Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of a piezoelectric system as an alternative to electroencephalogram/ electromyogram recordings in mouse sleep studies.

STUDY OBJECTIVES Traditionally, sleep studies in mammals are performed using electroencephalogram/electromyogram (EEG/EMG) recordings to determine sleep-wake state. In laboratory animals, this requires surgery and recovery time and causes discomfort to the animal. In this study, we evaluated the performance of an alternative, noninvasive approach utilizing piezoelectric films to determine sleep and wakefulness in mice by simultaneous EEG/EMG recordings. The piezoelectric films detect the animal's movements with high sensitivity and the regularity of the piezo output signal, related to the regular breathing movements characteristic of sleep, serves to automatically determine sleep. Although the system is commercially available (Signal Solutions LLC, Lexington, KY), this is the first statistical validation of various aspects of sleep. DESIGN EEG/EMG and piezo signals were recorded simultaneously during 48 h. SETTING Mouse sleep laboratory. PARTICIPANTS Nine male and nine female CFW outbred mice. INTERVENTIONS EEG/EMG surgery. MEASUREMENTS AND RESULTS The results showed a high correspondence between EEG/EMG-determined and piezo-determined total sleep time and the distribution of sleep over a 48-h baseline recording with 18 mice. Moreover, the piezo system was capable of assessing sleep quality (i.e., sleep consolidation) and interesting observations at transitions to and from rapid eye movement sleep were made that could be exploited in the future to also distinguish the two sleep states. CONCLUSIONS The piezo system proved to be a reliable alternative to electroencephalogram/electromyogram recording in the mouse and will be useful for first-pass, large-scale sleep screens for genetic or pharmacological studies. CITATION Mang GM, Nicod J, Emmenegger Y, Donohue KD, O'Hara BF, Franken P. Evaluation of a piezoelectric system as an alternative to electroencephalogram/electromyogram recordings in mouse sleep studies.
Use of standard toxicity tests with Typhlodromus pyri and Aphidius rhopalosiphi to establish a dose-response relationship

The existing standardised test systems for assessing the toxicity of crop protection products to the non-target arthropods Typhlodromus pyri (Acari: Phytoseiidae) and Aphidius rhopalosiphi (Hymenoptera: Aphidiidae) are limit tests designed to compare a single-use rate of the product with a water control. The suitability of these test systems for generating dose-response data as required for refined ecotoxicological risk assessment was evaluated. Data on dose-response toxicity of crop protection products to T. pyri and A. rhopalosiphi were generated under worst-case laboratory and to T. pyri under extended laboratory conditions and analysed using the standard Probit method, a logistic regression, a generalised Probit analysis, and the moving average-angle method in order to calculate the LR50-values (application rate killing 50 % of the exposed organisms). The fit of the models, the precision of the resulting LR50 values, and the required minimum number of replicates were compared. In 85 % of the studies, at least one of the statistical methods led to satisfactory results. The moving average-angle method was the most widely applicable method. The results show that the existing guidelines can be used to perform dose-response tests. Implications for risk assessment are discussed.
Using quality farms in multi-objective genetic software architecture synthesis

Genetic algorithms have become a popular heuristic technique to solve difficult search problems. However, in multi-objective problem solving, like software architecture generation, the basic variation mechanisms of genetic algorithms (mutation and crossover) tend to lead to mediocre solutions as the evolution favors balancing of several quality properties. In this paper, we explore the acceleration of genetic software architecture generation using a novel approach based on so-called quality farms, i.e., populations which favor a certain quality property. We hypothesize that by crossbreeding individuals from different quality farms it is possible to create beneficial variance that raises the fitness value to a significantly higher level. Experiments suggest that farm-based crossbreeding improves fitness value about 10%.
Vision-based techniques for efficient Wireless Capsule Endoscopy examination

Although there are several devices for screening the digestive tract, Wireless Capsule Endoscopy (WCE) is now the gold standard for a non-invasive viewing of small intestine. However, in each examination, more than 55,000 images are recorded. Reading so many images can be time consuming. Thus, image processing and vision recognition techniques are being created to help doctors to save the time for diagnosis. This paper presents a comprehensive overview of WCE devices and recent progresses in vision-based techniques on reducing the time needed for WCE video reading. The recently developed techniques can be classified into three categories: disease (bleeding) detection, image-level and video-level summarizations. Firstly, the features and classification strategies employed for automatic bleeding, disease or abnormal detection are presented. Second, this paper presents the image-level summarization based on motion estimation, C-mean clustering and epitome techniques. Third, we present and compare the various color-bar based global-level WCE video summarizations. The capabilities and advantages of different techniques for improving the efficiency of diagnosis are evaluated.
The blood neutrophil-to-lymphocyte ratio predicts survival in patients with advanced hepatocellular carcinoma receiving sorafenib.

BACKGROUND AND AIM Increasing evidence correlates the presence of systemic inflammation with poor survival in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the prognostic significance of the blood neutrophil-to-lymphocyte ratio (NLR) in patients with advanced HCC who received sorafenib monotherapy. METHODS A total of sixty-five patients with advanced HCC, not eligible for locoregional therapy, treated with sorafenib were enrolled. Potential prognostic factors such as age, gender, tumoral characteristics, performance status and NLR were analyzed. RESULTS Median OS and TTP for the entire cohort were 10.0 months (95%CI, 7.6-12.3 months) and 4.5 months (95% CI, 4.0-4.9 months). The mean NLR at baseline was 2.89. The median OS of patients with a high NLR (>4) was 6.5 months (95%CI, 5.2-7.7 months) compared with 12.5 months (95%CI, 9.9-15.0) for patients with a normal NLR (≤ 4) (P = 0.01). Age ≤ 65, NLR >4, extrahepatic metastases and vascular invasion were all predictors of poorer overall survival. Multivariate analysis showed that NLR > 4, vascular invasion and extrahepatic metastases were independent predictors of poorer overall survival. The median TTP of patients with a high NLR was 2.5 months (95%CI, 1.4-3.6 months) compared with 4.5 months (95%CI, 3.9-5.1 months) for patients with a normal NLR (P=0.012). CONCLUSIONS High baseline NLR was associated with worse OS and TTP for patients with advanced HCC treated with sorafenib.
The Prevalence and Impact of Mortality of the Acute Respiratory Distress Syndrome on Admissions of Patients With Ischemic Stroke in the United States

Purpose: To determine the epidemiology of the acute respiratory distress syndrome (ARDS) and impact on in-hospital mortality in admissions of patients with acute ischemic stroke (AIS) in the United States. Methods: Retrospective cohort study of admissions with a diagnosis of AIS and ARDS from 1994 to 2008 identified through the Nationwide Inpatient Sample. Results: During the 15-year study period, we found 55 58 091 admissions of patients with AIS. The prevalence of ARDS in admissions of patients with AIS increased from 3% in 1994 to 4% in 2008 (P < .001). The ARDS was more common among younger men, nonwhites, and associated with history of congestive heart failure, hypertension, chronic obstructive pulmonary disease, renal failure, chronic liver disease, systemic tissue plasminogen activator, craniotomy, angioplasty or stent, sepsis, and multiorgan failures. Mortality due to AIS and ARDS decreased from 8% in 1994 to 6% in 2008 (P < .001) and 55% in 1994 to 45% in 2008 (P < .001), respectively. The ARDS in AIS increased in-hospital mortality (odds ratio, 14; 95% confidence interval, 13.5-14.3). A significantly higher length of stay was seen in admissions of patients with AIS having ARDS. Conclusion: Our analysis demonstrates that ARDS is rare after AIS. Despite an overall significant reduction in mortality after AIS, ARDS carries a higher risk of death in this patient population.
The Feasibility of Reducing Sitting Time in Overweight and Obese Older Adults

Background. Overweight and obese older adults have high sedentary time. We tested the feasibility and preliminary effects of a sedentary time reduction intervention among adults over age 60 with a body mass index over 27 kg/m2 using a nonrandomized one-arm design. Methods. Participants (N = 25, mean age = 71.4, mean body mass index = 34) completed an 8-week theory-based intervention targeting reduced total sitting time and increased sit-to-stand transitions. An inclinometer (activPAL™) measured the primary outcomes, change in total sitting time and sit-to-stand transitions. Secondary outcomes included physical activity (ActiGraph GT3X+ accelerometer), self-reported sedentary behaviors, physical function (Short Physical Performance Battery), depressive symptoms (8-item Patient Health Questionnaire), quality of life (PROMIS), and study satisfaction. Paired t tests examined pre–post test changes in sitting time, sit-to-stand transitions, and secondary outcomes. Results. Inclinometer measured sitting time decreased by 27 min/day (p < .05) and sit-to-stand transitions increased by 2 per day (p > .05), while standing time increased by 25 min/day (p < .05). Accelerometer measured sedentary time, light-intensity, and moderate-to-vigorous physical activity improved (all p values ≤ .05). Self-reported sitting time, gait speed, and depressive symptoms also improved (all p values < .05). Effect sizes were small. Study satisfaction was high. Conclusions. Reducing sitting time is feasible, and the intervention shows preliminary evidence of effectiveness among older adults with overweight and obesity. Randomized trials of sedentary behavior reduction in overweight and obese older adults, most of whom have multiple chronic conditions, may be promising.
Calcification of human valve interstitial cells is dependent on alkaline phosphatase activity.

BACKGROUND AND AIM OF THE STUDY The calcification of heart valves is associated with valve degeneration and failure, but the mechanisms involved are poorly understood. The presence of lamellar bone has been demonstrated in calcified aortic valves. Since osseous calcification is closely associated with alkaline phosphatase (ALP) activity, it was hypothesized that ALP activity might be implicated in the calcification of isolated leaflet interstitial cells (ICs). METHODS Human valve leaflet ICs were isolated from transplant-explanted hearts at the time of transplantation (n = 12). RESULTS Isolated leaflet ICs expressed the fibroblast-specific antigen (100% of cells) and smooth muscle (SM) alpha-actin (70-80% of cells), but osteoblastic markers were not expressed. Cultured ICs did not calcify spontaneously, however when the growth medium was supplemented with beta-glycerophosphate (an organic phosphate) it induced the formation of calcified nodules that expressed osteonectin and ALP, but not SM alpha-actin. Beta-glycerophosphate-induced calcification of ICs showed a time-dependent effect on the calcium content of treated cells over a 14-day period. ALP activity was considerably increased in beta-glycerophosphate-treated ICs, and this correlated with the calcium content (r = 0.5: p = 0.01). Levamisol (an ALP inhibitor) inhibited the beta-glycerophosphate-induced calcification process, as well as the expression of osteoblastic differentiation markers. CONCLUSION Isolated and cultured leaflet ICs did not calcify spontaneously, though organic phosphate induced the formation of calcified nodules that expressed osteoblastic markers. The calcification of isolated ICs was seen to be dependent on ALP activity.
Dispersion of Horse Allergen from Stables and Areas with Horses into Homes

Background/Aim: To protect susceptible subjects from exposure to horse allergen, a Swedish national report recommended a distance of at least 500 m between homes and stables and other areas with horses. The aim of this project was to study indoor and outdoor levels of horse allergen in relation to distance from stables and horse tracks. Methods: Indoor and outdoorsamples were collected with Petri dishes at 49 sites in different housing areas and near to a track for trotting horses. In the apartments, Petri dishes were placed on a bookshelf in the living room at a height of approximately 1.5 m. Outdoors, cages containing Petri dishes were attached to tree branches at various distances from the horse track. Results: Six of 45 indoor samples had detectable levels of horse allergen, 3 of those despite the fact that no family member had had any contact with horses, and 16 of 26 outdoor samples were positive. Outdoors, allergen levels drop quickly when the distance from stables or horses increases. Further, the allergen level found at a distance of 45 m from a horse track was around 1% of the allergen level found at 1 m from the track. Conclusions: Allergens dispersed from horses decline rapidly outdoors and are barely found indoors in homes. We support the view that indirect exposure to horses such as exposure from clothing of horse riders, should be taken into account when measures to protect susceptible people from undesired exposure to horse allergens are taken.
PKA independent and cell type specific activation of the expression of caudal homeobox gene Cdx‐2 by cyclic AMP

Cdx‐2 is a transactivator for the proglucagon gene in pancreatic and intestinal endocrine cells. Cdx‐2 is also expressed in differentiated intestinal epithelia of nonendocrine origin. Cdx‐2–/– mice are embryonic lethal, while Cdx‐2+/– mutants show multiple malfunctions including the formation of intestinal polyps. Within the polyps, the remaining wild type Cdx‐2 allele ceases its expression, while the expression of both Cdx‐2 and proglucagon in the endocrine cells remains unaltered, indicating that Cdx‐2 could be haplo‐insufficient for nonendocrine cells, but not for proglucagon producing endocrine cells. We propose that mechanisms underlying Cdx‐2 expression and auto‐regulation [Xu F, Li H & Jin T (1999), J Biol Chem274, 34310–34316] differ in these two types of cells. We show here that forskolin and cAMP upregulate Cdx‐2 expression in proglucagon producing cells, but not in colon cancer cells and primary intestinal cell cultures. It is unlikely that the activation is mainly mediated by PKA, because the activation was observed in a PKA deficient cell line. Cotransfecting a dominant negative Ras expression plasmid substantially repressed the Cdx‐2 promoter, in contrast to a previous finding that Ras is a negative factor for Cdx‐2 expression in colon cancer cells. Furthermore, forskolin activated ERK1/2 phosphorylation in the endocrine cells, and attenuation of ERK1/2 phosphorylation by its inhibitor is associated with attenuated Cdx‐2 expression. Finally, an Epac pathway specific cAMP analogue stimulated both ERK1/2 phosphorylation and Cdx‐2 expression. Taken together, our observations suggest that Cdx‐2 expression is regulated by the second messenger cAMP, cell‐type specifically, via the Epac pathway.
Esophageal Expression of Active IκB Kinase-β in Mice Up-Regulates Tumor Necrosis Factor and Granulocyte-Macrophage Colony-Stimulating Factor, Promoting Inflammation and Angiogenesis.

BACKGROUND & AIMS IκB kinase-β (IKKβ) mediates activation of the nuclear factor-κB, which regulates immune and inflammatory responses. Although nuclear factor-κB is activated in cells from patients with inflammatory diseases or cancer, little is known about its roles in the development and progression of esophageal diseases. We investigated whether mice that express an activated form of IKKβ in the esophageal epithelia develop esophageal disorders. METHODS We generated ED-L2-Cre/Rosa26-IKK2caSFL mice, in which the ED-L2 promoter activates expression of Cre in the esophageal epithelia, leading to expression of a constitutively active form of IKKβ (IKKβca) in epithelial cells but not in inflammatory cells or the surrounding stroma (IKKβca mice). Mice lacking the Cre transgene served as controls. Some mice were given intraperitoneal injections of neutralizing antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) or tumor necrosis factor (TNF), or immunoglobulin G1 (control), starting at 1 month of age. Epithelial tissues were collected and analyzed by immunofluorescence, immunohistochemical, and quantitative real-time polymerase chain reaction assays. Transgenes were overexpressed from retroviral vectors in primary human keratinocytes. RESULTS IKKβca mice developed esophagitis and had increased numbers of blood vessels in the esophageal stroma, compared with controls. Esophageal tissues from IKKβca mice had increased levels of GM-CSF. Expression of IKKβca in primary human esophageal keratinocytes led to 11-fold overexpression of GM-CSF and 200-fold overexpression of TNF. Incubation of human umbilical vein endothelial cells with conditioned media from these keratinocytes increased endothelial cell migration by 42% and promoted formation of capillary tubes; these effects were blocked by a neutralizing antibody against GM-CSF. Injections of anti-GM-CSF reduced angiogenesis and numbers of CD31+ blood vessels in esophageal tissues of IKKβca mice, but did not alter the esophageal vasculature of control mice and did not alter recruitment of intraepithelial leukocytes to esophageal tissues of IKKβca mice. Injections of anti-TNF prevented the development of esophagitis in IKKβca mice. CONCLUSIONS Constitutive activation of IKKβ in the esophageal epithelia of mice leads to inflammation and angiogenesis, mediated by TNF and GM-CSF, respectively.
EFFECTS OF AGAR AND PECTIN ON GASTRIC EMPTYING AND POST‐PRANDIAL GLYCAEMIC PROFILES IN HEALTHY HUMAN VOLUNTEERS

1 Dietary fibre, such as pectin, delays gastric emptying and may enhance post‐prandial glucose tolerance. Agar, which is high in fibre content, is widely used in the traditional Japanese diet. Although long‐term diet therapy with agar decreases fasting plasma glucose levels in diabetes, knowledge is lacking about the acute effects of agar on gastric emptying and the post‐prandial glycaemic profiles. The present study was designed to investigate the acute effects of agar. 2 Ten healthy male volunteers were studied on three occasions with three different test meals (450 kcal/500 mL): (i) a fibre‐free meal; (ii) a meal with 2.0 g agar; or (iii) a meal with 5.2 g pectin. On each occasion, participants underwent a [13C]‐acetate breath test along with serial blood sampling. To quantify gastric emptying, the half [13CO2] excretion time () and the time for maximal [13CO2] excretion rate (tlag) were determined. The post‐prandial glycaemic response was expressed as an incremental change from the fasting value at each sampling time. Data were analysed using repeated‐measures analysis of variance (anova), followed by a post hoc paired Student's t‐test with Bonferroni adjustment. 3 The time‐course for respiratory [13CO2] excretion differed significantly among the three test meals (P = 0.0004, anova). Compared with the control meal, [13CO2] excretion was significantly lower following consumption of the agar meal (between 40 and 105 min post‐prandially; P < 0.025, Student's t‐test) and the pectin meal (between 40 and 180 min post‐prandially; P < 0.025, Student's t‐test). Among the three meals, significant differences were found in (P = 0.002, anova) and tlag (P = 0.011, anova). Compared with the control meal, the agar and pectin meals exhibited a significantly prolonged (P = 0.007 and P < 0.0001, respectively, Student's t‐test) and tlag (P = 0.006 and P = 0.002, respectively, Student's t‐test). Neither the agar nor pectin meal affected the post‐prandial glucose profile. 4 In healthy adults, agar and pectin delay gastric emptying but have no impact on the post‐prandial glucose response.
Loss of EphA2 receptor tyrosine kinase reduces Apcmin/+ tumorigenesis

The Eph receptor A2 (EphA2) is overexpressed in a range of human epithelial cancers, a phenotype that is associated with cancer cell proliferation, progression and angiogenesis. Mouse models of mammary neoplasia have confirmed the role of EphA2 as mice carrying a knockout allele of EphA2 were resistant to breast cancer, a phenotype that was associated with interactions between EphA2 and ErbB2. We investigated in vivo the role of EphA2 in GI cancer. To determine whether EphA2 influences intestinal tumorigenesis, we used qRT‐PCR to examine the mRNA expression levels of EphA2 in tumors from the small intestine and colon of ApcMin/+ mice. We found that EphA2 was significantly up‐regulated in tumors from both regions when compared with normal control tissues. We then evaluated the spatial expression patterns of EphA2 protein using immunohistochemistry in both the small intestine and colon and found that in normal tissues EphA2 was robustly expressed in highly differentiated cells, such as cells of the villi, but that EphA2 expression was largely absent from the stem cell niche and proliferative zones of intestinal crypts. In contrast, in tumors EphA2 was broadly expressed. Finally, we created a strain of ApcMin/+ mice carrying a genetic knockout of the EphA2 gene. These mice developed significantly fewer and smaller tumors in both the small and large intestine. Overall, our results indicate that EphA2 plays an oncogenic role in the mammalian intestine suggesting that strategies to target EphA2 activity may offer new therapeutic modalities for colorectal cancer. © 2008 Wiley‐Liss, Inc.
The Interaction of Protein-tyrosine Phosphatase α (PTPα) and RACK1 Protein Enables Insulin-like Growth Factor 1 (IGF-1)-stimulated Abl-dependent and -independent Tyrosine Phosphorylation of PTPα*

Background: Insulin-like growth factor 1 (IGF-1) stimulates PTPα tyrosine phosphorylation to enhance cell migration. Results: The scaffold protein RACK1 binds PTPα and the IGF-1 receptor, enabling IGF-1-stimulated phosphorylation of PTPα by Abl and other kinases. Conclusion: RACK1 coordinates PTPα within a signaling complex to mediate PTPα phosphorylation. Significance: RACK1 may link PTPα to diverse upstream signals that regulate PTPα tyrosine phosphorylation-dependent cell motility. Protein tyrosine phosphatase α (PTPα) promotes integrin-stimulated cell migration in part through the role of Src-phosphorylated PTPα-Tyr(P)-789 in recruiting and localizing p130Cas to focal adhesions. The growth factor IGF-1 also stimulates PTPα-Tyr-789 phosphorylation to positively regulate cell movement. This is in contrast to integrin-induced PTPα phosphorylation, that induced by IGF-1 can occur in cells lacking Src family kinases (SFKs), indicating that an unknown kinase distinct from SFKs can target PTPα. We show that this IGF-1-stimulated tyrosine kinase is Abl. We found that PTPα binds to the scaffold protein RACK1 and that RACK1 coordinates the IGF-1 receptor, PTPα, and Abl in a complex to enable IGF-1-stimulated and Abl-dependent PTPα-Tyr-789 phosphorylation. In cells expressing SFKs, IGF-1-stimulated phosphorylation of PTPα is mediated by RACK1 but is Abl-independent. Furthermore, expressing the SFKs Src and Fyn in SFK-deficient cells switches IGF-1-induced PTPα phosphorylation to occur in an Abl-independent manner, suggesting that SFK activity dominantly regulates IGF-1/IGF-1 receptor signaling to PTPα. RACK1 is a molecular scaffold that integrates growth factor and integrin signaling, and our identification of PTPα as a RACK1 binding protein suggests that RACK1 may coordinate PTPα-Tyr-789 phosphorylation in these signaling networks to promote cell migration.