A new robust approach for the polytomous logistic regression model based on Rényi's pseudodistances.

This paper presents a robust alternative to the maximum likelihood estimator (MLE) for the polytomous logistic regression model, known as the family of minimum Rènyi Pseudodistance (RP) estimators. The proposed minimum RP estimators are parametrized by a tuning parameter $\alpha \ge 0$, and include the MLE as a special case when $\alpha =0$. These estimators, along with a family of RP-based Wald-type tests, are shown to exhibit superior performance in the presence of misclassification errors.

Implementing precision oncology in Latin America to improve patient outcomes: the status quo and a call to action for key stakeholders and decision-makers.

Background: The advent of precision oncology (PO) has revolutionised diagnostic and follow up strategies and improved clinical outcomes for cancer patients. However, socio-economic inequalities in the level of implementation of PO in different countries is a prevailing issue. To improve this situation, the Latin America Patients Academy has gathered the recommendations of healthcare professionals and social civil members experienced in cancer management from Mexico, Guatemala, Costa Rica, Dominican Republic, Panama, Colombia, Chile, Ecuador, Peru and Argentina regarding the areas that need to be prioritised to improve the access to PO in Latin American (LATAM) countries.

Robust Minimum Divergence Estimation for the Multinomial Circular Logistic Regression Model.

Circular data are extremely important in many different contexts of natural and social science, from forestry to sociology, among many others. Since the usual inference procedures based on the maximum likelihood principle are known to be extremely non-robust in the presence of possible data contamination, in this paper, we develop robust estimators for the general class of multinomial circular logistic regression models involving multiple circular covariates. Particularly, we extend the popular density-power-divergence-based estimation approach for this particular set-up and study the asymptotic properties of the resulting estimators.

SDR9C7 missense variant in a Chihuahua with non-epidermolytic ichthyosis.

Ichthyoses represent a heterogeneous group of cornification disorders that are associated with skin barrier defects. We investigated a 9-month-old Chihuahua showing excessive scale formation. Clinical and histopathological examinations revealed non-epidermolytic ichthyosis and a genetic defect was suspected.

HIGEA: An Intelligent Conversational Agent to Detect Caregiver Burden.

Mental health disorders increasingly affect people worldwide. As a consequence, more families and relatives find themselves acting as caregivers. Most often, these are untrained people who experience loneliness, abandonment, and often develop signs of depression (i.

A large, ten-generation family with autosomal dominant preaxial polydactyly/triphalangeal thumb: Historical, clinical, genealogical, and molecular studies.

We present a large, ten-generation family of 273 individuals with 84 people having preaxial polydactyly/triphalangeal thumb due to a pathogenic variant in the zone of polarizing activity regulatory sequence (ZRS) within the exon 5 of LMBR1. The causative change maps to position 396 of the ZRS, located at position c.423 + 4909C > T (chr7:156791480; hg38; LMBR1 ENST00000353442.

The portrayal of dwarfism without skeletal dysplasia in art: Proportionate short stature due to growth hormone deficiency and other disorders.

In this article, we analyze several works of art which portray individuals with short stature ("dwarfism"). We have focused on eight individuals who we believe have short stature due to growth hormone deficiency (GHD) or closely related disorders, rather than skeletal dysplasia. We discuss them individually, suggest the potential diagnosis, review the characteristics of their life and personal history, and briefly outline the artistic framework in which these works of art were created.

Model Selection in a Composite Likelihood Framework Based on Density Power Divergence.

This paper presents a model selection criterion in a composite likelihood framework based on density power divergence measures and in the composite minimum density power divergence estimators, which depends on an tuning parameter α . After introducing such a criterion, some asymptotic properties are established. We present a simulation study and two numerical examples in order to point out the robustness properties of the introduced model selection criterion.

Simultaneous Loss of Both Atypical Protein Kinase C Genes in the Intestinal Epithelium Drives Serrated Intestinal Cancer by Impairing Immunosurveillance.

Serrated adenocarcinoma, an alternative pathway for colorectal cancer (CRC) development, accounts for 15%-30% of all CRCs and is aggressive and treatment resistant. We show that the expression of atypical protein kinase C ζ (PKCζ) and PKCλ/ι was reduced in human serrated tumors. Simultaneous inactivation of the encoding genes in the mouse intestinal epithelium resulted in spontaneous serrated tumorigenesis that progressed to advanced cancer with a strongly reactive and immunosuppressive stroma.

Clusters of genetic diseases in Brazil.

The aim of this paper is to present a database of isolated communities (CENISO) with high prevalence of genetic disorders or congenital anomalies in Brazil. We used two strategies to identify such communities: (1) a systematic literature review and (2) a "rumor strategy" based on anecdotal accounts. All rumors and reports were validated in a stepwise process.

New robust statistical procedures for the polytomous logistic regression models.

This article derives a new family of estimators, namely the minimum density power divergence estimators, as a robust generalization of the maximum likelihood estimator for the polytomous logistic regression model. Based on these estimators, a family of Wald-type test statistics for linear hypotheses is introduced. Robustness properties of both the proposed estimators and the test statistics are theoretically studied through the classical influence function analysis.

Adipocyte p62/SQSTM1 Suppresses Tumorigenesis through Opposite Regulations of Metabolism in Adipose Tissue and Tumor.

Obesity is a leading risk factor for cancer. However, understanding the crosstalk between adipocytes and tumor cells in vivo, independently of dietary contributions, is a major gap in the field. Here we used a prostate cancer (PCa) mouse model in which the signaling adaptor p62/Sqstm1 is selectively inactivated in adipocytes.

Neural tube defects: Sex ratio changes after fortification with folic acid.

Background: Historically, neural tube defects (NTDs) have predominated in female infants but the reasons remain unclear. In South America, the pre- folic acid fortification (FAF) rates of NTDs were around 18/10,000 births for females and 12/10,000 births for males, with an estimated sex ratio (male/female) of 0.67.

ICD-10 impact on ascertainment and accuracy of oral cleft cases as recorded by the Brazilian national live birth information system.

We compared Brazilian oral cleft (OC) frequencies between the population-based Brazilian System of Live Birth (SINASC) and the hospital-based Latin American Collaborative Study of Congenital Malformations (ECLAMC), trying to understand the paucity of cleft of lip and palate (CLP) in the first system. SINASC uses the International Classification of Disease version 10 (ICD-10) for congenital defects coding, ECLAMC uses ICD-8 with modifications. In SINASC, the CLP frequency was 1.

PVR/CD155 Ala67Thr Mutation and Cleft Lip/Palate.

The 19q13 locus has been linked to cleft lip and palate by our group and independently by others. Here we fine mapped the region in an attempt to identify an etiological variant that can explain cleft lip and palate occurrence. A total of 2739 individuals born with cleft lip and palate, related to individuals born with cleft lip and palate, and unrelated were studied.

Third molar agenesis as a potential marker for craniofacial deformities.

Unlabelled: The identification of clinical patterns of tooth agenesis in individuals born with craniofacial deformities may be a useful tool for risk determination of these defects. We hypothesize that specific craniofacial deformities are associated with third molar agenesis.

Objective: The aim of this study was to identify if third molar agenesis could have a relation with other craniofacial structure alterations, such as cleft lip and palate, skeletal malocclusion, or specific growth patterns in humans.

Composite Likelihood Methods Based on Minimum Density Power Divergence Estimator.

In this paper, a robust version of the Wald test statistic for composite likelihood is considered by using the composite minimum density power divergence estimator instead of the composite maximum likelihood estimator. This new family of test statistics will be called Wald-type test statistics. The problem of testing a simple and a composite null hypothesis is considered, and the robustness is studied on the basis of a simulation study.

Prevalence and clinical profile of microcephaly in South America pre-Zika, 2005-14: prevalence and case-control study.

 To describe the prevalence and clinical spectrum of microcephaly in South America for the period 2005-14, before the start of the Zika epidemic in 2015, as a baseline for future surveillance as the Zika epidemic spreads and as other infectious causes may emerge in future. Prevalence and case-control study. ECLAMC (Latin American Collaborative Study of Congenital Malformations) database derived from 107 hospitals in 10 South American countries, 2005 to 2014.

Identification of 16q21 as a modifier of nonsyndromic orofacial cleft phenotypes.

Orofacial clefts (OFCs) are common, complex birth defects with extremely heterogeneous phenotypic presentations. Two common subtypes-cleft lip alone (CL) and CL plus cleft palate (CLP)-are typically grouped into a single phenotype for genetic analysis (i.e.

ATF4-Induced Metabolic Reprograming Is a Synthetic Vulnerability of the p62-Deficient Tumor Stroma.

Tumors undergo nutrient stress and need to reprogram their metabolism to survive. The stroma may play a critical role in this process by providing nutrients to support the epithelial compartment of the tumor. Here we show that p62 deficiency in stromal fibroblasts promotes resistance to glutamine deprivation by the direct control of ATF4 stability through its p62-mediated polyubiquitination.

Association studies of low-frequency coding variants in nonsyndromic cleft lip with or without cleft palate.

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a group of common human birth defects with complex etiology. Although genome-wide association studies have successfully identified a number of risk loci, these loci only account for about 20% of the heritability of orofacial clefts. The "missing" heritability may be found in rare variants, copy number variants, or interactions.

Association between a Maternal History of Miscarriages and Birth Defects.

Background: Some studies, mainly in the older literature, observed a significant association between miscarriages and birth defects (BDs) occurring in the same sibship. However, few studies examined the BD/miscarriage relationship in depth. In addition nothing has been added to the underlying mechanisms possibly linking both events.

Genome-wide meta-analyses of nonsyndromic orofacial clefts identify novel associations between FOXE1 and all orofacial clefts, and TP63 and cleft lip with or without cleft palate.

Nonsyndromic orofacial clefts (OFCs) are a heterogeneous group of common craniofacial birth defects with complex etiologies that include genetic and environmental risk factors. OFCs are commonly categorized as cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP), which have historically been analyzed as distinct entities. Genes for both CL/P and CP have been identified via multiple genome-wide linkage and association studies (GWAS); however, altogether, known variants account for a minority of the estimated heritability in risk to these craniofacial birth defects.

p62/SQSTM1 by Binding to Vitamin D Receptor Inhibits Hepatic Stellate Cell Activity, Fibrosis, and Liver Cancer.

Hepatic stellate cells (HSCs) play critical roles in liver fibrosis and hepatocellular carcinoma (HCC). Vitamin D receptor (VDR) activation in HSCs inhibits liver inflammation and fibrosis. We found that p62/SQSTM1, a protein upregulated in liver parenchymal cells but downregulated in HCC-associated HSCs, negatively controls HSC activation.

Uniparental ancestry markers in Chilean populations.

The presence of Native Americans, Europeans, and Africans has led to the development of a multi-ethnic, admixed population in Chile. This study aimed to contribute to the characterization of the uniparental genetic structure of three Chilean regions. Newborns from seven hospitals in Independencia, Providencia, Santiago, Curicó, Cauquenes, Valdívia, and Puerto Montt communes, belonging to the Chilean regions of Santiago, Maule, and Los Lagos, were studied.