Miracle-dz/UniFAR-FTUs huggingface dataset:
Metronomic scheduling of imatinib abrogates clonogenicity of neuroblastoma cells and enhances their susceptibility to selected chemotherapeutic drugs in vitro and in vivo

Imatinib is currently in early clinical trials as targeted therapy for relapsed neuroblastomas and other childhood solid tumors expressing platelet‐derived growth factor receptors (PDGFR) or c‐Kit. Short‐term treatment with imatinib in clinically achievable concentrations is ineffective in neuroblastoma in vitro. However, clinically, imatinib is administered daily over long time periods. The effects of combining imatinib with chemotherapy in neuroblastoma are unknown. Here, a panel of neuroblastoma cell lines (n = 5) were studied, representing tumors with different biological (MYCN‐amplification +/−) and clinical (drug resistance) features. Using a protracted low‐dose treatment schedule (1–3 weeks; 0.5–5μM) imatinib dose‐dependently inhibited proliferation and clonogenic survival for all tested cell lines with IC50 <2. 5μM. In contrast, short‐term treatment (<96 hrs) was ineffective. Low‐dose imatinib was synergistic in combination with doxorubicin and caused increased G2/M‐ and S‐phase arrest and apoptosis as evidenced by enhanced caspase‐3 activation and sub‐G1 DNA accumulation. A significant but less pronounced effect was observed when imatinib was combined with etoposide or vincristine, as opposed to cisplatin, melphalan, or irinotecan. All cell lines expressed PDGFRβ, whereas no protein expression of PDGFRα was detected in MYCN amplified cell lines. PDGF‐BB caused PDGFRβ phosphorylation and partially rescued neuroblastoma cells from doxorubicin‐induced apoptosis, in an imatinib‐sensitive manner. In vivo, treatment with imatinib in combination with doxorubicin induced a significant growth inhibition of established neuroblastoma xenografts. These findings suggest clinical testing of imatinib in combination with selected chemotherapeutic drugs, in particular doxorubicin, in children with high‐risk neuroblastoma. © 2008 Wiley‐Liss, Inc.
Interferon‐γ down‐regulates NKG2D ligand expression and impairs the NKG2D‐mediated cytolysis of MHC class I‐deficient melanoma by natural killer cells

NKG2D operates as an activating receptor on natural killer (NK) cells and costimulates the effector function of αβ CD8+ T cells. Ligands of NKG2D, the MHC class I chain‐related (MIC) and UL16 binding protein (ULBP) molecules, are expressed on a variety of human tumors, including melanoma. Recent studies in mice demonstrated that NKG2D mediates tumor immune surveillance, suggesting that antitumor immunity in humans could be enhanced by therapeutic manipulation of NKG2D ligand (NKG2DL) expression. However, signals and mechanisms regulating NKG2DL expression still need to be elucidated. Here, we asked whether the proinflammatory cytokine Interferon‐γ (IFN‐γ) affects NKG2DL expression in melanoma. Cell lines, established from MHC class I‐negative and ‐positive melanoma metastases, predominantly expressed MICA and ULBP2 molecules on their surface. Upon IFN‐γ treatment, expression of MICA, in some cases, also of ULBP2 decreased. Besides melanoma, this observation was made also for glioma cells. Down‐regulation of NKG2DL surface expression was dependent on the cytokine dose and the duration of treatment, but was neither due to an intracellular retention of the molecules nor to an increased shedding of ligands from the tumor cell surface. Instead, quantitative RT‐PCR revealed a decrease of MICA‐specific mRNA levels upon IFN‐γ treatment and siRNA experiments pointed to an involvement of STAT‐1 in this process. Importantly, IFN‐γ‐treated MHC class I‐negative melanoma cells were less susceptible to NKG2D‐mediated NK cell cytotoxicity. Our study suggests that IFN‐γ, by down‐regulating ligand expression, might facilitate escape of MHC class I‐negative melanoma cells from NKG2D‐mediated killing by NK cells. © 2008 Wiley‐Liss, Inc.
Exploring the relationship of phase and peak-frequency EEG alpha-band and beta-band activity to temporal judgments of stimulus duration

ABSTRACT Pre-stimulus phase has been shown to influence temporal judgments concerning order, causality and simultaneity. One hypothesis is that phase cycles frame discrete perceptual snapshots over time. Yet, existing studies have explored the effect of pre-stimulus phase on fine-grained temporal judgments whereas no study has shown whether pre-stimulus phase influences sub-second temporal judgments lasting several phase cycles. If effects of phase on fine-grained temporal judgments reflect perceptual framing, then the perception of longer intervals might show some dependency on the frequency of phase cycles. Higher frequencies should promote increased temporal resolution and discrimination. We tested the relationship between the phase and frequency of oscillations and temporal judgments for longer durations. Participants judged the relative duration of two successive intervals lasting several phase cycles each. Pre-stimulus alpha-band and beta-band phase was associated with subsequent temporal judgments, although not sensitivity, therein providing evidence that pre-stimulus phase is related to temporal judgments that span a longer time-scale than has been previously demonstrated. Although we report evidence that peak-frequency of the alpha-band is related to one measure of task performance, this study does not provide evidence that higher peak frequencies of alpha- or beta-band activity are related to improved duration discrimination of longer intervals.
The clonal evolution of metastases from primary serous epithelial ovarian cancers

Several models of evolution from primary cancers to metastases have been proposed; but the most widely accepted is the clonal evolution model proposed for colorectal cancer in which tumors develop by a process of linear clonal evolution driven by the accumulation of somatic genetic alterations. Various other models of cancer progression and metastasis have been proposed, including parallel evolution and the same gene model. The aim of this study was to investigate the evolution of metastases from primary cancer in 22 patients diagnosed with high‐grade serous epithelial ovarian cancer. We established somatic genetic profiles based on the pattern of loss of heterozygosity, in several different regions of tumor tissue within the primary tumor and metastatic deposits from each case. Maximum parsimony tree analysis was used to examine the evolutionary relationship between the primary and metastatic samples for each patient. In addition, we investigated the extent of genetic heterogeneity within and between metastatic tumors compared with primary ovarian tumors. Our data suggest that most, if not all, metastases are clonally related to the primary tumors. However, the data oppose a single model of linear‐clonal evolution whereby a late stage clone within the primary tumor acquires additional genetic changes that enable metastatic progression. Instead, the data support a model in which primary ovarian cancers have a common clonal origin, but become polyclonal, with different clones at both early and late stages of genetic divergence acquiring the ability to progress to metastasis. © 2009 Wiley‐Liss, Inc.
Modulation of pentose phosphate pathway during cell cycle progression in human colon adenocarcinoma cell line HT29

Cell cycle regulation is dependent on multiple cellular and molecular events. Cell proliferation requires metabolic sources for the duplication of DNA and cell size. However, nucleotide reservoirs are not sufficient to support cell duplication and, therefore, biosynthetic pathways should be upregulated during cell cycle. Here, we reveal that glucose‐6‐phosphate dehydrogenase (G6PDH) and transketolase (TKT), the 2 key enzymes of oxidative and nonoxidative branches of the pentose phosphate pathway (PPP), respectively, which is necessary for nucleotide synthesis, are enhanced during cell cycle progression of the human colon cancer cell line HT29. These enhanced enzyme activities coincide with an increased ratio of pentose monophosphate to hexose monophosphate pool during late G1 and S phase, suggesting a potential role for pentose phosphates in proliferating signaling. Isotopomeric analysis distribution of nucleotide ribose synthesized from 1,2‐13C2‐glucose confirms the activation of the PPP during late G1 and S phase and reveals specific upregulation of the oxidative branch. Our data sustain the idea of a critical oxidative and nonoxidative balance in cancer cells, which is consistent with a late G1 metabolic check point. The distinctive modulation of these enzymes during cell cycle progression may represent a new strategy to inhibit proliferation in anticancer treatments. © 2009 UICC
Special Education Management and Formalism in Inclusive Public Policies: The Case of Brazil

The idea of inclusive education has gained prominence in the ideological context of modern Western democracies. Thus, this analysis focuses on the understanding of how the Brazilian inclusive education has been managed from the Decree-Law n° 6.571/2008, which was repealed on November 17, 2011, considering the formalism perspective. Formalism is taken as a perspective of analysis of the inclusive public policies, which allows us to question the apparent stability and uniformity of institutional practices and discourse of the national administration. The work´s approach is largely qualitative, and uses multiple methods. Two steps were taken, starting with all the Brazilian State Boards of Education (survey research), and concluding with the Rio Grande do Norte State Board of Education and one of its school (case study). Data was collected through documental research and interviews with key actors, and analyzed by content analysis. It was found that, despite the legal pressure on the environment to an isomorphism of practices among State Boards, there are peculiarities among them, justified by the contextual and cultural aspects that are shared by actors and organizations. In the specific case study of the Rio Grande do Norte State Board of Education, it was concluded that the formalistic practice allows questioning the effectiveness of the official knowledge policies and its other form of narrative that regards not only the special education, but the very plurality of logical and social experiences. From a theoretical point of view, the study has called attention to the presence of formalism in special education administration.
Common immune‐related risk factors and incident non‐Hodgkin lymphoma: The multiethnic cohort

Severe immune dysfunction is an established risk factor of lymphoma, but the role of moderate alterations of immunity is not clear and prospective investigations are needed. We examined several immune‐related disorders and medications in relation to non‐Hodgkin lymphoma (NHL) in the Multiethnic Cohort. Over 215,000 subjects of African American, Caucasian, Japanese American, Latino and Native Hawaiian ancestry aged 45–75 years completed a questionnaire, including information on medical history, in 1993–1996. After exclusions, we performed Cox regression among 193,050 cohort members including 939 incident NHL cases while adjusting for sex, age, ethnicity, education, body mass index and alcohol intake. Self‐reported diabetes was not associated with NHL overall, but was positively associated with risk among Japanese Americans [hazard ratio (HR) = 1.55; 95% confidence interval (CI): 1.10–2.17]. Participants with a history of blood transfusion were at increased risk with HR = 1.39 (95% CI: 1.06–1.84) in men and HR = 1.22 (95% CI: 0.94–1.58) in women, especially for the diffuse large B‐cell lymphoma subtype. History of asthma or other allergies was associated with elevated risk only among Latinos (HR = 1.46; 95% CI: 1.07–2.00) who also showed a significant relation between current use of antihistamines and NHL (HR = 1.80; 95% CI: 1.09–2.97). Use of nonsteroidal anti‐inflammatory drugs was not associated with NHL. Our findings from this large prospective study support a moderate risk for NHL related to blood transfusions, current long‐term antihistamine use and diabetes, but the associations were limited to certain ethnic groups and require further replications. © 2009 UICC
Treatment of neurological injury with thymosin β4

Neurorestorative therapy targets multiple types of parenchymal cells in the intact tissue of injured brain tissue to increase neurogenesis, angiogenesis, oligodendrogenesis, and axonal remodeling during recovery from neurological injury. In our laboratory, we tested thymosin β4 (Tβ4) as a neurorestorative agent to treat models of neurological injury. This review discusses our results demonstrating that Tβ4 improves neurological functional outcome in a rat model of embolic stroke, a mouse model of multiple sclerosis, and a rat model of traumatic brain injury. Tβ4 is a pleiotropic peptide exhibiting many actions in several different types of tissues. One mechanism associated with improvement of neurological improvement from Tβ4 treatment is oligodendrogenesis involving the differentiation of oligodendrocyte progenitor cells to mature myelin‐secreting oligodendrocytes. Moreover, our preclinical data provide a basis for movement of Tβ4 into clinical trials for treatment of these devastating neurological diseases and injuries.
Intrusion Detection Models Based on Data Mining

Abstract Computer intrusions are taking place everywhere, and have become a major concern for information security. Most intrusions to a computer system may result from illegitimate or irregular calls to the operating system, so analyzing the system-call sequences becomes an important and fundamental technique to detect potential intrusions. This paper proposes two models based on data mining technology, respectively called frequency patterns (FP) and tree patterns (TP) for intrusion detection. FP employs a typical method of sequential mining based on frequency analysis, and uses a short sequence model to find out quickly frequent sequential patterns in the training system-call sequences. TP makes use of the technique of tree pattern mining, and can get a quality profile from the training system-call sequences of a given system. Experimental results show that FP has good performances in training and detecting intrusions from short system-call sequences, and TP can achieve a high detection precision in han.
Computer aids for detection and diagnosis in mammography

Screening: Interpreting screening mammograms is difficult; radiologists must maintain specificity while reading films with a very low incidence of cancer. Estimates suggest sensitivity is no higher than 75%. CAD: Commercial systems are now available that prompt radiologists to look at suspicious regions. Such systems achieve high sensitivity but at low specificity.Evaluations: Evaluations of these CAD systems reveal that they do well at detecting microcalcifications but less well at detecting masses.Impact on decision-making: The low specificity of the computer prompts seems to hinder their capacity to influence radiologists' decision-making.Prospective trials: Only one prospective trial has been carried out of a CAD system for mammography. A replication of this trial in a UK setting is awaited.
Coloscopy — Technique, Results, Indication

Using new flexible endoscopes and a special technique we are able to examine the entire large intestine and the terminal ileum with a high percentage of success. Thus, new and important possibilities are opened up for the diagnosis. In addition, therapeutic measures can also be carried out through the coloscope, thus saving the patient a laparotomy and the associated lengthy stay in hospital. Endoscopy 3 (1971) 143-151
Weighting of Features in Content-Based Filtering with Entropy and Dependence Measures

AbstractContent-based recommender systems (CBRS) are tools that help users to choose items when they face a huge amount of options, recommending items that better fit the user's profile. In such a process, it is very interesting to know which features of the items are more important for each user, thus the CBRS provides them higher weight. The Term Frequency-Inverse Document Frequency (TF-IDF) method is one of the most used for weighting of features, however, it does not provide the best results when the features are multi-valued. In this contribution, it is proposed a new method for obtaining the weights of the features by means of entropy and coefficients of dependency.
Pergamon Press Ltd. Printed in Great Britain Canine Vaginal Cytology—II Cyclic Changes

— —The different cellular elements which are encountered in vaginal smears made during pre-oestrum, oestrous and metoestrum and the degree of variation during these phases, are discussed. Resume— —Les differents elements cellulaires se trouvant dans les macules vaginales durant les phases preoestrus, oestrus et postoestrus et le degre de variations durant ces phases, sont discutes. Zusammenfassung— —Es werden die verschiedenartigen Zellengrundstoffe, die vor, wahrend und in der transzendentalen Brunstperiode in Scheidenausstrichen vorgefunden werden und der Variationsbreitengrad wahrend dieser Stadien besprochen.
Prevalence and risk factors of human papillomavirus infection by penile site in uncircumcised Kenyan men

Human papillomavirus (HPV) prevalence was estimated from 2,705 sexually active, uncircumcised, human immunodeficiency virus seronegative men aged 17–28 years in Kisumu, Kenya. HPV prevalence was 51.1% (95% confidence interval: 49.2–53.0%) in penile cells from the glans/coronal sulcus and/or shaft. HPV prevalence varied by anatomical site, with 46.5% positivity in the glans/coronal sulcus compared with 19.1% in the shaft (p < 0.0001). High‐risk HPV was detected in 31.2% of glans and 12.3% of shaft samples (p < 0.0001). HPV16 was the most common type and 29.2% of men were infected with more than one HPV type. Risk factors for HPV infection included presence of C. trachomatis, N. gonorrhea, self‐reported sexually transmitted infections, and less frequent bathing. Lifetime number of sexual partners and herpes simplex virus type‐2 seropositivity were also marginally associated with HPV infection.
Being Forced to Become Your Own Doctor: Men Who Have Sex with Men's Experiences of Stigma in the Tanzanian Healthcare System

ABSTRACT Objective: To acquire a deepened understanding of how stigma in healthcare affects health-seeking behaviors of same-sex practising men in Tanzania. Methods: In-depth interviews with 12 men were conducted in Dar es Salaam, 2012. Data were interpreted through qualitative content analysis. Results: Narratives revealed that men's healthcare perceptions were shaped by previous encounters, rumors in gay community, norms, and legislation around homosexuality. Fears of exposure aggravated men's possibilities of giving full anamnesis and detached them from formal healthcare services. Conclusions: Stigma in healthcare might lead to severe public health problems due to perceived exclusion from the health system by sexual minorities.
Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer

Tristetraprolin (TTP) is an AU‐rich element‐binding protein that regulates mRNA stability. Here, we report that TTP suppress the growth of human colon cancer cells both in vivo and in vitro by regulating of the expression of vascular endothelial growth factor (VEGF). TTP protein expression in human colonic tissues was markedly decreased in colonic adenocarcinoma compared with in normal mucosa and adenoma. VEGF expression was higher in colonic adenocarcinoma than in normal mucosa and adenoma. Specific inhibition of TTP expression by RNA‐interference increased the expression of VEGF in cultured human colon cancer cells, and TTP overexpression markedly decreased it. In addition, elevated expression of TTP decreased the expression level of luciferase linked to a 3′ terminal AU‐rich element (ARE) of VEGF mRNA. Colo320/TTP cells overexpressing TTP grew slowly in vitro and became tumors small in size when xenografted s.c into nude mice. These findings demonstrate that TTP acts as a negative regulator of VEGF gene expression in colon cancer cells, suggesting that it can be used as novel therapeutic agent to treat colon cancer.
Diş hekimliği araştırmalarında mikrobilgisayarlı tomografi uygulamaları

The application of microcomputed tomography in dental research recently gains popularity with the advancements in digital technologies. The aim of this review was to give information about the micro-computed tomography use in experimental studies in dentistry, especially in endodontics. In this review, detailed information was given on the main applications of microcomputed tomography in dental research, including evaluation of root canal morphology, root canal preparation, root canal fillings, residual root filling analysis following retreatment procedures, craniofacial skeletal development, implant and peri-implant bone structure, measurement of enamel thickness and dental mineral concentrations. The advantages of micro-computed tomography were also discussed.
W8, a new Sup35 prion strain, transmits distinctive information with a conserved assembly scheme

ABSTRACT Prion strains are different self-propagating conformers of the same infectious protein. Three strains of the [PSI] prion, infectious forms of the yeast Sup35 protein, have been previously characterized in our laboratory. Here we report the discovery of a new [PSI] strain, named W8. We demonstrate its robust cellular propagation as well as the protein-only transmission. To reveal strain-specific sequence requirement, mutations that interfered with the propagation of W8 were identified by consecutive substitution of residues 5–55 of Sup35 by proline and insertion of glycine at alternate sites in this segment. Interestingly, propagating W8 with single mutations at residues 5–7 and around residue 43 caused the strain to transmute. In contrast to the assertion that [PSI] existed as a dynamic cloud of sub-structures, no random drift in transmission characteristics was detected in mitotically propagated W8 populations. Electron diffraction and mass-per-length measurements indicate that, similar to the 3 previously characterized strains, W8 fibers are composed of about 1 prion molecule per 4.7-Å cross-β repeat period. Thus differently folded single Sup35 molecules, not dimeric and trimeric assemblies, form the basic repeating units to build the 4 [PSI] strains.
Comparison of HPV and cytology triage algorithms for women with borderline or mild dyskaryosis in population‐based cervical screening (VUSA‐screen study)

We studied the effectiveness of high‐risk human papillomavirus (hrHPV) triage for immediate colposcopy in women with borderline or mild dyskaryosis (BMD). In the Utrecht province of the Netherlands, women aged 30–60 years who participated in the regular cervical screening programme were offered hrHPV testing and cytology (intervention group) or cytology only (control group). In the intervention group (n = 337), women with BMD were immediately referred for colposcopy only if the sample was hrHPV positive. Women with a hrHPV negative test were advised to repeat cytology at 6 and 18 months and were referred for colposcopy if and when the repeat test result was positive (BMD or worse). In the control group (n = 329), referral of women with BMD was delayed until cytology was repeatedly positive at 6 or 18 months. The CIN3 detection rates were 10.7% (36/337) in the intervention group and 6.4% (21/329) in the control group (p = 0.047). Moreover, hrHPV triaging resulted in shorter time to diagnosis (154 vs. 381 days). Although the number of colposcopy referrals was 51.5% higher in the intervention group than in the control group, the medical costs per detected CIN3 were slightly lower ([euro] 4781 vs. [euro] 6235). If, in addition, hrHPV negative women had been referred back to routine screening at baseline, the CIN3 rate would have been 10.1% (34/337) and colposcopy rate would only have been 30.4% higher than in the control group. This study shows that hrHPV triaging of women with BMD is at least as effective for detecting CIN3 as repeat cytology, also when hrHPV negative women are referred back to routine screening.