Miracle-dz/UniFAR-FTUs huggingface dataset:
Activity of a specific inhibitor, gefitinib (Iressa, ZD1839), of epidermal growth factor receptor in refractory non-small-cell lung cancer.

BACKGROUND Gefitinib (Iressa(TM), ZD1839) is an orally active, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Phase I studies showed that it is well tolerated, with evidence of tumor regression in patients with advanced non-small-cell lung cancer (NSCLC). Therefore, we aimed to assess the antitumor activity and tolerability of gefitinib in a series of patients with previously treated, advanced NSCLC, as a part of a compassionate use program. PATIENTS AND METHODS To be eligible, all patients were required to have histologically or cytologically proven advanced or metastatic NSCLC, prior chemotherapy with at least one cisplatin-containing chemotherapy regimen or contraindication to cytotoxic drugs, Eastern Cooperative Oncology Group performance status < or =2, and adequate hematological, renal and hepatic parameters. All patients provided signed informed consent. Patient re-evaluation was performed every 4-6 weeks. RESULTS Seventy-three consecutive patients were enrolled. Response rate, including complete and partial response, was 9.6%; an additional 43.8% of patients achieved stable disease, for an overall disease control of 53.4%. EGFR1 status was evaluated by immunocytochemistry in 25 patients. According to EGFR1 immunoreactivity all responses were observed with medium/strong imunoreactivity while three out of four responses were observed in high expressive patients. Median survival for all patients was 4 months while it reached 6 months for patients with disease control. The 1-year survival rate was 13.1% for the entire series and 23.2% for patients with disease control. Non-hematological toxicity was generally mild. CONCLUSION Gefitinib has promising activity with a good toxicity profile in patients with progressive NSCLC who have received one or two prior chemotherapy regimens. A possible relationship within response and EGFR1 expression is suggested.
Experimental Evolution of Metabolic Dependency in Bacteria

Bacteria frequently lose biosynthetic genes, thus making them dependent on an environmental uptake of the corresponding metabolite. Despite the ubiquity of this ‘genome streamlining’, it is generally unclear whether the concomitant loss of biosynthetic functions is favored by natural selection or rather caused by random genetic drift. Here we demonstrate experimentally that a loss of metabolic functions is strongly selected for when the corresponding metabolites can be derived from the environment. Serially propagating replicate populations of the bacterium Escherichia coli in amino acid-containing environments revealed that auxotrophic genotypes rapidly evolved in less than 2,000 generations in almost all replicate populations. Moreover, auxotrophs also evolved in environments lacking amino acids–yet to a much lesser extent. Loss of these biosynthetic functions was due to mutations in both structural and regulatory genes. In competition experiments performed in the presence of amino acids, auxotrophic mutants gained a significant fitness advantage over the evolutionary ancestor, suggesting their emergence was selectively favored. Interestingly, auxotrophic mutants derived amino acids not only via an environmental uptake, but also by cross-feeding from coexisting strains. Our results show that adaptive fitness benefits can favor biosynthetic loss-of-function mutants and drive the establishment of intricate metabolic interactions within microbial communities.
Network dynamics of mobile social networks

With the rapid development of smartphones and mobile Internet technology, we witness an overwhelming growth of mobile social networks (MSN), which is a type of social network, forming virtual communities among people with similar interests or commonalities. In MSNs, users play a crucial role for their development, deployment and success. Understanding the MSN user behavior therefore attracts interests of different entities - ISPs, service providers, and researchers. However, it is hard to gather a comprehensive real data set, little is known and even less has been published about MSN user activities. In this paper, we focus on analyzing MSN user behavior from the perspective of ISP network, which is seldom reported in literature. Based on the real data set collected from the mobile network gateway of a major mobile carrier who has more than five million subscribers, we present an in-depth user behavior analysis of four popular social networks. We study the MSN user behavior from six aspects: user requests, active online time, sessions, inter-session, the number of requests in a session, and inter-request. We found that power law and lognormal are two popular features of the studied objects, and exposed some interesting findings as well. We hope our work could be helpful for ISPs, MSN content providers, and researchers.
Visual-based Sensory Motor Learning During Dynamic Balance Tasks Viewed in a Virtual Environment

In this research, we applied a transformation to the normal trajectory used to move and track a visual target in a virtual environment, in order to evaluate adaptation to a visual-based sensory motor transformation. The ability to recalibrate internal to external spatial reference frames is important when changing the relationship between the self and the environment. The virtual task was controlled by the subject's center of foot pressure (COP); the physical COP location is mapped (slaved) to an on-screen cursor (avatar). Target balloons appeared randomly on the screen and the subject was instructed to move the cursor (COP) to intersect the balloon and burst it. When the experimental transformation was applied, the trajectory of the avatar underwent a counter-clockwise rotation of 60deg this required the subjects to update their spatial reference coordinates between the physical COP position and the game avatar. Two parameters were calculated in order to investigate if learning occurred: 1) the displacement angle between the COP trajectory and the direct line path between the starting COP position and target position; and 2) the maximum perpendicular displacement between the COP trajectory and the direct line path to the balloon target. The results showed a decrease in movement error with learning.
A Systems Approach to Prefrontal-Limbic Dysregulation in Schizophrenia

Introduction: Using a prefrontal-limbic dysregulation model for schizophrenia, we tested whether a dynamic control systems approach in conjunction with neuroimaging might increase detection sensitivity in characterizing the illness. Our analyses were modeled upon diagnostic tests for other dysregulatory diseases, such as diabetes, in which trajectories for the excitatory and inhibitory components of the negative feedback loops that reestablish homeostasis are measured after system perturbation. We hypothesized that these components would show distinct coupling dynamics within the patient population, as compared to healthy controls, and that these coupling dynamics could be quantified statistically using cross-correlations between excitatory and inhibitory time series using fMRI. Methods: As our perturbation, we activated neural regions associated with the emotional arousal response, using affect-valent facial stimuli presented to 11 schizophrenic patients (all under psychotropic medication) and 65 healthy controls (including 11 individuals age- and sex-matched to the patients) during fMRI scanning. We first performed a random-effects analysis of the fMRI data to identify activated regions. Those regions were then analyzed for group differences, using both standard analyses with respect to the time series peaks, as well as a dynamic analysis that looked at cross-correlations between excitatory and inhibitory time series and group differences over the entire time series. Results: Patients and controls showed significant differences in signal dynamics between excitatory and inhibitory components of the negative feedback loop that controls emotional arousal, specifically between the right amygdala and Brodmann area 9 (BA9), when viewing angry facial expressions (p = 0.002). Further analyses were performed with respect to activation amplitudes for these areas in response to angry faces, both over the entire time series as well as for each time point along the time series. While the amygdala responses were not significantly different between groups, patients showed significantly lower BA9 activation during the beginning of the response (0.000 ≤ p ≤ 0.021) and significantly higher BA9 activation towards the end of the response (0.008 ≤ p ≤ 0.025), suggesting longer time-lags between patients’ excitatory responses and the inhibitory activation that modulates it. Conclusions: Our results capture a significant dysregulation between the excitatory (amygdala) and inhibitory (prefrontal) limbic regions in medicated schizophrenic patients versus healthy controls. They suggest that, analogously to diagnostic tests used in other physiological diseases, quantifying dysregulation using a control systems approach may provide an appropriate model to investigate further in developing presymptomatic neurobiological assessments of risk, or illness severity in symptomatic patients.
Enamel matrix derivative and low-level laser therapy in the treatment of intra-bony defects: a randomized placebo-controlled clinical trial.

AIM The aim of this study was to evaluate the immediate post-operative pain, wound healing and clinical results after the application of an enamel matrix protein derivative (EMD) alone or combined with a low-level laser therapy (LLLT) for the treatment of deep intra-bony defects. MATERIAL AND METHODS This study was an intra-individual longitudinal test of 12 months' duration conducted using a blinded, split-mouth, placebo-controlled and randomized design. In 22 periodontitis patients, one intra-bony defect was randomly treated with EMD+LLLT, while EMD alone was applied to the contra-lateral defect site. LLLT was used both intra- and post-operatively. Clinical measurements were performed by a blinded periodontist at the time of surgery, in the first week and in the first, second, sixth and 12th month. Visual analogue scale (VAS) scores were recorded for pain assessment. RESULTS The results have shown that the treatment of intra-bony defects with EMD alone or EMD+LLLT leads to probing depth reduction and attachment-level gain. In addition, EMD+LLLT had resulted in less gingival recession (p<0.05), less swelling (p<0.001) and less VAS scores (p<0.02) compared with EMD alone. CONCLUSION This study shows that EMD is an effective, safe and predictable biomaterial for periodontal regeneration and LLLT may improve the effects of EMD by reducing post-operative complications.
Performance evaluation of non-ideal RF transmitter in LTE/LTE-Advanced systems

The Long Term Evolution (LTE) and LTE-Advanced (LTE-A) standards are under development for the next generation mobile communication systems. High peak data rates and high spectral efficiency are some of the requirements of these standards, which should also include Flexible Spectrum Usage (FSU) techniques for an efficient use of the limited available bandwidth (BW). Considering Non-Contiguous Orthogonal Frequency Division Multiplexing (NC-OFDM) as a possible FSU proposal for LTE/LTE-Advanced, in this paper an analysis of the effects of the RF imperfections —such as IQ imbalance, phase noise and non-linear power amplifier— on the downlink transmission in LTE/LTE-Advanced is presented. Two different aspects are pointed out. First, concerning NC-OFDM, it is shown that the RF transmitter causes an increase of the Power Spectral Density (PSD) in the subchannels not used for transmission, which means interference with the other systems using those subchannels. Second, concerning the high data rates and high spectral efficiency, it turns out that the 64-QAM rate 3/4, used to reach these requirements, is deeply affected by the RF transmitter imperfections.
Essays in economic development: education, child labour and wage inequality

This thesis presents four self-contained essays that explore issues that are crucial in improving human well-being in a developing country: improving health, minimising child labour and reducing gender inequality. The analysis is focused on Bangladesh where the prevalence of child labour and gender differences in several domains is still widespread. The first essay aims to examine the gender wage gap along the entire wage distribution into an endowment effect and a discrimination effect, taking into account possible selection into full-time employment. Applying a new decomposition approach to the Bangladesh Labour Force Survey (LFS) datasets of 1999 and 2005, we find that women are paid less than men everywhere on the wage distribution and the gap is higher at the lower end of the distribution. Discrimination against women is the primary determinant of the wage gap. We also find that this gap has widened between 1999 and 2005. The second essay examines whether gender differences in tertiary enrolment rates can be explained by wage premiums in returns from secondary to tertiary education levels. Using LFS data, we find that wage premiums do not have any significant effect on the gender gap in tertiary enrolment rates. We also note that wage premiums in returns from secondary to tertiary education significantly influence tertiary enrolment rates for males but not for females, once additional variables are added. We offer evidence that part of the explanation for low female enrolment in tertiary education is attributable to demographic factors. The third essay investigates whether there is any trade-off between child labour hours and schooling. By drawing on the 2002 dataset of the Bangladesh National Child Labour Survey (NCLS), we find that working hours adversely affect child schooling from the very first hour of work. However, the marginal impact of child labour hours weakens when working hours increase; yet, working hours always negatively affect schooling when we use a non-parametric approach. We find that parents do not have identical preferences towards schooling decisions concerning boys and girls. Both mother and father show a significant preference for educating a female child. The same incentive effect is not found for a male child. These conclusions persist, even after allowing for sample selection in child labour. The fourth essay tests the effect of child labour on child health outcomes in Bangladesh. We use self-reported injury or illness due to work as a general measure of health status. Using NCLS data, we find that child labour is positively and significantly associated with the probability of being injured or becoming ill, once the endogenous relationship between these factors is accounted for. These findings remain robust when we consider child labour hours and restrict our analysis to rural areas. Moreover, the intensity of injury or illness is significantly higher in construction and manufacturing than in other sectors.
Intra-individual variability and circadian rhythm of vascular endothelial growth factors in subjects with normal glucose tolerance and type 2 diabetes

Increased levels of systemic vascular endothelial growth factors (VEGFs) in patients with diabetes are associated with increased risk of microvessel disease. On the other hand, low VEGF levels after intravitreal antibody application may be associated with acute cardiovascular complications and treatment failure. Individual levels of systemic VEGF vary in a wide range depending on analytical methods and quality of diabetes control. So far only limited information exists on intraindividual fluctuations over longer periods and circadian rhythms. We analysed the intraindividual variance of VEGF-A, VEGF-C and placental growth factor (PLGF) in CTAD (citrate-theophylline-adenine-dipyridamol) plasma as well as VEGF-A in serum over a period of 6 months in patients with stable controlled type 2 diabetes (10 M, 10 F) and age and sex matched subjects with normal glucose tolerance (NGT). Furthermore, circadian levels of VEGFs were controlled hourly from 7:30 a.m. to 7:30 p.m. under standardized metabolic ward conditions. In addition, the relationship to metabolic, hormonal and inflammatory biomarkers was analyzed. VEGF-A, VEGF-C and PLGF remained stable in plasma and VEGF-A in serum over 6 months in both groups. No circadian change was observed in VEGF-A serum and plasma concentrations. A minor decrease of VEGF-C plasma levels was evident after 5 p.m. in both groups and a significant peak of PLGF concentrations occurred after lunch, which was more pronounced in T2DM. In multivariate analysis, only serum VEGF-A correlated to diabetes duration, whereas VEGF-C only correlated to HbA1c and fasting blood glucose. We did not observe significant intraindividual variances for VEGF-A in serum and VEGF-A, VEGF-C and PLGF in CTAD plasma over a period of 6 months. Taken together, a single morning measurement of systemic VEGF levels after 7:30 am appears to be a reliable parameter for the individual risk associated with abnormal VEGF concentrations in blood. Trial Registration: NCT02325271
Two HIV‐1 Epidemics in Argentina: Different Genetic Subtypes Associated With Different Risk Groups

Summary: This study determined the risk behaviors and viral subtypes of HIV‐1 found in 134 heterosexual HIV‐seroprevalent maternity patients, 41 of their sexual partners (men who have sex with women [MSW]), and 95 homosexual men (men who have sex with men [MSM]) from Buenos Aires, Argentina. Peripheral blood mononuclear cells (PBMCs) were purified from blood and used for DNA extraction, amplification, and genotyping by the envelope heteroduplex mobility assay (env HMA). Most of the women had been infected by having sex with an already infected partner (84%), whereas most of the male partners had been infected via drug use (76%). Both the patients and their sexual partners were poorly educated, only 30% having completed secondary school. The MSM study subjects, however, were significantly better educated and had a lower prevalence of injecting drug use. Env HMA subtype F was found in 77% (103 of 134) of the maternity patients, with similar rates in their partners (73%). Most of the remaining samples were env subtype B. All but one of the couples was concordant in subtype. In the MSM risk group, however, only 10% were env HMA subtype F. Ninety percent of the MSM samples were subtype B. There are at least two independent epidemics of HIV‐1 infection in Buenos Aires, Argentina. One, in heterosexual men and women, is dominated by env subtype F whereas the other, in homosexual men, is dominated by env subtype B, as determined by env HMA.
HER-2/neu amplification in benign breast disease and the risk of subsequent breast cancer.

PURPOSE The purpose of this study was to determine whether the presence of HER-2/neu gene amplification and/or overexpression in benign breast disease was associated with an increased risk of subsequent breast cancer. PATIENTS AND METHODS We conducted a nested case-control study of a cohort of women who were diagnosed with benign breast disease at the Mayo Clinic and who were subsequently observed for the development of breast cancer. Patients who developed breast cancer formed the case group, and a matched sample from the remaining cohort served as controls. Benign tissue samples from 137 cases and 156 controls and malignant tissues from 99 cases provided DNA or tissue for evaluation of HER-2/neu amplification and protein overexpression. RESULTS Among the controls, seven benign tissues (4.5%) demonstrated low-level HER-2/neu amplification, whereas 13 benign (9.5%) and 18 malignant (18%) tissue specimens from cases exhibited amplification. HER-2/neu amplification in benign breast biopsies was associated with an increased risk of breast cancer (odds ratio ¿OR = 2.2; 95% confidence interval ¿CI, 0.9 to 5.8); this association approached statistical significance. The risks for breast cancer associated with benign breast histopathologic diagnoses were OR = 1.1 (95% CI, 0.6 to 1.9) for lesions exhibiting proliferation without atypia and OR = 1.5 (95% CI, 0.4 to 5.6) for the diagnosis of atypical ductal hyperplasia. For women having both HER-2/neu amplification and a proliferative histopathologic diagnosis (either typical or atypical), the risk of breast cancer was more than seven-fold (OR = 7.2; 95% CI, 0.9 to 60.8). Overexpression of the HER-2/neu protein product, defined as membrane staining in 10% or more of epithelial cells, was found in 30% of the breast tumors but was not detected in any of the benign breast tissues. Case patients who had HER-2/neu gene amplification in their malignant tumor were more likely to have had HER-2/neu amplification in their prior benign biopsy (P =.06, Fisher's exact test). CONCLUSION Women with benign breast biopsies demonstrating both HER-2/neu amplification and a proliferative histopathologic diagnosis may be at substantially increased risk for subsequent breast cancer.
An exploratory analysis of social media use and the structure of young people’s public affairs participation in China

This study focuses on the impact of social media use on young adults’ public affairs participation on the issues of environment, education, and politics in China. It is interested in not only levels of participation but also the structure of participation, especially the degree to which young adults’ public affairs participation is issue-specific. Analysis of a representative survey of university students (N = 897) in Guangzhou, China, shows that, generally speaking, online and offline participation on the three issues are explained by different sets of factors. Social media communication concerning public affairs is a strong predictor of online participation related to political issues, but it does not predict the other participation variables. Connection with public actors via social media, meanwhile, consistently predicts participation on different issues both online and offline. Moreover, time spent on social media is a consistent and significant predictor of degree of issue specificity of young people’s participation. Implications of the findings are discussed.
Pulmonary injuries and cytokine levels after the intraperitoneal administration of pancreatic homogenates in rats.

INTRODUCTION Our objective was to investigate the effects of the administration of pancreatic homogenates, with or without enzymatic activation, to healthy animals regarding cytokine serum levels and the development of pulmonary distress. MATERIAL AND METHODS 106 male Wistar rats, divided into three groups, were studied: group A, intraperitoneal administration of homogenates activated with enterokinase; group B, homogenates without enterokinase; and group C, control group with administration of physiological saline solution. Each group was divided into 4 subgroups according to the time of sacrifice: 0, 2, 6 and 24 hours. We studied the pulmonary and pancreatic histology, serum parameters of renal and hepatic function, and serum levels of IL-1beta, IL-6 and TNFalpha. RESULTS There was no mortality in any group. Pancreatic disorders in A and B groups were noted at 24 hours. These two groups had statistically significant higher transaminase serum levels than those of the control group, as well as statistically significant higher creatinine levels in group A. IL-1beta showed a statistically significant higher level at 6 h in both groups, A and B, but was higher in group A, which also exhibited significant pulmonary histologic damage with respect to controls at 6 h. CONCLUSIONS The higher IL-1beta level in group A may result from production by peritoneal macrophages under the influence of homogenate enzymatic activation. This may be the reason for lung damage.