Activation of Bivalent Gene POU4F1 Promotes and Maintains Basal-like Breast Cancer.

Basal-like breast cancer (BLBC) is the most aggressive molecular subtype of breast cancer with worse prognosis and fewer treatment options. The underlying mechanisms upon BLBC transcriptional dysregulation and its upstream transcription factors (TFs) remain unclear. Here, among the hyperactive candidate TFs of BLBC identified by bioinformatic analysis, POU4F1 is uniquely upregulated in BLBC and is associated with poor prognosis. POU4F1 is necessary for the tumor growth and malignant phenotypes of BLBC through regulating G1/S transition by direct binding at the promoter of CDK2 and CCND1. More importantly, POU4F1 maintains BLBC identity by repressing ERα expression through CDK2-mediated EZH2 phosphorylation and subsequent H3K27me3 modification in ESR1 promoter. Knocking out POU4F1 in BLBC cells reactivates functional ERα expression, rendering BLBC sensitive to tamoxifen treatment. In-depth epigenetic analysis reveals that the subtype-specific re-configuration and activation of the bivalent chromatin in the POU4F1 promoter contributes to its unique expression in BLBC, which is maintained by DNA demethylase TET1. Together, these results reveal a subtype-specific epigenetically activated TF with critical role in promoting and maintaining BLBC, suggesting that POU4F1 is a potential therapeutic target for BLBC.

Biodegradable plastics: Green hope or greenwashing?

The universality of plastic has an inescapable responsibility for the large-scale production of plastic wastes. Fossil-based plastics, which account for the majority of the market, are dazzling, and the global environmental pollution caused by them is also becoming more and more complicated. In addition to controlling the total amount at the source, people have also actively sought some emerging materials to replace existing conventional plastics so that they can be handled better and easier at the end. Biodegradable plastics (BPs) can theoretically shorten the life cycle of plastics and reduce environmental stress. However, in the natural environment, many factors are uncontrollable, and whether BPs can alleviate white pollution needs further certification. Due to the wide and complex physical and chemical conditions encountered in natural ecosystems, great care must be taken in trying to define this term. The current standards and test methods are insufficient to predict the biodegradability of BPs in the natural environment. Additionally, the existing standards and test methods for biodegradability of water environment do not involve toxicity tests, nor do they consider the potentially adverse ecological effects of BPs or micro BPs particles that may be produced by crushing. Therefore, this article mainly discusses whether BPs are green hope or greenwashing: 1) Degradability in the environment; 2) Impact of existing waste management; and 3) Recycling Impact of resources and impact on global carbon sequestration. Successfully solving these knowledge gaps is the key requirement of the new standard for the production of BPs.

Recent advances in the analysis methodologies for microplastics in aquatic organisms: current knowledge and research challenges.

The widespread occurrence and high bioavailability of microplastics have increasingly attracted wide attention of society. Because of the presence of microplastics in aquatic organisms, it is necessary to investigate their abundance in different species. Recently, the diversity of research methods for microplastics in aquatic organisms has resulted in different detection rates of microplastics; problematically, different results are poorly comparable. As a new global environmental problem, there is an urgent need to reach a consensus on the investigation and analysis methods involving microplastics. The formulation of standardized methods for microplastics in aquatic organisms is a scientific problem that needs to be resolved urgently in the research of microplastics. The current review systematically summarizes the recent progress in the extraction, separation, quantitative analysis and qualitative identification of microplastics in aquatic organisms. The advantages and disadvantages of the different methods are discussed. In addition, challenges faced by the development of standardized analytical methods for microplastics are discussed from the perspectives of the sampling representativeness of aquatic organisms, control of background values, analysis of nanoplastics, and application of identification technology. Further, the necessity and urgency of the standardization of analytical methods for microplastics are discussed.

Overlap between dissociation and other psychological characteristics in patients with psychogenic nonepileptic seizures.

Patients with psychogenic nonepileptic seizures (PNES) often report symptoms of dissociation. However, it is unclear how these symptoms relate to psychotherapeutic treatment, for example, with cognitive-behavioral therapy (CBT). Here, we investigated the degree of overlap between symptoms of dissociation and other psychiatric features that are more traditional targets for CBT. We used a hierarchical linear regression to measure the variance associated with dissociative symptoms (as assessed by the Dissociative Experiences Scale - DES) among 46 individuals with PNESs. The regression predictor variables are indices of participants' self-rated mood, self-efficacy, quality of life, locus of control, and life outlook (e.g., optimism). Results revealed that 70.2% of the variance associated with DES score was explained by psychological distress and locus of control. The other factors examined did not make a significant contribution to the regression model. These results suggest that traditional CBT targets - mood symptoms, mood distress, and dysfunctional beliefs about locus of control - overlap substantially with self-reported dissociative symptoms.

The effect of terminal cleaning on environmental contamination rates of multidrug-resistant Acinetobacter baumannii.

We evaluated the prevalence of multidrug-resistant Acinetobacter baumannii environmental contamination before and after discharge cleaning in rooms of infected/colonized patients. 46.9% of rooms and 15.3% of sites were found contaminated precleaning, and 25% of rooms and 5.5% of sites were found contaminated postcleaning. Cleaning significantly decreased environmental contamination of A baumannii; however, persistent contamination represents a significant risk factor for transmission. Further studies on this and more effective cleaning methods are needed.

Recovery of Gram-negative bacilli in stored endotracheal aspirates.

This study assessed the recovery rates of Gram-negative bacilli from stored endotracheal aspirates frozen with and without glycerol. Samples frozen with glycerol showed a significant difference in isolate recovery, 89.7% versus 69.2% (P = 0.02). This study demonstrates that it is possible to achieve high recovery rates of potentially pathogenic organisms from endotracheal aspirates when stored with glycerol, thus broadening the scope of active surveillance cultures for both clinical and research purposes.

Comorbidity risk-adjustment measures were developed and validated for studies of antibiotic-resistant infections.

OBJECTIVES: Comorbidities are often included in risk-factor models for nosocomial antibiotic-resistant bacterial infections, and aggregate comorbidity measures are valuable because they allow one variable to represent many. This study aimed to develop new aggregate comorbidity measures based upon the Chronic Disease Score (CDS) for assessing the comorbidity-attributable risk of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) nosocomial infections. STUDY DESIGN AND SETTING: For each outcome, two retrospective cohort studies of hospitalized patients were conducted. Outcomes were a first MRSA or VRE positive clinical culture obtained 48 hours or more postadmission. Each cohort was divided into development (July 1998-2001) and validation (August 2001-2003) samples. New comorbidity measures were created for MRSA (CDS-MRSA), VRE (CDS-VRE), or any nosocomial infection outcome (CDS-ID) using logistic regression and subsequently validated. Model discrimination was measured using the c-statistic. RESULTS: Discrimination of the CDS-MRSA (c=0.60), CDS-VRE (c=0.65), and CDS-ID (MRSA: c=0.57; VRE: c=0.64) was greater than that of the original CDS (MRSA: c=0.52; VRE: c=0.57). CONCLUSION: The CDS-MRSA, CDS-VRE, and CDS-ID are new infectious disease specific comorbidity risk-adjustment measures that will be useful for the quality of future epidemiologic studies of MRSA, VRE, and other infectious diseases.

Population antibiotic susceptibility for Streptococcus pneumoniae and treatment outcomes in common respiratory tract infections.

PURPOSE: Antibiotic-resistant Streptococcus pneumoniae potentially threatens the successful treatment of common respiratory tract infections (RTIs); however, the relationship between antibiotic resistance and treatment outcomes remains unclear. We aimed to test the hypothesis that higher in vitro penicillin and erythromycin nonsusceptibility levels among clinical isolates of S. pneumoniae are associated with higher risk of treatment failure in suppurative acute otitis media (AOM), acute sinusitis, and acute exacerbation of chronic bronchitis (AECB). METHODS: We conducted a population-level analysis using treatment outcomes data from a national, managed-care claims database, and antibiotic susceptibility data from a national repository of antimicrobial susceptibility results between 1997 and 2000. Treatment outcomes in patients with suppurative AOM, acute sinusitis, or AECB receiving selected macrolides or beta-lactams were assessed. Associations between RTI-specific treatment outcomes and antibiotic nonsusceptibility were determined using Spearman correlation coefficients with condition-specific paired outcome and susceptibility data for each region and each year. RESULTS: There were 649 552 available RTI outcomes and 7252 susceptibility tests performed on S. pneumoniae isolates. There were no statistically significant trends across time for resolution proportions following treatment by either beta-lactams or macrolides among any of the RTIs. Correlation analyses found no statistically significant association between S. pneumoniae susceptibility and RTI treatment outcomes apart from a significant positive association between of erythromycin nonsusceptibility in ear isolates and macrolide treatment resolution for suppurative AOM. CONCLUSION: On the population level, in vitro S. pneumoniae nonsusceptibility to macrolide or beta-lactam antibiotics was not associated with treatment failure in conditions of probable S. pneumoniae etiology.

The use and interpretation of quasi-experimental studies in medical informatics.

Quasi-experimental study designs, often described as nonrandomized, pre-post intervention studies, are common in the medical informatics literature. Yet little has been written about the benefits and limitations of the quasi-experimental approach as applied to informatics studies. This paper outlines a relative hierarchy and nomenclature of quasi-experimental study designs that is applicable to medical informatics intervention studies. In addition, the authors performed a systematic review of two medical informatics journals, the Journal of the American Medical Informatics Association (JAMIA) and the International Journal of Medical Informatics (IJMI), to determine the number of quasi-experimental studies published and how the studies are classified on the above-mentioned relative hierarchy. They hope that future medical informatics studies will implement higher level quasi-experimental study designs that yield more convincing evidence for causal links between medical informatics interventions and outcomes.

Prediction rules to identify patients with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci upon hospital admission.

BACKGROUND: In 2003, the Society of Healthcare Epidemiology of America (SHEA) recommended surveillance cultures upon hospital admission for patients at high risk for carriage of vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to assess the validity of factors from past medical history in defining patients at high risk for subsequent positive cultures with VRE or MRSA upon hospital admission. METHODS: Subjects were adult inpatients admitted to nonintensive care wards of the index hospital during 2001-2002. Cases had MRSA or VRE positive clinical cultures within 48 hours of hospital admission. Patients with previous history of MRSA or VRE were excluded. RESULTS: Nineteen thousand three hundred ninety-nine patients were included, with 273 cases of VRE or MRSA. Previous admission within 1 year of current admission had a sensitivity of 56.8% and a specificity of 88.4% for predicting a case of MRSA or VRE. Individually, the sensitivity and specificity for admission within the past year were 50.5% and 88.4%, respectively, for MRSA and 76.9% and 88.4%, respectively, for VRE. CONCLUSIONS: Patients with a previous hospital admission represent a high-risk population for positive culture for VRE and MRSA and may be a group of which active surveillance is indicated.