Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of drug‐induced apoptotic death on processing and presentation of tumor antigens by dendritic cells

Here we have studied the effects of apoptotic cell death induced by chemotherapic agents on tumor phagocytosis by dendritic cells (DC) and presentation of the relevant antigen to T lymphocytes. Annexin‐V‐FITC (Ann‐V) and propidium iodide (PI) staining was used to assess early apoptotic (Ann‐V+/PI−) vs. late apoptotic/secondary necrotic (Ann‐V+/PI+) death after a 24 hr observation of untreated and drug‐treated gastric carcinoma cells. After treatments, the HLA‐A*0201+ tumor cell line KATO III was exposed for 24 hr to allogeneic, HLA‐related GM‐CSF, IL‐4‐driven immature (i) DC. Tumor‐loaded iDC were tested for IL‐12 release in an ELISA assay, incubated with the DC‐maturating factor TNF‐α and used as stimulators for autologous T lymphocytes. Generation of antitumor T response against KATO cells was evaluated in an anti‐MHC class I MAb‐blocked Interferon‐γ ELISPOT assay. After treatment with Cis‐platin (cis), all dying cells were in early apoptosis, whereas secondary necrosis was the prevalent death pattern observed after epirubicin (epi) and doxorubicin (doxo). Doxo and epi increased tumor expression of heat shock protein (hsp) 70 and uptake of tumor cell components by DC, whereas cis treatment had no effect on hsp70 and was associated with poor tumor uptake by DC. Significant upmodulation of IL‐12 was observed by DC that had taken up the doxo‐ and epi‐treated tumors (p< 0.005 and p< 0.01, respectively). Increased IFN‐γ release was also observed after stimulation of T lymphocytes with DC loaded with doxo‐ and epi‐treated (p< 0.02 and p< 0.005, respectively) but not with cis‐treated DC. These data show that the products of early apoptosis cannot efficiently cross‐activate MHC class I‐restricted anti‐tumor lymphocytes even in the presence of DC maturating factors, whereas secondary necrosis is associated with robust T cell response. © 2003 Wiley‐Liss, Inc.
Why do parents choose not to immunise their children?

AIMS To ascertain the reasons why some parents choose not to immunise their children and where these parents obtained their immunisation information. METHODS Seventy general practitioners (GPs) in Christchurch who kept a record of children whose parents declined immunisation were asked to recruit these parents. Half of the GPs were able to invite the 76 parents of children declining immunisation to take part in this study. Twenty one (28%) of these parents agreed to completing a structured questionnaire. RESULTS Parents in this sample were highly educated and had used information from a variety of sources in making their decision not to immunise. Almost half of the parents had not discussed immunisation with their lead maternity carer. They viewed information from the Ministry of Health as biased. They were concerned about vaccine safety and efficacy and the effects of immunisation on their child's immune system. CONCLUSIONS Parents who choose not to immunise their children are distrustful of information provided by the Ministry of Health. General practitioners are the main source of immunisation information for these parents and they must be able to provide accurate, unbiased information regarding the risks and benefits of immunisation.
Corruption and audit market concentration: an international investigation

ABSTRACT This paper examines the association between the corruption level of a country and audit market concentration. Using a sample from 78 countries over the 2003–2012 period, we document a positive association between corruption and Big 4 audit market concentration, suggesting that in more corrupt countries, the audit market at the industry level is dominated by one or two Big 4 audit firms rather than shared equally. To provide further understanding about how corruption is associated with Big 4 audit market concentration, we conduct a path analysis and find that corruption has an indirect effect on audit market concentration through collusion. These results are consistent with the notion that corrupt governments do not effectively control collusion and thus decrease market competition, leading to a decrease in the perceived severity of information leakage and a lower concern about sharing a common auditor. Finally, we conduct a battery of sensitivity tests. Our results are robust to change analysis, to controlling for other factors that are likely to influence auditor choices and the market structure, to an alternative measure of concentration, and to alternative samples. Overall, we provide evidence to suggest that country-level corruption plays a role in Big 4 audit market concentration.
Remain or leave? : How British newspapers frame the EU referendum 2016 : a framing analysis of the Brexit debate

The following study examines British news coverage of the EU referendum 2016 (Brexit) in order to identify and investigate the most frequently used news frames and attitude of the newspapers towards Brexit. Based on previous framing research, five news frames were found to be applied continuously in issues regarding EU politics and EU integration, these include: the conflict, economic consequences, attribution of responsibility, human interest and the strategy frame. Based on the literature review, I hypothesize that the conflict and strategy frame are the most apparent frames in the media coverage, followed by the economic consequences frame. The results of this paper are in line with the hypothesis. The second focus of the analysis regards the tone of the media regarding the EU referendum, with previous media analysis pointing to a heavily positive attitude towards Brexit. From the five newspapers under investigation, The Daily Mail and The Daily Telegraph were found as being in favour of LEAVE, while The Daily Mirror, The Guardian and The Times were in favour of REMAIN. The results of this study thereby are in line with previous findings and thus strengthen further research on the frequency of frames and the news media’s bias towards Brexit.
Task Encoding across the Multiple Demand Cortex Is Consistent with a Frontoparietal and Cingulo-Opercular Dual Networks Distinction

Multiple-demand (MD) regions of the human brain show coactivation during many different kinds of task performance. Previous work based on resting-state functional magnetic resonance imaging (fMRI) has shown that MD regions may be divided into two closely coupled subnetworks centered around the lateral frontoparietal (FP) and cingulo-opercular cortex. Here, we used on-task fMRI to test whether this division is apparent during the performance of an executive task. Furthermore, we investigated whether there is a difference in the encoding of task between the two subnetworks. Using connectivity methods, we found that activity across the entire MD cortex is correlated during task performance. Meanwhile, however, there was significantly stronger connectivity within each of the subnetworks than between them. Using multivoxel pattern analysis, we also found that, although we were able to decode task-relevant information from all regions of the MD cortex, classification accuracy scores were significantly higher in the FP subnetwork. These results suggest a nested picture with MD regions as a whole showing coactivation and broad rule representation, but with significant functional distinctions between component subnetworks. SIGNIFICANCE STATEMENT Multiple-demand (MD) regions of frontal and parietal cortex appear essential for the orchestration of goal-directed behavior and problem solving. Understanding the relative specialization of regions within the MD cortex is crucial to understanding how we can coordinate and execute complex action plans. By examining functional connectivity during task performance, we extend previous findings suggesting that the MD cortex can be divided into two subnetworks centered around the frontoparietal (FP) and cingulo-opercular (CO) cortex. Furthermore, using multivoxel pattern analysis, we show that, compared with the CO subnetwork, the FP subnetwork manifests more differentiated coding of specific task events.
A comparison between SVM and PLS for E-nose based gas concentration monitoring

The present paper deals with gas concentration monitoring based on an electronic nose. The proposed approach investigates two regression methods for gas concentration estimation: the first is the most used in gas quantification with electronic nose and known as the partial least squares (PLS) and the second, known as the support vector machine (SVM) regression, is recently used by the electronic nose community. Data used in this work are collected using an E-nose device developed in our laboratory and responding to various concentrations of pine essential oil vapours. The comparison between the two regression methods studied in this paper is related to the accuracy, the universality as well as the number of samples needed for learning. The results are analyzed in order to select the more suitable prediction model for gas concentration estimation.
An International Pooled Analysis for Obtaining a Benchmark Dose for Environmental Lead Exposure in Children

Lead is a recognized neurotoxicant, but estimating effects at the lowest measurable levels is difficult. An international pooled analysis of data from seven cohort studies reported an inverse and supra‐linear relationship between blood lead concentrations and IQ scores in children. The lack of a clear threshold presents a challenge to the identification of an acceptable level of exposure. The benchmark dose (BMD) is defined as the dose that leads to a specific known loss. As an alternative to elusive thresholds, the BMD is being used increasingly by regulatory authorities. Using the pooled data, this article presents BMD results and applies different statistical techniques in the analysis of multistudy data. The calculations showed only a limited variation between studies in the steepness of the dose‐response functions. BMD results were quite robust to modeling assumptions with the best fitting models yielding lower confidence limits (BMDLs) of about 0.1–1.0 μ g/dL for the dose leading to a loss of one IQ point. We conclude that current allowable blood lead concentrations need to be lowered and further prevention efforts are needed to protect children from lead toxicity.
TEMPERATURE RELATIONSHIPS OF THE LOCOMOTOR RHYTHM OF CARCINUS

1. The locomotor rhythm of Carcinus maenas was shown to be relatively similar at 10°, 15°, 20° and 25° C. , but it was shown to be modified by changes in temperature. 2. A fall of about 5-10° C. just before the onset of activity usually advanced and enhanced the initial peak of activity, whilst a rise of the same magnitude usually delayed and partly suppressed the initial peak, each without affecting the basic rhythm. 3. A fall in temperature of about 10° C. or more between activity peaks usually initiated transient outbursts of activity, again without affecting the normal rhythm. 4. Chilling to 40° C. for more than 6 hr. , irrespective of the time of onset of chilling, resulted in a rephasing of the rhythm with the initial outburst occurring immediately on return to room temperature. 5. In Carcinus from non-tidal docks chilling resulted in a change from the normal approximately nocturnal rhythm to an overt tidal rhythm, but in Carcinus from the virtually tideless Mediterranean the character of the normal nocturnal rhythm was unaffected by chilling.
Distinct Membrane Effects of Spinal Nerve Ligation on Injured and Adjacent Dorsal Root Ganglion Neurons in Rats

Background:Painful peripheral nerve injury results in disordered sensory neuron function that contributes to the pathogenesis of neuropathic pain. However, the relative roles of neurons with transected axons versus intact adjacent neurons have not been resolved. An essential first step is identification of electrophysiologic changes in these two neuronal populations after partial nerve damage. Methods:Twenty days after spinal nerve ligation (SNL), intracellular recordings were obtained from axotomized fifth lumbar (L5) dorsal root ganglion neurons and adjacent, intact L4 neurons, as well as from control neurons and others subjected to sham-SNL surgery. Results:Pronounced electrophysiologic changes were seen only in L5 neurons after SNL. Both Aα/β and A&dgr; neuron types showed increased action potential duration, decreased afterhyperpolarization amplitude and duration, and decreased current threshold for action potential initiation. Aα/β neurons showed resting membrane potential depolarization, and increased repetitive firing during sustained depolarization developed in A&dgr; neurons. The afterhyperpolarization duration in neurons with C fibers shortened after axotomy. In contrast to the axotomized L5 neurons, neighboring L4 neurons showed no changes in action potential duration, afterhyperpolarization dimensions, or excitability after SNL. Depolarization rate (dV/dt) increased after SNL in L4 Aα/β and A&dgr; neurons but decreased in L5 neurons. Time-dependent rectification during hyperpolarizing current injection (sag) was greater after SNL in Aα/β L4 neurons compared with L5. Sham-SNL surgery produced only a decreased input resistance in Aα/β neurons and a decreased conduction velocity in medium-sized cells. In the L5 ganglion after axotomy, a novel set of neurons, consisting of 24% of the myelinated population, exhibited long action potential durations despite myelinated neuron conduction velocities, particularly depolarized resting membrane potential, low depolarization rate, and absence of sag. Conclusions:These findings indicate that nerve injury–induced electrical instability is restricted to axotomized neurons and is absent in adjacent intact neurons.
Contribution to the study of the genus Lemniscomys (Rodentia: Muridae). Morphometric and molecular approaches

A total of 204 specimens belonging to eight species of the genus Lemniscomys were examined with standard morphometric measurements. Our results show that the seven Sub-Saharan species seem to follow a latitudinal gradient from the Center to the South of the African continent. The only North African species L. barbarus looks close to L. griselda and L. rosalia. We also applied a molecular analysis through PCR (Polymerase Chain Reaction) method for the amplification of the 16S rRNA gene. For the purpose of constructing a phylogenetic tree with Maximum Likelihood method, we extracted eight sequences from the GenBank library; seven belonging to the genus Lemniscomys and one to the genus Arvicanthis used as outgroup. We managed to identify a region comprised of 458 nucleotides of which 388 were common for all species and 70 were variable. The phylogenetic tree shows us that the sister group L. bellieri and L. macculus, is the most basal, while L. striatus and L. rosalia appears to be close to the sister group L. barbarus and L. zebra. We also noticed a difference between morphometric and molecular results; the latter are more in agreement with pelage patterns subdivision between Lemniscomys species. These differences can be explained by a high rate of phenotypic evolution that can surpass the molecular counterpart as in the case of the genus Gerbillus.
Diamine Oxidase Supplementation in Chronic Spontaneous Urticaria: A Randomized, Double-Blind Placebo-Controlled Study

Introduction: Diamine oxidase (DAO) catabolizes and inactivates histamine, a key player in a wide range of invalidating conditions, such as migraine and chronic spontaneous urticaria (CSU). The highest expression of DAO occurs in the gastrointestinal tract, possibly to control the burden of histamine intake from food. Methods: Here, we tested the hypothesis that a 30-day oral supplementation with DAO (1 capsule b.i.d., 15 min before a meal) could reduce the severity of CSU as estimated by the 7-Day Urticaria Activity Score (UAS-7). The study was designed as a double-blind, placebo-controlled, crossover investigation of 22 patients with CSU incompletely controlled by first-line antihistamine therapy. Results: Twenty patients completed the study. Supplemental therapy with DAO caused a 3.8 ± 1.2 point mean ± SEM UAS-7 score reduction in patients with low serum DAO levels at time 0 (p = 0.041 compared to placebo). The degree of UAS-7 improvement was inversely correlated with the levels of basal DAO (p = 0.019). Patients receiving DAO supplementation were able to slightly reduce their daily antihistamine dose (p = 0.049). Conclusion: These data suggest that DAO may be involved in the pathogenic cascade of CSU and that DAO supplementation could be effective for symptom relief in patients with low DAO levels in serum.
Contralateral prophylactic mastectomy rate and predictive factors among patients with breast cancer who underwent multigene panel testing for hereditary cancer

Although multigene panel testing is increasingly common in patients with cancer, the relationship between its use among breast cancer patients with non‐BRCA mutations or variants of uncertain significance (VUS) and disease management decisions has not been well described. This study evaluated the rate and predictive factors of CPM patients who underwent multigene panel testing. Three hundred and fourteen patients with breast cancer who underwent multigene panel testing between 2014 and 2017 were included in the analysis. Of the 314 patients, 70 elected CPM. Election of CPM by gene status was as follows: BRCA carriers (42.3%), non‐BRCA carriers (30.1%), and VUS (10.6%). CPM election rates did not differ between non‐BRCA carriers and BRCA carriers (P = 0.6205). Among non‐BRCA carriers, negative hormone receptor status was associated with CPM (P = 0.0115). For those with a VUS, hormone receptor status was not associated with CPM (P = 0.1879). Although the rate of CPM between BRCA carriers and non‐BRCA carriers was not significantly different, the predictors of CPM were different in each group. Our analyses shed the light on the increasing use of CPM among patients who are non‐BRCA carriers as well those with a VUS. Our study elucidates the differing predictive factors of CPM election among BRCA carriers, non‐BRCA carries, and those with a VUS. Our findings reveal the need for providers to be cognizant that non‐BRCA genes and VUS drive women to elect CPM despite the lack of data for contralateral breast cancer risk associated with these genes.
Essays on technology and international trade

ix Chapter 1: Introduction . 1 Chapter 2: Optimal IPR Protection, Directed Imitation and Economic Development . 5 2.
First successful percutaneous treatment of a totally occluded HeartWare outflow graft: Case report and literature review

As the number of implanted left ventricular assist devices (LVADs) used increases, the frequency of chronic complications encountered also increases. The pause of blood flow in the outflow graft is a rare, but fatal, complication. The aim of this article was to present the case of a patient in whom HeartWare outflow graft occlusion was removed by balloon angioplasty and to examine the treatment modalities of HeartWare outflow graft occlusions that have been percutaneously performed to date. The literature was searched for percutaneous interventions on outflow grafts of the left ventricular assist devices. The results of six patients who underwent interventions on outflow grafts were analyzed. Three of six patients with HeartWare outflow graft stenosis were treated with covered stents, while the remaining three were treated with bare metal stents. All procedures were applied successfully. Percutaneous interventions can be performed with appropriate equipment in patients with HeartWare outflow graft stenosis or total occlusion.
A review of Cushing's disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism

ABSTRACT The treatment objectives for a patient with Cushing's disease (CD) are remission of hypercortisolism, adequate management of co-morbidities, restoration of the hypothalamic-pituitary-adrenal axis, preservation of fertility and pituitary function, and improvement of visual defects in cases of macroadenomas with suprasellar extension. Transsphenoidal pituitary surgery is the main treatment option for the majority of cases, even in macroadenomas with low probability of remission. In cases of surgical failure, another subsequent pituitary surgery might be indicated in cases with persistent tumor imaging at post surgical magnetic resonance imaging (MRI) and/or pathology analysis of adrenocorticotropic hormone-positive (ACTH+) positive pituitary adenoma in the first procedure. Medical treatment, radiotherapy and adrenalectomy are the other options when transsphenoidal pituitary surgery fails. There are several options of medical treatment, although cabergoline and ketoconazole are the most commonly used alone or in combination. Novel treatments are also addressed in this review. Different therapeutic approaches are frequently needed on an individual basis, both before and, particularly, after surgery, and they should be individualized. The objective of the present review is to provide the necessary information to achieve a more effective treatment for CD. It is recommended that patients with CD be followed at tertiary care centers with experience in treating this condition.
An impedance-controlled system for endometrial ablation: five-year follow-up of 107 patients.

OBJECTIVE To assess the safety, efficacy and data durability of the NovaSure endometrial ablation system 5 years after the procedure in women with severe menorrhagia secondary to dysfunctional uterine bleeding (DUB). STUDY DESIGN A prospective, single-arm, pilot study of 107 women undergoing endometrial ablation using the NovaSure system (Canadian Task Force classification II-1) at a specialized center for gynecologic endoscopy. The premenopausal women, with menorrhagia secondary to DUB unresponsive to medical therapy, had completed childbearing. A Pictorial Blood-Loss Assessment Chart was used to conduct a posttreatment evaluation of menstrual blood loss and bleeding pattern. Ablation was performed without any type of endometrial pretreatment. RESULTS No intraoperative or postoperative complications were observed. Treatment time averaged 94 seconds. At the 5-year follow-up, amenorrhea was reported by 75% of patients and successful reduction of bleeding was achieved in 98%, with hysterectomy and retreatment rates of 2.9% and 3.8%, respectively. CONCLUSION Long-term clinical results indicate that the NovaSure system is a safe and effective method for treatment of women with menorrhagia secondary to DUB. NovaSure yields high amenorrhea and success rates and low surgical reintervention rates 5 years after treatment.
Comparison of Heterosubtypic Protection in Ferrets and Pigs Induced by a Single-Cycle Influenza Vaccine

Influenza is a major health threat, and a broadly protective influenza vaccine would be a significant advance. Signal Minus FLU (S-FLU) is a candidate broadly protective influenza vaccine that is limited to a single cycle of replication, which induces a strong cross-reactive T cell response but a minimal Ab response to hemagglutinin after intranasal or aerosol administration. We tested whether an H3N2 S-FLU can protect pigs and ferrets from heterosubtypic H1N1 influenza challenge. Aerosol administration of S-FLU to pigs induced lung tissue-resident memory T cells and reduced lung pathology but not the viral load. In contrast, in ferrets, S-FLU reduced viral replication and aerosol transmission. Our data show that S-FLU has different protective efficacy in pigs and ferrets, and that in the absence of Ab, lung T cell immunity can reduce disease severity without reducing challenge viral replication.