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1.
Clin Chem Lab Med ; 62(2): 312-321, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-37548423

RESUMEN

OBJECTIVES: Flow cytometry analyses of lymphocyte subpopulations (T, B, NK) are crucial for enhancing clinical algorithms and research workflows. Estimating the total error (TE) values for the percentage and absolute number of lymphocyte subpopulations using the state-of-the-art (SOTA) approach with real data from an external proficiency testing (EPT) scheme was performed. A comparison with previously published Biological Variability (BV)-based specifications was carried out. METHODS: A total of 44,998 results from 86 laboratories over 10 years were analysed and divided into two five-year periods (2012-2016) and (2017-2021). Data come from the IC-1 Lymphocytes scheme of the Spanish External Quality Assurance System (EQAS) GECLID Program. This quantitative scheme includes percentages and absolute numbers of CD3+, CD3+CD4+, CD3+CD8+, CD19+, and CD3-CD56+CD16+ NK cells. The percentage of TE was calculated as: |reported value - robust mean|*100/robust mean for each laboratory and parameter. The cut-off for TE is set at 80 % best results of the laboratories. RESULTS: A significant reduction in the SOTA-based TE for all lymphocyte subpopulations in 2017-2021 was observed compared to 2012-2016. The SOTA-based TE fulfils the minimum BV-based TE for percentages of lymphocyte subpopulations. The parameter with the best analytical performance calculated with SOTA (2017-2021 period)-based TE was the percentage of CD3+ (TE=3.65 %). CONCLUSIONS: The values of SOTA-based specifications from external quality assurance program data are consistent and can be used to develop technical specifications. The technological improvement, quality commitment, standardization, and training, reduce TE. An update of TE every five years is therefore recommended. TE assessment in lymphocyte subsets is a helpful and reliable tool to improve laboratory performance and data-based decision-making trust.


Asunto(s)
Células Asesinas Naturales , Subgrupos Linfocitarios , Humanos , Citometría de Flujo , Recuento de Linfocitos , Ensayos de Aptitud de Laboratorios
2.
Neurol Sci ; 45(4): 1471-1480, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37864751

RESUMEN

INTRODUCTION: As Hearing loss and dementia affect people with the same profile, several epidemiological studies have evaluated their relationship. However, the link between age-related hearing loss and Alzheimer's disease is still unclear. METHODS: We selected subjects with no history of exposure to loud noises, blasts, head trauma with hearing loss, or sudden sensorineural hearing loss from a cohort intended to study preclinical phases of Alzheimer's disease. Participants are volunteers over 55 years without cognitive impairment. We correlated the results of an objective auditory evaluation with brain amyloid and p-tau181 levels and with the outcomes of a comprehensive neuropsychological assessment. RESULTS: Fifty-five subjects at different stages of the Alzheimer's disease continuum were evaluated. There were no statistically significant correlations between amyloid-ß and p-tau levels and any of the objective auditory measures. A weak but significant correlation was found between amyloid-ß values and the Hearing Handicap Inventory for the Elderly. The neuropsychological domains more correlated to hearing loss were executive function and processing speed. DISCUSSION: Age-related hearing loss is not linked to any pathological markers of Alzheimer's disease nor to neuropsychological domains typically affected in this disease. The Hearing Handicap Inventory for the Elderly has an important component of subjectivity and further studies are needed to explore its relationship with amyloid-ß levels.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Anciano , Enfermedad de Alzheimer/patología , Proteínas tau/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Disfunción Cognitiva/líquido cefalorraquídeo
3.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38338759

RESUMEN

Plasma biomarkers for Alzheimer's disease (AD) are a promising tool that may help in early diagnosis. However, their levels may be influenced by physiological parameters and comorbidities that should be considered before they can be used at the population level. For this purpose, we assessed the influences of different comorbidities on AD plasma markers in 208 cognitively unimpaired subjects. We analyzed both plasma and cerebrospinal fluid levels of Aß40, Aß42, and p-tau181 using the fully automated Lumipulse platform. The relationships between the different plasma markers and physiological variables were studied using linear regression models. The mean differences in plasma markers according to comorbidity groups were also studied. The glomerular filtration rate showed an influence on plasma Aß40 and Aß42 levels but not on the Aß42/Aß40 ratio. The amyloid ratio was significantly lower in diabetic and hypertensive subjects, and the mean p-tau181 levels were higher in hypertensive subjects. The glomerular filtration rate may have an inverse relationship on plasma Aß40 and Aß42 levels but not on the amyloid ratio, suggesting that the latter is a more stable marker to use in the general population. Cardiovascular risk factors might have a long-term effect on the amyloid ratio and plasma levels of p-tau181.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Humanos , Péptidos beta-Amiloides/líquido cefalorraquídeo , Enfermedad de Alzheimer/diagnóstico , Comorbilidad , Biomarcadores , Proteínas tau/líquido cefalorraquídeo , Fragmentos de Péptidos
4.
Clin Chem Lab Med ; 61(6): 1095-1104, 2023 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-36634098

RESUMEN

OBJECTIVES: Autoantibodies and, specifically antinuclear antibodies (ANA), are the hallmark of systemic autoimmune diseases (AID). In the last decades, there has been great technical development to detect these autoantibodies along with an increased request for this test by clinicians, while the overall pre-test probability has decreased. In this study, we compare the diagnostic performance of three different methods for ANA screening (indirect immunofluorescence [IIF], addressable laser bead immunoassay [ALBIA], and fluorescence enzyme immunoassay [FEIA]). METHODS: Serum samples at baseline visit from 2,997 participants from the Camargo Cohort, a population with an overall low pre-test probability for systemic AID, were analyzed with the three methods. Participants have a minimum follow-up of 10 years and the development of autoimmune diseases was collected from clinical records. RESULTS: The highest frequency of positive ANA was observed by IIF assay. However, ALBIA showed high sensitivity for AID. Likewise, solid phase assays (SPA) presented higher specificity than IIF for AID. ANA prevalence with any method was significantly higher in females and overall increased with age. Triple positivity for ANA was significantly related to the presence of anti-dsDNA-SSA/Ro60, Ro52, SSB/La, RNP, Scl-70, and centromere-specificities. No association was found for anti-Sm - RNP68, or ribosomal P - specificities. Noteworthy, triple positivity for ANA screening was associated with diagnosis of systemic AID both at baseline visit and follow-up. CONCLUSIONS: ANA detection by IIF may be better when the pre-test probability is high, whereas SPA techniques are more useful in populations with an overall low pre-test probability for systemic AID.


Asunto(s)
Anticuerpos Antinucleares , Enfermedades Autoinmunes , Femenino , Humanos , Autoanticuerpos , Enfermedades Autoinmunes/diagnóstico , Técnica del Anticuerpo Fluorescente Indirecta/métodos , Inmunoensayo/métodos
5.
BMC Med Educ ; 23(1): 37, 2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36653767

RESUMEN

BACKGROUND: Universities' training process intensely relies on face-to-face education. The COVID-19 pandemic interrupted it and forced them to reinvent their process online. But this crisis seems not to be the last we will face, and we take it as a lesson to prepare for future crises. These critical contexts are especially challenging because they imply changing teaching strategies, and students may not have the technology access or the living conditions to connect as they need. They also lived through a pandemic where the virus and the life changes added stress to their learning process and threatened their well-being. So, this study aims to analyze how well-being variations reported by Health sciences students relate to their learning opportunities, access conditions, and daily activities. METHOD: We surveyed 910 Health sciences students from six different Chilean universities at the end of the first semester of 2020, the first in pandemic conditions. Respondents answered online questionnaires about 1) Remote teaching activities, 2) Learning resources availability, 3) Daily life activities, and 4) Well-being changes. We performed descriptive analysis and Structural Equation Modelling. RESULTS: Live videoconference classes were the most frequent teaching activity; only a third of the students had quiet spaces to study online, and most had to housekeep daily. More than two third reported some well-being deterioration. The structural equation model showed a good fit. CONCLUSION: Results show an online learning scenario that tries to emulate traditional learning focusing on expositive strategies. Most students reported that their well-being deteriorated during the semester, but tutorials, workplace availability, and social support were protective factors.


Asunto(s)
COVID-19 , Educación a Distancia , Humanos , Pandemias , COVID-19/epidemiología , Estudiantes , Aprendizaje , Escolaridad
6.
Glia ; 70(12): 2426-2440, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35980256

RESUMEN

Promoting remyelination is considered as a potential neurorepair strategy to prevent/limit the development of permanent neurological disability in patients with multiple sclerosis (MS). To this end, a number of clinical trials are investigating the potential of existing drugs to enhance oligodendrocyte progenitor cell (OPC) differentiation, a process that fails in chronic MS lesions. We previously reported that oligodendroglia express GABAB receptors (GABAB Rs) both in vitro and in vivo, and that GABAB R-mediated signaling enhances OPC differentiation and myelin protein expression in vitro. Our goal here was to evaluate the pro-remyelinating potential of GABAB R agonist baclofen (Bac), a clinically approved drug to treat spasticity in patients with MS. We first demonstrated that Bac increases myelin protein production in lysolecithin (LPC)-treated cerebellar slices. Importantly, Bac administration to adult mice following induction of demyelination by LPC injection in the spinal cord resulted in enhanced OPC differentiation and remyelination. Thus, our results suggest that Bac repurposing should be considered as a potential therapeutic strategy to stimulate remyelination in patients with MS.


Asunto(s)
Esclerosis Múltiple , Remielinización , Animales , Baclofeno/metabolismo , Baclofeno/farmacología , Baclofeno/uso terapéutico , Diferenciación Celular , Sistema Nervioso Central/metabolismo , Agonistas de Receptores GABA-B/metabolismo , Agonistas de Receptores GABA-B/farmacología , Agonistas de Receptores GABA-B/uso terapéutico , Lisofosfatidilcolinas/metabolismo , Ratones , Ratones Endogámicos C57BL , Esclerosis Múltiple/patología , Vaina de Mielina/metabolismo , Oligodendroglía/metabolismo
7.
Rheumatology (Oxford) ; 60(8): 3904-3912, 2021 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-33437990

RESUMEN

OBJECTIVES: ANA are the most extensively used test for the diagnosis of systemic autoimmune diseases. However, testing by indirect immunofluorescence assays (IIFAs) on HEp-2 cells, the gold standard test, is time-consuming and needs expertise. Thus there is a trend to replace it with other automated solid-phase assays directed against specific ANA. Nonetheless, the Hep-2 cell is an autoantigen array and ANA have been classified into 29 types, some of them with no clear association with a specificity to be detected. It is especially in these uncommon patterns where no clinical relationship is found and no antigenic specificity is detected. Here we retrospectively collected clinical data from patients with confirmed uncommon HEp-2 IIFA patterns to search for an associated clinical condition. METHODS: We conducted an observational retrospective study including 608 patients with organ-specific and non-organ-specific autoimmune diseases (OSADs and NOSADs, respectively) with a confirmed rare pattern of ANA detected by IIFA on HEp-2 cells in the routine practice of the Spanish European Autoantibodies Standardization Initiative laboratories. Inclusion criteria are the existence of a minimum follow-up of 2 years and the availability of clinical data. RESULTS: Nuclear patterns were more frequent in SLE (P = 0.001) and SS (P = 0.001), whereas the cytoplasmic ones were significantly higher in SSc (P = 0.022) and inflammatory myositis (P = 0.016). Mitotic patterns did not show any preferences for a specific disease and 62.7% of them corresponded to the nuclear mitotic apparatus pattern (AC-26). The most frequent NOSADs in patients with the AC-26 pattern were SLE (28.6%), SS (11.9%) and RA (11.9%). The cytoplasmic HEp-2 IIFA patterns were equally distributed in both groups of patients. In the OSAD patients there was no predominant pattern, except for AC-6 in primary biliary cholangitis due to Sp-100 antibodies (P < 0.001). CONCLUSION: Detection of infrequent ANA might be a unique finding with no disease-associated specificities and could lead to the suspicion of an autoimmune disease.


Asunto(s)
Anticuerpos Antinucleares/inmunología , Lupus Eritematoso Sistémico/inmunología , Esclerodermia Sistémica/inmunología , Síndrome de Sjögren/inmunología , Adulto , Anciano , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/inmunología , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/inmunología , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Enfermedad de Graves/diagnóstico , Enfermedad de Graves/inmunología , Enfermedad de Hashimoto/diagnóstico , Enfermedad de Hashimoto/inmunología , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Masculino , Persona de Mediana Edad , Esclerodermia Sistémica/diagnóstico , Síndrome de Sjögren/diagnóstico , España
8.
Molecules ; 26(10)2021 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-34068920

RESUMEN

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.


Asunto(s)
Antineoplásicos/farmacología , Compuestos de Boro/química , Oligosacáridos/síntesis química , Coloración y Etiquetado , Antineoplásicos/química , Glicosilación , Oligosacáridos/química , Oligosacáridos/farmacología , Espectrometría de Fluorescencia , Estereoisomerismo
9.
Chemistry ; 26(24): 5388-5399, 2020 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-31999023

RESUMEN

A series of fluorescent boron-dipyrromethene (BODIPY, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) dyes have been designed to participate, as aglycons, in synthetic oligosaccharide protocols. As such, they served a dual purpose: first, by being incorporated at the beginning of the process (at the reducing-end of the growing saccharide moiety), they can function as fluorescent glycosyl tags, facilitating the detection and purification of the desired glycosidic intermediates, and secondly, the presence of these chromophores on the ensuing compounds grants access to fluorescently labeled saccharides. In this context, a sought-after feature of the fluorescent dyes has been their chemical robustness. Accordingly, some BODIPY derivatives described in this work can withstand the reaction conditions commonly employed in the chemical synthesis of saccharides; namely, glycosylation and protecting-group manipulations. Regarding their photophysical properties, the BODIPY-labeled saccharides obtained in this work display remarkable fluorescence efficiency in water, reaching quantum yield values up to 82 %, as well as notable lasing efficiencies and photostabilities.


Asunto(s)
Compuestos de Boro/química , Boro/química , Colorantes Fluorescentes/química , Porfobilinógeno/análogos & derivados , Fluorescencia , Glicosilación , Luz , Porfobilinógeno/química
10.
Int J Mol Sci ; 21(3)2020 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-31991734

RESUMEN

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.


Asunto(s)
Citotoxicidad Celular Dependiente de Anticuerpos/inmunología , Factor Activador de Células B/sangre , Subgrupos de Linfocitos B/inmunología , Subgrupos de Linfocitos B/metabolismo , Rechazo de Injerto/inmunología , Rechazo de Injerto/metabolismo , Memoria Inmunológica , Activación de Linfocitos/inmunología , Biomarcadores , Femenino , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Periodo Perioperatorio , Modelos de Riesgos Proporcionales , Linfocitos T/inmunología , Linfocitos T/metabolismo
11.
Chemistry ; 25(65): 14959-14971, 2019 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-31515840

RESUMEN

The development of efficient and stable red and near-IR emitting materials under hard radiation doses and/or prolonged times is a sought-after task due to their widespread applications in optoelectronics and biophotonics. To this aim, novel symmetric all-BODIPY-triads, -pentads, and -hexads have been designed and synthesized as light-harvesting arrays. These photonic materials are spectrally active in the 655-730 nm region and display high molar absorption across UV-visible region. Furthermore, they provide, to the best of our knowledge, the highest lasing efficiency (up to 68 %) and the highest photostability (tolerance >1300 GJ mol-1 ) in the near-IR spectral region ever recorded under drastic pumping conditions. Additionally, the modular synthetic strategy to access the cassettes allows the systematic study of their photonic behavior related to structural factors. Collectively, the outstanding behavior of these multichromophoric photonic materials provides the keystone for engineering multifunctional systems to expedite the next generation of effective red optical materials.

13.
J Neuroinflammation ; 15(1): 63, 2018 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-29490673

RESUMEN

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.


Asunto(s)
Índice de Masa Corporal , Citocinas/sangre , Sobrepeso/sangre , Trastornos Psicóticos/sangre , Aumento de Peso/fisiología , Adulto , Estudios de Cohortes , Femenino , Humanos , Estudios Longitudinales , Masculino , Sobrepeso/diagnóstico , Sobrepeso/epidemiología , Estudios Prospectivos , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/epidemiología , Adulto Joven
14.
J Biomed Inform ; 80: 1-13, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29462669

RESUMEN

With the proliferation of heterogeneous health care data in the last three decades, biomedical ontologies and controlled biomedical terminologies play a more and more important role in knowledge representation and management, data integration, natural language processing, as well as decision support for health information systems and biomedical research. Biomedical ontologies and controlled terminologies are intended to assure interoperability. Nevertheless, the quality of biomedical ontologies has hindered their applicability and subsequent adoption in real-world applications. Ontology evaluation is an integral part of ontology development and maintenance. In the biomedicine domain, ontology evaluation is often conducted by third parties as a quality assurance (or auditing) effort that focuses on identifying modeling errors and inconsistencies. In this work, we first organized four categorical schemes of ontology evaluation methods in the existing literature to create an integrated taxonomy. Further, to understand the ontology evaluation practice in the biomedicine domain, we reviewed a sample of 200 ontologies from the National Center for Biomedical Ontology (NCBO) BioPortal-the largest repository for biomedical ontologies-and observed that only 15 of these ontologies have documented evaluation in their corresponding inception papers. We then surveyed the recent quality assurance approaches for biomedical ontologies and their use. We also mapped these quality assurance approaches to the ontology evaluation criteria. It is our anticipation that ontology evaluation and quality assurance approaches will be more widely adopted in the development life cycle of biomedical ontologies.


Asunto(s)
Ontologías Biológicas , Informática Médica/normas , Registros Electrónicos de Salud , Humanos , Garantía de la Calidad de Atención de Salud , Semántica
15.
BMC Med Inform Decis Mak ; 18(Suppl 2): 55, 2018 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-30066655

RESUMEN

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.


Asunto(s)
Colaboración de las Masas , Bases del Conocimiento , Neoplasias , Obesidad , Curaduría de Datos , Medicina Basada en la Evidencia , Humanos , Almacenamiento y Recuperación de la Información , Aprendizaje Automático , PubMed , Semántica , Programas Informáticos
16.
J Immunoassay Immunochem ; 38(5): 514-522, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28613137

RESUMEN

IgG2 is the most efficient subclass for providing protection against pneumococcal pathogens. We hypothesised that some individuals may be unable to mount an effective pneumococcal capsular polysaccharide (PCP) IgG2 response despite having a normal PCP IgG concentration (PCP IgG2 deficient). The median pre-vaccination PCP IgG2 concentration was significantly lower in individuals referred for immunological investigation compared to healthy controls (2.8 mg/L range, 95% CI 1.1-88 vs. 29.5mg/L, 95% CI 13.5-90, p = 0.0002). PCP IgG:IgG2 ratios were significantly higher for the referral population than for healthy controls suggesting the increased production of PCP specific subclasses other than IgG2. The percentage of individuals with PCP IgG2 deficiency was significantly higher in referral groups compared to controls (31% vs. 5%; p = 0.0009) and in an individual with PCP IgG2 deficiency, the balance of PCP specific IgG subclass antibodies post vaccination changed from IgG2>IgG1>IgG3>IgG4 to IgG1>IgG3>IgG2>IgG4. The median PCP IgG2 concentration in those with PCP IgG2 deficiency was significantly lower in the referral groups compared to controls (7.8 mg/L, 95% CI 1.1-12 vs. 12.7 mg/L, 95% CI 11.8-13.1; p = 0.006). The data suggests a defect in the production PCP IgG2 may be present in individuals with normal PCP IgG referred for immunological investigation.


Asunto(s)
Anticuerpos Antibacterianos/análisis , Anticuerpos Antibacterianos/inmunología , Deficiencia de IgG/diagnóstico , Deficiencia de IgG/inmunología , Inmunoglobulina G/análisis , Inmunoglobulina G/inmunología , Polisacáridos Bacterianos/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antibacterianos/genética , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoglobulina G/genética , Lactante , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Adulto Joven
17.
EMBO J ; 31(16): 3431-41, 2012 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-22828869

RESUMEN

The cellular and molecular mechanisms that control lung homeostasis and regeneration are still poorly understood. It has been proposed that a population of cells exists in the mouse lung with the potential to differentiate into all major lung bronchioalveolar epithelium cell types in homeostasis or in response to virus infection. A new population of E-Cad/Lgr6(+) putative stem cells has been isolated, and indefinitely expanded from human lungs, harbouring both, self-renewal capacity and the potency to differentiate in vitro and in vivo. Recently, a putative population of human lung stem cells has been proposed as being c-Kit(+). Unlike Integrin-α6(+) or c-Kit(+) cells, E-Cad/Lgr6(+) single-cell injections in the kidney capsule produce differentiated bronchioalveolar tissue, while retaining self-renewal, as they can undergo serial transplantations under the kidney capsule or in the lung. In addition, a signalling network involving the p38α pathway, the activation of p53 and the regulation of the miR-17-92 cluster has been identified. Disruption of the proper cross-regulation of this signalling axis might be involved in the promotion of human lung diseases.


Asunto(s)
Regulación de la Expresión Génica , Pulmón/citología , MicroARNs/metabolismo , Células Madre/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Diferenciación Celular , Células Cultivadas , Citometría de Flujo , Perfilación de la Expresión Génica , Humanos , Microscopía Fluorescente , Transducción de Señal
18.
Nat Genet ; 39(6): 750-8, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17468755

RESUMEN

Stem cell function is central for the maintenance of normal tissue homeostasis. Here we show that deletion of p38alpha mitogen-activated protein (MAP) kinase in adult mice results in increased proliferation and defective differentiation of lung stem and progenitor cells both in vivo and in vitro. We found that p38alpha positively regulates factors such as CCAAT/enhancer-binding protein that are required for lung cell differentiation. In addition, p38alpha controls self-renewal of the lung stem and progenitor cell population by inhibiting proliferation-inducing signals, most notably epidermal growth factor receptor. As a consequence, the inactivation of p38alpha leads to an immature and hyperproliferative lung epithelium that is highly sensitized to K-Ras(G12V)-induced tumorigenesis. Our results indicate that by coordinating proliferation and differentiation signals in lung stem and progenitor cells, p38alpha has a key role in the regulation of lung cell renewal and tumorigenesis.


Asunto(s)
Diferenciación Celular , Proliferación Celular , Pulmón/citología , Proteína Quinasa 14 Activada por Mitógenos/fisiología , Células Madre/citología , Animales , Células Cultivadas , Femenino , Genes ras/fisiología , Técnicas para Inmunoenzimas , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Masculino , Ratones , Ratones Noqueados , Proteína Quinasa 14 Activada por Mitógenos/genética , Proteínas Proto-Oncogénicas c-jun/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-jun/genética , Proteínas Proto-Oncogénicas c-jun/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal
19.
JMIR Ment Health ; 11: e50150, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38271138

RESUMEN

BACKGROUND: Health care providers and health-related researchers face significant challenges when applying sentiment analysis tools to health-related free-text survey data. Most state-of-the-art applications were developed in domains such as social media, and their performance in the health care context remains relatively unknown. Moreover, existing studies indicate that these tools often lack accuracy and produce inconsistent results. OBJECTIVE: This study aims to address the lack of comparative analysis on sentiment analysis tools applied to health-related free-text survey data in the context of COVID-19. The objective was to automatically predict sentence sentiment for 2 independent COVID-19 survey data sets from the National Institutes of Health and Stanford University. METHODS: Gold standard labels were created for a subset of each data set using a panel of human raters. We compared 8 state-of-the-art sentiment analysis tools on both data sets to evaluate variability and disagreement across tools. In addition, few-shot learning was explored by fine-tuning Open Pre-Trained Transformers (OPT; a large language model [LLM] with publicly available weights) using a small annotated subset and zero-shot learning using ChatGPT (an LLM without available weights). RESULTS: The comparison of sentiment analysis tools revealed high variability and disagreement across the evaluated tools when applied to health-related survey data. OPT and ChatGPT demonstrated superior performance, outperforming all other sentiment analysis tools. Moreover, ChatGPT outperformed OPT, exhibited higher accuracy by 6% and higher F-measure by 4% to 7%. CONCLUSIONS: This study demonstrates the effectiveness of LLMs, particularly the few-shot learning and zero-shot learning approaches, in the sentiment analysis of health-related survey data. These results have implications for saving human labor and improving efficiency in sentiment analysis tasks, contributing to advancements in the field of automated sentiment analysis.


Asunto(s)
COVID-19 , Análisis de Sentimientos , Estados Unidos/epidemiología , Humanos , COVID-19/epidemiología , Encuestas Epidemiológicas , Aprendizaje , Disentimientos y Disputas
20.
Immunol Res ; 72(2): 260-270, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37924421

RESUMEN

Autoantibodies are the hallmark of autoimmunity, and specifically, antinuclear antibodies (ANA) are one of the most relevant antibodies present in systemic autoimmune diseases (AID). In the present study, we evaluate the relationship between ANA and sociodemographic and biobehavioral factors in a population with a low pre-test probability for systemic AID. ANA were determined in serum samples at baseline visit from 2997 participants from the Camargo Cohort using indirect immunofluorescence assay, and two solid phase assays (SPA), addressable laser bead immunoassay, and fluorescence enzyme immunoassay. Sociodemographic and biobehavioral features of the subjects were obtained at baseline visit using a structured questionnaire. The prevalence of ANA positive results was significantly higher when indirect immunofluorescence assay was used as screening method in comparison with SPAs, being higher in females, older subjects, and those with higher C-reactive protein levels. Considering biobehavioral features, the prevalence was higher in those individuals with a sedentary lifestyle, and in ex- and non-alcohol users. Moreover, considering the relevance of the antibody load using ANA Screen, the prevalence of the antibody load also increased with age, especially in females. In conclusion, the prevalence of ANA varies depending on sociodemographic and biobehavioral features of the subjects, which could be relevant specifically in a population with a low pre-test probability for systemic AIDs.

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