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1.
Immunol Res ; 72(1): 128-133, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37676628

RESUMO

ANCA-associated vasculitis (AAV) comprises a group of necrotizing vasculitis that mainly affects small- and medium-sized vessels. Serum anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (anti-MPO) and anti-proteinase 3 (anti-PR3), levels may correlate to severity, prognosis, and recurrence of the disease. A retrospective analysis of 101 patients with MPO-positive and 54 PR3-positive vasculitis was performed, using laboratory established cut-off value, measured by chemiluminescence. Furthermore, data of renal disease and pulmonary involvement were collected at vasculitis diagnosis, as well as the progress, requiring dialysis, transplant, or mortality. For anti-MPO antibodies with a diagnosis of vasculitis (n = 77), an area under the curve (AUC) was calculated (AUC = 0.8084), and a cut-off point of 41.5 IU/ml was determined. There were significant differences in anti-MPO levels between patients with renal or pulmonary dysfunction (n = 65) versus those without them (n = 36) (p = 0.0003), and a cut-off threshold of 60 IU/ml was established. For anti-PR3 antibodies with a diagnosis of vasculitis (n = 44), an area under the curve (AUC) was calculated (AUC = 0.7318), and a cut-off point of 20.5 IU/ml was determined. Significant differences in anti-PR3 levels were observed between those patients with renal or pulmonary dysfunction (n = 30) and those without them (n = 24) (p = 0.0048), and a cut-off threshold of 41.5 IU/ml was established. No significant differences between those patients who had a worse disease progression and those who did not were found for anti-MPO and anti-PR3. Anti-MPO and anti-PR3 levels at the moment of vasculitis diagnosis are related with disease severity but not with disease outcome or vasculitis recurrence.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Humanos , Anticorpos Anticitoplasma de Neutrófilos , Estudos Retrospectivos , Luminescência , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Mieloblastina , Peroxidase
2.
Carbohydr Res ; 516: 108557, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35461048

RESUMO

Convergent synthetic routes to PI-88 tetra- and pentasaccharide-component analogues, have been developed featuring regioselective glycosylations of mannose-polyol n-pentenyl glycosides (NPG) acceptors with 1,2-methyl orthoesters (MeOE) glycosyl donors.


Assuntos
Antineoplásicos , Oligossacarídeos , Glicosídeos , Manose
3.
Cells ; 10(12)2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34943945

RESUMO

Chronic lung diseases (CLDs) represent a set of disorders characterized by the progressive loss of proper lung function. Among severe CLDs, the incidence of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) has grown over the last decades, mainly in the elderly population. Several studies have highlighted an increased expression of senescence-related markers in the resident progenitor cells in COPD and IPF, possibly undermining epithelial integrity and contributing to the progression and the aggravation of both diseases. Recently, the chronic activation of the canonical Wnt/ß-catenin pathway was shown to induce cellular senescence. Here, we investigated the localization and the expression of leucin-rich repeat-containing G-protein-coupled receptor 6 (LGR6), a protein that activates and potentiates the canonical Wnt signalling. Through immunohistochemical analyses, we identified a lesion-associated rise in LGR6 levels in abnormal lung epithelial progenitors in COPD and IPF when compared to histologically normal tissues. Moreover, in areas of aberrant regeneration, chronic damage and fibrosis, LGR6-expressing epithelial progenitors displayed a major increase in the expression of senescence-associated markers. Our study suggests the involvement of LGR6 in the chronic activation of the Wnt/ß-catenin pathway, mediating the impairment and exhaustion of epithelial progenitors in COPD and IPF.


Assuntos
Senescência Celular/genética , Fibrose Pulmonar Idiopática/genética , Doença Pulmonar Obstrutiva Crônica/genética , Receptores Acoplados a Proteínas G/genética , Adulto , Idoso , Linhagem Celular , Células Epiteliais/metabolismo , Feminino , Regulação da Expressão Gênica/genética , Humanos , Fibrose Pulmonar Idiopática/patologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/patologia , Células-Tronco/metabolismo , Proteínas Wnt/genética , Via de Sinalização Wnt/genética
4.
Front Oncol ; 11: 705384, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367990

RESUMO

Triple-Negative Breast Cancer (TNBC) is the most aggressive breast cancer subtype, characterized by limited treatment options and higher relapse rates than hormone-receptor-positive breast cancers. Chemotherapy remains the mainstay treatment for TNBC, and platinum salts have been explored as a therapeutic alternative in neo-adjuvant and metastatic settings. However, primary and acquired resistance to chemotherapy in general and platinum-based regimens specifically strongly hampers TNBC management. In this study, we used carboplatin-resistant in vivo patient-derived xenograft and isogenic TNBC cell-line models and detected enhanced Wnt/ß-catenin activity correlating with an induced expression of stem cell markers in both resistant models. In accordance, the activation of canonical Wnt signaling in parental TNBC cell lines increases stem cell markers' expression, formation of tumorspheres and promotes carboplatin resistance. Finally, we prove that Wnt signaling inhibition resensitizes resistant models to carboplatin both in vitro and in vivo, suggesting the synergistic use of Wnt inhibitors and carboplatin as a therapeutic option in TNBC. Here we provide evidence for a prominent role of Wnt signaling in mediating resistance to carboplatin, and we establish that combinatorial targeting of Wnt signaling overcomes carboplatin resistance enhancing chemotherapeutic drug efficacy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34444579

RESUMO

Breastfeeding mothers were excluded from the clinical trials conducted for vaccines against SARS-CoV-2. Since the start of the vaccination, some doubts have arisen regarding its compatibility with breastfeeding. The aim of this study was to analyse the presence of anti-SARS-CoV-2 antibodies in breast milk and serum (IgG and IgA) of vaccinated breastfeeding women. The main variables of the observational study were: adverse related events after vaccination and determination of the presence of IgG and IgA isotypes antibodies in serum and in breast milk of vaccinated women against the SARS-CoV-2 antigens. Results: 110 breastfeeding mothers were included; 70 women (63.6%) were vaccinated with two doses of BNT162b2, 20 women (18.2%) with two doses of mRNA-1273, and 20 women (18.2%) with a single dose of ChAdOx1-S. Regarding adverse reactions and vaccine safety, 38 women had no adverse reactions; 20 (18.2%) had general malaise or adenopathies; 10 (9.1%) had a headache; and 7 (6.4%) had fever. When analysing IgG antibodies, significantly higher levels of antibodies were found in serum and breast milk from mothers vaccinated with BNT162b2 or mRNA-1273 vs. ChAdOx1-S (p < 0.001 and p = 0.001, respectively). Analysing IgA antibodies, significant differences were found when comparing mean values in serum from mothers vaccinated with BNT162b2 or mRNA-1273 vs. ChAdOx1-S (0.12, 0.16, and 0.02, respectively; p < 0.001) and breast milk of mothers vaccinated when comparing BNT16b2 vs. ChAdOx1-S. All vaccinated breastfeeding mothers had serum anti-S1 IgG antibodies in response to vaccination against SARS-CoV-2, regardless of the commercial vaccine administered. Conclusions: the anti-SARS-CoV-2 vaccines were well tolerated by the mothers and the breastfed infant. In addition, breastfeeding mothers offer their infants IgA and IgG isotype antibodies directed against SARS-CoV-2 protein S in breast milk.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vacina BNT162 , Aleitamento Materno , Estudos Transversais , Feminino , Humanos , Imunoglobulina A , Imunoglobulina G , Leite Humano , SARS-CoV-2 , Espanha
6.
Cancer Lett ; 520: 57-67, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34216687

RESUMO

KRAS-mutant lung adenocarcinomas represent the largest molecular subgroup of non-small cell lung cancers (NSCLC) and are notorious for their dismal survival perspectives. To gain more insights in etiology and therapeutic response, we focused on the tumor suppressor Protein Phosphatase 2A (PP2A) as a player in KRAS oncogenic signaling. We report that the PP2A activator PTPA (encoded by PPP2R4) is commonly affected in NSCLC by heterozygous loss and low-frequent loss-of-function mutation, and this is specifically associated with poorer overall survival of KRAS-mutant lung adenocarcinoma patients. Reduced or mutant PPP2R4 expression in A549 cells increased anchorage-independent growth in vitro and xenograft growth in vivo, correlating with increased Ki67 and c-MYC expression. Moreover, KrasG12D-induced lung tumorigenesis was significantly accelerated in Ppp2r4 gene trapped mice as compared to Ppp2r4 wild-type. A confined kinase inhibitor screen revealed that PPP2R4-depletion induced resistance against selumetinib (MEK inhibitor), but unexpectedly sensitized cells for temsirolimus (mTOR inhibitor), in vitro and in vivo. Our findings underscore a clinically relevant role for PTPA loss-of-function in KRAS-mutant NSCLC etiology and kinase inhibitor response.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Fosfoproteínas Fosfatases/genética , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Células A549 , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Animais , Benzimidazóis/farmacologia , Linhagem Celular Tumoral , Humanos , Antígeno Ki-67/genética , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Proteína Fosfatase 2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Sirolimo/análogos & derivados , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/genética , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Molecules ; 26(10)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34068920

RESUMO

A convergent synthetic route to a tetrasaccharide related to PI-88, which allows the incorporation of a fluorescent BODIPY-label at the reducing-end, has been developed. The strategy, which features the use of 1,2-methyl orthoesters (MeOEs) as glycosyl donors, illustrates the usefulness of suitably-designed BODIPY dyes as glycosyl labels in synthetic strategies towards fluorescently-tagged oligosaccharides.


Assuntos
Antineoplásicos/farmacologia , Compostos de Boro/química , Oligossacarídeos/síntese química , Coloração e Rotulagem , Antineoplásicos/química , Glicosilação , Oligossacarídeos/química , Oligossacarídeos/farmacologia , Espectrometria de Fluorescência , Estereoisomerismo
8.
Artif Intell Med ; 117: 102096, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34127235

RESUMO

BACKGROUND: Internet provides different tools for communicating with patients, such as social media (e.g., Twitter) and email platforms. These platforms provided new data sources to shed lights on patient experiences with health care and improve our understanding of patient-provider communication. Several existing topic modeling and document clustering methods have been adapted to analyze these new free-text data automatically. However, both tweets and emails are often composed of short texts; and existing topic modeling and clustering approaches have suboptimal performance on these short texts. Moreover, research over health-related short texts using these methods has become difficult to reproduce and benchmark, partially due to the absence of a detailed comparison of state-of-the-art topic modeling and clustering methods on these short texts. METHODS: We trained eight state-of- the-art topic modeling and clustering algorithms on short texts from two health-related datasets (tweets and emails): Latent Semantic Indexing (LSI), Latent Dirichlet Allocation (LDA), LDA with Gibbs Sampling (GibbsLDA), Online LDA, Biterm Model (BTM), Online Twitter LDA, and Gibbs Sampling for Dirichlet Multinomial Mixture (GSDMM), as well as the k-means clustering algorithm with two different feature representations: TF-IDF and Doc2Vec. We used cluster validity indices to evaluate the performance of topic modeling and clustering: two internal indices (i.e. assessing the goodness of a clustering structure without external information) and five external indices (i.e. comparing the results of a cluster analysis to an externally known provided class labels). RESULTS: In overall, for number of clusters (k) from 2 to 50, Online Twitter LDA and GSDMM achieved the best performance in terms of internal indices, while LSI and k-means with TF-IDF had the highest external indices. Also, of all tweets (N = 286, 971; HPV represents 94.6% of tweets and lynch syndrome represents 5.4%), for k = 2, most of the methods could respect this initial clustering distribution. However, we found model performance varies with the source of data and hyper-parameters such as the number of topics and the number of iterations used to train the models. We also conducted an error analysis using the Hamming loss metric, for which the poorest value was obtained by GSDMM on both datasets. CONCLUSIONS: Researchers hoping to group or classify health related short-text data can expect to select the most suitable topic modeling and clustering methods for their specific research questions. Therefore, we presented a comparison of the most common used topic modeling and clustering algorithms over two health-related, short-text datasets using both internal and external clustering validation indices. Internal indices suggested Online Twitter LDA and GSDMM as the best, while external indices suggested LSI and k-means with TF-IDF as the best. In summary, our work suggested researchers can improve their analysis of model performance by using a variety of metrics, since there is not a single best metric.


Assuntos
Correio Eletrônico , Mídias Sociais , Análise por Conglomerados , Comunicação , Humanos , Aprendizado de Máquina
9.
Clin Cancer Res ; 27(5): 1491-1504, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33262138

RESUMO

PURPOSE: Recurrent and/or metastatic unresectable cutaneous squamous cell carcinomas (cSCCs) are treated with chemotherapy or radiotherapy, but have poor clinical responses. A limited response (up to 45% of cases) to EGFR-targeted therapies was observed in clinical trials with patients with advanced and metastatic cSCC. Here, we analyze the molecular traits underlying the response to EGFR inhibitors, and the mechanisms responsible for cSCC resistance to EGFR-targeted therapy. EXPERIMENTAL DESIGN: We generated primary cell cultures and patient cSCC-derived xenografts (cSCC-PDXs) that recapitulate the histopathologic and molecular features of patient tumors. Response to gefitinib treatment was tested and gefitinib-resistant (GefR) cSCC-PDXs were developed. RNA sequence analysis was performed in matched untreated and GefR cSCC-PDXs to determine the mechanisms driving gefitinib resistance. RESULTS: cSCCs conserving epithelial traits exhibited strong activation of EGFR signaling, which promoted tumor cell proliferation, in contrast to mesenchymal-like cSCCs. Gefitinib treatment strongly blocked epithelial-like cSCC-PDX growth in the absence of EGFR and RAS mutations, whereas tumors carrying the E545K PIK3CA-activating mutation were resistant to treatment. A subset of initially responding tumors acquired resistance after long-term treatment, which was induced by the bypass from EGFR to FGFR signaling to allow tumor cell proliferation and survival upon gefitinib treatment. Pharmacologic inhibition of FGFR signaling overcame resistance to EGFR inhibitor, even in PIK3CA-mutated tumors. CONCLUSIONS: EGFR-targeted therapy may be appropriate for treating many epithelial-like cSCCs without PIK3CA-activating mutations. Combined EGFR- and FGFR-targeted therapy may be used to treat cSCCs that show intrinsic or acquired resistance to EGFR inhibitors.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Gefitinibe/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Animais , Apoptose , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proliferação de Células , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Mutação , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , Inibidores de Proteínas Quinases/farmacologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
10.
J Alzheimers Dis ; 79(2): 863-874, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33361588

RESUMO

BACKGROUND: Major surgery has been associated with perioperative neurocognitive disorders (PND), but the contributing factors and long-term prognosis are uncertain. We hypothesize that preclinical Alzheimer's disease (AD) might predispose to cognitive deterioration after surgery. OBJECTIVE: To analyze the effect of amyloid-ß on the cognitive trajectory after orthopedic surgery in a sample of non-demented subjects. METHODS: Non-demented individuals older than 65 years that were on the waiting list for orthopedic surgery with spinal anesthesia underwent a neuropsychological assessment before and after surgery. During surgery, cerebrospinal fluid samples were obtained to determine AD biomarkers. RESULTS: Cumulative incidence of PND was 55.2%during a mean follow-up of nine months. The most affected cognitive domains were executive function and constructional praxis. The presence of abnormal levels of amyloid-ß was associated to a postoperative impairment in verbal and visual memory tests. According to their AD biomarker profile, participants were categorized as either Amyloid Positive (A+) or Amyloid Negative (A-). The incidence of PND did not differ between both groups. The A- group showed a tendency similar to the global sample, worsening in executive function tests and improving on memory scales due to practice effects. In contrast, the A + group showed a notable worsening on memory performance. CONCLUSION: Our findings support the hypothesis that surgery may promote or accelerate memory decline in cognitively asymptomatic subjects with brain amyloid-ß deposits.


Assuntos
Transtornos da Memória/etiologia , Procedimentos Ortopédicos/efeitos adversos , Placa Amiloide/complicações , Idoso , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/metabolismo , Encéfalo/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Placa Amiloide/patologia
11.
Radiother Oncol ; 157: 63-69, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33217499

RESUMO

PURPOSE: To introduce a contouring guideline for the taste bud bearing tongue mucosa for head and neck cancer patients receiving radiotherapy. METHODS AND MATERIALS: CT simulation images of oropharyngeal cancer patients were used to delineate both the whole tongue (extrinsic/intrinsic tongue muscles, floor of mouth) and the taste bud bearing tongue mucosa (method A: adaptation of the whole tongue structure; method B: axial adaptation of a mid-sagittal contour). Volumetric and dosimetric parameters of the whole tongue and the two methods of mucosal delineation, spatial overlap between methods A and B, and inter-observer variability for method B were calculated. RESULTS: The study cohort was comprised of 70 patients with T1-4 N0-1 tonsillar (83%) and base of tongue (17%) cancers. Most of the comparative parameters between the whole tongue and mucosa (method A) significantly differed (mean, minimum, and maximum dose, V5-V70, D40-D90). The mean dose calculated for the whole tongue deviated on average 3.77 Gy compared to method A. No significant differences were found between methods A and B of the taste bud bearing tongue mucosa structure, and none of the dosimetric parameters differed more than 1.03 Gy on average. The mean Dice similarity coefficient for both mucosal structures was 0.79 ± 0.05, and 0.63 ± 0.12 for the inter-observer analysis of method B. CONCLUSIONS: We defined two methods for delineating the taste bud bearing mucosa and both are equally satisfactory procedures. Either method is preferable over delineation of the whole tongue as organ at risk for taste impairment.


Assuntos
Neoplasias de Cabeça e Pescoço , Papilas Gustativas , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Mucosa Bucal , Variações Dependentes do Observador , Língua
13.
Int J Mol Sci ; 21(3)2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31991734

RESUMO

Antibody-mediated rejection (AbMR) is one of the leading causes of graft loss in kidney transplantation and B cells play an important role in the development of it. A B-cell activating factor (BAFF) is a cytokine involved in B cell ontogeny. Here, we analyzed whether B cell maturation and the effect of B cell soluble factors, such as BAFF could be involved in AbMR. Serum BAFF levels and B and T cell subpopulations were analyzed 109 kidney transplant patients before transplantation and at 6 and 12 months after kidney transplantation. Pretransplant serum BAFF levels as well as memory B cell subpopulations were significantly higher in those patients who suffered clinical AbMR during the first 12 months after kidney transplantation. Similar results were observed in the prospective analysis of patients with subclinical antibody-mediated rejection detected in the surveillance biopsy performed at 12 months after kidney transplantation. A multivariate analysis confirmed the independent role of BAFF in the development of AbMR, irrespective of other classical variables. Pretransplant serum BAFF levels could be an important non-invasive biomarker for the prediction of the development of AbMR and posttransplant increased serum BAFF levels contribute to AbMR.


Assuntos
Citotoxicidade Celular Dependente de Anticorpos/imunologia , Fator Ativador de Células B/sangue , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Memória Imunológica , Ativação Linfocitária/imunologia , Biomarcadores , Feminino , Humanos , Transplante de Rim/efeitos adversos , Masculino , Período Perioperatório , Modelos de Riscos Proporcionais , Linfócitos T/imunologia , Linfócitos T/metabolismo
14.
Hematol Oncol Clin North Am ; 34(1): 293-306, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31739950

RESUMO

Imaging in radiation oncology is essential for the evaluation of treatment response in tumors and organs at risk. This influences further treatment decisions and could possibly be used to adapt therapy. This review article focuses on the currently used imaging modalities for response assessment in radiation oncology and gives an overview of new and promising techniques within this field.


Assuntos
Imageamento por Ressonância Magnética , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Humanos , Radioterapia (Especialidade)
15.
J Lung Health Dis ; 3(1): 12-15, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31236545

RESUMO

Lung cancer is the leading cause of cancer-related deaths worldwide with poor prognosis, mainly due to the delay in the diagnosis. Adenocarcinoma, a subtype of non-small cell lung cancer, has the highest incidence and significant recurrence rates. Experimental and clinical researches suggested that the presence of cancer stem cells could support the development, malignization and resistance of lung cancer. Unfortunately, our knowledge in the field is still limited. Here we report our findings regarding a cell population expressing LGR6, an epithelial stem cell marker. Under the pressure of a fine regulated p38α MAPK/mir-17-92 axis, LGR6+ stem cells produce differentiated bronchioalveolar cells, in the normal lung. LGR6 is enriched in tumour cells during adenocarcinoma progression. Similar to normal stem cells, LGR6+ cancer cells show self-renewal and differentiation capacities, alongside with a higher oncogenic potential. Our studies suggest a disruption in the p38α MAPK/mir-17-92 network, that enhances Wnt pathway activity, could be responsible for the selection of malignant LGR6+ tumour cells. These results support the existence of a cell population with stem-like characteristics and strong oncogenic potential. This population could be useful for predictive diagnosis and a novel target for improved and more effective therapies against metastases and recurrences of lung adenocarcinomas.

16.
BMC Med Inform Decis Mak ; 18(Suppl 2): 55, 2018 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-30066655

RESUMO

BACKGROUND: There is strong scientific evidence linking obesity and overweight to the risk of various cancers and to cancer survivorship. Nevertheless, the existing online information about the relationship between obesity and cancer is poorly organized, not evidenced-based, of poor quality, and confusing to health information consumers. A formal knowledge representation such as a Semantic Web knowledge base (KB) can help better organize and deliver quality health information. We previously presented the OC-2-KB (Obesity and Cancer to Knowledge Base), a software pipeline that can automatically build an obesity and cancer KB from scientific literature. In this work, we investigated crowdsourcing strategies to increase the number of ground truth annotations and improve the quality of the KB. METHODS: We developed a new release of the OC-2-KB system addressing key challenges in automatic KB construction. OC-2-KB automatically extracts semantic triples in the form of subject-predicate-object expressions from PubMed abstracts related to the obesity and cancer literature. The accuracy of the facts extracted from scientific literature heavily relies on both the quantity and quality of the available ground truth triples. Thus, we incorporated a crowdsourcing process to improve the quality of the KB. RESULTS: We conducted two rounds of crowdsourcing experiments using a new corpus with 82 obesity and cancer-related PubMed abstracts. We demonstrated that crowdsourcing is indeed a low-cost mechanism to collect labeled data from non-expert laypeople. Even though individual layperson might not offer reliable answers, the collective wisdom of the crowd is comparable to expert opinions. We also retrained the relation detection machine learning models in OC-2-KB using the crowd annotated data and evaluated the content of the curated KB with a set of competency questions. Our evaluation showed improved performance of the underlying relation detection model in comparison to the baseline OC-2-KB. CONCLUSIONS: We presented a new version of OC-2-KB, a system that automatically builds an evidence-based obesity and cancer KB from scientific literature. Our KB construction framework integrated automatic information extraction with crowdsourcing techniques to verify the extracted knowledge. Our ultimate goal is a paradigm shift in how the general public access, read, digest, and use online health information.


Assuntos
Crowdsourcing , Bases de Conhecimento , Neoplasias , Obesidade , Curadoria de Dados , Medicina Baseada em Evidências , Humanos , Armazenamento e Recuperação da Informação , Aprendizado de Máquina , PubMed , Semântica , Software
17.
J Neuroinflammation ; 15(1): 63, 2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-29490673

RESUMO

BACKGROUND: Low-grade inflammation has been repeatedly associated with both excess weight and psychosis. However, no previous studies have addressed the direct effect of body mass index (BMI) on basal serum cytokines in individuals with first-episode psychosis (FEP). OBJECTIVES: The aim of this study is to analyze the effect of BMI on basal serum cytokine levels in FEP patients and control subjects, separating the total sample into two groups: normal-weight and overweight individuals. METHODS: This is a prospective and open-label study. We selected 75 FEP patients and 75 healthy controls with similar characteristics to patients according to the following variables: sex, age, and cannabis and tobacco consumption. Both controls and patients were separated into two groups according to their BMI: subjects with a BMI under 25 were considered as normal weight and those with a BMI equal to or more than 25 were considered as overweight. Serum levels of 21 cytokines/chemokines were measured at baseline using the Human High Sensitivity T Cell Magnetic Bead Panel protocol from the Milliplex® Map Kit. We compared the basal serum levels of the 21 cytokines between control and patient groups according to their BMI. RESULTS: In the normal-weight group, IL-8 was the only cytokine that was higher in patients than in the control group (p = 0.001), whereas in the overweight group, serum levels of two pro-inflammatory cytokines (IL-6, p = 0.000; IL-1ß, p = 0.003), two chemokines (IL-8, p = 0.001; MIP-1ß, p = 0.001), four Th-1 and Th-2 cytokines (IL-13, p = 0.009; IL-2, p = 0.001; IL-7, p = 0.001; IL-12p70, p = 0.010), and one Type-3 cytokine (IL-23, p = 0.010) were higher in patients than in controls. CONCLUSIONS: Most differences in the basal serum cytokine levels between patients and healthy volunteers were found in the overweight group. These findings suggest that excess weight can alter the homeostasis of the immune system and therefore may have an additive pro-inflammatory effect on the one produced by psychosis in the central nervous system.


Assuntos
Índice de Massa Corporal , Citocinas/sangue , Sobrepeso/sangue , Transtornos Psicóticos/sangue , Aumento de Peso/fisiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Sobrepeso/diagnóstico , Sobrepeso/epidemiologia , Estudos Prospectivos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Adulto Jovem
18.
Cell Death Dis ; 8(11): e3164, 2017 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-29095436

RESUMO

Hepatic progenitor cells (HPCs) are small cells with a relative large oval nucleus and a scanty cytoplasm situated in the canals of Hering that express markers of (immature) hepatocytes and cholangiocytes. HPCs are present in large numbers in alcoholic steatohepatitis (ASH), one of the leading causes of chronic liver disease. To date, the mechanisms responsible for proliferation and differentiation of human HPCs are still poorly understood and the role of HPCs in ASH development is unknown. In this study, we aimed to characterise human HPCs and their interactions with other cells through comparison, on both protein and RNA level, of HPC-enriched cell populations from adult human liver tissue using different isolation methods. Fresh human liver tissue was collected from ASH explant livers and HPC-enriched cell populations were obtained via four different isolation methods: side population (SP), epithelial cell adhesion molecule (EpCAM) and trophoblast antigen 2 (TROP-2) membrane marker isolation and laser capture microdissection. Gene expression profiles of fluorescent-activated cell-sorted HPCs, whole liver extracts and laser microdissected HPC niches were determined by RNA-sequencing. Immunohistochemical evaluation of the isolated populations indicated the enrichment of HPCs in the SP, EpCAM+ and TROP-2+ cell populations. Pathway analysis of the transcription profiles of human HPCs showed an enrichment and activation of known HPC pathways like Wnt/ß-catenin, TWEAK and HGF. Integration of the HPC niche profile suggests autocrine signalling by HPCs (TNFα, PDGFB and VEGFA) as well as paracrine signalling from the surrounding niche cells including MIF and IGF-1. In addition, we identified IL-17 A signalling as a potentially novel pathway in HPC biology. In conclusion, we provide the first RNA-seq-based, comparative transcriptome analysis of isolated human HPCs from ASH patients and revealed active signalling between HPCs and their surrounding niche cells in ASH livers and suggest that HPCs can actively contribute to liver inflammation.


Assuntos
Fígado Gorduroso Alcoólico/patologia , Células-Tronco/metabolismo , Antígenos de Neoplasias/metabolismo , Comunicação Autócrina , Moléculas de Adesão Celular/metabolismo , Técnicas de Cultura de Células , Análise por Conglomerados , Citocina TWEAK/metabolismo , Molécula de Adesão da Célula Epitelial/metabolismo , Fígado Gorduroso Alcoólico/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Imuno-Histoquímica , Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-17/metabolismo , Fígado/citologia , Fatores Inibidores da Migração de Macrófagos/metabolismo , Microscopia de Fluorescência , Comunicação Parácrina , RNA/química , RNA/isolamento & purificação , RNA/metabolismo , Análise de Sequência de RNA , Transdução de Sinais , Células-Tronco/citologia
19.
Rev. méd. panacea ; 6(1): 23-27, ene.-abr. 2017. tab
Artigo em Espanhol | LILACS | ID: biblio-1022562

RESUMO

Objetivo: Determinar los conocimientos y actitudes sobre los principales signos y síntomas de alarma durante el embarazo en las gestantes hospitalizadas en el Servicio de Obstetricia del Hospital Regional de Ica, enero 2017.Material y métodos: Se realizó un estudio de tipo prospectivo, descriptivo y de corte transversal. En 150 gestantes hospitalizadas en el Servicio de Obstetricia del Hospital Regional de Ica. Se empleó una encuesta como instrumento de recolección de datos. Resultados: Existe una asociación entre el nivel de conocimientos y las actitudes adoptadas por las gestantes (X2 =89.303; gl=4; p=0.000). El nivel de conocimiento es alto con un 70.7% y las actitudes son favorables con un 95.3%. El 70.7% tiene entre 20 a 34 años; el 61.3% son de estado civil conviviente, el 50% tienen grado superior y el 85.3% convive con su pareja, el 37.3% están gestando por primera vez, el 67.3% se encuentran en la segunda mitad del embarazo, el 86.7% conoce sobre los signos y síntomas de alarma, de estos el 96.7% refiere haber recibido la información por parte de un profesional de la salud. Los signos y síntomas de alarma más reconocidos por las gestantes fueron: el Sangrado vaginal, fiebre y pérdida de líquido amniótico. Conclusiones: Existe una correlación entre las variables de estudio, ya que a mayor nivel de conocimiento se muestra una mejor actitud frente a los signos y síntomas de alarma. (AU)


Objetive: To determine the knowledge and attitudes about the main signs and symptoms of alarm during pregnancy in pregnant women hospitalized at the Obstetrics Service of the Regional Hospital of Ica, January 2017. Materials and Methods: A prospective, descriptive and Of cross-section. In 150 pregnant women hospitalized in the Obstetrics Service of the Regional Hospital of Ica. A survey was used as an instrument of data collection. Results: There is an association between the level of knowledge and the attitudes adopted by pregnant women (X2 = 89.303; gl = 4; p = 0.000). The level of knowledge is high with 70.7% and attitudes are favorable with 95.3%. 70.7% are between 20 and 34 years old; 61.3% are married, 50% have a higher degree and 85.3% live with their partner, 37.3% are pregnant for the first time, 67.3% are in the second half of pregnancy, 86.7% are aware of The signs and symptoms of alarm, of these 96.7% refer to having received the information from a health professional. The signs and symptoms of alarm most recognized by pregnant women were: Vaginal bleeding, fever and loss of amniotic fluid.Conclusions: There is a correlation between the study variables, since a higher level of knowledge shows a better attitude towards the signs and symptoms of alarm. (AU)


Assuntos
Humanos , Feminino , Sinais e Sintomas , Gravidez , Conhecimentos, Atitudes e Prática em Saúde , Epidemiologia Descritiva , Estudos Transversais , Estudos Prospectivos
20.
J Thorac Dis ; 9(1): E85-E86, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28203443
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