Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic value of lymphocyte surface markers in acute myeloid leukemia.

We studied the expression of cell surface antigens associated with myeloid and lymphoid leukemias on bone marrow-derived blast cells from 339 patients with newly diagnosed de novo acute myeloid leukemia (AML) enrolled on Cancer and Leukemia Group B (CALGB) chemotherapy protocols. Surprisingly, of 211 cases studied for the expression of CD2 (T-cell marker, sheep erythrocyte binding receptor for T lymphocytes) 45 were positive (21%). In addition, of 298 patients studied for CD19 (B-lymphocyte marker), 41 were positive (14%). Overall, of 170 patients studied for both CD2 and CD19, 56 (33%) were positive. Interestingly, central review of the French-American-British (FAB) morphology of the CD2- and CD19-positive cases showed that FAB M3 was twice as frequent, and M4E eight times as frequent compared with the CD2- and CD19-negative cases. Of 22 lymphocyte antigen-positive cases in which cells were available for studies of Ig or T-cell antigen receptor (TCR) gene rearrangement, 20 were germline, one had a rearranged Ig heavy chain gene, and one had rearranged TCR beta and Ig heavy chain genes. The presence of messenger RNA for CD2 was demonstrated in four CD2 surface antigen-positive cases, thus validating the cell surface data. Lymphocyte antigen-positive cases had karyotypes commonly seen in AML; 71% of cases with an abnormal clone had t(8;21)(q22;q22), inversion 16(p13q22), t(15;17)(q22;q12), or t(9;11)(p22;q23). The patients with lymphocyte markers had a significantly higher incidence of these karyotypic abnormalities compared with patients with lymphocyte antigen-negative AML (34% v 15%, P less than .02). When the outcome to therapy of the lymphocyte antigen-positive cases was compared with that for the CD2, CD19-negative cases, we found that the CD2, CD19-positive cases actually had higher complete remission rates (75% v 59%, P = .04), and significantly longer time to failure (P = .02; 32.4% +/- 6.0% v 18.0% +/- 4.1% at 2 years) and overall survival (P = .02; 43.5% +/- 6.3% v 26.0% +/- 4.5% at 2 years). CD2 antigen-positive cases also had a significantly superior survival (P = .02; 43.8% +/- 7.9% v 29.8% +/- 3.8% at 2 years). There were no significant differences (P less than or equal to .05) between the two groups in age, leukocyte count at diagnosis, incidence of extramedullary disease, or FAB classification. (ABSTRACT TRUNCATED AT 400 WORDS)
Current status of vaccine development against Theileria parasites

The tick-borne protozoan parasites Theileria parva and Theileria annulata cause economically important diseases of cattle in tropical and sub-tropical regions. Because of shortcomings in disease control measures based on therapy and tick control, there is a demand for effective vaccines against these diseases. Vaccines using live parasites have been available for over two decades, but despite their undoubted efficacy they have not been used on a large scale. Lack of infrastructure for vaccine production and distribution, as well as concerns about the introduction of vaccine parasite strains into local tick populations have curtailed the use of these vaccines. More recently, research has focused on the development of subunit vaccines. Studies of immune responses to different stages of the parasites have yielded immunological probes that have been used to identify candidate vaccine antigens. Immunisation of cattle with antigens expressed in the sporozoite, schizont or merozoite stages has resulted in varying degrees of protection against challenge. Although the levels of protection achieved have not been sufficient to allow exploitation for vaccination, there are clearly further lines of investigation, relating to both the choice of antigens and the antigen delivery systems employed, that need to be pursued to fully explore the potential of the candidate vaccines. Improved knowledge of the molecular biology and immunology of the parasites gained during the course of these studies has also opened up opportunities to refine and improve the quality of live vaccines.
Utility of PTEN and ERG Immunostaining for Distinguishing High-grade PIN From Intraductal Carcinoma of the Prostate on Needle Biopsy

Intraductal carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia (PIN) have markedly different implications for patient care but can be difficult to distinguish in needle biopsies. In radical prostatectomies, we demonstrated that PTEN and ERG immunostaining may be helpful to resolve this differential diagnosis. Here, we tested whether these markers are diagnostically useful in the needle biopsy setting. Separate or combined immunostains were applied to biopsies containing morphologically identified intraductal carcinoma, PIN, or borderline intraductal proliferations more concerning than PIN but falling short of morphologic criteria for intraductal carcinoma. Intraductal carcinoma occurring with concurrent invasive tumor showed the highest rate of PTEN loss, with 76% (38/50) lacking PTEN and 58% (29/50) expressing ERG. Of biopsies containing isolated intraductal carcinoma, 61% (20/33) showed PTEN loss and 30% (10/33) expressed ERG. Of the borderline intraductal proliferations, 52% (11/21) showed PTEN loss and 27% (4/15) expressed ERG. Of the borderline cases with PTEN loss, 64% (7/11) had carcinoma in a subsequent needle biopsy specimen, compared with 50% (5/10) of PTEN-intact cases. In contrast, none of the PIN cases showed PTEN loss or ERG expression (0/19). On needle biopsy, PTEN loss is common in morphologically identified intraductal carcinoma yet is very rare in high-grade PIN. Borderline intraductal proliferations, especially those with PTEN loss, have a high rate of carcinoma on resampling. If confirmed in larger prospective studies, these results suggest that PTEN and ERG immunostaining may provide a useful ancillary assay to distinguish intraductal carcinoma from high-grade PIN in this setting.
Salmeterol plus theophylline combination therapy in the treatment of COPD.

BACKGROUND Patients with COPD often require multiple therapies to improve lung function and decrease symptoms and exacerbations. Salmeterol and theophylline are indicated for the treatment of COPD, but the use of these agents in combination has not been extensively studied. OBJECTIVES To compare the efficacy and safety of salmeterol plus theophylline vs either agent alone in COPD. METHODS Randomized, double-blind, double-dummy, parallel-group trial in 943 patients with COPD. After an open-label theophylline titration period (serum levels, 10 to 20 microg/mL), patients were randomly assigned to receive salmeterol (42 microg bid) plus theophylline, salmeterol (42 microg bid), or theophylline for 12 weeks. Serial pulmonary function tests were completed on day 1 and treatment week 12. Patients kept diary cards and noted their peak flow rates, symptom scores, and albuterol use, and periodically completed quality-of-life and dyspnea questionnaires. RESULTS All three groups significantly improved compared with baseline. Combination treatment with salmeterol plus theophylline provided significantly (p < or = 0.045) greater improvements in pulmonary function; significantly (p < or = 0.048) greater decreases in symptoms, dyspnea, and albuterol use; and significantly fewer COPD exacerbations (p = 0.023 vs theophylline). In general, treatment with salmeterol provided greater improvement in lung function and satisfaction with treatment compared with theophylline. Salmeterol treatment was also associated with significantly fewer drug-related adverse events (p < or = 0.042) than either treatment that included theophylline. The safety profile (adverse events, vital signs, and ECG findings) of the two treatments that included theophylline were similar. CONCLUSION Patients with COPD may benefit from combination treatment with salmeterol plus theophylline, without a resulting increase in adverse events or other adverse sequelae.
Ardennite in a high- P / T meta-conglomerate near Vitolište in the westernmost Vardar zone, Republic of Macedonia

A new occurrence of ardennite near Vitoliste in the southernmost Republic of Macedonia (FYROM) is described. In the westernmost Vardar zone, a high- P / T metamorphic conglomerate contains reddish clasts (up to 20–30 vol% of the rock) that consist of quartz, hematite, ardennite, pyrophyllite, sudoite, cookeite, phengite rimmed by muscovite, epidote/piemontite, lawsonite, tourmaline, titanite, albite, apatite and ±rutile. Epidote may contain inclusions of pumpellyite–(Fe 2+ ) and is partially transformed to piemontite. Ardennite is generally poor in As and its composition essentially follows the T4 exchange vector (Si + Al + P) −1 V, whereby Al and P are relatively low. Three compositional types of ardennite can be distinguished: ardennite-(V), ‘ardennite-(V,Si)’ and ‘ardennite-(Si)’, the latter possibly representing lavoisierite inter- and overgrowths. Metamorphic conditions of 0.65–0.80 GPa and 340–370 °C are deduced. The reddish Fe–Mn–(V–As)-rich detritus may have originated from a hydrothermal Fe–Mn deposit or, more likely, from a nickel–laterite deposit developed from weathered ophiolites. Such laterites and bauxites resulted from re-deposition of ophiolite material in shallow seawater during the Lower Cretaceous.
Convergence of solutions of quasi-variational inequalities and applications

where fn : E × E → R, f : E × E → R, φn : E × E → R ∪ {∞}, φ : E × E → R ∪ {∞}. The aim of this paper is to give suitable conditions on the convergence of (fn)n to f and (φn)n to φ in order to obtain a convergence result for the solutions of (1.1)n to solutions of (1.2). This study was motivated by the increasing interest in the topic of generalized quasi-variational inequalites (in short g.q.v.i.), taking into account that a g.q.v.i. (see (3.2)) can be represented by a q.v.i. (1.2) with appropriate functions f and φ. Moreover, while the problem of the existence of solutions of q.v.i. and g.q.v.i. has been investigated in many papers (see for example [5], [6], [14]), the problem of convergence of solutions of q.v.i. has been studied, in a particular setting, only in [3]. Finally, in Section 4, we consider Nash equilibria with dependent constraints (called in [7] generalized Nash equilibrium), which can be thought
Vulnerability assessment of Gnidia glauca (Thymelaeaceae) exploitation, traditional uses and domestication potential in the community forest of Kilum-Ijim, North Western Cameroon

A study was conducted in the western highland region of Cameroon with the aim to assess sustainability of Gnidia glauca exploitation in its natural habitat. In 33 plots of 40 x 40 m, the unexploited, exploited and dead trees were evaluated for vitality using a multi-criteria vulnerability assessment method. An ethnobotanical survey was conducted with 60 respondents in six villages around Mount Oku area. Data were submitted to ANOVA and means separated using Duncan test. The results revealed that 95 % of G. glauca trees were unexploited and only 3.92% showed signs of exploitation, among which 1.08% were dead. Among the exploited stems, 18% showed a completely dead crown, whereas 73% were described to be regular and healthy. Wood (29%) and bark (28%) were the main products being exploited. However, the species’ bark was the most frequently harvested product (64%). G. glauca was shown to be more vulnerable in forests (2.6) than in savanna (2.4). The motivating factors for the species’ domestication were the fragility of its habitat, the potential high future demand for its products and the unsustainable exploitation techniques being applied. It is therefore recommended to promote the species uses, conservation and cultivation within its national distribution range for local livelihood improvement. Key words: Ethnobotany, Gnidia glauca, sustainable management, vulnerability, Cameroon.
Comparative study of flex heart rate in colombian children and in pregnant, lactating, and non‐pregnant, nonlactating women

The heart rate (HR) value employed to separate resting and active portions of the calibration curves used to estimate energy expenditure (EE) from minute‐by‐minute HR recordings is called the flex‐HR. The present study has characterized it, the resting HR and the average daily HR during the awake portion of the day (12–14 h) by comparing age, gender and nutritional status effects related to measured maximum oxygen consumption (V̇ O 2 max; ml/min/kg body weight)in school‐aged Colombian children (145 boys and 132 girls), 6–16 years of age. The same HR variables have been individually measured in nutritionally normal, nonpregnant, nonlactating (NPNL; n = 48), pregnant (n = 26), and lactating (n = 18) women, 19–43 years of age, on three occasions separated by 3 months. In general, the flex‐HR followed the differences observed in resting and average daily HRs. All three values decreased with age in children, were higher in girls than boys, and did not exhibit differences between nutritionally normal and undernourished children. All three HRs had a statistically significant negative relationship with V̇ O 2 max in boys but not in girls. NPNL and lactating women showed no significant change in the mean values of the repeated HR measurements but exhibited maximum individual differences of flex‐HR of −56 to +42 beats/min. Pregnant women had higher HRs in all 3 rounds of measurement compared to NPNL subjects. The data support the generalization that the flex‐HR method of estimating EE is appropriate in groups of subjects but not in individuals, and that individual calibration of subjects close to the time of application to the making of EE measurements is an important feature of its use. Am. J. Hum. Biol. 9:647–657, 1997. © Wiley‐Liss, Inc.
Oncogenic Notch signaling in T-cell and B-cell lymphoproliferative disorders

Purpose of reviewThis article highlights recent discoveries about Notch activation and its oncogenic functions in lymphoid malignancies, and discusses the therapeutic potential of Notch inhibition. Recent findingsNOTCH mutations arise in a broad spectrum of lymphoid malignancies and are increasingly scrutinized as putative therapeutic targets. In T-cell acute lymphoblastic leukemia (T-ALL), NOTCH1 mutations affect the extracellular negative regulatory region and lead to constitutive Notch activation, although mutated receptors remain sensitive to Notch ligands. Other NOTCH1 mutations in T-ALL and NOTCH1/2 mutations in multiple B-cell malignancies truncate the C-terminal proline (P), glutamic acid (E), serine (S), threonine (T)-rich (PEST) domain, leading to decreased Notch degradation after ligand-mediated activation. Thus, targeting Notch ligand-receptor interactions could provide therapeutic benefits. In addition, we discuss recent reports on clinical testing of Notch inhibitors in T-ALL that influenced contemporary thinking on the challenges of targeting Notch in cancer. We review advances in the laboratory to address these challenges in regards to drug targets, the Notch-driven metabolome, and the sophisticated protein–protein interactions at Notch-dependent superenhancers that underlie oncogenic Notch functions. SummaryNotch signaling is a recurrent oncogenic pathway in multiple T- and B-cell lymphoproliferative disorders. Understanding the complexity and consequences of Notch activation is critical to define optimal therapeutic strategies targeting the Notch pathway.
Developing Neuromuscular Junctions: First Signs of Chemical Transmission during Formation in Tissue Culture

Electrophysiological study of rat neuromuscular junctions in the early stage of formation in tissue culture showed that chemical transmission begins with discrete, localized release of transmitter about the time when nerve-muscle contacts are first visible with light microscopy. Noncontractile myotubes with as few as three nuclei showed evidence of junctional transmission.
Multicenter evaluation of the use of Haemophilus test medium for broth microdilution antimicrobial susceptibility testing of Streptococcus pneumoniae and development of quality control limits

A five-laboratory collaborative study was undertaken to determine the precision and accuracy of broth microdilution susceptibility tests of Streptococcus pneumoniae isolates performed with Haemophilus test medium (HTM) compared with tests performed with lysed horse blood-supplemented Mueller-Hinton broth (LHB). The intra-and interlaboratory reproducibilities of MICs of 10 antimicrobial agents determined with the two media were found to be quite similar and highly reproducible in both media. On the basis of favorable performance in this study, S. pneumoniae ATCC 49619 is recommended as a quality control strain to assess the performance of HTM when this medium is used for testing of pneumococci. Testing of 293 unique clinical isolates of S. pneumoniae with both media in the respective participant laboratories allowed a direct comparison of MIC results and a calculation of interpretive error rates. Although there were some slight differences between MICs determined with HTM and MICs determined with LHB, few very major or major errors resulted from testing the clinical isolates against the 10 antimicrobial agents. However, MIC-interpretive criteria specific for S. pneumoniae should be developed and promulgated through a national consensus mechanism.
Synthetic and Biological Studies of Sesquiterpene Polygodial: Activity of 9‐Epipolygodial against Drug‐Resistant Cancer Cells

Polygodial, a terpenoid dialdehyde isolated from Polygonum hydropiper L. , is a known agonist of the transient receptor potential vanilloid 1 (TRPV1). In this investigation a series of polygodial analogues were prepared and investigated for TRPV1‐agonist and anticancer activities. These experiments led to the identification of 9‐epipolygodial, which has antiproliferative potency significantly exceeding that of polygodial. 9‐Epipolygodial was found to maintain potency against apoptosis‐resistant cancer cells as well as those displaying the multidrug‐resistant (MDR) phenotype. In addition, the chemical feasibility for the previously proposed mechanism of action of polygodial, involving the formation of a Paal–Knorr pyrrole with a lysine residue on the target protein, was demonstrated by the synthesis of a stable polygodial pyrrole derivative. These studies reveal rich chemical and biological properties associated with polygodial and its direct derivatives. These compounds should inspire further work in this area aimed at the development of new pharmacological agents, or the exploration of novel mechanisms of covalent modification of biological molecules with natural products.
Association of tamoxifen with meningioma: a population-based study in Sweden

Previous studies suggest that hormone therapy may play an important role in the development of meningioma. However, it is unclear whether medication with tamoxifen can prevent meningioma. Our study cohort included all women who were diagnosed with breast cancer between 1961 and 2010, and a total of 227 535 women were identified with breast cancer with a median age at diagnosis of 63 years. Women diagnosed with breast cancer after 1987 were defined as tamoxifen exposed; those diagnosed with breast cancer before or during 1987 were defined as not exposed to tamoxifen. Standardized incidence ratios (SIRs) were used to calculate the risk of subsequent meningioma. Of these women, 223 developed meningioma. For women without tamoxifen exposure, the risk of meningioma was significantly increased, with an SIR of 1.54 (95% confidence interval 1.30–1.81); the risk was not increased in those with tamoxifen exposure (SIR=1.06, 95% confidence interval 0.84–1.32). The increased risk of meningioma in women without tamoxifen exposure persisted during 10 years of follow-up. In this historical cohort study, we found that women diagnosed with breast cancer but not treated with tamoxifen had an increased incidence of meningioma, whereas the incidence was close to that of the general population in patients treated with tamoxifen. This suggests that tamoxifen may prevent the development of meningioma.
secretory PLA 2 in neutrophils plays a pathogenic role in abdominal aortic aneurysms in mice

Watanabe K, Fujioka D, Saito Y, Nakamura T, Obata J, Kawabata K, Watanabe Y, Mishina H, Tamaru S, Hanasaki K, Kugiyama K. Group X secretory phospholipase A2 in neutrophils plays a pathogenic role in abdominal aortic aneurysms in mice. Am J Physiol Heart Circ Physiol 302: H95–H104, 2012. First published October 7, 2011; doi:10.1152/ajpheart.00695. 2011. —Group X secretory PLA2 (sPLA2-X) is expressed in neutrophils and plays a role in the pathogenesis of neutrophil-mediated tissue inflammation and injury. This study tested the hypothesis that sPLA2-X in neutrophils may contribute to the pathogenesis of abdominal aortic aneurysms (AAA) using sPLA2-X / mice. AAA was created by application of CaCl2 to external surface of aorta. As a result, the aortas of sPLA2X / mice had smaller diameters (percent increase from baseline; 24.8 3.5% vs. 49.9 9.1%, respectively; P 0.01), a reduced grade of elastin degradation, and lower activities of elastase and gelatinase (26% and 19% lower, respectively) after CaCl2 treatment compared with sPLA2-X / mice. In sPLA2-X / mice, immunofluorescence microscopic images showed that the immunoreactivity of sPLA2-X was detected only in neutrophils within aortic walls 3 days, 1, 2, and 6 wk after CaCl2 treatment, whereas the immunoreactivity was not detected in macrophages or mast cells in aortic walls. sPLA2-X immunoreactivity also was colocalized in cells expressing matrix metalloproteinase (MMP)-9. Neutrophils isolated from sPLA2X / mice had lower activities of elastase, gelatinase, and MMP-9 in response to stimuli compared with sPLA2-X / mice. The attenuated release of elastase and gelatinase from sPLA2-X / neutrophils was reversed by exogenous addition of mouse sPLA2-X protein. The adoptive transfer of sPLA2-X / neutrophils days 0 and 3 after CaCl2 treatment reversed aortic diameters and elastin degradation grades in the lethally irradiated sPLA2-X / mice reconstituted with sPLA2X / bone marrow to an extent similar to that seen in sPLA2-X / mice. In conclusion, sPLA2-X in neutrophils plays a pathogenic role in AAA in a mice model.
DNA barcoding a highly diverse group of parasitoid wasps (Braconidae: Doryctinae) from a Mexican nature reserve

Background and aims. The preliminary results of a DNA barcoding study of the doryctine fauna of parasitoid wasps from the Chamela–Cuixmala Biosphere Reserve in Mexico, a region dominated by tropical dry forest, are presented. So far, three field trips have been carried out to the reserve and 468 specimens have been collected, of which 407 cox1 sequences were obtained. Materials and methods. The general mixed Yule-coalescent model was applied to a phylogram to investigate the number of evolutionary units that can be detected from the DNA sequence data examined. Results. A total of 185 barcoding species assigned to 20 identified doryctine genera were discriminated using the above model, 115 of which belong to the speciose genus Heterospilus, pointing out the extraordinary species richness of this subfamily of insects in a Mexican tropical dry forest. Conclusion. On the basis of the DNA barcodes generated, Ptesimogastroides Braet & van Achterberg is proposed to be a junior synonym of Ptesimogaster Marsh syn. nov. Neoheterospilus was also found deeply nested within a large Heterospilus clade, suggesting the paraphyly of the latter genus.