Mother and newborn survival according to point of entry and type of human resources in a maternal referral system in Kayes (Mali)

The study assesses maternal and newborn survival in women presenting with an obstetric complication in Kayes (Mali). It compares the effects of the point of entry into the referral system on joint mother-newborn survival, and the effects of the configuration of healthcare teams at the community health centers (CHC). Results show that entry at the CHC while coming from a distance of less than 5 km increased the likelihood of joint survival by 8.50%. The size of the healthcare team at the CHC is significantly associated with mother-newborn survival only when distance traveled is 5 km or less

Realización profesional en docentes de Lima Este en un contexto de emergencia sanitaria COVID-19

El objetivo general de la presente investigación fue determinar las diferencias que existen en los factores que describen la realización profesional en los docentes de educación primaria en instituciones educativas de Lima Este en un contexto de enseñanza no presencial por la emergencia sanitaria COVID-19. La investigación fue de enfoque cuantitativo, tipo descriptivo, diseño no experimental, nivel comparativo, de corte transversal; la población constituida por los docentes quienes son los principales protagonistas; la muestra de 384 y el muestreo probabilístico; siendo el instrumento un cuestionario elaborado en Formulario Google. Los resultados indicaron que se evidencia que en los niveles de satisfacción en los factores que comprende la realización profesional existen diferencias significativas estadísticamente; es decir, la realización personal y la realización en el centro de trabajo, difieren, si se les compara en los niveles alcanzados; siendo que la realización en el centro de trabajo presentó mejor situación en cuanto a la satisfacción

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Clonal Hematopoiesis and Risk of Prostate Cancer in Large Samples of European Ancestry Men

Little is known regarding the potential relationship between clonal hematopoiesis (CH) of indeterminate potential (CHIP), which is the expansion of hematopoietic stem cells with somatic mutations, and risk of prostate cancer, the fifth leading cause of cancer death of men worldwide. We evaluated the association of age-related CHIP with overall and aggressive prostate cancer risk in two large whole-exome sequencing studies of 75 047 European ancestry men, including 7663 prostate cancer cases, 2770 of which had aggressive disease, and 3266 men carrying CHIP variants. We found that CHIP, defined by over 50 CHIP genes individually and in aggregate, was not significantly associated with overall (aggregate HR = 0.93, 95% CI = 0.76-1.13, P = 0.46) or aggressive (aggregate OR = 1.14, 95% CI = 0.92-1.41, P = 0.22) prostate cancer risk. CHIP was weakly associated with genetic risk of overall prostate cancer, measured using a polygenic risk score (OR = 1.05 per unit increase, 95% CI = 1.01-1.10, P = 0.01). CHIP was not significantly associated with carrying pathogenic/likely pathogenic/deleterious variants in DNA repair genes, which have previously been found to be associated with aggressive prostate cancer. While findings from this study suggest that CHIP is likely not a risk factor for prostate cancer, it will be important to investigate other types of CH in association with prostate cancer risk

Neonatal Fc Receptor: From Immunity to Therapeutics

The neonatal Fc receptor (FcRn), also known as the Brambell receptor and encoded by Fcgrt, is a MHC class I like molecule that functions to protect IgG and albumin from catabolism, mediates transport of IgG across epithelial cells, and is involved in antigen presentation by professional antigen presenting cells. Its function is evident in early life in the transport of IgG from mother to fetus and neonate for passive immunity and later in the development of adaptive immunity and other functions throughout life. The unique ability of this receptor to prolong the half-life of IgG and albumin has guided engineering of novel therapeutics. Here, we aim to summarize the basic understanding of FcRn biology, its functions in various organs, and the therapeutic design of antibody- and albumin-based therapeutics in light of their interactions with FcRn

Economic inequality is linked to biased self-perception

People’s self-perception biases often lead them to see themselves as better than the average person (a phenomenon known as self-enhancement). This bias varies across cultures, and variations are typically explained using cultural variables, such as individualism versus collectivism. We propose that socioeconomic differences among societies—specifically, relative levels of economic inequality—play an important but unrecognized role in how people evaluate themselves. Evidence for self-enhancement was found in 15 diverse nations, but the magnitude of the bias varied. Greater self-enhancement was found in societies with more income inequality, and income inequality predicted cross-cultural differences in self-enhancement better than did individualism/collectivism. These results indicate that macrosocial differences in the distribution of economic goods are linked to microsocial processes of perceiving the self

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Tears evoke the intention to offer social support: A systematic investigation of the interpersonal effects of emotional crying across 41 countries

Tearful crying is a ubiquitous and likely uniquely human phenomenon. Scholars have argued that emotional tears serve an attachment function: Tears are thought to act as a social glue by evoking social support intentions. Initial experimental studies supported this proposition across several methodologies, but these were conducted almost exclusively on participants from North America and Europe, resulting in limited generalizability. This project examined the tears-social support intentions effect and possible mediating and moderating variables in a fully pre-registered study across 7007 participants (24,886 ratings) and 41 countries spanning all populated continents. Participants were presented with four pictures out of 100 possible targets with or without digitally-added tears. We confirmed the main prediction that seeing a tearful individual elicits the intention to support, d = 0.49 [0.43, 0.55]. Our data suggest that this effect could be mediated by perceiving the crying target as warmer and more helpless, feeling more connected, as well as feeling more empathic concern for the crier, but not by an increase in personal distress of the observer. The effect was moderated by the situational valence, identifying the target as part of one's group, and trait empathic concern. A neutral situation, high trait empathic concern, and low identification increased the effect. We observed high heterogeneity across countries that was, via split-half validation, best explained by country-level GDP per capita and subjective well-being with stronger effects for higher-scoring countries. These findings suggest that tears can function as social glue, providing one possible explanation why emotional crying persists into adulthood.</p