Miracle-dz/UniFAR-FTUs huggingface dataset:
Coping with school bullying: A cross national pilot intervention study

In Australia and Greece the issue of school bullying is a significant concern of educators and students. While victims are not to be blamed for being bullied, research suggests that the strategies utilised by victims to cope with bullying may inadvertently reinforce victimisation. This paper will outline the successful Australian “Coping with School Bullying” (CWSB) program, including the use of a translated Greek version of the CWSB DVD, and describe the outcomes of the replication of the CWSB questionnaire with Greek students to identify effective and ineffective coping. Preliminary research conducted in Greek schools indicates that the CWSB program was successful in significantly reducing bullying amongst Greek students who had reported being seriously bullied pre-program. The intervention will now be rolled out to a larger number of schools in Greece in 2013.
Glaucocalyxin B Alleviates Lipopolysaccharide-Induced Parkinson’s Disease by Inhibiting TLR/NF-κB and Activating Nrf2/HO-1 Pathway

Background/Aims: Parkinson’s disease (PD) is a common neurodegenerative disease in the old population, characterized by dopaminergic neuron loss, inflammation and oxidative stress injury in the substantia nigra. Glaucocalyxin B (GLB), an ent-kauranoid diterpenoid isolated from Rabdosia japonica, has anti-inflammation and anti-tumor effects. However, its effects on PD remain unclear. Methods: PD was introduced in rats via injection of lipopolysaccharide (LPS) into cerebral corpus striatum, and GLB was given intracerebroventricularly to these rats. Their walking, climbing and sensory states were detected by Stepping, Whisker and Cylinder Tests. The expression of tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), CD11b and ionized calcium binding adaptor molecule (IBA)-1 were detected by immunohischemical staining. The levels of a series of inflammatory factors, oxidative stress-related factors and apoptosis-related factors were measured by real-time PCR, immunoblotting and ELISA. In addition, Toll-like receptor (TLR)/nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 pathways were investigated to illustrate the underlying mechanism. In vitro, microglial cells exposed to LPS were treated with GLB. Results: The injection of LPS caused walking, climbing and sensory disturbances in rats, induced inflammation, oxidative stress response and apoptosis, and activated TLR/NF-κB and Nrf2/ HO-1 pathways in the cerebral tissue. GLB administration attenuated LPS-induced alterations. The TLR/NF-κB pathway was deactivated and Nrf2/HO-1 was activated after application of GLB. In vitro, cytotoxic effects induced by the conditioned medium derived from microglial cells exposed to LPS in PC12 cells were attenuated by GLB. Conclusion: GLB suppresses LPS-induced PD symptoms by modification of TLR/NF-κB and Nrf2/HO-1 pathways in vivo and in vitro.
NF-κB and Therapeutic Approach

Since NF-κB has been identified as a transcription factor associated with immune cell activation, groups of researchers have dedicated to reveal detailed mechanisms of nuclear factor of κB (NF-κB) in inflammatory signaling for decades. The various molecular components of NF-κB transcription factor pathway have been being evaluated as important therapeutic targets due to their roles in diverse human diseases including inflammation, cystic fibrosis, sepsis, rheumatoid arthritis, cancer, atherosclerosis, ischemic injury, myocardial infarction, osteoporosis, transplantation rejection, and neurodegeneration. With regards to new drugs directly or indirectly modulating the NF-κB pathway, FDA recently approved a proteasome inhibitor bortezomib for the treatment of multiple myeloma. Many pharmaceutical companies have been trying to develop new drugs to inhibit various kinases in the NF-κB signaling pathway for many therapeutic applications. However, a gene knock-out study for IKKβ in the NF-κB pathway has given rise to controversies associated with efficacy as therapeutics. Mice lacking hepatocyte IKKβ accelerated cancer instead of preventing progress of cancer. However, it is clear that pharmacological inhibition of IKKβ appears to be beneficial to reduce HCC. This article will update issues of the NF-κB pathway and inhibitors regulating this pathway.
Allopurinol for fetal neuro- and cardiovascular protection

The studies presented in this thesis indicate that maternally administered allopurinol rapidly crosses the placenta, is effective in suppressing xanthine oxidase activity, has little adverse side effects (as long as clinically compatible dosages are used) and is potentially effective in preventing hypoxic ischemic damage to the heart and brain in fetal sheep and human female neonates. The latter, however, is based on post-hoc analyses and should be more intensively investigated before being implemented in perinatal medicine. Maternally administered allopurinol seems to have too little beneficial effects when used as a solemn therapeutic approach for perinatal asphyxia in a clinical setting, probably because fetal surveillance during labor is still too insensitive to optimally detect imminent fetal asphyxia. This may result in a suboptimal selection of patients really needing the treatment. Future research could therefore combine fetal allopurinol (pre)treatment (prevention) with another promising fetal neuroprotective agent like melatonin, and postnatal neuroprotective interventions (repair), such as hypothermia, postnatally administered allopurinol, 2-IB, erythropoietin or stem cells if the newborn infant appears to be really asphyxiated at birth (i.e. Apgar score <7 at 5 minutes, pH umbilical artery <7.05). Alternatively, in case of unexpected birth asphyxia, allopurinol treatment via the umbilical cord at the resuscitation table might result in a more optimal selection of infants needing treatment. This approach bypasses any placental problems, which may result in suboptimal placental transfer of allopurinol. And finally, any future research focusing on perinatal neuroprotective strategies should always take gender differences into account.
Substratum compliance modulates corneal fibroblast to myofibroblast transformation.

PURPOSE The transformation of fibroblasts to myofibroblasts is critical to corneal wound healing, stromal haze formation, and scarring. It has recently been demonstrated that the provision of biomimetic substratum topographic cues inhibits the progression toward the myofibroblast phenotype under the influence of transforming growth factor β1 (TGF-β1). The objective of this study was to determine the effect of another fundamental biophysical cue, substrate compliance, on TGF-β1-induced myofibroblast transformation of primary corneal cells isolated from human and rabbit corneas. METHODS Human and rabbit corneal fibroblasts were cultured on surfaces of varying substrate compliance (4-71 kPa) and tissue culture plastic (TCP) (> 1 gigapascal [GPa]). Cells were cultured in media containing TGF-β1 at concentrations of 0, 1, or 10 ng/mL for 72 hours. RNA and protein were collected from cells cultured on polyacrylamide gels and TCP and were analyzed for the expression of α-smooth muscle actin (α-SMA), a key marker of myofibroblast transformation, using quantitative PCR, immunocytochemistry, and Western blot. RESULTS Cells grown on more compliant substrates demonstrated significantly reduced amounts of α-SMA mRNA compared with TCP. Immunocytochemistry and Western blot analysis determining the presence of α-SMA corroborated this finding, thus confirming a reduced transformation to the myofibroblast phenotype on more compliant substrates compared with cells on TCP in the presence of TGF-β1. CONCLUSIONS These data indicate that substrate compliance modulates TGF-β1-induced expression of α-SMA and thus influences myofibroblast transformation in the corneal stroma. This provides further evidence that biomimetic biophysical cues inhibit myofibroblast transformation and participate in stabilizing the native cellular phenotype.
Treatment strategies for Zollinger–Ellison syndrome

Background: Zollinger–Ellison syndrome (ZES) is a rare disorder caused by tumor secretion of the hormone gastrin, which results in gastric acid hypersecretion and secondarily complicated peptic ulcer and diarrhea. Until the development of H2-receptor antagonists and later proton pump inhibitors (PPIs), the disease was virulent, often associated with ulcer-related mortality, and the mainstay of treatment was total gastrectomy. Objective: To evaluate current approaches to diagnosis and therapy, focusing on the role of PPIs. Methods: An extensive literature search through PubMed using the search term ‘Zollinger–Ellison syndrome’ from 1964 to the present was performed. Primary articles were identified, and pertinent articles obtained from the reference lists were also examined. Results/conclusions: The clinical manifestations of ZES are well described, but overlaps with other more common disorders delay diagnosis. The use of abdominal imaging with somatostatin receptor scintigraphy and endoscopic ultrasound has improved tumor staging. PPI therapy is remarkably effective in controlling gastric acid hypersecretion, thereby reducing morbidity and potential mortality of this syndrome. The dose of drug necessary to control symptoms is highly variable but, even when used in high doses for prolonged periods of time, the disease remained controlled with very few drug-related side effects.
The What and How of Observational Learning

Neuroimaging evidence increasingly supports the hypothesis that the same neural structures subserve the execution, imagination, and observation of actions. We used repetitive transcranial magnetic stimulation (rTMS) to investigate the specific roles of cerebellum and dorsolateral prefrontal cortex (DLPFC) in observational learning of a visuomotor task. Subjects observed an actor detecting a hidden sequence in a matrix and then performed the task detecting either the previously observed sequence or a new one. rTMS applied over the cerebellum before the observational training interfered with performance of the new sequence, whereas rTMS applied over the DLPFC interfered with performance of the previously observed one. When rTMS applied over cerebellar or prefrontal site was delivered after the observational training, no influence was observed on the execution of the task. These results furnish new insights on the neural circuitry involved in the single component of observational learning and allow us to hypothesize that cerebellum and DLPFC interact in planning actions, the former by permitting the acquisition of procedural competencies and the latter by providing flexibility among already acquired solutions.
Advanced Glycation End-Products and Advanced Oxidation Protein Products in Patients with Insulin Dependent Diabetes Mellitus and First Degree Relatives

Objective: There is no comprehensive information on the relationship of diabetic complications and the duration and severity of hyperglycemia. In this study, we aimed to determine oxidative stress markers in patients with insulin dependent diabetes mellitus and their first degree relatives. Materials and Methods: 45 patients with Type I diabetes mellitus and 24 relatives of these patients were included in our study. Plasma advanced oxide protein products (AOPP), serum glucose, urea, creatinine, cholesterol, triglyceride, HDL-cholesterol, total protein, albumin, advanced glication end products (AGE) and HbA1c measurements were measured by appropriate methods. Results: AOPP and AGE levels were found to be slightly elevated in diabetic patients with or without complications compared to the levels of first degree relatives however the difference was not statistically significant. Conclusion: When we had compared the parameteres in two groups (insulin dependent diabetic patients and non diabetic parents or siblings), we found weak relation between glucose and AGE (r= 0.25, p
Hematobiochemical changes induced by lead intoxication in male and female albino mice

Background: Lead is one of the main environmental contaminants that can threaten living organisms in many ways. Lead toxicity may affect multiple organs of human body and is associated with a number of physiological, biochemical, and morphological alterations. Aims and Objective: To investigate the risk that may result from exposure to different doses of lead acetate on the body weight and the weight of different organs, hematological indices, and the functions of liver and kidney. Materials and Methods: The experiment was performed on 80 mice. They were divided into four groups. The first group represented the healthy control animals, while groups II, III, and IV were given sublethal doses of lead acetate (0.4, 0.8, and 1.2 mg/kg body weight, respectively) in drinking water for 12 weeks. At the end of the experimental period, blood was collected and used for hematological and biochemical analysis. Result: The results indicated that mice treated with lead acetate showed significant reduction in total erythrocyte count, packed cell volume, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration compared with the healthy control ones while there were significant elevations in total leukocyte count and the amount of platelets. The results also showed significant increase in the activities of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and lactate dehydrogenase, indicating liver dysfunction. In addition, the serum levels of blood urea nitrogen and creatinine were also increased indicating renal deficiency. Conclusion: Treatment with lead acetate at low doses has harmful effects on experimental animals and induced hematological and biochemical alterations. Therefore, this study advises people to avoid any exposure to this toxic metal to prevent its hazardous effects on health.
Levels of Gingival Crevicular Metalloproteinases-8 and -9 in Periodontitis

Objective: To determine the levels of GCF matrix metalloproteinase-8 (MMP-8) and metalloproteinase-9 (MMP-9) patients with periodontitis and in healthy controls. Methods: Ten patients with periodontitis, and 10 healthy controls were included in this study. Samples were collected and processed at the Jain Diagnostic Centre, New Delhi. Informed consent was taken from subjects. Levels of crevicular MMP-8 and MMP-9 were determined by ELISA in subjects with healthy gingiva (n=10)and periodontitis (n=10). Two examiners recorded the clinical periodontal parameters and unstimulated saliva was collected. Clinical loss of attachment was determined by measuring the interproximal sites only. Results: Significantly higher crevicular MMP-8 and-9 were observed in cases of periodontitis compared to healthy adults. Conclusion: Crevicular MMP- 8 and 9 may serve as biomarkers of periodontal disease and aid in early detection of periodontitis.
Supporting Mathematical Problem Posing with a System for Learning Generation Processes through Examples

Problem posing, by which learners create new problems by themselves, is an important activity in mathematics education. However, novice learners have difficulty in posing problems, particularly when formulating appropriate solution structures of problems. Although they are provided with example problems that can serve as hints for composing novel problems, they do not necessarily understand the key ideas used to generate the examples. To improve problem posing for novices, this study discusses an approach that supports learning from examples as a production task. We propose a method of learning from examples through imitation, where a learner reproduces problems identical to given examples. We implement a system that presents examples of problem posing and supports learners in understanding the examples by having the learners reproduce them. We conducted an experimental evaluation in which learners learned from an example that embeds useful ideas to alter solution structures in the system. The results demonstrated that the learners successfully adapted the example when posing their own problems if they learned the example by the reproduction method. Thus, learning from examples through reproduction appears to be effective in the domain of problem posing as a production task.
EXTRACORPOREAL SHOCKWAVE THERAPY FOR REFRACTORY GREATER TROCHANTERIC PAIN SYNDROME

Introduction Greater trochanteric pain syndrome (GTPS) is a common and disabling condition characterised by pain and tenderness at or around the trochanteric area. Extracorporeal shockwave therapy (ESWT) has been described as a method of treatment. The National Institute for Clinical Excellence (NICE, UK) guidance suggests a possible benefit but with limited evidence. Materials and Methods We retrospectively identified 71 consecutive patients who underwent ESWT for refractory GTPS over a period of 16 months. The diagnosis was made clinically. ESWT was offered to patients with refractory symptoms despite conservative treatment. Telephone interviews were used to collect data including pain scores (0–10), change in symptoms, discomfort of the procedure, and complications. Results Fifty-nine patients (83%) were followed up. The mean time to follow up was 8 months (3 to 19). The mean age was 59 (29 to 88) with 86% females. Two-thirds had improvement in their symptoms with a significant drop of 6 points in their pain score (p Conclusion This study shows an improvement in the symptoms of 67% of patients with refractory GTPS, for up to 15 months, but with frequent relapsed. Further research is required to confirm whether MRI may be useful in selecting patients for ESWT.
Longitudinal Analysis and Prognostic Effect of Cancer-Testis Antigen Expression in Multiple Myeloma

Purpose: Reliable data on the persistence of tumor expression of cancer-testis (CT) antigens over time and consequent analyses of the effect of CT antigen expression on the clinical course of malignancies are crucial for their evaluation as diagnostic markers and immunotherapeutic targets. Experimental Design: Applying conventional reverse transcription-PCR, real-time PCR, and Western blot, we did the first longitudinal study of CT antigen expression in multiple myeloma analyzing 330 bone marrow samples from 129 patients for the expression of four CT antigens (MAGE-C1/CT7, MAGE-C2/CT10, MAGE-A3, and SSX-2). Results: CT antigens were frequently and surprisingly persistently expressed, indicating that down-regulation of these immunogenic targets does not represent a common tumor escape mechanism in myeloma. We observed strong correlations of CT antigen expression levels with the clinical course of myeloma patients as indicated by the number of bone marrow–residing plasma cells and peripheral paraprotein levels, suggesting a role for CT antigens as independent tumor markers. Investigating the prognostic value of CT antigen expression in myeloma patients after allogeneic stem cell transplantation, we found that expression of genes, such as MAGE-C1, represents an important indicator of early relapse and dramatically reduced survival. Conclusions: Our findings suggest that CT antigens might promote the progression of multiple myeloma and especially MAGE-C1/CT7, which seems to play the role of a “gatekeeper” gene for other CT antigens, might characterize a more malignant phenotype. Importantly, our study also strongly supports the usefulness of CT antigens as diagnostic and prognostic markers as well as therapeutic targets in myeloma.
Prognostic Value of Angiopoietin-2 for Death Risk Stratification in Patients with Metastatic Colorectal Carcinoma

Background: Baseline prognostic biomarkers stratifying treatment strategies in first-line metastatic colorectal cancer (mCRC) are lacking. Angiopoietin-2 (Ang-2) is proposed as a potential biomarker in several cancers. We therefore decided to establish the additional prognostic value of Ang-2 for overall survival (OS) in patients with first-line mCRC. Methods: We enrolled 177 patients treated with a bevacizumab containing chemotherapy in two prospective phase II clinical trials. Patient plasma samples were collected at baseline. ELISAs were used to measure Ang-2. Results: The multivariable Cox model identified increased lactate dehydrogenase [HR, 1.60; 95% confidence interval (CI), 1.04–2.45; P = 0.03] and Ang-2 log-transformation level (HR, 1.59; 95% CI, 1.14–2.21; P = 0.0065) as two significant independent OS prognostic factors. It exhibited good calibration (P = 0.8) and discrimination (C-index: 0.64; 95% CI, 0.58–0.68). Ang-2 parameter inclusion in the GERCOR reference model significantly and strongly improved its discriminative ability because the C-statistic increased significantly from 0.61 to 0.63 (bootstrap mean difference = 0.07; 95% CI, 0.069–0.077). Interestingly, the addition of Ang-2 binary information with a 5 ng/mL cutoff value to the GERCOR model allowed the reclassification of intermediate-risk profile patients (41%) into two subsets of low and high risks. Conclusions: Our study provides robust evidence in favor of baseline Ang-2 prognostic value for OS adding to the conventional factors. Its assessment appears to be useful for the improvement in risk stratification for patients with intermediate-risk profile. Impact: Ang-2 ability to predict OS at diagnosis could be of interest in the selection of patients eligible for intermittent or sequential therapeutic strategies dedicated to the optimization of patients' quality of life and chemotherapy cost-effectiveness. Cancer Epidemiol Biomarkers Prev; 24(3); 603–12. ©2015 AACR.
A Comparative Analysis of Pulmonary and Critical Care Medicine Guideline Development Methodologies

Rationale: The Institute of Medicine (IOM) standards for guideline development have had unintended negative consequences. A more efficient approach is desirable. Objectives: To determine whether a modified Delphi process early during guideline development discriminates recommendations that should be informed by a systematic review from those that can be based upon expert consensus. Methods: The same questions addressed by IOM‐compliant pulmonary or critical care guidelines were addressed by expert panels using a modified Delphi process, termed the Convergence of Opinion on Recommendations and Evidence (CORE) process. The resulting recommendations were compared. Concordance of the course of action, strength of recommendation, and quality of evidence, as well as the duration of recommendation development, were measured. Measurements and Main Results: When 50% agreement was required to make a recommendation, all questions yielded recommendations, and the recommended courses of action were 89.6% concordant. When 70% agreement was required, 17.9% of questions did not yield recommendations, but for those that did, the recommended courses of action were 98.2% concordant. The time to completion was shorter for the CORE process (median, 19.3 vs. 1,309.0 d; P = 0.0002). Conclusions: We propose the CORE process as an early step in guideline creation. Questions for which 70% agreement on a recommendation cannot be achieved should go through an IOM‐compliant process; however, questions for which 70% agreement on a recommendation can be achieved can be accepted, avoiding a lengthy systematic review.