RESUMO
PURPOSE: The cure rate in Hodgkin lymphoma is high, but the response along with treatment is still unpredictable and highly variable among patients. Detecting those patients who do not respond to treatment at early stages could bring improvements in their treatment. This research tries to identify the main biological prognostic variables currently gathered at diagnosis and design a simple machine learning methodology to help physicians improve the treatment response assessment. METHODS: We carried out a retrospective analysis of the response to treatment of a cohort of 263 Caucasians who were diagnosed with Hodgkin lymphoma in Asturias (Spain). For that purpose, we used a list of 35 clinical and biological variables that are currently measured at diagnosis before any treatment begins. To establish the list of most discriminatory prognostic variables for treatment response, we designed a machine learning approach based on two different feature selection methods (Fisher's ratio and maximum percentile distance) and backwards recursive feature elimination using a nearest-neighbor classifier (k-NN). The weights of the k-NN classifier were optimized using different terms of the confusion matrix (true- and false-positive rates) to minimize risk in the decisions. RESULTS AND CONCLUSIONS: We found that the optimum strategy to predict treatment response in Hodgkin lymphoma consists in solving two different binary classification problems, discriminating first if the patient is in progressive disease; if not, then discerning among complete and partial remission. Serum ferritin turned to be the most discriminatory variable in predicting treatment response, followed by alanine aminotransferase and alkaline phosphatase. The importance of these prognostic variables suggests a close relationship between inflammation, iron overload, liver damage and the extension of the disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Inflamação/epidemiologia , Sobrecarga de Ferro/epidemiologia , Hepatopatias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bleomicina/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Doença de Hodgkin/patologia , Humanos , Incidência , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Vimblastina/uso terapêuticoRESUMO
Desde su aparición en 1825, la curva sigmoidea propuesta por Benjamin Gompertz ha sido aplicada en diferentes campos. En ciencias animales se usa frecuentemente para describir el crecimiento de los individuos. En el presente trabajo se muestra un análisis matemático de la función y la construcción de algunos de los parámetros que se obtienen de la misma.
Since its appearing in 1825, the sigmoideal curve proposed by Benjamin Gompertz has been applied in different fields. In animal sciences it is frequently used to describe the individual´s growth. The present work shows a mathematical analysis of the function and the construction of some of the parameters obtained from it.
Assuntos
Animais , Animais , CrescimentoRESUMO
The Notch signaling pathway is an evolutionary conserved mechanism that plays an important role in cell-cell communication and cell fate in a wide range of tissues. The mammalian family of Notch receptors consists of 4 members: Notch1/2/3/4. The Notch ligand family consists of 5 members: Delta1/3/4 and Jagged1/2. Math1 encodes a murine Basic helix-loop-helix (bHLH) transcription factor that acts as positive regulator of cell differentiation. Recently, links between Notch and Math1 pathways were demonstrated in various tissues. Expression of Notch1, Jagged2 and Math1 were analyzed in the mouse molar tooth germ during embryonic stage (E) 13 and E15 and during postnatal stage (PN) 1, PN3, PN5, PN10 and PN14 by using in situ hybridization. Positive Notch1 expression was found at the tooth bud during embryonic stages, but its expression was absent from the basal cells in contact with the dental mesenchyme. Jagged2 and Math1 were strongly expressed in differentiated ameloblasts and odontoblasts and Math1 strong expression was even maintained until PN14 stage. Math1 showed the strongest expression. Our results suggest that the Notch1 signaling pathway through Jagged2 could be importantly related to Math1, directing the process of odontogenesis toward cell differentiation.(AU)
Assuntos
Animais , Ratos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Transdução de Sinais/fisiologia , Germe de Dente/citologia , Germe de Dente/fisiologia , Camundongos Endogâmicos BALB C , Dente Molar/anatomia & histologia , Dente Molar/fisiologia , Odontogênese/fisiologia , Receptor Notch1/genética , Receptor Notch1/metabolismoRESUMO
The Notch signaling pathway is an evolutionary conserved mechanism that plays an important role in cell-cell communication and cell fate in a wide range of tissues. The mammalian family of Notch receptors consists of 4 members: Notch1/2/3/4. The Notch ligand family consists of 5 members: Delta1/3/4 and Jagged1/2. Math1 encodes a murine Basic helix-loop-helix (bHLH) transcription factor that acts as positive regulator of cell differentiation. Recently, links between Notch and Math1 pathways were demonstrated in various tissues. Expression of Notch1, Jagged2 and Math1 were analyzed in the mouse molar tooth germ during embryonic stage (E) 13 and E15 and during postnatal stage (PN) 1, PN3, PN5, PN10 and PN14 by using in situ hybridization. Positive Notch1 expression was found at the tooth bud during embryonic stages, but its expression was absent from the basal cells in contact with the dental mesenchyme. Jagged2 and Math1 were strongly expressed in differentiated ameloblasts and odontoblasts and Math1 strong expression was even maintained until PN14 stage. Math1 showed the strongest expression. Our results suggest that the Notch1 signaling pathway through Jagged2 could be importantly related to Math1, directing the process of odontogenesis toward cell differentiation.
Assuntos
Animais , Ratos , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Regulação da Expressão Gênica no Desenvolvimento , Germe de Dente/citologia , Germe de Dente/fisiologia , Camundongos Endogâmicos BALB C , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Transdução de Sinais/fisiologia , Dente Molar/anatomia & histologia , Dente Molar/fisiologia , Odontogênese/fisiologia , Receptor Notch1/genética , Receptor Notch1/metabolismoRESUMO
In the present work, protein bands from in vitro embriogenic callus (Citrus sinensis L. Osbeck) were investigated using micro-synchrotron radiation X-ray fluorescence (muSR-XRF) after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separation. Metal-binding protein quantification was done after microwave oven decomposition of gel by synchrotron radiation total reflection X-ray fluorescence (SR-TXRF), flame atomic absorption spectrometry (FAAS) and flame atomic emission spectrometry (FAES). According to the analysis of the protein bands, it is possible to observe that both 81 and ca. 14 kDa proteins present different Fe signal intensity at different positions. The analysis of 53 kDa protein, showed even more interesting results. Besides Fe, the muSR-XRF experiments indicate the presence of Ca, Cu, K and Zn. Chemical elements such as Cu, K, Fe and Zn were determined by SR-TXRF, Mg by FAAS and Na by FAES. Ca was determined by SR-TXRF and FAAS only for accuracy check. In the mineralised protein bands of 81 and around 14 kDa band, only Fe was determined (105 and 21.8 microg g(-1)). For those protein bands (86-ca. 14 kDa) were determined, Ca, K, Cu and Zn in a wide concentration range (42.4-283, 2.47-96.8, 0.91-15.9 and 3.39-29.7 microg g(-1), respectively).
Assuntos
Biofísica/métodos , Metais/química , Espectrofotometria Atômica/métodos , Síncrotrons , Cálcio/análise , Citrus/metabolismo , Cobre/análise , Eletroforese em Gel de Poliacrilamida , Peso Molecular , Potássio/análise , Ligação Proteica , Proteínas/química , Sódio/análise , Espectrometria de Fluorescência , Temperatura , Raios X , Zinco/análiseRESUMO
The behaviour of bacterial meningitis with identified agent in the City of Havana in 1998. The implementation of Geographic Information System Mapinfo 4.1 made it possible to know the spatial distribution of the sick people. As a result, we found an area of circulation of Neisseria meningitidis located to the northeast center; an area of prevalence of Streptococcus pneumoniae to the north and northeast of the city and zones located to the center, east and south where Haemophlus influenzae prevailed. These areas were related to the main sources of environmental pollution in the province. THe importance of the spatial analysis for expanding the knowledge for an epidemiological study was evidenced.
Assuntos
Meningites Bacterianas/epidemiologia , Cuba/epidemiologia , Humanos , Saúde da População UrbanaRESUMO
The incidence of invasive meningococcal disease (IMD) before (1984-1988) and after (1989-1994), a nationwide intervention with VA-MENGOC-BC vaccination started in 1989, was compared. The prevaccination period incidence density (ID> 8.8/10(5) year-person) was higher than the postvaccination ID (ID< 6.5/10(5) year-person). The percentage proportional differences from the start to the end of each period of ID in the vaccinal period was higher (87%) than the prevaccinal (37%) with significant differences among vaccinated groups (< 25 years old). A break-point (Chow test) was confirmed by the decrease in the ID between 1989 and 1990 in children under 1 year old, 5-9, 10-14, 15-19 and 50-54 years. Comparison of ID using maps showed a decrease in IMD in all municipalities during the postvaccination period. These findings support the epidemiological impact of VA-MENGOC-BC vaccination in the reduction of IMD morbidity.