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ABSTRACT The study aimed to identify available instruments in the literature to evaluate the structure of primary health network in health systems. An integrated review of literature was carried out in health sciences, education, and management Databases, as follows: Medical Literature Analysis and Retrieval System Online (Medline), including the Cochrane Library, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ABI Inform, Latin American and Caribbean on Health Sciences Literature (Lilacs), and the Business Source Complete (Ebsco). Manuscripts published in English and Portuguese from 1995 to 2019 were included. The final sample contained nine articles, in which eight instruments were identified. They had as a common feature the approach on longitudinality, interprofessional communication, care coordination, access to health services, and quality of care. An emphasis was noted on an instrument developed in the Brazilian health system context as a useful tool to support health care workers and managers in the situational diagnosis of potentialities and fragilities of Primary Health Care and Health Care Networks.

Additional file 3 : Table S2. Exact file IDs and links to all data obtained from ENCODE and Roadmap Epigenome.

Additional file 12: Table S1. Total number of ones, zeros and nulls in the sparse matrix for the 163 TFs used in this study.

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Additional file 1: Table S1. List of candidate genes examined in the current study. Table S2. Results obtained from the sex-based expression analysis performed on the autosomal genes (segregated by tissues). Table S3. Results obtained from the sex-based expression analysis performed on the X-linked genes (segregated by tissues). Table S4. Results obtained from the sex-based DNA methylation analysis performed on the autosomal genes (segregated by tissues). Table S5. Results obtained from the sex-based DNA methylation analysis performed on the X-linked genes (segregated by tissues). Table S6. Results obtained from the exposure-based DNA methylation analysis performed on the autosomal genes (segregated by tissues).

Additional file 1. An additional table is available describing the variables and regression results included in each binary logistic regression model created for each survey question separated by imputed and complete case datasets. The file name is “BLR-Additional Table 1-BMC.xlsx” and it titled “Logistic Regression Models”.

A common feature of solid tumours that are resistant to therapy is the presence of regions with low oxygen content (i.e., hypoxia). Oxygen electrode studies suggest that localized prostate adenocarcinoma is commonly hypoxic, although conflicting data have been reported between immunohistochemical detection of hypoxia-induced proteins in biopsy specimens and positron emission tomography (PET) imaging of 18F-labeled hypoxia reporters. Although the 2-nitroimidazole 18F-EF5 is well-established to label hypoxic tumour cells in pre-clinical tumour models and clinical trials of multiple primary tumour sites, it has yet to be tested in prostate cancer. The purpose of this study was to evaluate the feasibility of using 18F-EF5 to detect hypoxia in clinical prostate tumours. Patients with localized adenocarcinoma of the prostate were recruited for pre-treatment 18F-EF5 PET scans. Immunohistochemistry was conducted on diagnostic biopsies to assess the expression of glucose transporter 1 (GLUT1), osteopontin (OPN), and carbonic anhydrase IX (CAIX). Immunoreactivity scores of staining intensity and frequency were used to indicate the presence of tumour hypoxia. We found low tumour-to-muscle ratios of 18F-EF5 uptake that were not consistent with tumour hypoxia, causing early termination of the study. However, we observed GLUT1 and OPN expression in all prostate tumour biopsies, indicating the presence of hypoxia in all tumours. Our data do not support the use of 18F-EF5 PET to detect hypoxia in prostate adenocarcinoma, and suggest the use of immunohistochemistry to quantify expression of the hypoxia-inducible proteins GLUT1 and OPN as indications of prostate tumour hypoxia.