Social Determinants of Health Among Pregnant Hispanic Women and Associated Psychological Outcomes.

BACKGROUND: There has been a concerning surge in maternal mortality among Hispanic women in recent years. Compromised mental health is present in nearly half of all maternal deaths, and risk factors include poor social support and depression. OBJECTIVE: Among Hispanic women who were born in the USA versus those not born in the USA, we sought to describe and compare social determinants of health and maternal psychological outcomes. METHODS: Hispanic pregnant women (n = 579) were recruited from two clinics in Tampa, FL, and completed various questionnaires related to social determinants of health, depression, stress, and social support. STATISTICAL ANALYSIS: Descriptive statistics, t-tests, and chi-square analyses were used to compare relationships between maternal nativity and subsequent psychosocial outcomes. Pearson correlations were used to explore associations between variables. RESULTS: Hispanic pregnant women who were not born in the USA had lower incomes (χ2 = 5.68, p = 0.018, df = 1), were more likely to be unemployed (χ2 = 8.12, p = 0.004, df = 1), and were more likely to be married (χ2 = 4.79, p = 0.029, df = 1) when compared with those born in the USA. Those not born in the USA reported lower social support (t = 3.92, p<0.001), specifically the tangible (t = 4.18, p < 0.001) and emotional support subscales (t = 4.4, p<0.001). When compared with those born in the USA, foreign-born Hispanic women reported less stress (t = 3.23, p = 0.001) and depression (t = 3.3, p = 0.002). CONCLUSION: Pregnant Hispanic women not born in the USA are at increased risk for suboptimal social determinants of health, including less social support. US-born women were more stressed and depressed and had higher BMIs.

A Preliminary Study Exploring the Relationship between Occupational Health Hazards and Gut Microbiota among Firefighters.

Firefighters are exposed to occupational hazards and have a higher prevalence of health issues. The gut microbiota plays a crucial role in the immune, endocrine, and neural systems, and disruptions in its composition can impact health outcomes. This pilot study aimed to investigate the potential association between occupational factors, changes in gut microbiota, and the development of adverse health outcomes in firefighters. To test this hypothesis, we recruited 15 firefighters and age/sex-matched controls to investigate the relationship between occupational environment and gut microbiota. Firefighters exhibit lower intestinal bacterial alpha diversity and a higher presence of pathogenic bacteria than the control. Moreover, unique gut bacterial taxa were observed in firefighters with high post-traumatic stress disorder (PTSD) scores, which could contribute to immune dysregulation and higher susceptibility to pathogen colonization. These preliminary findings suggest that occupational factors, including exposure to traumatic stressors and chemicals, may influence firefighters' health by modulating their gut microbiota. The observed changes in gut microbiota composition and the potential link to occupational hazards highlight the need for further research in larger sample-size studies. Understanding the role of gut microbiota in firefighter health may have implications for preventive measures and interventions to mitigate occupational health risks and improve overall well-being.

Tryptophan metabolism and immune alterations in pregnant Hispanic women with chronic Toxoplasma gondii infection.

PROBLEM: Pregnancy markedly modifies women's metabolism and immune functions. We hypothesized that pregnancy might alter the immune and metabolic responses to chronic Toxoplasma gondii infection in pregnancy. METHOD OF STUDY: A population of 690 pregnant Hispanic women were screened for antibodies to T. gondii and 158 women were positive (23% positivity) with 83% showing high avidity indices. These seropositive women were followed through their pregnancies with four data collection time points and a postpartum collection at two clinics in Tampa, Florida. A T. gondii seronegative group (N = 128) was randomly selected to serve as a control group and measured along pregnancy in the same way. Serum levels of tryptophan, kynurenine, and their ratio, phenylalanine, tyrosine and their ratio, neopterin, and nitrite were measured through pregnancy and the postpartum. A plasma cytokine panel (IFN-γ, TNFα, IL-2, IL-10, IL-12, IL-6, IL-17) was analyzed in parallel. RESULTS: The major findings suggest that indoleamine 2,3-dioxygenase (IDO-1) was less activated in T. gondii seropositive pregnant Hispanic women with chronic infection. Evidence for IDO-1 suppression was that tryptophan catabolism was less pronounced and there were lower levels of multiple inflammatory cytokines including IFN-γ, which is the major inducer of IDO-1, and higher nitrite concentration, a surrogate marker for nitric oxide, an inhibitor of IDO. CONCLUSIONS: Latent T. gondii infection was associated with higher plasma tryptophan levels, and lower inflammatory cytokines across pregnancy, suggesting suppression of the IDO-1 enzyme, and possible T cell exhaustion during pregnancy.

A pilot study: Validation of dried blood spots (DBS) to assess SARS-CoV2 IgG antibody immunoassays in underserved minority population.

Underserved, low-income, rural and certain migrant populations have greater risks and higher incidences of Coronavirus disease 2019 (COVID-19) than more privileged populations. Current in-person testing methods have limitations, namely exposure risk, a requirement of accessible transportation to healthcare facilities, and economic barriers. Dried blood spots (DBS) samples are widely used for diagnostics in many infectious diseases including Rabies, HIV, Ebola viruses and newborn screening. Our goal was to determine the accuracy and reliability of measuring COVID-19 IgG in DBS compared to paired plasma samples in a population with known infection status and then apply this method to screen an underserved minority population with high risk for COVID-9 infection (unvaccinated, pregnant, low income, Hispanic women). To optimize the assay, we tested 22 nonpregnant women, 12 with positive prior PCR testing for SARS-CoV2 infection and 10 with negative PCR results. After the assay was optimized, we tested the assay in a vulnerable population with a high risk for infection, who were 52 Hispanic pregnant women without prior PCR testing or vaccination. DBS assay results in both groups showed an agreement of 100% with paired plasma samples. The availability of a DBS assay could enable people who may not have access or transportation to healthcare facilities to use DBS as a COVID-19 testing vehicle.

Adverse pregnancy outcomes in Toxoplasma gondii seropositive Hispanic women.

AIMS: Chronic Toxoplasma gondii infection is not thought to affect pregnancy or birth outcomes, but there are few prospective studies. The study aims were T. gondii immunoglobulin G measurement and relationship of chronic T. gondii infection with gestational age at birth and adverse pregnancy outcomes in 690 Hispanic women in Tampa, Florida. METHODS: Hispanic women, born either in the United States or in Latin America or the Caribbean had a venous blood sample drawn to measure T. gondii IgG and T. gondii serotype at the first prenatal visit, along with collection of demographic and health-related measures. Seropositive and seronegative women were followed throughout their pregnancy. Gestational age, infant weights, and adverse pregnancy outcomes (miscarriages, preterm births) were compared in the two groups. RESULTS: There were 740 women of self-reported Hispanic ethnicity screened and enrolled in Tampa, Florida, with 690 having birth data extracted from the electronic health record (538 T. gondii negative and 152 T. gondii seropositive). T. gondii seropositivity was 22.4% and the majority (83%) had high avidity titers, indicating chronic infection. Compared to T. gondii seronegative Hispanic women, seroseropositive women had more smaller for gestational age infants and higher prevalences of miscarriages and preterm birth. CONCLUSION: This is one of the largest longitudinal cohort studies of women with chronic T. gondii infection followed through pregnancy. There was a higher percentages of adverse pregnancy outcomes in this group compared to T. gondii seronegative controls. The mechanism for this is unknown and warrants reexamination of the dogma that chronic T. gondii infection in pregnant women has no significant clinical consequences.

Premature Infant Gut Microbiome relationships with childhood behavioral scales: preliminary insights.

Introduction: Very Low Birth Weight (VLBW) infants, born weighing less than 1,500 grams, are at risk for both gut dysbiosis and later neuropsychological developmental deficits. Behavioral effects, while related to neurodevelopment, are often more subtle and difficult to measure. The extent of later neurobehavioral consequences associated with such microbial dysbiosis has yet to be determined. We explored associations between the infants' gut microbiome and early childhood behavior at 4 years of age and identified the bacterial taxa through a multivariate analysis by linear models. Methods: Parents completed the Child Behavior Checklist (CBCL) focused on different DSM diagnostic categories: affective, anxiety, pervasive developmental, attention deficit/hyperactivity, and oppositional defiant. All the CBCL scores were corrected for gender, delivery method, gestational age, infant birth weight, occurrence of sepsis, and days on antibiotics prior statistical analyses. Canonical correlation analysis (CCA) was performed to determine the relationship between early life gut microbiome and the adjusted CBCL scores. The association of bacterial Amplicon sequence Variants (ASVs) to the CBCL scores were tested with multivariate analysis by linear models (MaAsLin). Results: Nineteen children who were previously born with very low birth weight and studied while hospitalized in the Neonatal Intensive Care Unit (NICU) were included in this study. Statistically significant associations were observed between early life gut bacteria such as Veillonella dispar, Enterococcus, Escherichia coli, and Rumincococcus to later behavior at 4 years. No significant association could be observed with early-life gut microbiome alpha diversity and behavioral measures at 4 years. Discussion: These preliminary observational data provide insight into the relationships between VLBW gut microbiome dysbiosis and childhood behavior. This study contributes to the literature on gut microbiome analysis by examining various behavioral domains using a standardized tool linked to the Diagnostic and Statistical Manual of Mental Disorders (DSM).

Relationships of the very low birth weight infant microbiome with neurodevelopment at 2 and 4 years of age.

Very low birth weight (VLBW) infants (<1500 g) are at risk for poor neurodevelopmental outcomes depending on gestational age (GA), birth weight (BW), and morbidity in early life. The contribution of the gut microbiome is not well understood. Stool samples were collected weekly in the neonatal intensive care unit (NICU) from 24 VLBW infants for 6 weeks after admission and then again at 2 and 4 years of age. The Battelle Development Inventory-2 Screening Test (BDI-2 ST) was administered at 2- and 4-year time points. VLBW infants had dysbiotic microbiota in the NICU that progressed for most to an adult-type microbiota by 4 years of age. The BDI-2 ST results at age of 2 years triggered referral for further testing in 14 toddlers (70%), and by 4 years of age only seven of these 14 continued to require referral. Both NICU infant stool diversity and particular microbial amplicon sequence variants were associated with BDI-2 ST subscales, particularly for cognition, adaptive, and communication subscales, when controlled for GA, BW, and antibiotic exposure. Network analysis of the NICU infant stool microbial ecology showed differences in children needing neurodevelopmental referral. The results of this preliminary study indicate that the neonatal gut microbiome plays a role in early cognitive and behavioral neurodevelopment.

The gut mycobiome in health, disease, and clinical applications in association with the gut bacterial microbiome assembly.

The gut mycobiome (fungi) is a small but crucial component of the gut microbiome in humans. Intestinal fungi regulate host homoeostasis, pathophysiological and physiological processes, and the assembly of the co-residing gut bacterial microbiome. Over the past decade, accumulating studies have characterised the gut mycobiome in health and several pathological conditions. We review the compositional and functional diversity of the gut mycobiome in healthy populations from birth to adulthood. We describe factors influencing the gut mycobiome and the roles of intestinal fungi-especially Candida and Saccharomyces spp-in diseases and therapies with a particular focus on their synergism with the gut bacterial microbiome and host immunity. Finally, we discuss the underappreciated effects of gut fungi in clinical implications, and highlight future microbiome-based therapies that harness the tripartite relationship among the gut mycobiome, bacterial microbiome, and host immunity, aiming to restore a core gut mycobiome and microbiome and to improve clinical efficacy.

Gut Dysbiosis and Immune System in Atherosclerotic Cardiovascular Disease (ACVD).

Atherosclerosis is a leading cause of cardiovascular disease and mortality worldwide. Alterations in the gut microbiota composition, known as gut dysbiosis, have been shown to contribute to atherosclerotic cardiovascular disease (ACVD) development through several pathways. Disruptions in gut homeostasis are associated with activation of immune processes and systemic inflammation. The gut microbiota produces several metabolic products, such as trimethylamine (TMA), which is used to produce the proatherogenic metabolite trimethylamine-N-oxide (TMAO). Short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate, and certain bile acids (BAs) produced by the gut microbiota lead to inflammation resolution and decrease atherogenesis. Chronic low-grade inflammation is associated with common risk factors for atherosclerosis, including metabolic syndrome, type 2 diabetes mellitus (T2DM), and obesity. Novel strategies for reducing ACVD include the use of nutraceuticals such as resveratrol, modification of glucagon-like peptide 1 (GLP-1) levels, supplementation with probiotics, and administration of prebiotic SCFAs and BAs. Investigation into the relationship between the gut microbiota, and its metabolites, and the host immune system could reveal promising insights into ACVD development, prognostic factors, and treatments.

A Pilot Study To Establish an In Vitro Model To Study Premature Intestinal Epithelium and Gut Microbiota Interactions.

Intestinal microbiota has emerged as an important player in the health and disease of preterm infants. The interactions between intestinal flora and epithelium can lead to local injury and systemic diseases. A suitable in vitro cell model is needed to enhance our understanding of these interactions. In this study, we exposed fetal epithelial cell cultures (FHs-74 int cells, human, ATCC CCL 241) to sterile fecal filtrates derived from stool collected from preterm infants at <2 and at 3 to 4 weeks of age. We measured the cytokine levels from the culture media after 4, 24, and 48 h of exposure to the fecal filtrates. We analyzed the 16S rRNA V4 gene data of the fecal samples and transcriptome sequencing (RNA-seq) data from the fetal epithelial cells after 48 h of exposure to the same fecal filtrates. The results showed correlations between inflammatory responses (both cytokine levels and gene expression) and the Proteobacteria-to-Firmicutes ratio and between fecal bacterial genera and epithelial apoptosis-related genes. Our in vitro cell model can be further developed and applied to study how the epithelium responds to different microbial flora from preterm infants. Combining immature epithelial cells and preterm infant stool samples into one model allows us to investigate disease processes in preterm infants in a way that had not been previously reported. IMPORTANCE The gut bacterial flora influences the development of the immune system and long-term health outcomes in preterm infants. Studies of the mechanistic interactions between the gut bacteria and mucosal barrier are limited to clinical observations, animal models, and in vitro cell culture models for this vulnerable population. Most in vitro cell culture models of microbe-host interactions use single organisms or adult origin cell lines. Our study is innovative and significant in that we expose immature epithelial cells derived from fetal tissues to fecal filtrates from eight stool samples from four preterm infants to study the role of intestinal epithelial cells. In addition, we analyzed epithelial gene expression to examine multiple cellular processes simultaneously. This model can be developed into patient-derived two- or three-dimensional cell cultures exposed to their own fecal material to allow better prediction of patient physiological responses to support the growing field of precision medicine.

The Association between Early-Life Gut Microbiota and Long-Term Health and Diseases.

Early life gut microbiota have been increasingly recognized as major contributors to short and/or long-term human health and diseases. Numerous studies have demonstrated that human gut microbial colonization begins at birth, but continues to develop a succession of taxonomic abundances for two to three years until the gut microbiota reaches adult-like diversity and proportions. Several factors, including gestational age (GA), delivery mode, birth weight, feeding types, antibiotic exposure, maternal microbiome, and diet, influence the diversity, abundance, and function of early life gut microbiota. Gut microbial life is essential for assisting with the digestion of food substances to release nutrients, exerting control over pathogens, stimulating or modulating the immune system, and influencing many systems such as the liver, brain, and endocrine system. Microbial metabolites play multiple roles in these interactions. Furthermore, studies provide evidence supporting that imbalances of the gut microbiota in early life, referred to as dysbiosis, are associated with specific childhood or adult disease outcomes, such as asthma, atopic dermatitis, diabetes, allergic diseases, obesity, cardiovascular diseases (CVD), and neurological disorders. These findings support that the human gut microbiota may play a fundamental role in the risk of acquiring diseases that may be programmed during early life. In fact, it is critical to explore the role of the human gut microbiota in early life.

Correction: Yoo, J.Y., et al. Gut Microbiota and Immune System Interactions. Microorganisms 2020, 8, 1587.

Corrections have been made to "Gut Microbiota and Immune System Interactions" [...].

Comparative analysis of COVID-19 guidelines from six countries: a qualitative study on the US, China, South Korea, the UK, Brazil, and Haiti.

BACKGROUND: In late January, a worldwide crisis known as COVID-19 was declared a Public Health Emergency of International Concern by the WHO. Within only a few weeks, the outbreak took on pandemic proportions, affecting over 100 countries. It was a significant issue to prevent and control COVID-19 on both national and global scales due to the dramatic increase in confirmed cases worldwide. Government guidelines provide a fundamental resource for communities, as they guide citizens on how to protect themselves against COVID-19, however, they also provide critical guidance for policy makers and healthcare professionals on how to take action to decrease the spread of COVID-19. We aimed to identify the differences and similarities between six different countries' (US, China, South Korea, UK, Brazil and Haiti) government-provided community and healthcare system guidelines, and to explore the relationship between guideline issue dates and the prevalence/incidence of COVID-19 cases. METHODS: To make these comparisons, this exploratory qualitative study used document analysis of government guidelines issued to the general public and to healthcare professionals. Documents were purposively sampled (N = 55) and analyzed using content analysis. RESULTS: The major differences in the evaluation and testing criteria in the guidelines across the six countries centered around the priority of testing for COVID-19 in the general population, which was strongly dependent on each country's healthcare capacity. However, the most similar guidelines pertained to the clinical signs and symptoms of COVID-19, and methods to prevent its contraction. CONCLUSION: In the initial stages of the outbreak, certain strategies were universally employed to control the deadly virus's spread, including quarantining the sick, contact tracing, and social distancing. However, each country dealt with differing healthcare capacities, risks, threats, political and socioeconomic challenges, and distinct healthcare systems and infrastructure. Acknowledging these differences highlights the importance of examining the various countries' response to the COVID-19 pandemic with a nuanced view, as each of these factors shaped the government guidelines distributed to each country's communities and healthcare systems.

Gut Microbiota and Immune System Interactions.

Dynamic interactions between gut microbiota and a host's innate and adaptive immune systems play key roles in maintaining intestinal homeostasis and inhibiting inflammation. The gut microbiota metabolizes proteins and complex carbohydrates, synthesize vitamins, and produce an enormous number of metabolic products that can mediate cross-talk between gut epithelial and immune cells. As a defense mechanism, gut epithelial cells produce a mucosal barrier to segregate microbiota from host immune cells and reduce intestinal permeability. An impaired interaction between gut microbiota and the mucosal immune system can lead to an increased abundance of potentially pathogenic gram-negative bacteria and their associated metabolic changes, disrupting the epithelial barrier and increasing susceptibility to infections. Gut dysbiosis, or negative alterations in gut microbial composition, can also dysregulate immune responses, causing inflammation, oxidative stress, and insulin resistance. Over time, chronic dysbiosis and the translocation of bacteria and their metabolic products across the mucosal barrier may increase prevalence of type 2 diabetes, cardiovascular disease, inflammatory bowel disease, autoimmune disease, and a variety of cancers. In this paper, we highlight the pivotal role gut microbiota and their metabolites (short-chain fatty acids (SCFAs)) play in mucosal immunity.

Contributors to Dysbiosis in Very-Low-Birth-Weight Infants.

The objective of this commentary was to analyze the causes and outcomes of gut microbiome dysbiosis in preterm infants who are born at very low birth weight (VLBW). The intrauterine development of VLBW infants is interrupted abruptly with preterm birth and followed by extrauterine, health-threatening conditions and sequelae. These infants develop intestinal microbial dysbiosis characterized by low diversity, an overall reduction in beneficial and/or commensal bacteria, and enrichment of opportunistic pathogens of the Gammaproteobacteria class. The origin of VLBW infant dysbiosis is not well understood and is likely the result of a combination of immaturity and medical care. We propose that these factors interact to produce inflammation in the gut, which further perpetuates dysbiosis. Understanding the sources of dysbiosis could result in interventions to reduce gut inflammation, decrease enteric pathology, and improve health outcomes for these vulnerable infants.

An 8-gene signature for prediction of prognosis and chemoresponse in non-small cell lung cancer.

Identification of a potential gene signature for improved diagnosis in non-small cell lung cancer (NSCLC) patient is necessary. Here, we aim to establish and validate the prognostic efficacy of a gene set that can predict prognosis and benefits of adjuvant chemotherapy (ACT) in NSCLC patients from various ethnicities. An 8-gene signature was calculated from the gene expression of 181 patients using univariate Cox proportional hazard regression analysis. The prognostic value of the signature was robustly validated in 1,477 patients from five microarray independent data sets and one RNA-seq data set. The 8-gene signature was identified as an independent predictor of patient survival in the presence of clinical parameters in univariate and multivariate analyses [hazard ratio (HR): 2.84, 95% confidence interval CI (1.74-4.65), p=3.06e-05, [HR] 2.62, 95% CI (1.51-4.53), p=0.001], respectively. Subset analysis demonstrated that the 8-gene signature could identify high-risk patients in stage II-III with improved survival from ACT [(HR) 1.47, 95% CI (1.01-2.14), p=0.044]. The 8-gene signature also stratified risk groups in EGFR-mutated and wild-type patients. In conclusion, the 8-gene signature is a strong and independent predictor that can significantly stratify patients into low- and high-risk groups. Our gene signature also has the potential to predict patients in stage II-III that are likely to benefit from ACT.

Prognostic value and their clinical implication of 89-gene signature in glioma.

Gliomas are the most common and aggressive primary tumors in adults. The current approaches, such as histological classification and molecular genetics, have limitation in prediction of individual therapeutic outcomes due to heterogeneity within the tumor groups. Recent studies have proposed several gene signatures to predict glioma's prognosis. However, most of the gene expression profiling studies have been performed on relatively small number of patients and combined probes from diverse microarray chips. Here, we identified prognostic 89 common genes from diverse microarray chips. The 89-gene signature classified patients into good and bad prognostic groups which differed in the overall survival significantly, reflecting the biological characteristics and heterogeneity. The robustness and accuracy of the gene signature as an independent prognostic factor was validated in three microarray and one RNA-seq data sets independently. By incorporating into histological classification and molecular marker, the 89-gene signature could further stratify patients with 1p/19q co-deletion and IDH1 mutation. Additionally, subset analyses suggested that the 89-gene signature could predict patients who would benefit from adjuvant chemotherapy. Conclusively, we propose that the 89-gene signature would have an independent and accurate prognostic value for clinical use. This study also offers opportunities for novel targeted treatment of individual patients.

Probiotics and Prebiotics: Present Status and Future Perspectives on Metabolic Disorders.

Metabolic disorders, including type 2 diabetes (T2DM) and cardiovascular disease (CVD), present an increasing public health concern and can significantly undermine an individual's quality of life. The relative risk of CVD, the primary cause of death in T2DM patients, is two to four times higher in people with T2DM compared with those who are non-diabetic. The prevalence of metabolic disorders has been associated with dynamic changes in dietary macronutrient intake and lifestyle changes over recent decades. Recently, the scientific community has considered alteration in gut microbiota composition to constitute one of the most probable factors in the development of metabolic disorders. The altered gut microbiota composition is strongly conducive to increased adiposity, ß-cell dysfunction, metabolic endotoxemia, systemic inflammation, and oxidative stress. Probiotics and prebiotics can ameliorate T2DM and CVD through improvement of gut microbiota, which in turn leads to insulin-signaling stimulation and cholesterol-lowering effects. We analyze the currently available data to ascertain further potential benefits and limitations of probiotics and prebiotics in the treatment of metabolic disorders, including T2DM, CVD, and other disease (obesity). The current paper explores the relevant contemporary scientific literature to assist in the derivation of a general perspective of this broad area.

CRC-113 gene expression signature for predicting prognosis in patients with colorectal cancer.

Colorectal cancer (CRC) is the third leading cause of global cancer mortality. Recent studies have proposed several gene signatures to predict CRC prognosis, but none of those have proven reliable for predicting prognosis in clinical practice yet due to poor reproducibility and molecular heterogeneity. Here, we have established a prognostic signature of 113 probe sets (CRC-113) that include potential biomarkers and reflect the biological and clinical characteristics. Robustness and accuracy were significantly validated in external data sets from 19 centers in five countries. In multivariate analysis, CRC-113 gene signature showed a stronger prognostic value for survival and disease recurrence in CRC patients than current clinicopathological risk factors and molecular alterations. We also demonstrated that the CRC-113 gene signature reflected both genetic and epigenetic molecular heterogeneity in CRC patients. Furthermore, incorporation of the CRC-113 gene signature into a clinical context and molecular markers further refined the selection of the CRC patients who might benefit from postoperative chemotherapy. Conclusively, CRC-113 gene signature provides new possibilities for improving prognostic models and personalized therapeutic strategies.

Prognostic value of a 92-probe signature in breast cancer.

Clinical applications of gene expression signatures in breast cancer prognosis still remain limited due to poor predictive strength of single training datasets and appropriate invariable platforms. We proposed a gene expression signature by reducing baseline differences and analyzing common probes among three recent Affymetrix U133 plus 2 microarray data sets. Using a newly developed supervised method, a 92-probe signature found in this study was associated with overall survival. It was robustly validated in four independent data sets and then repeated on three subgroups by incorporating 17 breast cancer microarray datasets. The signature was an independent predictor of patients' survival in univariate analysis [(HR) 1.927, 95% CI (1.237-3.002); p < 0.01] as well as multivariate analysis after adjustment of clinical variables [(HR) 7.125, 95% CI (2.462-20.618); p < 0.001]. Consistent predictive performance was found in different multivariate models in increased patient population (p = 0.002). The survival signature predicted a late metastatic feature through 5-year disease free survival (p = 0.006). We identified subtypes within the lymph node positive (p < 0.001) and ER positive (p = 0.01) patients that best reflected the invasive breast cancer biology. In conclusion using the Common Probe Approach, we present a novel prognostic signature as a predictor in breast cancer late recurrences.