Miracle-dz/UniFAR-FTUs huggingface dataset:
Resveratrol metabolites inhibit human metastatic colon cancer cells progression and synergize with chemotherapeutic drugs to induce cell death.

SCOPE Resveratrol (RSV) has been proposed to prevent tumor growth; nevertheless, these preventive effects are controversial since RSV pharmacokinetics studies show a low bioavailability. Recent clinical trials show that patients with colorectal cancer and receiving oral RSV have high levels of RSV conjugates in the colorectum, mainly RSV-3-O-sulfate (R3S), RSV-3-O-glucuronide, and RSV-4'-O-glucuronide. However, their potential biological activity has not yet been established. This study thus investigated in human colorectal cancer cell lines whether RSV main metabolites retain anticarcinogenic properties as their parental molecule. METHODS AND RESULTS Proliferation, apoptosis assays and cell cycle analysis were performed to study the effect of RSV, R3S, RSV-3-O-glucuronide, or RSV-4'-O-glucuronide alone or of a mixture of the three metabolites. R3S inhibits colon cancer cells proliferation and an accumulation of cells in S phase. Interestingly, the mixture induced a synergistic effect. This process was associated with an induction of DNA damages and apoptotic process, which allowed sensitization of colon cancer cells to the anticancer drugs. CONCLUSION Altogether, our data provide significant new insight into the molecular mechanism of RSV and support the notion that despite low bioavailability in vivo, RSV biological effects could be mediated by its metabolites.
A Single-case Experiment for an Innovative Cognitive Behavioral Treatment of Auditory Hallucinations and Delusions in Schizophrenia

This single-case experiment evaluates the impact of an innovative rational-emotive cognitive treatment focused on hallucination and delusions on quality of life, depression, anxiety, and insight in a female patient suffering from schizophrenia. The cognitive treatment developed for this experiment was directly inspired by the work of Ellis and Chadwick, Birchwood, and Trower. The rational-emotive cognitive approach used in the present study effectively reduced the patient's anxiety and depression, increased the patient's overall quality of life and insight. The gains were maintained at 3-month, 6-month, and 12-month follow-up. Future investigations into treatments for psychosis should focus on patients' insight regarding the origin of their hallucinations. Further, the link between negative and positive psychotic symptoms should be explored.
Six Sigma Literature: A Review and Agenda for Future Research

Like quality management in general, Six Sigma has penetrated into most sectors of today's business world. Although Six Sigma originated in industry, it has inspired a considerable amount of academic literature. This paper reviews this literature describing the trends, sources, and findings. The paper also seeks to synthesize the literature, with an emphasis on establishing its relationship to quality management theory and topics for future research. In doing so, there is an attempt to answer the following fundamental questions. (i) What is Six Sigma? (ii) What are its impacts on operational performance? (iii) What roles can academics usefully play in relation to Six Sigma? Copyright © 2006 John Wiley & Sons, Ltd.
Growth monitoring with the British 1990 growth reference

AIM To provide a simple method for assessing centile change based on the British 1990 growth reference. STATISTICAL METHOD The change in SD score over a period of time has SD 2 ( 1 – r ) , wherer is the correlation between the first and second SD score. This leads to an SD score for centile change. DATA Annual height measurements from 2 to 9 years for 318 children from the French longitudinal growth study. RESULTS The correlations between heights at different ages are higher for shorter measurement intervals and at older ages. The chance of a child’s height centile falling one centile band width is correspondingly smaller for shorter measurement intervals and at older ages. An increase in height measurement error reduces the correlations and dramatically increases the chances of centile crossing. CONCLUSIONS Quantitative height monitoring based on centile change is provided for whole year periods between 2 and 9 years of age. Effective monitoring requires the measurement error to be as small as possible.
Stability of the Adenosine 5′-Triphosphate Pool in Coxiella burnetii: Influence of pH and Substrate

The ability of Coxiella burnetii to couple oxidation of metabolic substrates to adenosine 5′-triphosphate (ATP) synthesis in axenic reaction buffers was examined. Pyruvate, succinate, and glutamate were catabolized and incorporated at the highest rates of 11 substrates tested. Glutamate oxidation, however, resulted in the greatest stability of the ATP pool and highest intracellular ATP levels over a 48-h period. At pH 4.5, the optimum for metabolism by C. burnetii, glutamate oxidation resulted in maintenance of the ATP pool at a concentration of approximately 0.7 nmol of ATP per mg of dry weight over a 96-h period. In the absence of substrate, ATP declined by 96 h to less than 0.01 nmol/mg of dry weight. When cells were maintained at pH 7.0 in the presence or absence of glutamate, ATP pools were considerably more stable, presumably due to the minimal metabolic activity displayed by C. burnetii at pH 7. The stability of the ATP pool reflected viability as there was greater than an 8-log decrease in viable C. burnetii after incubation for 7 days at pH 4.5 in the absence of glutamate. Viability was retained in the presence of glutamate at pH 4.5 or 7.0 in the absence of any added substrate. The stability of the ATP pool was due to endogenous synthesis of ATP coupled to substrate oxidation as shown by depression of ATP levels in the presence of inhibitors of electron transport or oxidative phosphorylation. In addition, the adenylate energy charge increased from an initial value of 0.57 to 0.73 during glutamate oxidation with a concomitant rise in the total adenylate pool size. C. burnetii therefore appears able to regulate endogenous ATP levels in response to substrate availability and pH, thus effecting a conservation of metabolic energy in neutral or alkaline environments. Such a mechanism has been proposed to play a role in the resistance of C. burnetii to environmental conditions and subsequent activation upon entry into the phagolysosome in which this organism replicates.
Osmolality as a Measure of Dehydration in the Neonatal Period

True dehydration implies an increase in the osmolality of the extracellular fluid, of which the plasma provides a modified sample, and is conventionally measured by estimating the plasma sodium level which in most circumstances represents half the plasma osmolality (sodium in millinormals and osmolality in milliosmoles/kg. water); however, this relationship does not always hold, for instance in the dying (Rubin, Braveman, Dexter, Vanamee, and Roberts, 1956). It is known that there is a physiological mechanism for the control of the concentration of the extracellular fluid which is geared to total osmolality (Verney, 1946) and is independent of the control of the concentrations of individual solutes (e.g. sodium ions). Plasma sodium levels are very variable immediately after birth (Acharya and Payne, 1965), but hitherto it has not been shown whether these changes reflect equivalent alterations in plasma osmolality. Direct measurement ofosmolality should settle this point and provide a more accurate assessment than sodium levels of hydration and dehydration in the newborn. It is of course normal for an infant to lose some weight in the first few days of life, the loss being made up by about the tenth day, and J. Puga and J. P. M. Tizard (1965, personal communication) have shown that this loss amounts to 40-50 g. /kg. day for the first 2 days of life in the full-term baby. About half this loss is insensible, and it is reasonable to postulate that it will represent loss of water rather than of isotonic fluid, and should, therefore, be accompanied by a rise in the osmolality of the extracellular fluid. It is part of the folklore of paediatrics that fever at this time of life may be the result of dehydration, which presumably limits the ability of the infant to keep cool in a warm environment, and in that case it should be accompanied by an excessive rise in plasma osmolality rather than by signs of infection. For these reasons, and because both in practice and from a theoretical point of view knowledge of the
Dietary patterns and colorectal cancer: systematic review and meta-analysis

Studies on the association between single foods or nutrients and colorectal cancer have provided inconsistent results. Previous reviews did not conduct a quantitative synthesis of the relation with dietary patterns. We conducted a systematic review and meta-analysis of studies addressing the association between dietary patterns and colorectal cancer. Studies quantifying the association between dietary patterns (defined a posteriori) and colorectal cancer were identified in PubMed (until 01.08.2010) and through backward and forward citation tracking (ISI Web of Science and Scopus). Summary relative risk (RR) estimates and 95% confidence intervals (95% CI) were computed for highest versus lowest levels of exposure, for colon cancer (CC) and rectal cancer (RC), and for proximal and distal CC, by random effects meta-analysis. Heterogeneity was quantified using the I2 statistic. Eight cohort and eight case–control studies defining patterns through principal components and factor analyses were included in the systematic review. Meta-analyses were conducted for three patterns: (i) ‘drinker,’ characterized by high alcohol consumption (CC: RRcombined=0.96, 95% CI: 0.82–1.12, I2=0.6%; RC: RRcombined=0.83, 95% CI: 0.47–1.45, I2=65.1%); (ii) ‘healthy,’ characterized by high fruit/vegetables consumption (CC: RRcombined=0.80, 95% CI: 0.70–0.90, I2=55.1%; RC: RRcombined=1.02, 95% CI: 0.89–1.17, I2=10.8%); (iii) ‘western,’ characterized by high red/processed meat consumption (CC: RRcombined=1.29, 95% CI: 1.13–1.48, I2=31.7%; RC: RRcombined=1.13, 95% CI: 0.92–1.39, I2=40.6%). Summary estimates for proximal and distal CC were similar. The risk of CC was increased with patterns characterized by high intake of red and processed meat and decreased with those labelled as ‘healthy. ’ No significant associations were observed for RC.
Can the Broselow tape be used to estimate weight and endotracheal tube size in Korean children?

BACKGROUND The Broselow pediatric emergency tape (BT) was developed to provide a length-based estimate of body weight and equipment size during resuscitation. OBJECTIVES To conduct a validation study on the use of the BT in Korean children. METHODS Anesthesia records from children were retrospectively reviewed. The measured weights of the subjects were compared with the BT weight estimates by using Bland-Altman analysis. The accuracy of the BT and age-based formula in predicting the endotracheal tube (ETT) size were also compared. The authors drew a receiver operating characteristics (ROC) curve to evaluate the cutoff height that would be acceptable for the application of BT without error in Korean children. RESULTS A total of 665 children (mean [+/- SD] age, 5.1 [+/- 3.3] years, 61.8% male) were enrolled. The average measured weight of the Korean children was 1.54 kg heavier than the BT estimates (95% CI = 1.24 to 1.85 kg). The BT estimates showed better agreement with the actually used ETT sizes than did the age-based formula estimates (86.9% vs. 34.9%, p < 0.001). The cutoff height of the ROC curve was 127.15 cm. When the BT was used in children who were shorter than the cutoff height, 98.8% of the enrolled children's estimated weights were within the limits of agreement. CONCLUSIONS The BT can be used in Korean children as a helpful adjunct during resuscitation to estimate the weight and ETT size.
Overexpression of Cyclin D1 Promotes Tumor Cell Growth and Confers Resistance to Cisplatin-Mediated Apoptosis in an Elastase-myc Transgene–Expressing Pancreatic Tumor Cell Line

Purpose: Elevated cyclin D1 in human pancreatic cancer correlates with poor prognosis. Because pancreatic cancer is invariably resistant to chemotherapy, the goal of this study was to examine whether the drug resistance of pancreatic cancer cells is in part attributed to cyclin D1 overexpression. Experimental Design: Stable overexpression and small interfering RNA (siRNA)–mediated knockdown of cyclin D1 were done in the newly established Ela-myc pancreatic tumor cell line. Cisplatin sensitivity of control, overexpressing, and siRNA-transfected cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, clonogenic, and apoptotic assays [DNA fragmentation, sub-G1, and poly(ADP-ribose) polymerase cleavage analysis]. The role of nuclear factor-κB and apoptotic proteins in cyclin D1-mediated chemoresistance was examined by EMSA and Western blotting, respectively. Results: Overexpression of cyclin D1 in Ela-myc pancreatic tumor cells promoted cell proliferation and anchorage-independent growth. Moreover, cyclin D1–overexpressing cells exhibited significantly reduced chemosensitivity and a higher survival rate upon cisplatin treatment, as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and clonogenic assays, respectively. Although overexpression of cyclin D1 rendered cells more resistant to cisplatin-induced apoptosis, siRNA-directed suppression of cyclin D1 expression resulted in enhanced susceptibility to cisplatin-mediated apoptosis. The attenuation of cisplatin-induced cell death in cyclin D1–overexpressing cells was correlated with the up-regulation of nuclear factor-κB activity and maintenance of bcl-2 and bcl-xl protein levels. Conclusions: These results suggest that overexpression of cyclin D1 can contribute to chemoresistance of pancreatic cancer cells because of the dual roles of cyclin D1 in promoting cell proliferation and in inhibiting drug-induced apoptosis.
The non‐immunosuppressive cyclosporin DEBIO‐025 is a potent inhibitor of hepatitis C virus replication in vitro

Cyclosporin A (CsA) inhibits the in vitro replication of HCV subgenomic replicons. We here report on the potent anti‐HCV activity of the non‐immunosuppressive cyclosporin DEBIO‐025. The 50% effective concentration for inhibition of HCV subgenomic replicon replication in Huh 5‐2 cells (luciferase assay) by DEBIO‐025 was 0.27 ± 0.03 μg/mL and for CsA 2.8 ± 0.4 μg/mL. The concentration that reduced the growth of exponentially proliferating Huh 5‐2 cells by 50% was greater than 27 μg/mL for DEBIO‐025 and 12 ± 6 μg/mL for CsA, resulting in a selectivity index of approximately 900 for DEBIO‐025 and 40 for CsA. The superior activity of DEBIO‐025, as compared with CsA, was corroborated by monitoring HCV RNA levels in Huh 5‐2, two other HCV subgenomic replicon‐containing cell lines, and by monitoring the luciferase signal and viral antigen production in hepatoma cells that had been infected with an infectious full‐length chimeric HCV construct. The combination of interferon alpha 2a with either CsA or DEBIO‐025 resulted in an additive to slightly synergistic antiviral activity. DEBIO‐025, at concentrations of 0.5 and 1 μg/mL, was able to clear cells from their HCV replicon within three to four passages, whereas treatment with CsA at the same concentrations for seven consecutive passages did not result in clearance of the HCV replicon. In conclusion, DEBIO‐025, a compound that is also endowed with potent anti‐HIV activity and is well tolerated in animals and humans, may form an attractive new option for the therapy of HCV infections, particularly in HCV/HIV co‐infected patients. (HEPATOLOGY 2006;43:761–770.)
Effects of relevance criteria and subjective factors on web image searching behaviour

Searching for images is an everyday activity. Nevertheless, even a highly skilled searcher often struggles to find what they are looking for. This article studies the factors that affect users’ online web image search behaviour, investigating (1) the use of criteria in making image relevance judgements and (2) the effect of familiarity, difficulty and satisfaction. The study includes 48 users who performed four online image search tasks using Google Images. Simulated work scenarios, questionnaires and screen capture recordings were used to collect data of their image search behaviour. The results show in judging image relevance, users may apply similar criterion, however, the importance of these criteria depends on the type of image search. Similarly, ratings of users’ perception on subjective aspects of performing image search shows they were task dependent. Users’ perception on subjective aspects of performing image search did not always correspond with their actual search behaviour. Correlation analysis shows that subjective factors cannot be definitively measured by using only one component of search behaviour. Future work includes further analysis on the effects of topic familiarity and satisfaction.
The presence of atopy does not determine the type of cellular infiltrate in nasal polyps.

BACKGROUND AND OBJECTIVES Any relationship between atopy and nasal polyposis remains to be further studied to determine the contribution of atopy to the pathogenesis of nasal polyps. MATERIALS AND METHOD We have compared the inflammatory cellular infiltrate in nasal polyp tissue taken during resection from 10 atopic and 11 non-atopic subjects. We have used immunohistochemistry to enumerate the individual inflammatory cell types using monoclonal antibodies against tryptase (AA1) to identify mast cells, the secreted forms of eosinophil cationic protein (EG2) to identify activated eosinophils, neutrophil elastase (NE+) to demonstrate neutrophils, and T cell surface markers (CD3) to identify pan T cells. RESULT The number of AA1+ and NE+ cells tended to be higher in atopics, but no statistical significance was found (p = 0.06, p = 0.12). Eosinophil numbers (EG2) were abundant in both groups and found to be not different between them (p = 0.65). Some subjects had CD3+ cells with no significant difference between atopic and non-atopic subjects (p = 0.21). Significant correlation was found between NE+ and AA1+ or EG2 cells (r = 0.59, r = 0.63, p < 0.05, respectively). CONCLUSION These results suggest that the presence of atopy does not determine either the type of extent of cellular infiltration of nasal polyps.
Programmers Should Still Use Slices When Debugging

—What is the best technique for fault localization? In a study of 37 real bugs (and 37 injected faults) in more than a dozen open source C programs, we compare the effectiveness of statistical debugging against dynamic slicing—the ﬁrst study ever to compare the techniques. On average, dynamic slicing is more effective than statistical debugging, requiring programmers to examine only 14% (42 lines) of the code before ﬁnding the defect, less than half the effort required by statistical debugging (30% or 157 lines). Best results are obtained by a hybrid approach : If programmers ﬁrst examine the top ﬁve most suspicious locations from statistical debugging, and then switch to dynamic slices, they will need to examine only 11% (35 lines) of the code.
mproving predictive models of glaucoma severity by incorporating uality indicators

Objective: In this paper we present an evaluation of the role of reliability indicators in glaucoma severity prediction. In particular, we investigate whether it is possible to extract useful information from tests that would be normally discarded because they are considered unreliable. Methods: We set up a predictive modelling framework to predict glaucoma severity from visual field (VF) tests sensitivities in different reliability scenarios. Three quality indicators were considered in this study: false positives rate, false negatives rate and fixation losses. Glaucoma severity was evaluated by considering a 3-levels version of the Advanced Glaucoma Intervention Study scoring metric. A bootstrapping and class balancing technique was designed to overcome problems related to small sample size and unbalanced classes. As a classification model we selected Naïve Bayes. We also evaluated Bayesian networks to understand the relationships between the different anatomical sectors on the VF map. Results: The methods were tested on a data set of 28,778 VF tests collected at Moorfields Eye Hospital between 1986 and 2010. Applying Friedman test followed by the post hoc Tukey’s honestly significant difference test, we observed that the classifiers trained on any kind of test, regardless of its reliability, showed comparable performance with respect to the classifier trained only considering totally reliable tests (p-value > 0.01). Moreover, we showed that different quality indicators gave different effects on prediction results. Training classifiers using tests that exceeded the fixation losses threshold did not have a deteriorating impact on classification results (p-value > 0.01). On the contrary, using only tests that fail to comply with the constraint on false negatives significantly decreased the accuracy of the results (p-value < 0.01). Meaningful patterns related to glaucoma evolution were also extracted. Conclusions: Results showed that classification modelling is not negatively affected by the inclusion of less reliable tests in the training process. This means that less reliable tests do not subtract useful information from a model trained using only completely reliable data. Future work will be devoted to exploring new quantitative thresholds to ensure high quality testing and low re-test rates. This could assist doctors in tuning patient follow-up and therapeutic plans, possibly slowing down disease progression.
Resection margins in rectal cancer

INTRODUCTION Adenocarcinoma of the colon and rectum has become one of the major health problems in the western countries due to its rapidly increasing incidence in recent decades. It is currently the second most common cause of death by cancer in the western world [1]. According to the Slovene Cancer Registry, colorectal cancer has already become the most common among all cancers in Slovenia [2]. Approximately one third of all colorectal cancers arise in the rectum (0–15 cm from the anal verge) [1,3]. Fortunately not only the incidence of rectal carcinoma has been increasing during the last decades. Technical innovations together with a better understanding of pelvic anatomy and the behaviour of rectal tumours have resulted in some radical changes in the surgical and nonsurgical treatment of these neoplasms. These changes have considerably improved outcome and survival [4]. Outcome in rectal cancer depends on stage, use of neoadjuvant and adjuvant chemoradiation and technical aspects of surgical excision [1,3]. One of the main objectives of surgical treatment is to provide adequate safety margins of healthy tissue around the tumour, since positive resection margins are associated with high risk for local recurrence, distal metastases and eventually death [3,5,6]. The aim of our study was to address the relative contributions of distal resection margin (DRM) and circumferential resection margin (CRM) status towards survival.