UniProt and Mass Spectrometry-Based Proteomics-A 2-Way Working Relationship.

The human proteome comprises of all of the proteins produced by the sequences translated from the human genome with additional modifications in both sequence and function caused by nonsynonymous variants and posttranslational modifications including cleavage of the initial transcript into smaller peptides and polypeptides. The UniProtKB database (www.uniprot.org) is the world's leading high-quality, comprehensive and freely accessible resource of protein sequence and functional information and presents a summary of experimentally verified, or computationally predicted, functional information added by our expert biocuration team for each protein in the proteome. Researchers in the field of mass spectrometry-based proteomics both consume and add to the body of data available in UniProtKB, and this review highlights the information we provide to this community and the knowledge we in turn obtain from groups via deposition of large-scale datasets in public domain databases.

Development and validation of circulating tumour cell enumeration (Epic Sciences) as a prognostic biomarker in men with metastatic castration-resistant prostate cancer.

PURPOSE: To evaluate the prognostic significance of circulating tumour cell (CTC) number determined on the Epic Sciences platform in men with metastatic castration-resistant prostate cancer (mCRPC) treated with an androgen receptor signalling inhibitor (ARSI). PATIENTS AND METHODS: A pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a first-, second- or third-line systemic therapy at Memorial Sloan Kettering Cancer Center (Discovery cohort, N = 171) or as a first- or second-line therapy as part of the multicenter PROPHECY trial (NCT02269982) (Validation cohort, N = 107). The measured CTC number was then associated with overall survival (OS) in the Discovery cohort, and progression-free survival (PFS) and OS in the Validation cohort. CTC enumeration was also performed on a concurrently obtained blood sample using the CellSearch® Circulating Tumor Cell Kit. RESULTS: In the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous (<3 CTCs/mL versus ≥ 3 CTCs/mL; hazard ratio [HR] = 1.8 [95% confidence interval {CI} 1.3-3.0]) and a continuous variable when adjusting for line of therapy, presence of visceral metastases, prostate-specific antigen, lactate dehydrogenase and alkaline phosphatase. The findings were validated in an independent datas et from PROPHECY (HR [95% CI] = 1.8 [1.1-3.0] for OS and 1.7 [1.1-2.9] for PFS). A strong correlation was also observed between CTC counts determined in matched samples on the CellSearch® and Epic platforms (r = 0.84). CONCLUSION: The findings validate the prognostic significance of pretreatment CTC number determined on the Epic Sciences platform for predicting OS in men with progressing mCRPC starting an ARSI.

QuantiFERON®-TB Gold In-Tube reliability for immigrants with parasitic infections in Boston, USA.

Accurate testing and treatment for latent tuberculous infection is necessary for tuberculosis elimination. Certain parasite infections are associated with increased tuberculin skin test positivity; species-specific effects on QuantiFERON®-TB Gold In-Tube (QGIT) have not been described. To determine whether infection with helminths or protozoa affects QGIT results. We retrospectively analyzed QGIT and parasite testing results for immigrants screened in Boston, MA, USA, from 2012 to 2017. We also prospectively measured cytokines in QGIT supernatants for a subset (n = 68) with 1) helminths, 2) Blastocystis hominis, 3) other protozoa, and 4) no parasites. Of 527 immigrants screened, 141 (26.8%) were QGIT-positive and 229 (43.4%) had parasites detected: 27/527 (5.1%) had helminths and 202/527 (38.3%) protozoa. Cytokine analysis revealed increased interleukin-10 concentrations with protozoa (P = 0.04), and non-significantly higher T-helper 2 concentrations with helminths compared with no parasites. No significant differences emerged in QGIT positivity or interferon-gamma concentrations in any group. Study results support the use of QGIT in parasite-endemic settings. .

High-risk psychotropic medications for US children with trauma sequelae.

Children exposed to trauma are predisposed to develop a number of mental health syndromes. They are prone to under-treatment with effective psychosocial interventions and over-treatment with high-risk psychotropic medications, especially polypharmacy and the use of antipsychotics for unapproved conditions. We review the evidence for psychosocial and pharmacological treatments for mental health problems associated with high exposure to childhood trauma - identifying those in foster care as an index group - and the frequency of high-risk pharmacological practices. We describe current efforts to reduce over-treatment of children with high-risk psychotropic medications and propose further recommendations to protect and provide effective care for these vulnerable children.

Transgenic IGF-IR overexpression induces mammary tumors with basal-like characteristics, whereas IGF-IR-independent mammary tumors express a claudin-low gene signature.

Molecular profiling has allowed a more precise classification of human cancers. With respect to breast cancer, this approach has been used to identify five subtypes; luminal A, luminal B, HER2-enriched, basal-like and claudin-low. In addition, this approach can be used to determine the type of tumor represented by particular cell lines or transgenic animal models. Therefore, this approach was utilized to classify the mammary tumors that develop in MTB-IGFIR transgenic mice. It was determined that the primary mammary tumors, which develop due to elevated expression of the type I insulin-like growth factor receptor (IGF-IR) in mammary epithelial cells, most closely resemble murine tumors with basal-like or mixed gene expression profiles and with human basal-like breast cancers. Downregulation of IGF-IR transgene in MTB-IGFIR tumor-bearing mice leads to the regression of most of the tumors, followed by tumor reappearance in some of the mice. These tumors that reappear following IGF-IR transgene downregulation do not express the IGF-IR transgene and cluster with murine mammary tumors that express a mesenchymal gene expression profile and with human claudin-low breast cancers. Therefore, IGF-IR overexpression in murine mammary epithelial cells induces mammary tumors with primarily basal-like characteristics, whereas tumors that develop following IGF-IR downregulation express a gene signature that most closely resembles human claudin-low breast tumors.

Does small mammal prey guild affect the exposure of predators to anticoagulant rodenticides?

Ireland has a restricted small mammal prey guild but still includes species most likely to consume anticoagulant rodenticide (AR) baits. This may enhance secondary exposure of predators to ARs. We compared liver AR residues in foxes (Vulpes vulpes) in Northern Ireland (NI) with those in foxes from Great Britain which has a more diverse prey guild but similar agricultural use of ARs. Liver ARs were detected in 84% of NI foxes, more than in a comparable sample of foxes from Scotland and similar to that of suspected AR poisoned animals from England and Wales. High exposure in NI foxes is probably due to greater predation of commensal rodents and non-target species most likely to take AR baits, and may also partly reflect greater exposure to highly persistent brodifacoum and flocoumafen. High exposure is likely to enhance risk and Ireland may be a sentinel for potential effects on predator populations.

Joint effects of social class and community occupational structure on coronary mortality among black men and white men, upstate New York, 1988-92.

STUDY OBJECTIVE: Occupational structure represents the unequal geographical distribution of more desirable jobs among communities (for example, white collar jobs). This study examines joint effects of social class, race, and county occupational structure on coronary mortality rates for men, ages 35-64 years, 1988-92, in upstate New York. DESIGN: Upstate New York's 57 counties were classified into three occupational structure categories; counties with the lowest percentages of the labour force in managerial, professional, and technical occupations were classified in category I, counties with the highest percentages were in category III. Age adjusted coronary heart disease (CHD) mortality rates, 35-64 years, (from vital statistics and census data) were calculated for each occupational structure category. MAIN RESULTS: An inverse association between CHD mortality and occupational structure was observed among blue collar and white collar workers, among black men and white men, with the lowest CHD mortality observed among white collar, white men in category III (135/100,00). About two times higher mortality was observed among blue collar than white collar workers. Among blue collar workers, mortality was 1.3-1.8 times higher among black compared with white workers, and the highest rates were observed among black, blue collar workers (689/100,00). Also, high residential race segregation was shown in all areas. CONCLUSIONS: Results suggest the importance of community conditions in coronary health of local populations; however, differential impact on subpopulations was shown. Blue collar and black workers may especially lack economic and other resources to use available community services and/or may experience worse working and living conditions compared with white collar and white workers in the same communities.

Local increases in coronary heart disease mortality among blacks and whites in the United States, 1985-1995.

OBJECTIVES: This study analyzed coronary heart disease (CHD) mortality trends from 1985 to 1995, by race and sex, among Black and White adults 35 years and older to determine whether adverse trends were evident in any US localities. METHODS: Log-linear regression models of annual age-adjusted death rates provided a quantitative measure of local mortality trends. RESULTS: Increasing trends in CHD mortality were observed in 11 of 174 labor market areas for Black women, 23 of 175 areas for Black men, 10 of 394 areas for White women, and 4 of 394 areas for White men. Nationwide, adverse trends affected 1.7% of Black women, 8.0% of Black men, 1.1% of White women, and 0.3% of White men. CONCLUSIONS: From 1985 to 1995, moderate to strong local increases in CHD mortality were observed, predominantly in the southern United States. Black men evidenced the most unfavorable trends and were 25 times as likely as White men to be part of a local population experiencing increases in coronary heart disease mortality.

Meningococcal disease among children who live in a large metropolitan area, 1981-1996.

Neisseria meningitidis is an important cause of serious bacterial infections in children. We undertook a study to identify meningococcal infections of the blood, cerebrospinal fluid, or both of children in a defined geographic area to describe the burden of disease and the spectrum of illness. We reviewed the medical records of all children aged <18 years who had meningococcal infections at the 4 pediatric referral hospitals in Boston, Massachusetts, from 1981 through 1996. We identified 231 patients with meningococcal disease; of these 231 patients, 194 (84%) had overt disease and 37 (16%) had unsuspected disease. Clinical manifestations included meningitis in 150 patients, hypotension in 26, and purpura in 17. Sixteen patients (7%) died. Although meningococcal disease is devastating to a small number of children, we found that the burden of pediatric disease that it caused at the 4 pediatric referral centers in this geographic region was limited; that patients with overt meningococcal disease are most likely to have meningitis; and that individual practitioners are unlikely to encounter a patient with unsuspected meningococcal disease.

Disparities in premature coronary heart disease mortality by region and urbanicity among black and white adults ages 35-64, 1985-1995.

OBJECTIVES: Regional and urban-rural disparities in premature coronary heart disease (CHD) mortality were evident in the US as early as 1950. Recent favorable trends at the national level may obscure less favorable outcomes for certain regions and localities. The authors examined trends in premature CHD mortality for 1985-1995 for black and white adults ages 35-64 years for four categories of urbanicity in two regions of the US (South and non-South). METHODS: All counties in the US (excluding Alaskan counties) were grouped by urbanicity and region. Annual age-adjusted CHD mortality rates were calculated for adults ages 35-64 by racial category (African American or white) and gender for each geographic area for the years 1985- 1995. Loglinear regression models were used to estimate average annual percent declines in mortality for each of 28 geo-demographic groups. Data were also collected on selected socioeconomic resources by urbanicity for the non-South (excluding Alaska) and South. RESULTS: For both white and black adults ages 35-64, the highest rates of premature CHD mortality and slowest mortality declines were observed in the rural South. For white men and women, marked disparities in premature CHD mortality across categories of urbanicity were noted in the South but not outside the South. Unexpectedly high rates of premature CHD mortality were observed for African Americans in major metropolitan areas outside the South despite favorable levels of socioeconomic resources. CONCLUSIONS: Disparities in premature CHD mortality by region and urbanicity appear to have widened between 1985 and 1995. Residents of the rural South had the highest rates of premature CHD mortality, and rural communities in the South face significant barriers to effective heart disease prevention and control.

War trauma experience and behavioral screening of Bosnian refugee children resettled in Massachusetts.

The authors assessed war violence exposure and behavioral symptoms in Bosnian refugee children in Massachusetts and the utility of behavioral screening of refugees during the Refugee Health Assessment (RHA), required of newly arrived refugees. The study was a survey of 31 Bosnian refugee children in 1996 at the International Clinic of Boston Medical Center, the state's largest contracted provider of the RHA. Subjects were also offered referrals to appropriate mental health services. Sixty-eight percent experienced long-term separation from a parent. Eighty-one percent were directly exposed to armed combat. Seventy-one percent experienced the death of a close friend or relative. Fifty-two percent experienced economic deprivation. Families reported behavioral symptoms for 77% of children. Only one family expressed interest in psychosocial services of any kind. Large numbers of Bosnian refugees are likely to have experienced traumatic war violence and are at risk of behavioral symptoms. The RHA affords opportunities to screen for behavioral problems but not to intervene. Primary care providers and other clinicians should be aware of likely recurrences of symptoms in high-risk children such as these.

Depressive symptoms in rural West Virginia: labor market and health services correlates.

The prevalence and socioeconomic correlates of depressive symptoms in rural West Virginia were assessed. A random-digit-dialed telephone interview was administered to a community-dwelling sample of adults, ages 18 to 64, residing in the 40 rural counties of the Appalachian State of West Virginia. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale (CES-D). Overall rates of depressive symptoms were substantially higher than in the nation as a whole. Gender differences were lower than expected due to a high rate of depressive symptoms among men. Depressive symptoms were inversely associated with higher socioeconomic position. One-third of those who described themselves in "good mental health" reported depressive symptoms. About half who reported depressive symptoms had never seen a mental health professional or a physician for mental health problems. Efforts to increase awareness and access to mental health services are needed to promote the mental health of rural West Virginian populations.

Metropolitan and non-metropolitan trends in coronary heart disease mortality within Appalachia, 1980-1997.

OBJECTIVES: In this article, we report on metropolitan and non-metropolitan trends in coronary heart disease (CHD) mortality within the Appalachian Region for the period 1980 to 1997. We hypothesized that trends in CHD mortality would be less favorable in non-metropolitan populations with diminished access to social, economic, and medical care resources at the community level. METHODS: Our study population consisted of adults aged 35 years and older who resided within the 399 counties of the Appalachian Region between 1980 and 1997. We examined mortality trends for sixteen geo-demographic groups, defined by gender, age, race, and metropolitan status of county of residence. For each geo-demographic group, we calculated annual age-adjusted CHD mortality rates. Line graphs of these temporal trends were created, and log-linear regression models provided estimates of the average annual percent change in CHD mortality from 1980 to 1997. Data on social, economic, and medical care resources for metropolitan vs. non-metropolitan counties were also analyzed. RESULTS: Rates of CHD mortality were consistently higher in non-metropolitan areas compared with metropolitan areas for blacks of all ages and for younger whites. CHD mortality declined among almost all geo-demographic groups, but rates of decline were slower among non-metropolitan vs. metropolitan residents, blacks vs. whites, women vs. men, and older vs. younger adults. Non-metropolitan areas had fewer socioeconomic and medical care resources than metropolitan areas in 1990. CONCLUSIONS: Appalachia, particularly non-metropolitan Appalachia, needs policies and programs that will enhance both primary and secondary prevention of CHD, and help diminish racial inequalities in CHD mortality trends.