Miracle-dz/UniFAR-FTUs huggingface dataset:
Doppler transcraniano convencional em voluntários assintomáticos: variabilidade e valores de referência para parâmetros de fluxo sanguíneo

OBJECTIVE: To establish reference values for measures of blood flow velocities and impedance indexes in healthy individuals through conventional transcranial Doppler (TCD) and to observe their variations in relation to the age and sex. METHOD: 88 asymptomatic volunteers were examined without antecedents of cardiac, peripheral or cerebrovascular diseases. The TCD were accomplished by the same examiner. The middle, anterior and posterior cerebral arteries were studied through the temporal acoustic window and the vertebral and basilar arteries through the suboccipital acoustic window. The values of mean velocity (MV), peak-systolic velocity (PSV), final diastolic velocity (FDV), resistance index (RI) and pulsatility index (PI) of each examined arterial segment were filed. RESULTS: The reference limits found by us were similar to the described by other authors for all of the studied parameters. There was tendency of the flow velocities decrease and of the impedance indexes increase with moving forward of the age. The values of velocities in the women were superior to the found in men. CONCLUSION: TCD was shown useful in the evaluation of hemodynamic cerebral for our population. Our results are similar to the other studies, so much in the reference values as in relationship with the age and the sex.
Simian Immunodeficiency Virus SIVmac239, but Not SIVmac316, Binds and Utilizes Human CD4 More Efficiently than Rhesus CD4

ABSTRACT Rhesus macaques are used to model human immunodeficiency virus type 1 (HIV-1) infections, but they are not natural hosts of HIV-1 or any simian immunodeficiency virus (SIV). Rather, they became infected with SIV through cross-species transfer from sooty mangabeys in captivity. It has been shown that HIV-1 utilizes rhesus CD4 less efficiently than human CD4. However, the relative ability of SIV envelope glycoproteins to bind or utilize these CD4 orthologs has not been reported. Here we show that several SIV isolates, including SIVmac239, are more efficiently neutralized by human CD4-Ig (huCD4-Ig) than by the same molecule bearing rhesus CD4 domains 1 and 2 (rhCD4-Ig). An I39N mutation in CD4 domain 1, present in human and sooty mangabey CD4 orthologs, largely restored rhCD4-Ig neutralization of SIVmac239 and other SIV isolates. We further observed that SIVmac316, a derivative of SIVmac239, bound to and was neutralized by huCD4-Ig and rhCD4-Ig with nearly identical efficiencies. Introduction of two SIVmac316 CD4-binding site residues (G382R and H442Y) into the SIVmac239 envelope glycoprotein (Env) markedly increased its neutralization sensitivity to rhesus CD4-Ig without altering neutralization by human CD4-Ig, SIV neutralizing antibodies, or sera from SIV-infected macaques. These changes also allowed SIVmac239 Env to bind rhCD4-Ig more efficiently than huCD4-Ig. The variant with G382R and H442Y (G382R/H442Y variant) also infected cells expressing rhesus CD4 with markedly greater efficiency than did unaltered SIVmac239 Env. We propose that infections of rhesus macaques with SIVmac239 G382R/H442Y might better model some aspects of human infections. IMPORTANCE Rhesus macaque infection with simian immunodeficiency virus (SIV) has served as an important model of human HIV-1 infection. However, differences between this model and the human case have complicated the development of vaccines and therapies. Here we report the surprising observation that SIVmac239, a commonly used model virus, more efficiently utilizes human CD4 than the CD4 of rhesus macaques, whereas the closely related virus SIVmac316 uses both CD4 orthologs equally well. We used this insight to generate a form of SIVmac239 envelope glycoprotein (Env) that utilized rhesus CD4 more efficiently, while retaining its resistance to antibodies and sera from infected macaques. This Env can be used to make the rhesus model more similar in some ways to human infection, for example by facilitating infection of cells with low levels of CD4. This property may be especially important to efforts to eradicate latently infected cells.
Vintafolide: a novel targeted therapy for the treatment of folate receptor expressing tumors

Despite advances in the development of molecularly targeted therapies, limited improvements in overall survival have been noted among many cancer patients with solid tumors, primarily due to development of drug resistance. Accordingly, there is an unmet need for new targeted therapies and treatment approaches for cancer, especially for overcoming resistance. Expression of the folate receptor is upregulated in many tumor types and thus represents an ideal target for cancer treatment. Several folate receptor targeted therapies are in development, including the small molecule drug conjugate vintafolide, the monoclonal antibody farletuzumab, and the antibody-drug conjugate IMGN853. The role of the folate receptor as a target in cancer progression and resistance as well as emerging preclinical and clinical data from studies on those folate receptor targeted agents that are in development with a focus on vintafolide are reviewed. The folate receptor has several unique properties, such as high expression in several tumor types, that make it a rational target for cancer treatment, and allow for selective delivery of folate receptor targeted agents. Early-stage clinical data in lung and ovarian cancer suggest that vintafolide has the potential for combination with other standard approved agents.
Chemotherapy use in stage III colon cancer: a National Cancer Database analysis

Background: Although adjuvant chemotherapy in stage III colon cancer improves overall survival, prior studies have shown that it is underused. We analyzed different factors that may influence its use. Methods: This is a retrospective study of stage III colon cancer patients (n = 207,718) diagnosed between 2000 and 2011 in the National Cancer Data Base (NCDB). The NCDB contains ~70% of new cancer diagnosis from >1500 American College of Surgeons accredited cancer programs in the United States and Puerto Rico. The chi-squared test was used to determine any difference in characteristics of patients who did or did not receive chemotherapy. Results: A total of 35% of all stage III colon cancer patients, and 38% of stage III cases undergoing surgery, did not receive adjuvant chemotherapy. The use of chemotherapy had increased in recent years (64% in 2007–2011 versus 59% in 2000–2002; p < 0.0001). Its use was lower in whites (61%), females (60%), patients ⩾60 years (55%), patients with one or more comorbidities (55%), nonacademic centers (62%), those with medicare insurance (52%), lower education (61%) and income levels (59%, all p < 0.0001). The nonwhite and uninsured were more likely to be <60 years old. Conclusion: More than one-third did not receive adjuvant chemotherapy, although its use has increased in more recent years. Age was one of the most important determinants of chemotherapy use, which may explain higher rates in nonwhite and uninsured. In addition to patient characteristics, race, gender and socioeconomic factors influence chemotherapy use. These findings have important implications for healthcare reform.
Caracterización por electroforesis de campo pulsado de aislamientos de Salmonella Typhimurium recuperados en el programa de vigilancia de enfermedad diarreica aguda en Colombia, 1997-2004

Introduction. In Colombia Salmonella Typhimurium is the second most frequently isolated Salmonella serotype (after S. Enteritidis) from human clinical samples. This serotype represents 28.2% (n = 468) of the 1659 Salmonella isolates recovered by the Instituto Nacional de Salud (INS) Acute Diarrheal Diseases Surveillance Program from 1997 to 2004. Previously, little was known about the molecular attributes of these strains and commonality of genetic subtypes among S. Typhimurium isolated from humans in Colombia. Objective. The purpose of this study was to characterize S. Typhimurium isolates circulating in Colombia using pulsed-field gel electrophoresis in order to establish genetic profiles and determine their potential relatedness. Materials and methods. 468 S. Typhimurium isolates were submitted to INS by 14 Public Health Laboratories from January 1997 to December 2004. The pulsed-field gel electrophoresis was performed using restriction enzyme XbaI according to the PulseNet standard protocol (CDC, Atlanta). Restriction pattern analysis and cluster definition were performed using Molecular Analyst Fingerprinting II software. Results. 180 distinct electrophoretic patterns were obtained. Pattern COINJPX.X01. 0062 was the most common (21.3% of the 473 isolates, n=101), followed by COINJPX.X01. 0001 (8.4%, n=40), COINJPX.X01. 0058 (3%, n=13), COINJPX.X01. 0003 (2.5%, n=12), COINJPX.X01. 0066 (2.3%, n=11), and COINJPX.X01. 0108 (1.4%, n=6). COINJPX.X01. 0001, was the most prevalent pattern among S. Typhimurium isolated in Bogota from 1997-2002, but appeared to be replaced both in Bogota and nationally by COINJPX.X01. 0062 in 2003-2004. Cluster analysis demonstrated three distinct groups with 53% and 82% similarity indicating heterogeneity within the serotype. Conclusions. The study provides important electrophoretic pattern baseline data, which will be useful for prospective real-time comparison of profiles of future isolates. Cluster detection using this method will facilitate outbreak detection and will enhance our ability to find common sources for seemingly unrelated infections.
Antiangiogenic therapy for refractory colorectal cancer: current options and future strategies

Even though significant improvements in the treatment of colorectal cancer (CRC) have been made in recent years, survival rates for metastatic colorectal cancer (mCRC) are poor. Effective treatment options for metastatic colorectal cancer remain limited, and new therapeutic strategies are desperately needed. Several tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) that target angiogenesis, a critical process for facilitating tumor cell growth, invasion, and metastasis, are either approved or in clinical development for the treatment of mCRC. Many of these agents have shown efficacy in mCRC, both as single agents and in combination with standard chemotherapy regimens. However, there is a need for predictive markers of response to identify those patients most likely to benefit from antiangiogenic therapy, and, to date, no markers of this type have been validated in patients. Additionally, because antiangiogenic agents typically cause cytostatic as opposed to cytotoxic antitumor effects, it is important to determine the best strategies for evaluating therapeutic response in mCRC to ensure maximum clinical benefit. In this review, we summarize the efficacy and tolerability of approved and investigational antiangiogenic agents for the treatment of mCRC. We also discuss potential markers of response to antiangiogenic agents and how these markers, along with appropriate endpoint selection, can improve clinical trial design.
The K186E Amino Acid Substitution in the Canine Influenza Virus H3N8 NS1 Protein Restores Its Ability To Inhibit Host Gene Expression

ABSTRACT Canine influenza viruses (CIVs) are the causative agents of canine influenza, a contagious respiratory disease in dogs, and include the equine-origin H3N8 and the avian-origin H3N2 viruses. Influenza A virus (IAV) nonstructural protein 1 (NS1) is a virulence factor essential for counteracting the innate immune response. Here, we evaluated the ability of H3N8 CIV NS1 to inhibit host innate immune responses. We found that H3N8 CIV NS1 was able to efficiently counteract interferon (IFN) responses but was unable to block general gene expression in human or canine cells. Such ability was restored by a single amino acid substitution in position 186 (K186E) that resulted in NS1 binding to the 30-kDa subunit of the cleavage and polyadenylation specificity factor (CPSF30), a cellular protein involved in pre-mRNA processing. We also examined the frequency distribution of K186 and E186 among H3N8 CIVs and equine influenza viruses (EIVs), the ancestors of H3N8 CIV, and experimentally determined the impact of amino acid 186 in the ability of different CIV and EIV NS1s to inhibit general gene expression. In all cases, the presence of E186 was responsible for the control of host gene expression. In contrast, the NS1 protein of H3N2 CIV harbors E186 and blocks general gene expression in canine cells. Altogether, our results confirm previous studies on the strain-dependent ability of NS1 to block general gene expression. Moreover, the observed polymorphism on amino acid 186 between H3N8 and H3N2 CIVs might be the result of adaptive changes acquired during long-term circulation of avian-origin IAVs in mammals. IMPORTANCE Canine influenza is a respiratory disease of dogs caused by two CIV subtypes, the H3N8 and H3N2 viruses, of equine and avian origins, respectively. Influenza NS1 is the main viral factor responsible for the control of host innate immune responses, and changes in NS1 can play an important role in host adaptation. Here we assessed the ability of H3N8 CIV NS1 to inhibit host innate immune responses and gene expression. The H3N8 CIV NS1 did not block host gene expression, but this activity was restored by a single amino acid substitution (K186E), which was responsible for NS1 binding to the host factor CPSF30. In contrast, the H3N2 CIV NS1, which contains E186, blocks general gene expression. Our results suggest that the ability to block host gene expression is not required for influenza virus replication in mammals but might be important in the long-term adaptation of avian-origin influenza viruses to mammals.
Anti-TNF therapy in ankylosing spondylitis: insights for the clinician

The introduction of tumour necrosis factor (TNF)-blocking therapy has revolutionized the management of ankylosing spondylitis (AS) over the last decade. This review highlights the current evidence relating to the use of TNF-blocking therapy in AS. International guidelines for the use of TNF blockers in AS are summarized. An outline of the evidence for efficacy and safety of these drugs is included, highlighting recent data from registries and real-life observational studies. Such cohort data is also reviewed highlighting the evidence for ‘switching’ TNF blockers in AS in the case of non-response or adverse events. The potential new application of TNF blockers in preradiographic axial spondyloarthropathy (SpA) or ‘early AS’ is discussed with reviews of two recent studies in this area. Finally research into the possible additional impacts of TNF therapies is reviewed. The question of whether TNF blockers are truly disease modifying in AS remains unanswered with conflicting reports. The additional burden of AS in terms of cardiovascular disease is now becoming understood. Recent data from basic science studies highlights the potential impact of TNF blockers on this excess cardiovascular morbidity and mortality. Future studies and registry data will be able to assess whether TNF blockers have an additional role in controlling systemic inflammation and its associated cardiovascular risk.
Adenovirus E1A Oncogene Induces Rereplication of Cellular DNA and Alters DNA Replication Dynamics

ABSTRACT The oncogenic property of the adenovirus (Ad) transforming E1A protein is linked to its capacity to induce cellular DNA synthesis which occurs as a result of its interaction with several host proteins, including pRb and p300/CBP. While the proteins that contribute to the forced induction of cellular DNA synthesis have been intensively studied, the nature of the cellular DNA replication that is induced by E1A in quiescent cells is not well understood. Here we show that E1A expression in quiescent cells leads to massive cellular DNA rereplication in late S phase. Using a single-molecule DNA fiber assay, we studied the cellular DNA replication dynamics in E1A-expressing cells. Our studies show that the DNA replication pattern is dramatically altered in E1A-expressing cells, with increased replicon length, fork velocity, and interorigin distance. The interorigin distance increased by about 3-fold, suggesting that fewer DNA replication origins are used in E1A-expressing cells. These aberrant replication events led to replication stress, as evidenced by the activation of the DNA damage response. In earlier studies, we showed that E1A induces c-Myc as a result of E1A binding to p300. Using an antisense c-Myc to block c-Myc expression, our results indicate that induction of c-Myc in E1A-expressing cells contributes to the induction of host DNA replication. Together, our results suggest that the E1A oncogene-induced cellular DNA replication stress is due to dramatically altered cellular replication events and that E1A-induced c-Myc may contribute to these events.
Robust Covariance Matrix Estimation in Heterogeneous Low Rank Context

This paper addresses the problem of robust covariance matrix (CM) estimation in the context of a disturbance composed of a low rank (LR) heterogeneous clutter plus an additive white Gaussian noise. The LR clutter is modeled by a spherically invariant random vector with assumed high clutter-to-noise ratio. In such a context, adaptive process should require less training samples than classical methods to reach equivalent performance as in a “full rank” clutter configuration. The main issue is that classical robust estimators of the CM cannot be computed in the undersampled configuration. To overcome this issue, the current approach is based on regularization methods. Nevertheless, most of these solutions are enforcing the estimate to be well conditioned, while in our context, it should be LR structured. This paper, therefore, addresses this issue and derives an algorithm to compute the maximum likelihood estimator of the CM for the considered disturbance model. Several relaxations and robust generalizations of the result are discussed. Performance is finally illustrated on numerical simulations and on a space time adaptive processing for airborne radar application.
A Study of Nurses' Resilience, Occupational Stress and Satisfaction

Purpose: The purpose of this study is to examine the clinical nurses' resilience, occupational stress, and occupational satisfaction and to identify the correlations among them. Methods: Structured questionnaires were administered with total 75 questions for 433 nurses working at a university hospital in Jin-ju from July 19 to 30, 2010. Data from the completed questionnaires were analyzed with the SPSS/WIN program. Results: The resilience had a significant difference according to the age, marital status, religion, education level, annual income, motive of choosing the nursing science, clinical career, position, and workplace. Resilience had a negative correlation with occupational stress (r=-.405), and had a positive correlation with occupational satisfaction (r=.380). Occupational stress had a negative correlation with occupational satisfaction (r=-.637). Conclusion: The higher their resilience was, the lower their occupational stress and the higher the occupational satisfaction. It is recommended that intervention program be developed that can enhance personal resilience in nurse.
Factors affecting birth weight, litter size and survival rates of goats in Bauchi, Nigeria

This study was carried out at the Research Farm of Abubakar Tafawa Balewa University, Bauchi, Nigeria (October, 2003 – May, 2006) to investigate the effects of some factors (breed, body condition score, season, type of birth and parity) on birth weight, litter size and survival rates in goats. The results showed that all the factors investigated had significant (p Animal Production Research Avancees Vol. 3 (1) 2007: pp. 46-51
Catastrophic antiphospholipid syndrome: how to diagnose a rare but highly fatal disease

Antiphospholipid syndrome (APS) is a multisystem autoimmune condition characterized by vascular thromboses and/or pregnancy loss associated with persistently positive antiphospholipid antibodies (aPL). Catastrophic APS (CAPS) is the most severe form of APS with multiple organ involvement developing over a short period of time, usually associated with microthrombosis. ‘Definite’ and ‘probable’ CAPS have been defined based on the preliminary classification criteria; however, in a real-world setting, aPL-positive patients with multiple organ thromboses and/or thrombotic microangiopathies exist who do not fulfill these criteria. Previous APS diagnosis and/or persistent clinically significant aPL positivity is of great importance for the CAPS diagnosis; however, almost half of the patients who develop CAPS do not have a history of aPL positivity. The purpose of this paper is to summarize the diagnostic challenges and the recently updated diagnostic algorithms for CAPS providing a ‘step-by-step’ approach for clinicians (and researchers) in the assessment of patients with multiple organ thromboses.
A New Two-Stage Scheme for the Recognition of Persian Handwritten Characters

In this paper, a two-stage scheme for the recognition of Persian handwritten isolated characters is proposed. In the first stage, similar shaped characters are categorized into groups and as a result, 8 groups are obtained from 32 Persian basic characters. In the second stage, the groups containing more than one similar shape characters are considered further for the final recognition. Feature extraction is based on under sampled bitmaps technique and modified chain-code direction frequencies. For the first stage features, we compute 49-dimension features based on under sampled bitmaps from 49 non-overlapping 7×7 window-maps. 196-dimension chain-code direction frequencies from 49 overlapping 9×9 window-maps are computed and used as features for the second stage of the proposed scheme. Classifiers are one-against-other support vector machines (SVM). We evaluated our scheme on a standard dataset of Persian handwritten characters. Using 36682 samples for training, we tested our scheme on other 15338 samples and obtained 98.10% and 96.68% correct recognition rates when considered 8-class and 32-class problems, respectively.