Miracle-dz/UniFAR-FTUs huggingface dataset:
The dual roles of inflammatory cytokines and chemokines in the regulation of autoimmune diseases and their clinical implications

Cytokines and chemokines are secreted, small cell‐signaling protein molecules, whose receptors are expressed on immune cells. These factors play a critical role in immune cell differentiation, migration, and polarization into functional subtypes and in directing their biological functions. Much attention has been devoted to exploring the role of key inflammatory cytokines and promigratory chemokines in autoimmune, autoinflammatory, and allergic diseases, leading to development of therapeutic strategies that are based on their targeted neutralization. Recent studies, including those coming from our groups, show that several major proinflammatory cytokines and chemokines, including IFN‐γ, IL‐2, CCL2, and CXCL12, may also function as anti‐inflammatory mediators and therefore, may have potential as anti‐inflammatory drugs. Likewise, major anti‐inflammatory mediators, such as TGF‐β, may under certain conditions, in combination with other cytokines, exhibit proinflammatory function and direct the polarization of the highly inflammatory CD4+ Th17 cells. We show here that the biological function of pro‐ and anti‐inflammatory cytokines is dependent on three key parameters: the local concentration of a given cytokine, the stage of disease in which it is administered, and its combination with other cytokines. The therapeutic implications of these findings are discussed, including two very recent studies summarizing clinical trials, in which low‐dose administration of IL‐2 was used to successfully suppress HCV and GVHD.
Treatment of unstable tibial fractures with interlocking nail versus Ender nail: a prospective evaluation.

BACKGROUND For unstable tibial fractures, there are many methods of surgical treatment. The efficacy of the Ender nail and the interlocking nail in the treatment of such fractures is examined. METHODS One hundred and seven cases of unstable tibial shaft fractures were collected for the prospective study. Randomly, 61 tibia were fixed with interlocking nails and 46, with Ender nails. The mean follow-up period was 30.5 (23 to 40) months. The results of the different treatments were compared. RESULTS In the group with interlocking nails, the average blood loss was 265 cc; operation time was 61 minutes; hospital days were 10.4; and union time was 15.1 weeks for closed fractures and 17 weeks for Winquist-Hansen type III and IV fractures. In the group with Ender nails, the average blood loss was 135 cc, operation time was 32 minutes, hospital days were 8.3 days, and union time was 17.6 weeks for closed fractures and 22.5 weeks for Winquist-Hansen type III and IV fractures. Student t-test revealed statistically significant difference between the groups in all of the data described above. However, treatment with the different nails showed no significant difference in results for open type I and II fractures. CONCLUSIONS Ender nail still has its superior usefulness in some aspects of treatment of less comminuted unstable tibial shaft fractures, but for the more comminuted unstable tibial shaft fractures, the interlocking nail is undoubtedly better used.
Granulocyte‐macrophage colony stimulating factor induces endothelial capillary formation through induction of membrane‐type 1 matrix metalloproteinase expression in vitro

In our study, we examined the mechanism by which granulocyte‐macrophage colony stimulating factor (GM‐CSF) regulates angiogenesis using in vitro models. GM‐CSF significantly increased precapillary sprout‐like formation from endothelial cell spheroids seeded in type‐I collagen gels and tubule formation on coculture of endothelial cells with fibroblasts. In both cases, sprout and tubule formation was highly dependent on metalloproteinase activity. Tissue Inhibitor of metalloproteinase (TIMP) profiling in the spheroid and coculture models showed inhibition by TIMP‐2 but not by TIMP‐1, indicative of activity of membrane‐type matrix metalloproteinases (MT‐MMPs). GM‐CSF induced sprout formation in spheroids was found to be potently inhibited by siRNA specific for MT1‐MMP. Subsequent analysis showed that GM‐CSF transiently increased MT1‐MMP mRNA in endothelial cells in a MEK‐dependent mechanism, which led to increased surface levels of MT1‐MMP. This was accompanied by an increase in MT1‐MMP‐dependent degradation of DQ‐collagen by lysates of GM‐CSF stimulated endothelial cells. GM‐CSF did not increase MT1‐MMP levels in fibroblasts. The effect of GM‐CSF on endothelial cell sprout formation could be mimicked by adenoviral transduction of intact spheroids with virus expressing MT1‐MMP, but not by transduction of endothelial cells before spheroid formation, suggesting that upregulation of MT1‐MMP must only occur in cells directly involved in tubule formation. © 2007 Wiley‐Liss, Inc.
Structural Equation Modelling and the Causal Effect of Permanent Income on Life Satisfaction: The Case of Air Pollution Valuation in Switzerland

This study examines the relationship between air quality and life satisfaction. Moreover, a panel structural equation modelling (SEM) is applied in order to capture the causal effect of permanent income on life satisfaction. Swiss Household Panel (SHP) Survey (2000–2013), which is a detailed micro level survey, is used for the analysis controlling for personal and household characteristics. Five air pollutants are examined in the entire analysis; ozone (O), particulate matter (PM), carbon monoxide (CO), sulphur dioxide (SO) and nitrogen dioxide (NO). Furthermore, the marginal willingness‐to‐pay (MWTP) values for reducing air pollution are calculated. For the robustness checks, the SEM estimates are compared with those derived by the adapted Probit Fixed Effects (FE) model. Overall results show that MWTP values are higher for SO followed by O and NO, while the lowest values are reported for CO and PM Moreover, it is found that the permanent income has a positive significant effect on life satisfaction. However, considering the SEM estimations, findings for the income effects on life satisfaction are stronger than those found from the adapted Probit FE estimates that lead to lower MWTP values.
Investigating the temperature effect of reliability on integration IC 3D packaging under drop test

Technological developments and increasing user demand have driven the evolution of electronic packaging from traditional single-chip packaging to multi-chip packaging, i.e., three-dimensional integrated circuit (3D-IC) packaging. The main advantages of 3D-IC packaging are its small size and lower signal delay. Thus, 3D-IC packaging has been broadly used in mobile electronic devices. Mobile electronic devices are prone to being dropped because of their portability. During drop impact, the temperature inside the packages becomes higher than ambient temperature especially for 3-D packaging, which would influence physical behavior of packaging. A simulation that uses the Input-G method was adopted to analyze the dynamic behavior of electronic packaging. Finite element (FE) model analysis that considers glass transition temperature (Tg) was performed to investigate the effect of temperature. The results showed that the reliability of electronic packaging with underfill might be worse than that without underfill when temperature loading is higher than Tg. This study focuses on drop reliability and considers the effect of Tg. An FE model was established based on a real 3D-IC integration package to predict the drop life by using CoffinManson semi-empirical equation. First, thermal stress analysis would be The drop analysis conducted after the thermal stress analysis indicates that the plastic strain of solder joint increased evidently when considering the effect of temperature during drop analysis and that a temperature higher than Tg has a more obvious influence on strain accumulation during thermal stress analysis than during drop impact analysis. Finally, the drop reliability of 3D-IC was predicted. For a structure without underfill, the drop life can be predicted reasonably, whereas it will be overestimated when the structure has underfill. These different findings may be due to the perfect bonding provided by the underfill during each drop in the simulation, which is unlike actual, real-world situations.
Acute laminar shear stress reversibly increases human glomerular endothelial cell permeability via activation of endothelial nitric oxide synthase

Laminar shear stress is a key determinant of systemic vascular behavior, including through activation of endothelial nitric oxide synthase (eNOS), but little is known of its role in the glomerulus. We confirmed eNOS expression by glomerular endothelial cells (GEnC) in tissue sections and examined effects of acute exposure (up to 24 h) to physiologically relevant levels of laminar shear stress (10–20 dyn/cm2) in conditionally immortalized human GEnC. Laminar shear stress caused an orientation of GEnC and stress fibers parallel to the direction of flow and induced Akt and eNOS phosphorylation along with NO production. Inhibition of the phophatidylinositol (PI)3-kinase/Akt pathway attenuated laminar shear stress-induced eNOS phosphorylation and NO production. Laminar shear stress of 10 dyn/cm2 had a dramatic effect on GEnC permeability, reversibly decreasing the electrical resistance across GEnC monolayers. Finally, the laminar shear stress-induced reduction in electrical resistance was attenuated by the NOS inhibitors l-NG-monomethyl arginine (l-NMMA) and l-NG-nitroarginine methyl ester (l-NAME) and also by inhibition of the PI3-kinase/Akt pathway. Hence we have shown for GEnC in vitro that acute permeability responses to laminar shear stress are dependent on NO, produced via activation of the PI3-kinase/Akt pathway and increased eNOS phosphorylation. These results suggest the importance of laminar shear stress and NO in regulating the contribution of GEnC to the permeability properties of the glomerular capillary wall.
The Hantown Street Play Project

ABSTRACT Street Play projects have become increasingly popular in Western contexts where children’s outdoor free play has been in decline. Street Play projects are generally organised by adults: children play on urban streets closed to traffic. This paper reports results from an evaluation focused on the Hantown Street Play Project (pseudonym) that took place in a large English town. Hantown Leisure Trust (pseudonym) set up the project, run by playworkers, and commissioned the evaluation ‘ … to identify the impact of the Street Play project on participating children’s perceptions of play in their community and residents’ perceptions of community spirit’. Children aged 3–11 years, parents and local residents participated in questionnaire surveys (n = 216) and semi-structured interviews (n = 25), eliciting 10 themes indicating that participants generally regarded the project positively. However, this paper argues that Street Play is a different proposition from children’s own play on the streets, according to widely recognised definitions of play.
Alteration of subcellular and cellular expression patterns of cyclin B1 in renal cell carcinoma is significantly related to clinical progression and survival of patients

Cyclin B1, identified as a regulator of late cell cycle, is involved in the development and progression of a variety of human malignancies. To clarify the role of cyclin B1 in the pathogenesis and prognosis of renal cell carcinoma (RCC), protein expression was compared with clinicopathological characteristics of patients as well as the long‐term survival after surgical therapy. Expression analysis was carried out by immunohistochemistry and tissue microarray analysis. The microarrays that represented the primary tumors, their invasion front and normal peritumoral renal parenchyma contained 753 tissue cores obtained from 251 randomly selected nephrectomy specimens. Immunopositivity within the primary tumors was significantly associated with tumor stage (pT) (p < 0.01), lymph node status (pN) (p < 0.01) as well as the presence of systemic metastatic disease (p = 0.01). Subcellular expression in the cytoplasm of tumor cells significantly correlated with pT (p = 0.02) and pN (p = 0.03). When peritumoral tissue samples exhibited a relative amount of <10% of positively reacting epithelial cells, cyclin B positivity was identified to predict long‐term survival of patients in univariate analysis (p < 0.01) whereas borderline significance was observed in multivariate statistical analysis (p = 0.05). Increased intratumoral cyclin B1 positivity and aberrant localization of signals within the cytoplasm of tumor cells is positively correlated with the tendency towards tumor progression, indicating the significant role of cyclin B1 in the development and pathogenesis of RCC. The result of uni‐ and multivariate statistical analysis suggests the prognostic value of cyclin B1 for RCC patients. © 2006 Wiley‐Liss, Inc.
Neuroprotective effect of an antioxidant, ebselen, in patients with delayed neurological deficits after aneurysmal subarachnoid hemorrhage.

OBJECTIVE The effect of ebselen, a seleno-organic compound with antioxidant activity through a glutathione peroxidase-like action, on the outcome of subarachnoid hemorrhage was evaluated in a multicenter placebo-controlled double-blind clinical trial. METHODS Patients who suffered aneurysmal subarachnoid hemorrhages of Hunt and Kosnik Grades II through IV at admission and were able to start drug treatment within 96 hours of the ictus were enrolled. Early surgery was performed whenever possible. Oral administration of ebselen granules suspended in water (150 mg, twice a day) or placebo was started immediately after admission and continued for 2 weeks. The major end points were the Glasgow Outcome Scale at 2 weeks, 1 month, and 3 months after the start of treatment. The incidence of delayed ischemic neurological deficits clinically diagnosed as resulting from vasospasm and the incidence and extent of low-density areas on postoperative computed tomographic scans were also studied as secondary outcome measures. RESULTS Intent-to-treat analysis of the 286 patients enrolled in the trial (145 patients administered ebselen and 141 administered placebo) revealed that the incidence of clinically diagnosed delayed ischemic neurological deficits was unaltered. There were 52 (receiving ebselen) and 58 (receiving placebo) patients with delayed deficits; however, a significantly better outcome was observed after ebselen treatment than after placebo (P = 0.005, chi2 test). There was a corresponding decrease in the incidence and extent of low-density areas (P = 0.032, Wilcoxon rank sum test). CONCLUSION Ebselen reduced brain damage in patients with delayed neurological deficits after subarachnoid hemorrhage and may be a promising neuroprotective agent.
Familial aggregation of Barrett’s oesophagus, oesophageal adenocarcinoma, and oesophagogastric junctional adenocarcinoma in Caucasian adults

Background: Although familial clusters of Barrett’s oesophagus and oesophageal adenocarcinoma have been reported, a familial predisposition to these diseases has not been systematically investigated. Aims: To determine whether Barrett’s oesophagus and oesophageal (or oesophagogastric junctional) adenocarcinoma aggregate in families. Patients and methods: A structured questionnaire eliciting details on reflux symptoms, exposure history, and family history was given to Caucasian case (n=58) subjects with Barrett’s oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma, and to Caucasian control (n=106) subjects with symptomatic gastro-oesophageal reflux disease without Barrett’s oesophagus. Reported diagnoses of family members were confirmed by review of medical records. Results: The presence of a positive family history (that is, first or second degree relative with Barrett’s oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma) was significantly higher among case subjects compared with controls (24% v 5%; p<0.005). Case subjects were more likely to be older (p<0.001) and male (74% v 43% male; p<0.0005) compared with control subjects. In a multivariate logistic regression analysis, family history was independently associated with the presence of Barrett’s oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma (odds ratio 12.23, 95% confidence interval 3.34–44.76) after adjusting for age, sex, and the presence of obesity 10 or more years prior to study enrolment. Conclusions: Individuals with Barrett’s oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma are more likely to have a positive family history of Barrett’s oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma than individuals without Barrett’s oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma. A positive family history should be considered when making decisions about screening endoscopy in patients with symptoms of gastro-oesophageal reflux.
Diagnosis of chronic thromboembolic pulmonary hypertension: comparison of ventilation/perfusion scanning and multidetector computed tomography pulmonary angiography with pulmonary angiography

ObjectiveThe correct and prompt diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) plays a pivotal role in determining appropriate therapy. This study aimed to compare the diagnostic efficacy of pulmonary ventilation/perfusion (V/Q) scanning and computed tomography pulmonary angiography (CTPA) using pulmonary angiography as the golden standard. MethodsA total of 114 consecutive patients (49 men and 65 women, age 43.3±15.3 years) suspected of having CTEPH were prospectively enrolled. All patients underwent V/Q scanning, CTPA, and pulmonary angiography within an interval of 7 days from one another. Interpretation of V/Q images was based on the refined Pulmonary Embolism Diagnosis criteria. For threshold 1, high-probability and intermediate-probability V/Q scan findings were considered to be positive, and low-probability/normal V/Q scan findings were negative. For threshold 2, only a high-probability V/Q scan finding was considered to be positive, and intermediate-probability and low-probability/normal V/Q scan findings were considered to be negative. ResultsFifty-one patients (44.7%) had a final diagnosis of CTEPH. V/Q scan showed high probability, intermediate probability, and low probability/normal scan in 52, three, and 59 patients, respectively. CTPA revealed 50 patients with CTEPH and 64 patients without CTEPH. The sensitivity, specificity, and accuracy of the V/Q scan were 100, 93.7, and 96.5%, respectively, with threshold 1, and 96.1, 95.2, and 95.6%, respectively, with threshold 2; similarly, the sensitivity, specificity, and accuracy of CTPA were 92.2, 95.2, and 93.9%, respectively. ConclusionIn conclusion, both V/Q scanning and CTPA are accurate methods for the detection of CTEPH with excellent diagnostic efficacy.
Comparative observations on the cyst shells of seven Artemia strains from China

The quiescent Artemia cysts of seven geographical origins in China were examined with scanning and transmission electron microscopes. SEM observations on cysts of these Artemia strains showed that the surface topography of cyst shells could be categorized into 6 types: complete smooth surface; smooth surface with sparsely distributed glabrate humps; surface with densely arranged wart‐like humps that are composed of packed minute tubercles; rugged surface, with densely arranged tubercles not piling up to form larger humps; shallow‐pocked surface; and surface with numerous and densely spaced pore‐like fossulae. Some of the patterns were strain specific [e.g., cysts from Ga Hai (GH) are characterized by having a surface with wart‐like ornaments that are composed of packed minute tubercles, rugged surface is only found in Chengkou (CK) cysts], and apparent intrastrain variation of cyst surface topography was found in Xizang (XZ), Jingyu Hu, and Xie Chi (SIN) strains. TEM studies on the ultrastructure of cyst shells revealed an apparent divergence in the structure of outer cuticular membrane (OCM) among Artemia strains. In CK, Aqqikkol Hu (AQK), SIN, and GH strains, it is a normal, asymmetrical, and multi‐layered structure similar to those described in previous works. In XZ, JYH, and Lagkor Co (LGC) strains, however, the OCM is not obviously multi‐layered and the borderlines between OCM and adjacent layers seem indistinct. The present results suggest that the diversity of the surface topography of Artemia cysts may be an available tool for identifying certain Artemia strains as well as for tracking the origins of some Artemia cysts, and the hypoplastic OCM may be a characteristic of the species A. tibetiana. Microsc. Res. Tech., 2007. © 2007 Wiley‐Liss, Inc.
Substrate selection for the optical analysis of nickel oxide thin films

The transmittance and absorbance data of nickel oxide films are crucial in determining it's optical properties. Selection of substrate is important for a greater understanding of optical constants and properties of a material. In view of this Nickel oxide films were deposited on Quartz substrates and it's properties are compared with Nickel oxide films deposited on glass. We show the difference in optical constants measured for Nickel oxide thin film deposited on glass and quartz substrates.
Efficacy of the peptidergic nootropic drug cerebrolysin in patients with senile dementia of the Alzheimer type (SDAT).

Cerebrolysin is a peptidergic nootropic drug with a multimodal mechanism of action. It is expected to have a positive influence on neurodegenerative diseases such as senile dementia of the Alzheimer type (SDAT). Experimental studies have shown Cerebrolysin to have a regulatory effect on energy metabolism, a positive influence on behavior through neuromodulation due to its peptide fraction, and most important, a neurotrophic stimulation. In SDAT and related disorders the neurotrophic effect of the drug could play a major role and influence the progress of the illness. A placebo-controlled double-blind trial was designed to examine the efficacy of the drug in SDAT. Confirmatory statistics were used for analysis. 120 subjects with mild to moderate dementia according to the Global Deterioration Scale (GDS) were included in the trial. Their performance on the Mini Mental State Examination (MMSE) was between 15 and 25. The diagnosis was substantiated by the Hachinski Ischemic Score and cranial computed tomography. The inclusion and exclusion criteria were formulated so as to prevent a distortion between the two arms by secondary dementia or other disease. The two arms received either placebo or the drug once a day (30 ml Cerebrolysin in 100 ml physiological saline i.v.) from Monday to Friday for four weeks. Physiological saline (130 ml) was used as placebo. Primary variables used for the statistical analysis were the Clinical Global Impression (CGI), which measures the improvement in symptoms, the SCAG score, and the performance in the trial-making test (ZVT-G). The self-assessment in the Bf-S and the activities of daily living in the NAI were used as secondary variables. (ABSTRACT TRUNCATED AT 250 WORDS)