Current Status of Poly(ADP-ribose) Polymerase Inhibitors as Novel Therapeutic Agents for Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer that is clinically defined as lacking estrogen and progesterone receptors, as well as being ERBB2 (HER-2) negative. Without specific therapeutic targets, TNBC carries a worse prognosis than other types of breast cancer in the absence of therapy. Research has now further differentiated breast cancer into subtypes based on genetic expression patterns. One of these subtypes, basal-like, frequently overlaps with the clinical picture of TNBC. Additionally, both TNBC and basal-like breast cancer link to BRCA mutations. Recent pharmaceutical advances have created a class of drugs, poly(ADP-ribose) polymerase (PARP) inhibitors, which are showing potential to effectively treat these patients. The aim of this paper is to summarize the basis behind PARP inhibitors and update the current status of their development in clinical trials for the treatment of TNBC

Outcome for Patients with Triple-Negative Breast Cancer Is Not Dependent on Race/Ethnicity

Introduction. Triple negative breast cancer (TNBC) is biologically aggressive and is associated with a worse prognosis. To understand the impact of race/ethnicity on outcome for patients with TNBC, confounding factors such as socioeconomic status (SES) need to be controlled. We examined the impact of race/ethnicity on a cohort of patients of low SES who have TNBC. Methods. 786 patients with Stage 0–III breast cancer were evaluated. Of these, 202 patients had TNBC (26%). Primary endpoints were cancer recurrence and death. ZIP code-based income tract and institutional financial data were used to assess SES. Data were analyzed using Kaplan-Meier survival analysis, log-rank tests, Cox Proportional hazard regression, chi square test, and t-tests. A P value ≤0.05 was considered statistically significant. Results. Of the 468 African-Americans (60%) in the database, 138 had TNBC; 64 of 318 Caucasians had TNBC. 80% of patients had an annual income of ≤$20,000. The 5-year overall survival was 77% for African-American women versus 72% for Caucasian women (P = 0.95). On multivariate analysis, race/ethnicity had an impact on disease-free survival (P = 0.027) but not on overall survival (P = 0.98). Conclusion. In a predominantly indigent population, race/ethnicity had no impact on overall survival for patients with triple negative breast cancer

Selection of nitrogen fixation and phosphate solubilizing bacteria from cultivating soil samples of Hung Yen province in Vietnam

The nitrogen fixing bacteria (NFB) and phosphate solubilizing bacteria (PSB) are used widely for producing of microbiological fertilizers. This study aims to seek nitrogen-fixing and phosphate-solubilizing bacteria strains to add to the collection of candidate strains for producing single and multi-function microbiological fertilizers. From 40 soil samples of 8 fields for cultivating rice, medicinal plants and vegetables, 15 NFB strains and 12 PSB strains were isolated and determined the ability of fixing nitrogen and solubilizing inorganic phosphate compound through creation of NH₄⁺ and PO₄⁻ in culture medium. Among 15 NFB strains, the fixing nitrogen activities of 7 strains were much higher than the remaining strains, including NFBR3, NFBV2, NFBM5, NFBM3, NFBM1, NFBV5 and NFBR2 with NH₄⁺ concentration 18.85 mg/l, 18.41 mg/l, 17.32 mg/l, 16.19 mg/l, 15.49 mg/l, 12.83 mg/l and 12.57 mg/l, respectively Among 12 PSB strains, The ability of solubilizing phosphate of 5 strains were higher than the others, including PSBM2, PSBR1, PSBV1, PSBR5 and PSBR3 with PO₄⁻ concentration 14.49 mg/l, 11.83 mg/l, 11.33 mg/l, 10.65 mg/l, 10.37 mg/l, respectively. 3 NFB strains (NFBR3, NFBV2, NFBM5) and 3 PSB strains (PSBM2, PSBR1, PSBV1) with higher activity were identified by 16S-rDNA sequence analysis and comparing to some homologous sequences in genbank. The results showed that NFBR3 was identified as Azotobacter vinelandii, NFBV2 as Azopirillum brasilense, NFBM5 as Azotobacter chroococum, PSBM2 and PSBV1 as Pseudomonas fluorescens and PSBR1 as Bacillus subtilis.Vi khuẩn cố định nitơ (NFB) và vi khuẩn phân giải phosphate (PSB) được sử dụng rộng rãi trong sản xuất phân bón vi sinh. Nghiên cứu này nhằm mục đích tìm kiếm các chủng vi khuẩn cố định nitơ và hòa tan phosphate, bổ sung vào bộ sưu tập các chủng dự tuyển cho sản xuất phân bón vi sinh đơn và đa chức năng. Từ 40 mẫu đất của 8 ruộng trồng lúa, cây dược liệu và rau màu, 15 chủng NFB và 12 chủng PSB đã được phân lập và xác định khả năng cố định nitơ và phân giải phosphate vô cơ thông qua sự tạo thành NH₄⁺ và PO₄⁻ trong môi trường nuôi cấy. Trong số 15 chủng NFB, có 7 chủng có hoạt tính cố định nitơ cao hơn những chủng còn lại, bao gồm các chủng NFBR3, NFBV2, NFBM5, NFBM3, NFBM1, NFBV5 và NFBR2 với nồng độ NH₄⁺ lần lượt là 18.85mg/l, 18.41 mg/l, 17.32 mg/l, 16.19 mg/l, 15.49 mg/l, 12.83 mg/l và 12.5 7mg/l. Trong số 12, có 5 chủng có khả năng phân giải phosphate cao hơn những chủng khác, bao gồm chủng PSBM2, PSBR1, PSBV1, PSBR5 và PSBR3 với nồng độ PO₄⁻ lần lượt là 14.49 mg/l, 11.83 mg/l, 11.33 mg/l, 10.65 mg/l và 10.37 mg/l. Các chủng NFB và PSB này đều xuất hiện ơ các mẫu đất trồng lúa, đất trồng cây dược liệu và đất trồng rau màu. 3 chủng NFB và 3 chủng PSB với hoạt tính cố định nitơ và phân giải phosphate cao hơn được định loại bằng phân tích trình tự gen 16S-rDNA và so sánh với một số trình tự tương đồng trong genebank. Kết quả chỉ ra rằng chủng NFBR3 được định danh là Azotobacter vinelandii, chủng NFBV2 là Azopirillum brasilense, chủng NFBM5 là Azotobacter chroococum, chủng PSBM2 và chủng PSBV1 là Pseudomonas fluorescens và chủng PSBR1 là Bacillus subtilis

Tissue microarray analysis of eIF4E and its downstream effector proteins in human breast cancer

Correction to Kleiner HE, Krishnan P, Tubbs J, Smith M, Meschonat C, Shi R, Lowery-Nordberg M, Adegboyega P, Unger M, Cardelli J et al: Tissue microarray analysis of eIF4E and its downstream effector proteins in human breast cancer. J Exp Clin Cancer Res 2009, 28:5

Global, regional, and national levels and trends in burden of oral conditions from 1990 to 2017 : a systematic analysis for the Global Burden of Disease 2017 Study

Government and nongovernmental organizations need national and global estimates on the descriptive epidemiology of common oral conditions for policy planning and evaluation. The aim of this component of the Global Burden of Disease study was to produce estimates on prevalence, incidence, and years lived with disability for oral conditions from 1990 to 2017 by sex, age, and countries. In addition, this study reports the global socioeconomic pattern in burden of oral conditions by the standard World Bank classification of economies as well as the Global Burden of Disease Socio-demographic Index. The findings show that oral conditions remain a substantial population health challenge. Globally, there were 3.5 billion cases (95% uncertainty interval [95% UI], 3.2 to 3.7 billion) of oral conditions, of which 2.3 billion (95% UI, 2.1 to 2.5 billion) had untreated caries in permanent teeth, 796 million (95% UI, 671 to 930 million) had severe periodontitis, 532 million (95% UI, 443 to 622 million) had untreated caries in deciduous teeth, 267 million (95% UI, 235 to 300 million) had total tooth loss, and 139 million (95% UI, 133 to 146 million) had other oral conditions in 2017. Several patterns emerged when the World Bank’s classification of economies and the Socio-demographic Index were used as indicators of economic development. In general, more economically developed countries have the lowest burden of untreated dental caries and severe periodontitis and the highest burden of total tooth loss. The findings offer an opportunity for policy makers to identify successful oral health strategies and strengthen them; introduce and monitor different approaches where oral diseases are increasing; plan integration of oral health in the agenda for prevention of noncommunicable diseases; and estimate the cost of providing universal coverage for dental care

Inference of Brain Networks with Approximate Bayesian Computation– assessing face validity with an example application in Parkinsonism

This paper describes and validates a novel framework using the Approximate Bayesian Computation (ABC) algorithm for parameter estimation and model selection in models of mesoscale brain network activity. We provide a proof of principle, first pass validation of this framework using a set of neural mass models of the cortico-basal ganglia thalamic circuit inverted upon spectral features from experimental in vivo recordings. This optimization scheme relaxes an assumption of fixed-form posteriors (i.e. the Laplace approximation) taken in previous approaches to inverse modelling of spectral features. This enables the exploration of model dynamics beyond that approximated from local linearity assumptions and so fit to explicit, numerical solutions of the underlying non-linear system of equations. In this first paper, we establish a face validation of the optimization procedures in terms of: (i) the ability to approximate posterior densities over parameters that are plausible given the known causes of the data; (ii) the ability of the model comparison procedures to yield posterior model probabilities that can identify the model structure known to generate the data; and (iii) the robustness of these procedures to local minima in the face of different starting conditions. Finally, as an illustrative application we show (iv) that model comparison can yield plausible conclusions given the known neurobiology of the cortico-basal ganglia-thalamic circuit in Parkinsonism. These results lay the groundwork for future studies utilizing highly nonlinear or brittle models that can explain time dependent dynamics, such as oscillatory bursts, in terms of the underlying neural circuits