Miracle-dz/UniFAR-FTUs huggingface dataset:
Passive Entrapment of Tumor Cells Determines Metastatic Dissemination to Spinal Bone and Other Osseous Tissues

During the metastatic process tumor cells circulate in the blood stream and are carried to various organs. In order to spread to different organs tumor cell—endothelial cell interactions are crucial for extravasation mechanisms. It remains unclear if tumor cell dissemination to the spinal bone occurs by passive entrapment of circulating tumor cells or by active cellular mechanisms mediated by cell surface molecules or secreted factors. We investigated the seeding of three different tumor cell lines (melanoma, lung and prostate carcinoma) to the microvasculature of different organs. Their dissemination was compared to biologically passive microbeads. The spine and other organs were resected three hours after intraarterial injection of tumor cells or microbeads. Ex vivo homogenization and fluorescence analysis allowed quantification of tumor cells or microbeads in different organs. Interestingly, tumor cell distribution to the spinal bone was comparable to dissemination of microbeads independent of the tumor cell type (melanoma: 5.646% ± 7.614%, lung: 6.007% ± 1.785%, prostate: 3.469% ± 0.602%, 7 μm beads: 9.884% ± 7.379%, 16 μm beads: 7.23% ± 1.488%). Tumor cell seeding differed significantly between tumor cells and microbeads in all soft tissue organs. Moreover, there were significant differences between the different tumor cell lines in their dissemination behaviour to soft tissue organs only. These findings demonstrate that metastatic dissemination of tumor cells to spinal bone and other osseous organs is mediated by passive entrapment of tumor cells similar to passive plugging of microvasculature observed after intraarterial microbeads injection.
Multicenter Analytical Evaluation of the Automated Electrochemiluminescence Immunoassay for Cyclosporine

Background: Cyclosporine A (CsA) is used as a posttransplantation immunosuppressant drug, and careful monitoring of CsA concentration in whole blood is essential. A new automated electrochemiluminescence immunoassay (ECLIA) for CsA measurement has been assessed in a multicenter evaluation. Methods: Residual EDTA whole blood samples from patients undergoing CsA therapy after organ transplant were used in assay evaluation at 5 clinical laboratories in Europe. Experiments included imprecision according to CLSI EP5-A2 (within-run and intermediate), lower limit of quantification, linearity according to CLSI EP6-A, and recovery of commercial external quality control samples. In addition, comparisons to liquid chromatography-tandem mass spectrometry methods in routine use at each investigational site and to commercial chemiluminescent microparticle immunoassay and antibody-conjugated magnetic immunoassay methods were performed. Results: Imprecision testing gave coefficients of variation of less than 9% in the 30–2000 mcg/L range for both within-run and intermediate imprecision. Lower limit of quantification of 6.8 mcg/L at one investigational site and 1.8 mcg/L at a second site at 20% coefficient of variation were observed. Linearity was measured over the concentration range 0–2000 mcg/L, yielding a deviation of less than ±12%. External quality control sample recovery by ECLIA was 93%–114% of LC-MS/MS sample recovery. Deming regression analysis of ECLIA method comparison to combined LC-MS/MS results yielded a slope of 1.04 [95% confidence interval (CI), 1.03–1.06] and intercept of 2.8 mcg/L (95% CI, 1.5–4.1 mcg/L). Comparison to chemiluminescent microparticle immunoassay yielded a slope of 0.87 (95% CI, 0.85–0.89) and intercept of 1.4 mcg/L (95% CI, −0.89 to 3.7 mcg/L); comparison to antibody-conjugated magnetic immunoassay yielded a slope of 0.96 (95% CI, 0.93–0.98) and intercept of −4.2 mcg/L (95% CI, −7.1 to −1.2 mcg/L). Conclusions: The data from this multicenter evaluation indicate that the new ECLIA-based cyclosporine assay is fit for its purpose, the therapeutic monitoring of CsA.
Phosphorus Supplementation Recovers the Blunted Diet-Induced Thermogenesis of Overweight and Obese Adults: A Pilot Study

Diet-induced thermogenesis (DIT) is believed to be largely related to ATP production, which is dependent on phosphorus (P) availability. We aimed to test the effect of P addition on DIT of lean and overweight/obese healthy subjects. DIT was measured with or without P in 10 lean and 13 overweight/obese adults in a double-blind randomized cross-over pilot study with one week washout period. After 10 h overnight fast, resting metabolic rate, respiratory quotient, and substrate utilization were measured at fasting and every 30 min for 3 h after subjects drank a standardized glucose solution, with P (500 mg) or placebo pills. Subjective ratings of hunger and satiety were assessed before and after the end of each experiment using validated visual analogue scale (VAS) questionnaires. Overweight/obese subjects had a blunted DIT with placebo, while P supplementation induced a 23% increase in their DIT area under the curve (p < 0.05), which was associated with a significant increase in carbohydrate oxidation. Subjects had lower appetite following P supplementation, which was expressed as a significantly (p = 0.02) lower desire to eat a meal (4.0 ± 0.7 cm) compared with placebo (5.8 ± 0.9 cm). P supplementation recovers the blunted diet-induced thermogenesis in overweight and obese subjects and enhances their postprandial satiety.
Patient characteristics and predictors of sleep medication use

The objective of this study was to investigate the characteristics of sleep medication users, and their satisfaction with treatment and subjective difficulty with quitting the drugs. A representative sample of 5000 adults in Norway was selected to participate in an epidemiologic study. The data were collected through a postal survey in which a total of 2645 (52.9%) participants responded. Weighted logistic regression was used to explore predictors for the drug pattern use. The prevalence of lifetime, current, and chronic use of sleep medications were 18.8, 7.9, and 4.2%. The use was associated with low socioeconomic status, older age, female sex, and frequent symptoms of sleep disorders, anxiety, and depression. Older age and low perceived control over sleep were the strongest predictors for use and difficulty in quitting sleep medications. Among responders who had ever used sleep medications, 80.3% would prefer a nonpharmacological treatment alternative. It is concluded that consumption of sleep medications is widespread in Norway, and that perception of control over sleep may play a significant role in the drug pattern use. Nonpharmacological treatment is to a small extent implemented in the health care sector.
Overnutrition and maternal obesity in sheep pregnancy alter the JNK‐IRS‐1 signaling cascades and cardiac function in the fetal heart

Maternal obesity in pregnancy predisposes offspring to insulin resistance and associated cardiovascular disease. Here, we used a well‐established sheep model to investigate the effects of maternal obesity on cardiac functions. Multiparous ewes were assigned to a control (CON) diet [100% of National Research Council (NRC) recommendations] or an obesogenic (OB) diet (150% of NRC recommendations) from 60 d before conception to necropsy on d 135 of pregnancy. Fetal blood glucose and insulin were increased (P<0.01, n=8) in OB (35.09±2.03 mg/dl and 3.40±1.43 μU/ml, respectively) vs. CON ewes (23.80±1.38 mg/dl and 0.769±0.256 μU/ml). Phosphorylation of AMP‐activated protein kinase (AMPK), a cardioprotective signaling pathway, was reduced (P<0.05), while the stress signaling pathway, p38 MAPK, was up‐regulated (P<0.05) in OB maternal and fetal hearts. Phosphorylation of c‐Jun N‐terminal kinase (JNK) and insulin receptor substrate‐1 (IRS‐1) at Ser‐307 were increased (P<0.05) in OB fetal heart associated with lower downstream PI3K‐Akt activity (P<0.05), indicating impaired cardiac insulin signaling. Although OB fetal hearts exhibited a normal contractile function vs. CON fetal hearts during basal perfusion, they developed an impaired heart‐rate‐left‐ventricular‐developed pressure product in response to high workload stress. Taken together, fetuses of OB mothers demonstrate alterations in cardiac PI3K‐Akt, AMPK, and JNK‐IRS‐1 signaling pathways that would predispose them to insulin resistance and cardiac dysfunction. —Wang, J., Ma, H. , Tong, C. , Zhang, H. , Lawlis, G. B. , Li, Y. , Zang, M. , Ren, J., Nijland, M. J., Ford, S. P., Nathanielsz, P. W. , Li, J. Overnutrition and maternal obesity in sheep pregnancy alter the JNK‐IRS‐1 signaling cascades and cardiac function in the fetal heart. FASEBJ. 24, 2066–2076 (2010). www.fasebj. org
Eosinophilic Esophagitis in Brazilian Pediatric Patients

We examined 11 pediatric patients with eosinophilic esophagitis with a tardy diagnosis. The symptoms were initially thought to be related to other diseases, leading to the use of inadequate therapeutic approaches. The patients were between 3 and 17 years old (mean 7.8 ± 3.8 years), and 8 of the patients were male. Common symptoms included abdominal pain, regurgitation, difficulty in gaining weight, vomiting, dysphagia, and coughing. The mean age for the onset of symptoms was 4.3 ± 2.9 years. Endoscopic findings included normal mucosa in five (45%) patients, thickening of the mucosa with longitudinal grooves in three (27%), erosive esophagitis in two (18%), and a whitish stippling in one (9%) patient. Treatment included the use of a topical corticosteroid for 10 patients. In eight (73%) cases, the treatment made the symptoms disappear. Ten patients underwent histopathological management after treatment, with a decrease in the number of eosinophils.
The role of volunteers in hospice bereavement support in New Zealand

The purpose of this study was to assess the role of hospice bereavement volunteers in New Zealand. Participants included 34 co-ordinators and 121 volunteers from 26 hospices. Co-ordinators and volunteers were asked about the perceived adequacy of their training, support and deployment. Findings revealed that most volunteers were recruited through personal contact and newspapers. They reported being strongly motivated to help others (88%) and most had previous bereavements (71%). Volunteers provided a wide range of bereavement support within the home and/or hospice. They listed twice as many ‘satisfying’ compared to ‘least satisfying’ (442 vs 207) aspects of their work, although 50% reported their work to be emotionally distressing and 28% had problems with ‘boundaries’. Two-thirds had generic volunteer training, but only a third had specific training in bereavement. Volunteers appeared to be largely unaware of the need for specialist training, or supervision, which raises issues about the quality of services provided.
Evaluation of two novel immunoassays designed to detect HIV antibodies in oral fluids

The testing of oral fluid samples for the detection of HIV antibodies offers several advantages over the testing of blood. Our objective was to evaluate a new generation of rapid and simple assays designed specifically to detect HIV‐1 and HIV‐2 antibodies in oral fluids (saliva). Serum and oral fluid pairs were collected from 615 high‐ and low‐risk individuals in the United States, Peru, and the Ivory Coast. Two different oral fluid collection devices and rapid assay systems included: (1) the Orapette/SalivaCard HIV‐1/HIV‐2 and (2) the Omni‐Sal/ImmunoComb II HIV‐1 and HIV‐2. The corresponding serum pairs were analyzed by conventional ELISAs, and all reactive sera were confirmed with HIV‐1 and HIV‐2 Western blots. The results indicated a 100% sensitivity for both rapid oral fluid assays, including successful detection of HIV‐2 antibodies. Specificities ranged from 99.8% to 100%. One sample produced a reactive result by the SalivaCard while being nonreactive by the other assays including the Western blots. Both assays performed excellently, indicating that antibodies to HIV can be detected reliably in oral fluids by simple and rapid assays. This combination of rapid testing technology and the use of easily collected oral fluid samples offers an efficient and accurate alternative to conventional testing and can be appropriately applied to a variety of testing situations for the laboratory diagnosis of HIV infection. J. Clin. Lab. Anal. 11:63–68. © 1997 Wiley‐Liss, Inc.
Adaptive output feedback for plants with direct feedthrough

In this paper, we present an adaptive output feedback controller using feedthrough components. This controller consists of an observer-based baseline controller with integral action and a closed-loop reference model and is shown to stabilize a class of linear plants with uncertain parameters including nonzero feedthrough matrices. The presence of direct feedthrough is addressed through the use of suitable feedback gains in the closed-loop reference model. The performance of the adaptive controller is illustrated using simulation studies of a model of an agile aircraft. The results show that a better performance with improved robustness can be obtained with the proposed adaptive controller. These results have important implications on aircraft problems where acceleration measurements are available.
Variation in cyclooxygenase expression levels within the colorectum

The positive association of decreased risk of colorectal cancer with nonsteroidal antiinflammatory drug (NSAID) use, combined with the observation that cyclooxygenase(COX)‐2 is present in a majority of colorectal tumors, has led to the proposed use of isozyme‐specific COX inhibitors as preventive agents in polyp and tumor formation in the colon. However, the exact biochemical mechanisms and disease stage at which reduced risk is mediated remain somewhat controversial, in part because of the complex biochemical changes that occur during the progression from aberrant crypt to polyp to tumor. In this study, COX‐1 and COX‐2 protein expression levels were determined in sets of tumor and normal colon tissue. Changes were characterized in COX‐1 and COX‐2 expression within individuals, in relation to such factors as sex, tumor grade, and location in the colorectum. COX‐1 expression levels were found to be significantly reduced in tumors compared to matched normal tissues (Dunn's method, P < 0.05). Additionally, COX‐1 expression was decreased in stage T3 tumors as compared to stage T2 tumors (Student's t‐test, P = 0.009). Similar to previous reports, COX‐2 protein expression was present in 73% of the tumors studied and appeared to be independent of tumor grade and sex. Interestingly, decreased COX‐2 expression correlated with tumor occurrence in rectal mucosa (Wilcoxon two‐sample test, P < 0.05). These results warrant further investigation, especially the identification of determinants that would predict which populations would be most responsive to COX‐2 inhibition as a means of colorectal cancer chemoprevention. Published 2003 Wiley‐Liss, Inc.
Neuronal activity enhances aryl hydrocarbon receptor‐mediated gene expression and dioxin neurotoxicity in cortical neurons

The aryl hydrocarbon receptor (AhR) is a ligand‐activated transcription factor activated by dioxin and polyaromatic hydrocarbons. Recent studies have revealed that AhR activity in central neurons depends on the NMDA receptor. In this study, we investigated how the neuronal activity influence AhR‐mediated dioxin‐responsive gene expression and neurotoxicity. Our results show that activation of AhR by the selective agonist 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin induced dioxin‐responsive gene expression and calcium entry, which were attenuated by AhR small interfering RNA, the NMDA receptor channel blocker MK801, and the action potential blocker tetrodotoxin (TTX). In addition, AhR‐mediated gene expression was enhanced in neurons during synaptogenesis (10 days in vitro) compared with younger neurons (4 days in vitro), as was sensitivity to TTX and MK801. Furthermore, TTX and MK801 differentially affected the association of AhR and its transcriptional co‐activator cAMP‐responsive‐element binding protein with the cytochrome P450 1A1 (cyp1A1) gene enhancer. Calcium/calmodulin‐dependent protein kinase IV, the cAMP‐responsive‐element binding protein activating enzyme, was also activated by 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin in an activity‐dependent manner. Finally, we found that neuronal susceptibility to dioxin insult was also maturation and activity‐dependent. Together, the results suggest that neuronal activity may facilitate AhR‐mediated calcium signaling, which in turn enhances AhR‐mediated gene regulation and mediated maturation‐dependent dioxin neurotoxicity.
Silicate absorption in heavily obscured galaxy nuclei

Spectroscopy at 8-13µm with T-ReCS on Gemini-S is presented for 3 galaxies with substantial silicate absorption features, NGC 3094, NGC 7172 and NGC 5506. In the galaxies with the deepest absorption bands, the silicate profile towards the nuclei is well represented by the emissivity function derived from the circumstellar emission from the red supergiant, � Cephei which is also representative of the midinfrared absorption in the diffuse interstellar medium in the Galaxy. There is spectral structure near 11. 2µm in NGC 3094 which may be due to a component of crystalline silicates. In NGC 5506, the depth of the silicate absorption increases from north to south across the nucleus, suggestive of a dusty structure on scales of 10s of parsecs. We discuss the profile of the silicate absorption band towards galaxy nuclei and the relationship between the 9.7 � m silicate and 3.4 � m hydrocarbon absorption bands.
Dual somatotopical representations in the primate subthalamic nucleus: evidence for ordered but reversed body-map transformations from the primary motor cortex and the supplementary motor area

The subthalamic nucleus (STN) is a key structure for somatic motor control via the basal ganglia. In the present study, we demonstrate that the STN of the macaque monkey has dual sets of body part representations. Each of the two separate portions of the STN is characterized with somatotopically arranged direct cortical inputs that are derived from the primary motor cortex (MI) and the supplementary motor area (SMA). The first set of body part representations is transformed from the MI to the lateral STN, whereas the second set is transformed from the SMA to the medial STN. Intracortical microstimulation mapping was carried out to guide paired injections of anterograde tracers into somatotopically corresponding regions of the MI and the SMA. We found that direct inputs from the MI were allocated mostly within the lateral half of the STN, whereas those from the SMA were distributed predominantly within its medial half. Of particular interest was that the arrangement of somatotopical representations from the SMA to the medial STN was reversed against the ordering of those from the MI to the lateral STN; the orofacial, forelimb, and hindlimb parts were represented from medial to lateral within the medial STN, whereas these body parts were represented, in the inverse order, mediolaterally within the lateral STN. Moreover, inputs from homotopical MI and SMA regions were found to converge only partially into the STN. The present findings could account for somatotopically specific involuntary movements manifested in hemiballism that is caused by destruction of the STN.
The impact of the sequence of pulmonary vessel ligation during anatomic resection for lung cancer on long-term survival--a prospective randomized trial.

PURPOSE The aim of this prospective randomized trial was to assess the influence of the sequence of pulmonary vessel ligation, during anatomic resection, on long term survival in patients with NSCLC. MATERIAL/METHODS This prospective randomized study included 385 patients treated surgically with lobectomy or pneumonectomy and standard lymphadenectomy between 1999 and 2003. Patients were randomly assigned to either primary ligation of the pulmonary artery or arteries (group A - 215 patients) or of the pulmonary vein or veins (group V - 170 patients). Patients were excluded if the sequence of vessel ligation was affected by technical difficulties or anatomic limitations. Univariate and multivariate analyses included: the sequence of vessel ligation, age, gender, tumor histology, stage (TNM), and cause of death (cancer related or non-cancer related). RESULTS Median follow-up was 63 months. The groups were comparable regarding gender, histology, type of resection, and T, N, and overall stage. Overall, 5-year survival reached 50% in group A and 54% in group V (p = 0.82) and did not differ significantly in cancer related and non-cancer related deaths (p = 0.67 and p = 0.26, respectively). Univariate analysis identified higher T and N factors, advanced stage, pneumonectomy, male sex, and older age as negative prognostic factors. Multivariate analysis demonstrated that age, T3-4 disease, and nodal involvement were associated with inferior survival. CONCLUSIONS The sequence of pulmonary vessel ligation during anatomic resection for non-small cell lung cancer does not significantly affect long-term survival.
Corticospinal Tract Integrity and Lesion Volume Play Different Roles in Chronic Hemiparesis and Its Improvement Through Motor Practice

Background. Initial evidence suggests that the integrity of the ipsilesional corticospinal tract (CST) after stroke is strongly related to motor function in the chronic state but not the treatment gain induced by motor rehabilitation. Objective. We examined the association of motor status and treatment benefit by testing patients with a wide range of severity of hemiparesis of the left and right upper extremity. Method. Diffusion tensor imaging was performed in 22 patients beyond 12 months after onset of stroke with severe to moderate hemiparesis. Motor function was tested before and after 2 weeks of modified constraint-induced movement therapy. Results. CST integrity, but not lesion volume, correlated with the motor ability measures of the Wolf Motor Function Test and the Motor Activity Log. No differences were found between left and right hemiparesis. Motor performance improved significantly with the treatment regime, and did so equally for patients with left and right arm paresis. However, treatment benefit was not associated with either CST integrity or lesion volume. Conclusion. CST integrity correlated best in this small trial with chronic long-term status but not treatment-induced improvements. The CST may play a different role in the mechanisms mediating long-term outcome compared to those underlying practice-induced gains after a chronic plateau in motor function.