Miracle-dz/UniFAR-FTUs huggingface dataset:
Astrocyte Elevated Gene-1 Increases Invasiveness of NSCLC Through Up-Regulating MMP7

Background/Aims: The aggressive manner of non-small cell lung cancer (NSCLC) cells accounts for the majority of the lethality of the disease. Recently, increased astrocyte elevated gene-1 (AEG-1) levels have been shown to closely correlate with poor prognosis of NSCLC, whereas the underlying mechanisms are not clear. Methods: We examined the AEG-1 and matrix metalloproteinase 7 (MMP7) levels in NSCLC tissues, compared to the paired adjacent non-tumor lung tissue. We modulated AEG-1 levels in NSCLC cells, and examined its effects on MMP7 levels by RT-qPCR, on cellular protein by Western blot, and on secreted protein by ELISA. We also examined the cell invasiveness in AEG-1-modified NSCLC cells in a transwell cell migration assay. We used specific signal pathway inhibitors to treat AEG-1-modified NSCLC cells and examined its effects on MMP7. Results: AEG-1 and MMP7 levels were both significantly increased in NSCLC tissues, compared to the paired adjacent non-tumor lung tissue. The AEG-1 and MMP7 levels were strongly correlated. Overexpression of AEG-1 in NSCLC cells significantly increased MMP7 levels and cell invasiveness, while AEG-1 depletion in NSCLC cells significantly decreased MMP7 levels and cell invasiveness. Application of a specific MAPK-p42/p44 inhibitor, but not application of specific inhibitors for MAPK-p38, PI3k/Akt, or JNK signaling pathways, to AEG-1-overexpressing NSCLC cells substantially abolished the AEG-1-mediated MMP7 up regulation. Conclusion: AEG-1 promotes NSCLC cell invasiveness through MAPK-p42/p44-dependent activation of MMP7.
Insulin in the ventral tegmental area reduces hedonic feeding and suppresses dopamine concentration via increased reuptake

Mesolimbic dopamine (DA) signaling has been implicated in the incentive, reinforcing and motivational aspects of food intake. Insulin receptors are expressed on dopaminergic neurons of the ventral tegmental area (VTA), and insulin may act in the VTA to suppress feeding. However, the neural mechanisms underlying insulin effects in the VTA are poorly understood. Here, we measured the effects of insulin on evoked DA concentration in the VTA using fast‐scan cyclic voltammetry. Insulin concentration‐dependently reduced evoked somatodendritic DA in the VTA, requiring activation of phosphoinositol 3‐kinase and mTOR signaling. Insulin depression of somatodendritic DA was abolished in the presence of a selective DA transporter (DAT) inhibitor, GBR 12909, as well as in VTA slices of DAT knockout mice, suggesting that insulin upregulated the number or function of DAT to reduce DA concentration. Finally, insulin administered to the VTA depressed sated feeding of sweetened high‐fat food. Taken together, these results indicate that insulin depresses DA concentration in the VTA via increased reuptake of DA through DAT. Insulin‐mediated decrease of DA in the VTA may suppress salience of food once satiety is reached.
Prevalence of Necrosis in C 2-Ceramide – Induced Cytotoxicity in NB 16 Neuroblastoma Cells

The mechanism of cell death triggered by C2-ceramide was investigated using the NB16 neuroblastoma cell line. Treatment of NB16 cells with 20 M C2-ceramide for 20 h resulted in approximately 75% loss of cell viability, but only 25% of cells were scored as apoptotic based on terminal deoxynucleotidyl transferase nick-end labeling. Ultrastructural analysis revealed early development of necrotic cytoplasmic vacuolization. After 20 h of treatment with C2-ceramide, the majority of cells possessed necrotic morphology with pronounced cytoplasmic vacuolization and without any nuclear changes, although a quarter of the cell population also exhibited clear perinuclear chromatin condensation characteristic of apoptosis. Flow cytometric analysis of cells labeled with both annexin V and propidium iodide showed the rapid accumulation of C2-ceramide–treated cells in the necrotic/ late apoptotic fraction. In contrast, cells treated with tumor necrosis factor plus cycloheximide (TNF CHX) first appeared in the early apoptotic fraction and then accumulated in the necrotic/late apoptotic fraction. Both C2-ceramide and TNF CHX increased caspase 8and 3-like activities in cytosolic extracts; however, treatment of cells with the broad-spectrum caspase inhibitor Nbenzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone protected NB16 cells from TNF CHX-induced cell death but did not prevent C2-ceramide cytotoxicity. Although C2-ceramide triggered apoptosis in a fraction of the cells, cell death in the population was primarily caused by necrosis. Thus, C2-ceramide does not faithfully mimic the effects of apoptotic ligands such as TNF , which are thought to be mediated by an accumulation of endogenous ceramide. The inhibition of phosphatidylcholine synthesis is a target for C2-ceramide–mediated cytotoxicity, and this work suggests that other agents that kill cells by inhibiting this pathway may also use a mixture of mechanisms, including necrosis as well as apoptosis. Cell death takes place through two possible mechanisms: necrosis or apoptosis. Chromatin condensation, cell shrinkage, and the appearance of apoptotic bodies are distinctive traits of apoptosis, whereas necrotic cell death is typically characterized by cytoplasmic vesiculation, cell swelling, and disturbance of cell membrane permeability (Kerr et al., 1972). Apoptosis is a tightly regulated process, unlike necrosis, and recent studies in neuronal excitotoxicity suggest the existence of a “twilight zone” between these two types of cell death (Lipton and Nicotera, 1998). Certain pathological conditions, such as some neurodegenerative diseases (Dal Canto and Gurney, 1994) and ischemia (Majno and Joris, 1995), involve neuronal cell death that does not fit either a typical pattern of apoptosis or necrosis. This nonapoptotic cell death is also a programmed process known as paraptosis (Clarke, 1990; Sperandio et al., 2000), which is characterized mainly by cytoplasmic vacuolization without prominent chromatin condensation and can be caspase-independent (Leist and
A network meta-analysis of randomized controlled trials of biologics for rheumatoid arthritis: a Cochrane overview

Background: We sought to compare the benefits and safety of 6 biologics (abatacept, adalimumab, anakinra, etanercept, infliximab and rituximab) in patients with rheumatoid arthritis. Methods: In this network meta-analysis, we included all completed and updated Cochrane reviews on biologics for rheumatoid arthritis. We included data from all placebo-controlled trials that used standard dosing regimens. The major outcomes were benefit (defined as a 50% improvement in patient- and physician-reported criteria of the American College of Rheumatology [ACR50]) and safety (determined by the number of withdrawals related to adverse events). We used mixed-effects logistic regression to carry out an indirect comparison of the treatment effects between biologics. Results: Compared with placebo, biologics were associated with a clinically important higher ACR50 rate (odds ratio [OR] 3.35, 95% confidence interval [CI] 2.62–4.29) and a number needed to treat for benefit of 4 (95% CI 4–6). However, biologics were associated with more withdrawals related to adverse events (OR 1.39, 95% CI 1.13–1.71), with a number needed to treat for harm of 52 (95% CI 29–152). Anakinra was less effective than all of the other biologics, although this difference was statistically significant only for the comparison with adalimumab (OR 0.45, 95% CI 0.21–0.99) and etanercept (OR 0.34, 95% CI 0.14–0.81). Adalimumab, anakinra and infliximab were more likely than etanercept to lead to withdrawals related to adverse events (adalimumab OR 1.89, 95% CI 1.18–3.04; anakinra OR 2.05, 95% CI 1.27–3.29; and infliximab OR 2.70, 95% CI 1.43–5.26). Interpretation: Given the limitations of indirect comparisons, anakinra was less effective than adalimumab and etanercept, and etanercept was safer than adalimumab, anakinra and infliximab. This summary of the evidence will help physicians and patients to make evidence-based choices about biologics for the treatment of rheumatoid arthritis.
The prevalence and impact of accommodations on the employment of persons 51-61 years of age with musculoskeletal conditions.

OBJECTIVE To provide estimates of the frequency with which persons 51 to 61 years of age with musculoskeletal conditions receive workplace accommodations from their employers and to determine if the receipt of such accommodations is associated with higher rates of employment two years later. METHODS The estimates derive from the Health and Retirement Survey, a national probability sample of 8,781 respondents who were interviewed both in 1992 and 1994 and who were between the ages of 51 and 61 years, of whom 5,495 reported one or more musculoskeletal conditions. We tabulated the frequency of accommodations provided in 1992 and then estimated the impact of accommodations and demographic and medical characteristics on 1994 employment status, using logistic regression. RESULTS In 1992, about 14.40 million persons aged 51-61 years reported a musculoskeletal condition. Of these, 1.32 million (9.2%) reported a disability and were employed, the target population for accommodations. Overall, fewer than 1 in 5 persons with musculoskeletal conditions who had a disability and were employed indicated that they had received any form of accommodation on their current jobs. Although no form of accommodation was reported with great frequency, the most commonly used ones included getting someone to help do one's job (12.1%), scheduling more breaks during the work day (9.5%), changing the time that the work day started and stopped (6.3%), having a shorter work day (5.6%), getting special equipment (5.3%), and changing the work tasks (5.3%). Persons with one or more accommodations in 1992, however, were no more likely to be working in 1994 than those with none. Only one specific accommodation--getting someone to help do one's job--was associated with a higher rate of employment in 1994. CONCLUSIONS Receipt of employment accommodations occurred infrequently, and was not generally associated with an improvement in the employment rate of persons with musculoskeletal conditions and disabilities.
The iron industry of the Weald

This revised and expanded second edition (the first appeared in 1985) provides a definitive regional study of the charcoal iron industry, as well as a major addition on Wealden history generally. The new edition reprints the whole of the original text (and all the illustrations), covering the geology of the Weald (by Bernard Worssam); prehistoric, Roman, and Medieval ironmaking; the rise and fall of the charcoal blast furnace in the Weald; and the archaeology and technology of the industry during the blast furnace period. The extensive gazetteers of sites, which are an essential feature of the book, have been revised and extended in the light of recent fieldwork and research, as has the bibliography. There is also a completely new index, compiled by Ann Hudson, which now includes the gazetteers, as well as the main text.
Measuring neuropsychological change following breast cancer treatment: An analysis of statistical models

This article considers the quantitative techniques currently in use in the evaluation of cognitive impairments associated with chemotherapy treatment for breast cancer. To illustrate differences among analytical approaches, all analyses were applied to baseline and posttreatment scores on neuropsychological tests obtained from Stages I and II breast cancer patients receiving either chemotherapy or hormonal therapy; a healthy control group with similar demographics to those of the treatment groups was also included. Conventional group analyses were compared with individual-based analyses (standardized regression-based and reliable change methods). Both univariate and multivariate techniques with and without covariates produced negligible effects. In contrast, results of the individual-based analyses identified a subset of participants in the chemotherapy group who experienced a severe decline in function on two or more tests. Differences between the control and treatment groups were greater than differences between the treatment groups alone. The standardized regression-based approach was more sensitive than the reliable change index in detecting chemotherapy and hormonal therapy subjects whose performance was different from baseline scores on two or more tests (roughly 80% vs. 50% of participants). From a clinical perspective, the degree of impairment determined on the basis of the individual-based methodologies could have a major impact on quality of life for those affected. On the whole, we argue that the standardized regression-based approach, allowing for the assessment of individual practice effects and evaluation of moderator variables, is the method of choice in this context.
Residues levels of organochlorine pesticide in cow's milk from industrial farms in Hidalgo, Mexico

A survey was carried out from 2008 to 2010 to determine the concentrations of 16 organochlorine pesticide residues (OPRs) from Tizayuca, Hidalgo, Mexico. Organochlorine residue determinations were made from milk fat, using chromatographic cleanup and analysis by gas chromatography with an electron capture detector. The OPR concentrations found were from below the detection limit (DL) to 0.91 ng g−1 in 2008, DL to 0.38 ng g−1 in 2009 and DL to 0.59 ng g−1 in 2010. In general concentrations of organochlorine pesticides were higher in the wet season (3.37 ng g−1 and 4.79 ng g−1) than the dry season (1.92 ng g−1 and 2.71 ng g−1) for 2009 and 2010, due to control of pests in the pasture and sheds. According to Codex Alimentarius regulations, individual pesticides did not exceed the permissible limits, which for example were 10 μg kg−1 for alpha hexachlorocyclohexane (HCH) and endosulfan I, 20 μg kg−1 for p,p’-DDT, and 6 μg kg−1 for dieldrin, endrin and heptachlor. A reduction of organochlorine pesticide concentrations in cow's milk was noted, indicating that the Mexican government has achieved reduction or elimination of some organochlorine pesticides in response to global agreements on persistent organic pollutants.
Using Epidemiological Studies to Check the Consistency of the Cancer Risks Predicted by High‐Dose Animal Experiments: A Methodological Review

Epidemiological studies have been cited in the literature as evidence both for and against the human cancer risks predicted by high‐exposure rodent studies. However, there has been little overall consistency in the ways that these animal‐to‐human comparisons have been made. This review examines some examples of these types of comparisons and describes the methods and techniques used by different investigators. Eleven “key decision areas” that need to be addressed are identified and recommendations for consistent, logical, and statistically appropriate approaches that might be taken to standardize the process are provided. In general, it is suggested that investigators provide the most useful information when they use logical, transparent, and statistically valid comparisons to pursue limited and focused objectives, such as directly testing the validity of an existing regulatory guidance value. Other recommendations include selecting biologically plausible extrapolative models that fit the data and drawing conclusions that are consistent with the study results and objectives.
Graphene pattern by gravure printing for wireless strain sensor

The paper shows the gravure printing technology is used as deposition method to pattern a graphene film on flexible polyimide substrates for a wireless strain sensor (WSS). According to the inductive coupling between the reader antenna and the graphene pattern (GP), a change in the GP characteristic can be detected wirelessly by a corresponding change in the complex impedance of the reader antenna. The WSS overcomes the inadequacy of the existing conventional sensors limited monitoring locations. And the WSS also exhibits a high sensitivity of 51% under a load of 100 N.
Being a young and inexperienced trainee anesthetist: a phenomenological study on tough working conditions

Background: Physicians at the beginning of their specialist education have been reported to be especially exposed to stress and difficult working conditions. Considerable worry has also been caused by reports about anaesthetists dying at a younger age than other specialists as well as by reports about higher than average suicide rates among anaesthetists. Maybe as a consequence, many young doctors are reluctant to choose anaesthesiology as their future specialty. The aim of this study was to investigate what difficulties trainee anaesthetists experience at work.
Distributed weighting fault-tolerant algorithm for event region detection in wireless sensor networks

In this paper, we propose a novel distributed weighting fault-tolerant algorithm for event region detection in wireless sensor networks. Considering the fault-tolerant range of ldquoneighborhoodpsilas neighborhoodrdquo, we first employ neighborhood nodes to exchange information with its surrounding nodes and estimate the status value of neighborhood nodes, and then weight and synthesize the estimating status value of neighborhood nodes via exploiting weighting fault-tolerant method, thus achieving the fault detection of central nodes. Simulation results show that more than 90 percent of faults can be detected and corrected using this algorithm, even when as many as 20 percent of the nodes are faulty.
Electrophysiologic mapping of the segmental anatomy of the muscles of the lower extremity

Our knowledge of the specific root innervation of skeletal muscles is derived from accumulated clinical experience. While performing selective posterior rhizotomy for treatment of spasticity in children with cerebral palsy, we made direct electrophysiologic measurement of the root innervation of the lower extremity. We stimulated ventral roots from L2 to S2 while recording from all muscles simultaneously. The size of the evoked compound muscle action potential was used as an indication of the amount of innervation derived from stimulation of a given spinal root. We found the major root innervation for the 8 muscles studied to be: adductor longus, vastus medialis, and vastus lateralis, L3; tibialis anterior; L4; peroneus longus, L5; and medial gastrocnemius, lateral gastrocnemius, and gluteus maximus, S1. In general, each muscle received innervation from 3 or more roots. Prefixed or postfixed innervation patterns were found in 27.9% of legs examined, and there was asymmetry of innervation in 29.8%. We conclude that the segmental innervation of lower extremity muscles is broader than previously thought. Anomalous innervation occurs so frequently that caution should be used in attributing any pattern of clinical or EMG findings to a specific spinal level.
Blind Extrathoracic Subclavian Venipuncture for Pacemaker Implant: A 3‐Year Experience in 250 Patients

We report our 3‐year experience using a modification of the percutaneous technique for extrathoracic subclavian Venipuncture proposed by Magney and colleagues for permanent pacing lead placement. Before surgery bony landmarks were marked on the skin according to Maguey's description to identify the needle entry point and the target point corresponding to the ideal location of the extrathoracic portion of the subclavian vein. Then the venipuncture was accomplished by inserting the needle through a standard infraclavicular pacemaker pocket. Two hundred fifty patients undergoing primary pacemaker implant (231 patients) or reimplant or change of mode of pacing (19 patients) were included in the study. The technique was successful in 245 (98%) cases. Inadvertent puncture of the subclavian artery occurred in 5 (2%) patients but in no case did it jeopardize the success of the implant procedure. No major complications were observed. Seven (2.9%) patients experienced early complications unrelated to the venous approach: 2 subclavian vein thrombosis, 5 lead dislodgment in 4 patients, and 1 pocket hematoma. During a mean follow‐up of 15.2 months (range 4–40) no lead or patient related complications occurred. In the present study the blind approach to the extrathoracic portion of the subclavian vein proved to be safe and effective for pacing lead insertion. Further observations are required to establish whether this method extends the lead survival.
Incidence, Resource Use, and Outcome of Acute Pancreatitis With/Without Intensive Care: A Nationwide Population-Based Study in Taiwan

Objectives: To investigate the nationwide epidemiology of acute pancreatitis (AP) in a developing country, with emphasis on the contribution of intensive care patients. Methods: We analyzed hospital patients with first-episode AP between 2005 and 2007, based on the claims data of a nationally representative sample of 1,000,000 people enrolled in the Taiwan National Health Insurance program. Severe AP was defined according to a modified Atlanta classification. Results: A total of 1693 patients with AP were identified. Crude and adjusted incidence rates of AP in 2005 were 56.9 and 42.8 per 100,000 persons, respectively. The age-specific incidence rates increased continuously with age in women, but showed a bimodal distribution in men. Severe AP was present in 20.4% of the patients; 47.4% of them received intensive care. The hospital days and charges of those receiving intensive care accounted for 22.1% of the total hospital days and for 40.8% of the total hospital charges of all patients with AP, respectively. Hospital mortality was 2.7%, ranging from 0.3% in nonsevere cases to 18.9% in those requiring intensive care. Conclusions: In Taiwan, 20% of patients with AP were severe; although only half of them received intensive care, they used significant resources and accounted for most deaths.
Cutaneous Leishmaniasis in Al‐Hassa, Saudi Arabia

ABSTRACT: Cutaneous leishmaniasis of the classical noduloulcerative variety is endemic in Al‐Hassa, Saudi Arabia. In a clinical study in which 56 Saudi patients and 66 non‐Saudi patients were examined, it was found that the Saudi patients were considerably younger and had significantly milder disease compared with the non‐Saudi patients.
The haemodynamic and metabolic effects of hypertonic-glucose and amino-acid-based peritoneal dialysis fluids.

BACKGROUND Continuous ambulatory peritoneal dialysis (CAPD) may exert significant effects on systemic haemodynamics. We have previously demonstrated that hypertonic glucose solutions are associated with higher blood pressure (BP) due to a rise in stroke volume (SV) and cardiac output (CO). However, the mechanisms underlying these changes have not been established. METHODS Ten non-diabetic CAPD patients entered a randomized crossover study (eight completed) to compare conventional glucose-based fluid, biocompatible pH-neutral glucose-based fluid and 1.1% amino acid solution (lactate-buffered but completely free of glucose degradation products). BP and haemodynamic variables were measured using continuous arterial pulse wave analysis, and serial plasma glucose and insulin concentrations were collected. Left ventricular (LV) diameters were measured at the start and end of each dwell period using M-mode echocardiography. RESULTS BP was similar during 1.36% glucose and 1.1% amino acid dwells, but was significantly higher during 3.86% glucose dwells with both conventional and biocompatible fluids (P < 0.001). This was associated with a significantly higher SV and CO (P < 0.001), although the haemodynamic response differed between conventional and biocompatible 3.86% solutions. Plasma glucose and insulin levels did not differ from baseline during 1.36% and amino acid dwells, but increased significantly during 3.86% glucose dwells. Despite a significantly higher ultrafiltration volume with 3.86% glucose, LV diameters were similar throughout. CONCLUSIONS In conclusion, we have confirmed our previous findings demonstrating higher BP and adverse haemodynamics during 3.86% glucose dwells. These changes are associated with hyperglycaemia and hyperinsulinaemia, but are not related to differences in cardiac filling.