Miracle-dz/UniFAR-FTUs huggingface dataset:
Desensitization to hydroxycarbamide following long‐term treatment of thalassaemia intermedia as observed in vivo and in primary erythroid cultures from treated patients

Hydroxycarbamide (HC) is a pharmacological agent capable of stimulating fetal haemoglobin (HbF) production during adult life. High levels of HbF may ameliorate the clinical course of β‐thalassaemia and sickle cell disease. The efficacy of HC for the treatment of thalassaemia major and thalassaemia intermedia is variable. Although an increase of HbF has been observed in most patients, only some patients experience significant improvement in total haemoglobin levels. This study aimed to determine the effectiveness and safety of short‐ (1 year) and long‐term (mean follow‐up 68 months) HC treatment in 24 thalassaemia intermedia patients. Additionally, we evaluated if primary erythroid progenitor cells cultured from treated patients responded to HC treatment in a manner similar to that observed in vivo. Our results confirm a good response to HC after a short‐term follow‐up in 70% of thalassaemia intermedia patients and a reduction of clinical response in patients with a long follow‐up. Erythroid cultures obtained from patients during treatment reproduced the observed in vivo response. Interestingly, haematopoietic stem cells from long‐term treated patients showed reduced ability to develop into primary erythroid cultures some months before the reduction of the ‘in vivo’ response. The mechanism of this loss of response to HC remains to be determined.
Population Pharmacokinetic Analysis of Colistin Methanesulfonate and Colistin after Intravenous Administration in Critically Ill Patients with Infections Caused by Gram-Negative Bacteria

ABSTRACT Colistin is used to treat infections caused by multidrug-resistant gram-negative bacteria (MDR-GNB). It is administered intravenously in the form of colistin methanesulfonate (CMS), which is hydrolyzed in vivo to the active drug. However, pharmacokinetic data are limited. The aim of the present study was to characterize the pharmacokinetics of CMS and colistin in a population of critically ill patients. Patients receiving colistin for the treatment of infections caused by MDR-GNB were enrolled in the study; however, patients receiving a renal replacement therapy were excluded. CMS was administered at a dose of 3 million units (240 mg) every 8 h. Venous blood was collected immediately before and at multiple occasions after the first and the fourth infusions. Plasma CMS and colistin concentrations were determined by a novel liquid chromatography-tandem mass spectrometry method after a rapid precipitation step that avoids the significant degradation of CMS and colistin. Population pharmacokinetic analysis was performed with the NONMEM program. Eighteen patients (6 females; mean age, 63.6 years; mean creatinine clearance, 82.3 ml/min) were included in the study. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.046 h and 2.3 h, respectively. The clearance of CMS was 13.7 liters/h. For colistin, a one-compartment model was sufficient to describe the data, and the estimated half-life was 14.4 h. The predicted maximum concentrations of drug in plasma were 0.60 mg/liter and 2.3 mg/liter for the first dose and at steady state, respectively. Colistin displayed a half-life that was significantly long in relation to the dosing interval. The implications of these findings are that the plasma colistin concentrations are insufficient before steady state and raise the question of whether the administration of a loading dose would benefit critically ill patients.
Response to Imatinib Mesylate in Patients with Early Chronic Phase Chronic Myeloid Leukemia and Derivative Chromosome 9 Deletion or Clonal Evolution

Objectives: The significance of clonal evolution and derivative chromosome 9 in Philadelphia-positive CML is not fully characterized and studies have yielded conflicting results. After working on emergence of clonal evolution from our region, we continued to find out the response of Imatinib Mesylate on such cases of CML treated in our center. Materials and methods: We conducted a cross sectional, prospective analysis on response of Imatinib Mesylate on patients with Philadelphia positive chronic myeloid leukemia with clonal evolution treated from period of September 2007 till 2010. Patients were grouped on basis of cytogenetic analysis performed by conventional cytogenetic and fluorescence in situ hybridization (FISH) techniques and followed for three years to see the response rate of imatinib mesylate. Results: We reported here the response rate in one hundred and two previously untreated cases of chronic myeloid leukemia (Philadelphia positive). Twelve patients (11.7%) exhibit derivative chromosome 9, three had trisomy 8, one with addition 15 and one had deletion 16. At follow-up of 30 months 78 cases were evaluable and 45% and 61% showed complete and major cytogenetic response respectively. There is no significant association of derivative chromosome 9 with the response of imatinib mesylate in our group. Conclusion: Imatinib mesylate is the first line therapy in chronic phase of CML but the role in patients with clonal evolution need to be established by larger group of patients.
MMP7 and activation of IGF-1R: A new insight into anti-EGFR therapeutic resistance in metastatic colorectal cancer

Commentary to: Co-expression of matrix metalloproteinase-7 (MMP-7) and phosphorylated insulin growth factor receptor I (pIGF-1R) correlates with poor prognosis in patients with wild-type KRAS treated with cetuximab or panitumumab. A GEMCAD study Carlos Hörndler, Rosa Gallego, Xabier García-Albeniz, Virginia Alonso-Espinaco, Vicente Alonso, Pilar Escudero, Mireya Jimeno, Javier Ortego, Jordi Codony-Servat, Carlos Fernández-Martos, Ana Calatrava, Mercedes Marín-Aguilera, Jenifer Muñoz, Sergi Castellví-Bel, Antoni Castells, Michele Rubini, Pere Gascón and Joan Maurel
B‐1 cells: the lineage question revisited

Summary: The origins and functions of B‐1 cells have sparked a good deal of controversy, largely centered on whether these B cells are developmentally distinct from the principal B cell populations (B‐2) found in peripheral lymphoid organs. However, the prime criteria for assigning B‐1 and B‐2 cells to separate developmental lineages are satisfied by studies published some time ago that 1) identify distinct sources of progenitors for B‐1 and B‐2 cells; 2) show that these progenitors express their inherent commitment developing under the same conditions in co‐transfer recipients; and, 3) have distinctive developmental patterns revealed by analysis of cells at various stages along the B‐cell development pathway. I review these developmental studies here both to clarify the issue and to set the stage for presentation of evidence from more recent studies, which further define the functional differences between B‐1 and B‐2 cells and reveal intriguing complexities in the selective and other mechanisms that control the VH composition of the B‐1 antibody repertoire.
Nondiscrete Functional Pathways and Asymmetric Transitional Zone: A New Concept for AV Nodal Electrophysiology

Dual AV nodal pathway electrophysiology has long been accepted as the basis for AV nodal reentrant tachycardia (AVNRT). 2 -5 More recent data from mapping and ablation studies suggest the following. (1) The fast and slow pathways represent different atrionodal connections rather than a result of longitudinal dissociation within the compact AV node.6 -8 (2) These pathways are functional pathways instead of cable-like structures.9 (3) Multiple AV nodal input pathways likely exist as suggested by the presence of residual AV nodal conduction after ablations of fast and slow pathways.7 (4) No direct relationship exists between dual AV nodal physiology and discontinuous AV nodal curve because a “jump” in AH intervals can be present or absent in patients with or without AVNRT.1 0 ,11 Therefore, the conventional concept of dual AV nodal pathways becomes a controversial hypothesis. In this issue of the Journal, Lin et al.1 2 characterize the electrophysiologic properties of the slow pathway in isolated rabbit heart preparations and directly demonstrated “manifest and concealed slow pathway conduction. ” The  ndings of this study provide objective evidence to support a very importance concept in AV nodal electrophysiology, that is, slow pathway conduction is present in all normal hearts with continuous AV nodal function curves and without AVNRT. Their results also are consistent with two of the previous conclusions that the slow pathway is located outside the compact AV node, as opposed to the original theory of longitudinal dissociation within the AV node, and that the AV nodal posterior extension is involved in slow pathway conduction.1 3 ,14 Using high-resolution optical mapping in isolated perfused canine AV nodal preparations, the reentrant circuits related to three forms of AVNRT were demonstrated recently.1 5 Based on the optical mapping data1 5 ,16 and the concept of concealed slow pathway conduction, it now is clear that functional nondiscrete AV nodal input pathways exist in normal hearts with continuous and discontinuous AV nodal function curves, regardless of the presence or absence of AVNRT. The  nding of the AV nodal posterior extension and its involvement in slow pathway conduction indicates that the AV node and the surrounding transitional zone are asymmetric structures, similar to the AV nodal model proposed by Mazgalev et al.9 The combinations of multiple nondiscrete functional pathways and an asymmetric transitional zone establish the basis for the developments of both slow AV nodal conduction with variable AH intervals and unidirectional block during AVNRT. Fast, Slow, and Intermediate Pathways
Reseña de "Efecto de la integración de aplicaciones agrícolas de biofertilizantes y fertilizantes minerales sobre las relaciones suelo-planta"

El irracional nivel de quimizacion que ha alcanzado la agricultura mundial constituye una de las causas de la elevada contaminacion que sufre el ambiente en todo el planeta, cuyas caracteristicas se describen en el trabajo. Por esta razon, hoy se esta imponiendo el redimensionamiento del empleo de las biotecnologias y, entre ellas, los biofertilizantes, con el objetivo de adaptarlas al desarrollo sustentable de las localidades mas pobres y necesitadas del planeta, y aprovechar los beneficios de su aplicacion para situar a los fertilizantes minerales en su justo lugar. La sustentabilidad agricola incluye los insumos industriales, pero utilizados de forma racional e integrados con elementos biologicos. Para lograr este fin, se requiere de un marco teorico y de supuestos nuevos, que permitan establecer compromisos adaptados a la situacion actual, en la busqueda de mayor productividad y calidad de los productos agricolas. Por otra parte, se analiza la necesidad de integrar los enfoques biologicos e ingenieriles que estan comenzando a desarrollarse en las ciencias agricolas, con los procedentes de las ciencias sociales, tales como la Ecologia Politica, que analiza las relaciones de poder economico y politico en el manejo de los recursos naturales, y el enfoque orientado a los actores para integrarlos a investigaciones interdisciplinarias y a escalas multiples.
PKC alpha phosphorylates cytosolic NF-kappaB/p65 and PKC delta delays nuclear translocation of NF-kappaB/p65 in U1242 glioblastoma cells.

AIM Protein kinase-C (PKC) and NF-kappaB are involved in cell survival, proliferation, migration and radioresistance in glioblastoma multiforme (GBM). We sought to determine the interaction between PKC and NF-kappaB pathways. MATERIAL AND METHODS The activation of NF-kappaB by PKC alpha and PKC delta was assessed by Western blotting after the stimulation with Phorbol 12- Myristate 13-Acetate (PMA). Gene silencing of PKC alpha , PKC delta and NFkappaB/ p65 with siRNA interference was utilized to evaluate their roles in NFkB activation and cell proliferation. RESULTS PMA induced the phosphorylation of NF-kappaB/p65 by PKC alpha. Gene silencing with siRNA against NF-kappaB/p65 inhibited [3H]-thymidine incorporation in U1242 GBM cells. PKC delta decelerated the nuclear translocation of activated NF-kappaB/p65 up to 4 hours after the stimulation. PMA induced death was not observed in PKC delta silenced cells where activated NF-kappaB/p65 was located immediately in the nucleus. CONCLUSION NF-kappaB/p65 is pro-survival and proliferative factor in U1242 GBM cells. PKC alpha is needed to phosphorylate NF-kappaB/p65. PKC delta delays the translocation of active NF-kappaB/p65 into the nucleus. PMA-induced cell death occurred if the phospho-NF-kappaB/p65 was prohibited from entering the nucleus in PKC delta positive cells. Translocation of phosphorylated form of NF-kappaB into the nucleus is critical in GBM cell proliferation.
Factores relevantes en la Intención de prescripción médica en el mercado colombiano

La presente investigacion busca identificar los factores que no han sido empleados tradicionalmente en la industria farmaceutica, que puedan ser determinantes en la intencion de prescripcion de medicamentos por parte del medico en el contexto colombiano. La determinacion de estos factores debe permitir crear un modelo de segmentacion util para generar acciones de marketing en Laboratorios La Sante. Laboratorios La Sante es un grupo farmaceutico de origen colombiano que produce y comercializa medicamentos de marca (Galeno), genericos y de venta libre el cual tiene presencia comercial en 13 paises de America latina.
Stillbirths and rate of neonatal deaths in 76,761 postterm pregnancies in Sweden, 1982‐1991

OBJECTIVE To study stillbirths and neonatal mortality in the postterm period. DESIGN Register study of information obtained from the Swedish Medical Birth Registry (MBR), National Board of Health and Welfare, Stockholm. METHODS Singleton pregnancies with deliveries occurring between 1982 and 1991 were selected involving 914,702 women (of whom 76,761 had a postterm pregnancy continuing beyond the 42nd week of amenorrhea). All 2,043 records of dead infants were scrutinized before analysis of neonatal deaths. Stratification was made for year of birth, maternal age, and parity. RESULTS Generally, the rates of stillbirths and neonatal deaths were low. The stillbirth rate was highest for primiparas at 38 completed weeks (2.72%), lowest at 40 weeks (1.23%), then increasing to 2.26% in the postterm period. The difference vs. multiparas was significant from 41 weeks onwards. Neonatal mortality was increased at 41 completed weeks for primiparas, but for multiparas it changed significantly first in the postterm period. The OR for a primipara to have an intrauterine death increased from 1.50 at 41 weeks (1.0 at 40 weeks) to 1.79 at 42 weeks and beyond. The OR for multiparas showed no sign of increase as gestation progressed. CONCLUSIONS The results of this study indicate an increased risk of stillbirth with gestational age for primiparas but not for multiparas. The neonatal death rate was increased for both primiparas and multiparas (after 42 completed weeks).
Using Time Series Analysis to Predict Cardiac Arrest in a PICU

Objectives: To build and test cardiac arrest prediction models in a PICU, using time series analysis as input, and to measure changes in prediction accuracy attributable to different classes of time series data. Design: Retrospective cohort study. Setting: Thirty-one bed academic PICU that provides care for medical and general surgical (not congenital heart surgery) patients. Subjects: Patients experiencing a cardiac arrest in the PICU and requiring external cardiac massage for at least 2 minutes. Interventions: None. Measurements and Main Results: One hundred three cases of cardiac arrest and 109 control cases were used to prepare a baseline dataset that consisted of 1,025 variables in four data classes: multivariate, raw time series, clinical calculations, and time series trend analysis. We trained 20 arrest prediction models using a matrix of five feature sets (combinations of data classes) with four modeling algorithms: linear regression, decision tree, neural network, and support vector machine. The reference model (multivariate data with regression algorithm) had an accuracy of 78% and 87% area under the receiver operating characteristic curve. The best model (multivariate + trend analysis data with support vector machine algorithm) had an accuracy of 94% and 98% area under the receiver operating characteristic curve. Conclusions: Cardiac arrest predictions based on a traditional model built with multivariate data and a regression algorithm misclassified cases 3.7 times more frequently than predictions that included time series trend analysis and built with a support vector machine algorithm. Although the final model lacks the specificity necessary for clinical application, we have demonstrated how information from time series data can be used to increase the accuracy of clinical prediction models.
Managing Coronary Heart Disease in Chronic Uremia

Cardiovascular complications are a major clinical problem in patients with chronic kidney disease and endstage renal failure; cardiac death accounts for approximately 40–50% of all deaths in these patients. Death from cardiovascular causes is up to 20 times more common in uremic patients than in the general population with the risk being even higher than in patients with diabetes mellitus. A high rate of myocardial infarction and excessive cardiac mortality have repeatedly been documented in patients with kidney disease and renal failure. Not only is the prevalence of myocardial infarction high, but also the case fatality rate is signifi cantly higher in uremic patients with and without diabetes, respectively, compared to nonuremic patients. This is of particular interest since the prevalence of coronary atheroma in uremic patients was shown to be approximately 30% by autopsy and coronary angiography studies. Thus, coronary factors, i.e. atherosclerosis, and non-coronary factors may play an important role in the genesis of cardiac complications in the renal patient. In addition, renal failure recently has also be identifi ed as a predictor of mortality in different stages of peripheral vascular disease. In particular, Published online: March 7, 2006 Prof. Dr. Kerstin Amann Department of Pathology, University of Erlangen-Nürnberg Krankenhausstrasse 8–10, DE–91054 Erlangen (Germany) Tel. +49 9131 852 2291, Fax +49 9131 852 2601 E-Mail kerstin.amann@patho.imed. uni-erlangen.de © 2005 S. Karger AG, Basel 1420–4096/05/0286–0280$22.00/0 Accessible online at:
The changing meaning of disaster

Adverse events such as disasters are interpreted through a system of meaning provided by culture. Historically, research into society's response to disasters provides numerous examples of community resilience in face of adversity. However, since the 1980s, numerous researchers have challenged the previous optimistic accounts and argue that such incidents result in long-term damage to the community. It is claimed that community response to a disaster episode is far more likely to be defined by its vulnerability than its resilience. This new vulnerability paradigm of disaster response is underpinned by the belief that contemporary technologically driven disasters have a peculiarly destructive outcome. This paper explores the changing conceptualisation of adversity. It suggests that the shift from the expectation of resilience to that of vulnerability is best understood as an outcome of a changing cultural conceptualisation of adversity.
The Evaluation of the Logistics Socialization Reform of Local Colleges: Theoretical Model and Practical Analysis

Constructing an objective, scientific back-Local Colleges social reform and the evaluation index system of comprehensive evaluation model, you can objectively and rationally find "short-board" of the logistics community reform, and the "benchmarking" of the reform establishment. At the same time, it can provide a useful theoretical tool for building market-oriented, efficient logistics support system for the new practice of reform. In this paper, Local Colleges of socialization of logistics reform model has been analyzed, we get six factors that affect the logistics socialization reform of the local colleges, those are management system, operation mechanism, the allocation of resources, choice of services, support capacity and monitoring mechanism.
Ensemble regularized linear discriminant analysis classifier for P300-based brain-computer interface

This paper demonstrates a better classification performance of an ensemble classifier using a regularized linear discriminant analysis (LDA) for P300-based brain-computer interface (BCI). The ensemble classifier with an LDA is sensitive to the lack of training data because covariance matrices are estimated imprecisely. One of the solution against the lack of training data is to employ a regularized LDA. Thus we employed the regularized LDA for the ensemble classifier of the P300-based BCI. The principal component analysis (PCA) was used for the dimension reduction. As a result, an ensemble regularized LDA classifier showed significantly better classification performance than an ensemble un-regularized LDA classifier. Therefore the proposed ensemble regularized LDA classifier is robust against the lack of training data.
Liquefaction, saccharification, and fermentation of ammoniated corn to ethanol

Treatment of whole corn kernels with anhydrous ammonia gas has been proposed as a way to facilitate the separation of nonfermentable coproducts before fermentation of the starch to ethanol, but the fermentability of ammoniated corn has not been thoroughly investigated. Also, it is intended that the added ammonia nitrogen in ammonia treated corn (∼1 g per kg corn) may satisfy the yeast nutritional requirement for free amino nitrogen (FAN). In this study, procedures for ammoniation, liquefaction, saccharification, and fermentation at two scales (12‐L and 50‐mL) were used to determine the fermentation rate, final ethanol concentration, and ethanol yield from starch in ammoniated or nonammoniated corn. The maximum achievable ethanol concentration at 50 h fermentation time was lower with ammoniated corn than with nonammoniated corn. The extra nitrogen in ammoniated corn satisfied some of the yeast requirements for FAN, thereby reducing the requirement for corn steep liquor. Based upon these results, ammoniation of corn does not appear to have a positive impact on the fermentability of corn to ethanol. Ammoniation may still be cost effective, if the advantages in terms of improved separations outweigh the disadvantages in terms of decreased fermentability.