates in the management of advanced, metastatic bone disease of lung cancer.
10 The Role of Glycogen Synthase Kinase-3 ( GSK-3 ) in Alzheimer ’ s Disease

Despite its initial discovery as one of five protein kinases activities found to phosphorylate glycogen synthase (GS) in fractioned extracts of rabbit skeletal muscle (Embi et al., 1980; Hemmings et al., 1981), Glycogen Synthase Kinase 3 (GSK-3) is by no means restricted to a role in glycogen metabolism. Indeed, the enzyme targets a wide variety of proteins involved in signalling, metabolism, structural proteins and a remarkable number of transcription factors and plays a far more pleiotropic role than first imagined (Woodgett, 2006). Genetic analyses and the use of selective inhibitors have shown that GSK-3 plays critical roles in development, metabolic homeostasis, neuronal growth and differentiation (Hur & Zhon, 2010), cell polarity, cell fate and apoptosis. Its unique position in modulating the function of a diverse series of proteins in combination with its association with a wide variety of human disorders, from neurodegenerative diseases, stroke, bipolar disorder to diabetes and cancer, has attracted significant attention to the protein both as a therapeutic target and as a means to understand the molecular basis of these disorders. In particular, the involvement of GSK-3 in several key pathophyisiological pathways leading to Alzheimer’s disease (AD) and neurodegenerative diseases has placed this enzyme in a central position in this disorder. Thus, GSK-3 has recently been proposed as a link between the two major pathological pathways in AD, amyloid and tau (Hernández et al., 2010; Muyllaert et al., 2008) and even a “GSK-3 hypothesis of AD”, suggesting that GSK-3 might be a casual mediator of the disease, has been put forward (Hooper et al., 2008). This review will focus on describing the key role that GSK-3 plays in AD pathobiology and the use of GSK-3 inhibition as a potential therapeutic approach to treat this disease.
Progressive viral-induced cirrhosis: serial MR imaging findings and clinical correlation.

PURPOSE To determine which magnetic resonance (MR) imaging findings of cirrhosis change as disease severity progresses. MATERIALS AND METHODS Seventy-six abdominal MR imaging studies in 38 patients (two per patient) with Child-Pugh grade A cirrhosis were retrospectively reviewed. All patients were followed up clinically and with MR imaging for 12 months or longer. MR images were used to determine volume indexes of the spleen and of each liver segment, as well as changes in hepatic contour, iron or fat deposition, and presence of varices and collateral vessels. RESULTS During follow-up in patients with progressive cirrhosis (n = 13), the volume indexes of the anterior, posterior, and medial segments of the liver decreased significantly (P = .011, .013, .002, respectively), and the number of varices and collateral vessels increased significantly (P = .018). In patients with stable cirrhosis (n = 25), the volume indexes of the spleen, caudate lobe, and lateral segment increased significantly (P = .032, .018, .003, respectively). The atrophic index was significantly greater in progressive cirrhosis than in stable cirrhosis (P = .009). CONCLUSION Progressive atrophy of the right hepatic lobe and the medial segment correlated with progression of clinical severity of cirrhosis, whereas increasing size of the caudate lobe and the lateral segment correlated with stability.
High Levels of Mannose-Binding Lectin Are Associated With Poor Outcomes After Lung Transplantation

Background. Mannose-binding lectin (MBL) is a key molecule of the innate immune system and, in addition to the classical and alternative pathways, a principle driver of complement activation. Genetic mutations of MBL are common, result in low serum levels of MBL, and are associated with increased infection risk in solid-organ transplant recipients. Methods. We performed a retrospective study of MBL2 genotype and plasma and bronchoalveolar lavage (BAL) MBL levels in 37 lung transplant recipients (LTR). Plasma MBL levels were measured pretransplant and both plasma and BAL MBL levels were measured at 3, 6, and 12 months after lung transplantation. MBL2 genotyping was performed on recipient and donor peripheral blood mononuclear cells. Clinical variables analyzed included primary graft dysfunction, intensive care unit stay, acute allograft rejection, infection, bronchiolitis obliterans syndrome (BOS), and mortality. Results. Plasma MBL levels posttransplant were predicted by recipient, and not donor MBL2 genotype. Compared with pretransplant levels, plasma MBL was significantly increased at 3, 6, and 12 months posttransplant (P<0.05). LTR who developed BOS or died during the study period had higher plasma MBL levels at 6 and 12 months posttransplant (P≤0.05) compared with LTR with stable graft function. MBL was not routinely detected in the lung allograft; however if present in the BAL at 3 and 6 months posttransplant, it was associated with the later development of BOS (P<0.05). Conclusions. Plasma MBL levels increase after lung transplantation and persistently increased MBL levels are associated with poor long-term outcomes.
Moving Average Convergence/Divergence (MACD)

Originally, Gerald Appel’s MACD was composed of a default setting (12,26,9) which displayed two lines. One line, the MACD, is the difference between the 26-period EMA and the12-period EMA. When an additional EMA (signal line, also known as the trigger line) such as the 9-period EMA is added to the mix, we have an indicator that reveals over bought (OB) and over sold (OS) conditions as well as providing us with buy/sell signals. This is accomplished through divergences or crossovers.
Understanding the Relationship between Governance and Forest Landscape Restoration

Restoring forested landscapes is being promoted widely as a solution to the world's deforestation and degradation problems, as well as for climate change mitigation and adaptation, for supporting poor rural communities, and for water and soil protection. Yet, while practitioners understand reasonably well many of the technical aspects of forest restoration, they have a much poorer understanding of governance dimensions. Governance challenges come under many guises—financial disincentives, poor institutional set up, unclear tenure and lack of local empowerment, amongst others. Not much has been written to date on forest landscape restoration and governance. This article aims to better understand the governance challenges that practitioners face when restoring forest landscapes and to explore the points of intersection between forest landscape restoration and governance. To achieve this, a broader review of concepts related to governance, forests and landscapes was conducted, followed by a review of existing landscape-scale forest restoration projects to identify the governance factors that have been considered (if any). Findings indicate the need for a more dynamic and process-orientated approach to address governance as it relates to forest landscape restoration. The author proposes a classification for the intersection between governance and forest landscape restoration.
Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings.

OBJECTIVE To determine the frequency and constellations of anatomic, pathophysiologic, and environmental factors involved in the development of incident diabetic foot ulcers in patients with diabetes and no history of foot ulcers from Manchester, U.K., and Seattle, Washington, research settings. RESEARCH DESIGN AND METHODS The Rothman model of causation was applied to the diabetic foot ulcer condition. The presence of structural deformities, peripheral neuropathy, ischemia, infection, edema, and callus formation was determined for diabetic individuals with incident foot ulcers in Manchester and Seattle. Demographic, health, diabetes, and ulcer data were ascertained for each patient. A multidisciplinary group of foot specialists blinded to patient identity independently reviewed detailed abstracts to determine component and sufficient causes present and contributing to the development of each patient's foot ulcer. A modified Delphi process assisted the group in reaching consensus on component causes for each patient. Estimates of the proportion of ulcers that could be ascribed to each component cause were computed. RESULTS From among 92 study patients from Manchester and 56 from Seattle, 32 unique causal pathways were identified. A critical triad (neuropathy, minor foot trauma, foot deformity) was present in > 63% of patient's causal pathways to foot ulcers. The components edema and ischemia contributed to the development of 37 and 35% of foot ulcers, respectively. Callus formation was associated with ulcer development in 30% of the pathways. Two unitary causes of ulcer were identified, with trauma and edema accounting for 6 and < 1% of ulcers, respectively. The majority of the lesions were on the plantar toes, forefoot, and midfoot. CONCLUSIONS The most frequent component causes for lower-extremity ulcers were trauma, neuropathy, and deformity, which were present in a majority of patients. Clinicians are encouraged to use proven strategies to prevent and decrease the impact of modifiable conditions leading to foot ulcers in patients with diabetes.
Survey of real option approach to analyze strategic investments of technology innovations

The real options approach is more suitable to analyze the problems of investment decisions under uncertainty than the traditional discounted cash flow approach (DCF) does. However, the firms' strategic investments under the imperfect competition can't be analyzed and evaluated accurately only by the real option approach. According to whether considering the strategic interactions among firms' decisions under the imperfect competition, this paper divides the real option approach into the general real option approach and the strategic real option approach. Mainly focusing the strategic real option approach, this paper surveys the existent real options theoretical models and approaches to analyze the firms' investments of technology innovations. Finally, recommendations are given for further research.
Myocardial ischaemia is associated with an elevated brain natriuretic pepide level even in the presence of left ventricular systolic dysfunction

Plasma BNP and high‐sensitivity cardiac troponin‐T (hs‐TnT) are elevated by both ischaemia and LV systolic dysfunction (LVSD). As a result, it is unknown whether BNP and/or hs‐TnT could be useful biomarkers to identify ischaemia in the presence of LVSD.