Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder.

The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we performed an exploratory study of the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. Overall, we observed relatively weak associations (p < 1 × 10-4) with BP phenotypes within immune-related genes. Network and functional enrichment analyses of the top findings from the association analyses of Li response variables showed an overrepresentation of pathways participating in cell adhesion and intercellular communication. These appeared to converge on the well-known Li-induced inhibition of GSK-3ß. Association analyses of age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation suggested modest contributions of genes such as RTN4, XKR4, NRXN1, NRG1/3 and GRK5 to disease characteristics. PGS analyses returned weak associations (p < 0.05) between inflammation markers and the studied BP phenotypes. Our results suggest a modest relationship between immunity and clinical features in BP. More research is needed to assess the potential therapeutic relevance.

Introduction of Breast Milk Substitutes During the First 3 Days of Life: Results of the Mexican National Survey of Demographic Dynamics, 2018.

Background: The introduction of foods or fluids other than breast milk in the first few days after birth interferes with the establishment of breastfeeding. This study aimed to investigate the association of formula introduction during the first 3 days of life with maternal sociodemographic characteristics, hospital practices, and breastfeeding duration. Materials and Methods: Information from the National Survey of Demographic Dynamics, 2018, which includes 17,686 mother-baby pairs was analyzed. Mother-baby pairs were classified into categories according to breastfeeding duration: <5 months and ≥5 months. Statistical methods and a machine learning algorithm (Bayesian network, BN) were used to analyze the data. Results: In general, 3,720 (21%) mothers reported introducing formula during the first 3 days of life. A lower education level, lower sociodemographic stratum, living in a rural area, and considering oneself indigenous were factors associated with not introducing formula during the first 3 days of life. A total of 5,168 (29.2%) mother-baby pairs practiced breastfeeding for <5 months, and 12,518 (70.8%) for ≥5 months. Almost twice as many mothers who practiced breastfeeding for <5 months introduced formula during the first 3 days of life (31.7%) compared with those who practiced breastfeeding for ≥5 months (16.6%). The BN model can sufficiently predict cases with a breastfeeding duration ≥5 months (precision-recall curve area = 0.792). Discussion: Introducing formula during the first 3 days of life was associated with a shorter breastfeeding duration. BN analysis showed a probabilistic dependency between the type of delivery and variables associated with the establishment of breastfeeding.

Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder.

The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1×10- 4 values, including HAS3, CNTNAP5 and NFIB. Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3ß. We also found various genes associated with BP's age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4, XKR4, NRXN1, NRG1/3 and GRK5. Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.

Optimization of Classification Strategies of Acetowhite Temporal Patterns towards Improving Diagnostic Performance of Colposcopy.

Efforts have been being made to improve the diagnostic performance of colposcopy, trying to help better diagnose cervical cancer, particularly in developing countries. However, improvements in a number of areas are still necessary, such as the time it takes to process the full digital image of the cervix, the performance of the computing systems used to identify different kinds of tissues, and biopsy sampling. In this paper, we explore three different, well-known automatic classification methods (k-Nearest Neighbors, Naïve Bayes, and C4.5), in addition to different data models that take full advantage of this information and improve the diagnostic performance of colposcopy based on acetowhite temporal patterns. Based on the ROC and PRC area scores, the k-Nearest Neighbors and discrete PLA representation performed better than other methods. The values of sensitivity, specificity, and accuracy reached using this method were 60% (95% CI 50-70), 79% (95% CI 71-86), and 70% (95% CI 60-80), respectively. The acetowhitening phenomenon is not exclusive to high-grade lesions, and we have found acetowhite temporal patterns of epithelial changes that are not precancerous lesions but that are similar to positive ones. These findings need to be considered when developing more robust computing systems in the future.

How good is crude MDL for solving the bias-variance dilemma? An empirical investigation based on Bayesian networks.

The bias-variance dilemma is a well-known and important problem in Machine Learning. It basically relates the generalization capability (goodness of fit) of a learning method to its corresponding complexity. When we have enough data at hand, it is possible to use these data in such a way so as to minimize overfitting (the risk of selecting a complex model that generalizes poorly). Unfortunately, there are many situations where we simply do not have this required amount of data. Thus, we need to find methods capable of efficiently exploiting the available data while avoiding overfitting. Different metrics have been proposed to achieve this goal: the Minimum Description Length principle (MDL), Akaike's Information Criterion (AIC) and Bayesian Information Criterion (BIC), among others. In this paper, we focus on crude MDL and empirically evaluate its performance in selecting models with a good balance between goodness of fit and complexity: the so-called bias-variance dilemma, decomposition or tradeoff. Although the graphical interaction between these dimensions (bias and variance) is ubiquitous in the Machine Learning literature, few works present experimental evidence to recover such interaction. In our experiments, we argue that the resulting graphs allow us to gain insights that are difficult to unveil otherwise: that crude MDL naturally selects balanced models in terms of bias-variance, which not necessarily need be the gold-standard ones. We carry out these experiments using a specific model: a Bayesian network. In spite of these motivating results, we also should not overlook three other components that may significantly affect the final model selection: the search procedure, the noise rate and the sample size.