Developing a guideline to standardize the citation of bioresources in journal articles (CoBRA).

BACKGROUND: Many biomedical publications refer to data obtained from collections of biosamples. Sharing such bioresources (biological samples, data, and databases) is paramount for the present governance of research. Recognition of the effort involved in generating, maintaining, and sharing high quality bioresources is poorly organized, which does not encourage sharing. At publication level, the recognition of such resources is often neglected and/or highly heterogeneous. This is a true handicap for the traceability of bioresource use. The aim of this article is to propose, for the first time, a guideline for reporting bioresource use in research articles, named CoBRA: Citation of BioResources in journal Articles. METHODS: As standards for citing bioresources are still lacking, the members of the journal editors subgroup of the Bioresource Research Impact Factor (BRIF) initiative developed a standardized and appropriate citation scheme for such resources by informing stakeholders about the subject and raising awareness among scientists and in science editors' networks, mapping this topic among other relevant initiatives, promoting actions addressed to stakeholders, launching surveys, and organizing focused workshops. RESULTS: The European Association of Science Editors has adopted BRIF's suggestion to incorporate statements on biobanks in the Methods section of their guidelines. The BRIF subgroup agreed upon a proposed citation system: each individual bioresource that is used to perform a study and that is mentioned in the Methods section should be cited as an individual "reference [BIORESOURCE]" according to a delineated format. The EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network mentioned the proposed reporting guideline in their "guidelines under development" section. CONCLUSIONS: Evaluating bioresources' use and impact requires that publications accurately cite such resources. Adopting the standard citation scheme described here will improve the quality of bioresource reporting and will allow their traceability in scientific publications, thus increasing the recognition of bioresources' value and relevance to research. Please see related article: http://dx.doi.org/10.1186/s12916-015-0284-9.

Early loss of bone mineral density is correlated with a gain of fat mass in patients starting a protease inhibitor containing regimen: the prospective Lipotrip study.

BACKGROUND: HIV-infected patients starting antiretroviral treatment (ART) experience deep and early disorders in fat and bone metabolism, leading to concomitant changes in fat mass and bone mineral density. METHODS: We conducted a prospective study in treatment-naive HIV-infected patients randomized to receive two nucleoside reverse transcriptase inhibitors in combination with either a protease inhibitor (PI) or a non-nucleosidic reverse transcriptase inhibitor (NNRTI), to evaluate early changes in body composition, bone mineral density and metabolic markers as differentially induced by antiretroviral therapies. We measured changes in markers of carbohydrate, of fat and bone metabolism, and, using dual-emission X-ray absorptiometry (DXA), body composition and bone mineral density (BMD). Complete data on changes between baseline and after 21 months treatment were available for 35 patients (16 in the PI group and 19 in the NNRTI group). RESULTS: A significant gain in BMI and in total and lower limb fat mass was recorded only in patients receiving PI. A loss of lumbar BMD was observed in both groups, being higher with PI. Plasma markers of bone metabolism (alkaline phosphatase, osteocalcin, collagen crosslaps) and levels of parathormone and of 1,25diOH-vitamin D3 significantly increased in both groups, concomitant with a decline in 25OH-vitamin D3. Lipids and glucose levels increased in both groups but rise in triglyceride was more pronounced with PI. A correlation between loss of BMD and gain of fat mass is observed in patients starting PI. CONCLUSIONS: We evidenced an early effect of ART on lipid and bone metabolisms. PI lead to a significant gain in fat mass correlated with a sharp drop in BMD but active bone remodelling is evident with all antiretroviral treatments, associated with low vitamin D levels and hyperparathyroidism. In parallel, signs of metabolic restoration are evident. However, early increases in lean and fat mass, triglycerides, waist circumference and leptin are much more pronounced with PI.

Assessing How Social Exposures Are Integrated in Exposome Research: A Scoping Review.

BACKGROUND: Exposome research aims to describe and understand the extent to which all the exposures in human environments may affect our health over the lifetime. However, the way in which humans interact with their environment is socially patterned. Failing to account for social factors in research exploring the exposome may underestimate the magnitude of the effect of exposures or mask inequalities in the distribution of both exposures and outcomes. OBJECTIVES: We aimed to describe the extent to which social factors appear in the exposome literature, the manner in which they are used in empirical analyses and statistical modeling, and the way in which they are considered in the overall scientific approach. METHODS: We conducted a scoping review of the literature using three databases (PubMed, Embase, and Web of Science) up to January 2022. We grouped studies based on the way in which the social variables were used in the analyses and quantified the type and frequency of social variables mentioned in the articles. We also qualitatively described the scientific approach used by authors to integrate social variables. RESULTS: We screened 1,001 records, and 73 studies were included in the analysis. Fifty-five (∼75%) used social variables as exposures or confounders or both, and a wide array of social variables were represented in the articles. Individual-level social variables were more often found, especially education and race/ethnicity, as well as neighborhood-level deprivation indices. Half of the studies used a hypothesis-free approach and the other half, a hypothesis-driven approach. However, in the latter group, of 35 studies, only 8 reported and discussed at least one possible social mechanism underlying the relationship observed between the social variable and the outcome. DISCUSSION: Social factors in exposome research should be considered in a more systematic way, considering their role in structuring both the specific external and the internal exposome. Doing so could help to understand the mechanisms of construction and, potentially, alleviate social inequalities in health and mitigate the emergence of new ones. https://doi.org/10.1289/EHP11015.

How to responsibly acknowledge research work in the era of big data and biobanks: ethical aspects of the Bioresource Research Impact Factor (BRIF).

Currently, a great deal of biomedical research in fields such as epidemiology, clinical trials and genetics is reliant on vast amounts of biological and phenotypic information collected and assembled in biobanks. While many resources are being invested to ensure that comprehensive and well-organised biobanks are able to provide increased access to, and sharing of biomedical samples and information, many barriers and challenges remain to such responsible and extensive sharing. Germane to the discussion herein is the barrier to collecting and sharing bioresources related to the lack of proper recognition of researchers and clinicians who developed the bioresource. Indeed, the efforts and resources invested to set up and sustain a bioresource can be enormous and such work should be easily traced and properly recognised. However, there is currently no such system that systematically and accurately traces and attributes recognition to those doing this work or the bioresource institution itself. As a beginning of a solution to the "recognition problem", the Bioresource Research Impact Factor/Framework (BRIF) initiative was proposed almost a decade and a half ago and is currently under further development. With the ultimate aim of increasing awareness and understanding of the BRIF, in this article, we contribute the following: (1) a review of the objectives and functions of the BRIF including the description of two tools that will help in the deployment of the BRIF, the CoBRA (Citation of BioResources in journal Articles) guideline, and the Open Journal of Bioresources (OJB); (2) the results of a small empirical study on stakeholder awareness of the BRIF and (3) a brief analysis of the ethical dimensions of the BRIF which allow it to be a positive contribution to responsible biobanking.

Biobankers: Treat the Poison of Invisibility with CoBRA, a Systematic Way of Citing Bioresources in Journal Articles.

Even though an increasing portion of biomedical research today relies on the use of bioresources, at present biobankers are not able to trace this use in scientific literature and measure its impact with a variety of citation metrics. The "BRIF (Bioresource Research Impact Factor) and journal editors" subgroup was created precisely with the aim to study this issue and to build a standardized system to cite bioresources in journal articles. This report aims at presenting a guideline for Citation of BioResources in journal Articles (CoBRA). The guideline offers for the first time a standard for citing bioresources (including biobanks) within journal articles. It will increase their visibility and promote their sharing.

Proliferation and wound healing of vascular cells trigger the generation of extracellular reactive oxygen species and LDL oxidation.

Cell proliferation of vascular cells is a key feature in vascular biology, wound healing, and pathophysiological processes such as atherosclerosis and restenosis. In atherosclerotic intima, cell proliferation colocalizes with oxidized LDL that indicate a local oxidative stress. This study aims to investigate whether cell proliferation is causally related with extracellular ROS generation and subsequent LDL oxidation. Sparse proliferating endothelial and smooth muscle cells generate higher levels of extracellular ROS (O2*- and H2O2) and LDL oxidation than confluent contact-inhibited cells. During wound healing of confluent cell layer, cell proliferation associated with healing also induced enhanced extracellular ROS generation and LDL oxidation. Proliferation-associated extracellular ROS generation is mediated through mitogenic signaling pathways, involving ERK1/2 and PKC, but is independent of de novo DNA synthesis, gene expression and protein synthesis. Data obtained with inhibitors of oxidases suggest that proliferation-associated extracellular ROS are not generated by a single ROS-generating system and are not essential for cell proliferation. In conclusion, our data show that proliferating vascular cells (in sparse culture or during wound healing) generate high levels of extracellular ROS and LDL oxidation through regulation of ROS-generating systems by mitogenic signaling. This constitutes a link between proliferative events and oxidative stress/LDL oxidation in atherosclerotic lesions and restenosis.

The embodiment of adverse childhood experiences and cancer development: potential biological mechanisms and pathways across the life course.

OBJECTIVES: To explore current evidence of the physiological embedding of stress to discuss whether adverse childhood experiences (ACE) causing chronic or acute stress responses may alter fundamental biological functions. METHODS: A non-systematic review of the literature was carried out using keyword searches in Pubmed and the web of science from May to October 2011. In reference to the literature identified, we examine the potential biological pathways potentially linking exposure to ACE and cancer development and progression in adulthood. RESULTS: These mechanisms, in interaction with social position, and mediated by subsequent environmental exposures, may ultimately lead to the development of cancer. The experience of acute or chronic stressors during sensitive periods of childhood development which can induce several known biological responses, are likely to have an impact on subsequent biological and behavioural functions depending on the timing of initial exposures, and subsequently mediated by later exposures. For this reason, childhood exposure to adversity is a likely source of both acute and chronic stressors, and can be examined as an important initial exposure on a pathway towards adult ill health. CONCLUSIONS: Such pathways justify a life course approach to understanding cancer aetiology, which may have its origins early in life.

Open data sharing in the context of bioresources.

Recently many international initiatives have been developed to improve access to scientific information and to promote open data sharing. In the complex field of bioresources, the BRIF (Bioresource Research Impact Factor) project aims to create suitable methods to recognise and measure the use and impact of biological resources in scientific/academic work, in order to maximize access by researchers to collections of biological materials and attached databases, and to recognize efforts involved in their maintenance. The lack of a proper recognition of scientific contribution is in fact a major obstacle which impedes bioresource sharing. In this context, the BRIF initiative can be considered as a tool to facilitate research resource sharing.

Measuring the contribution of tumor biobanks to research in oncology: surrogate indicators and bibliographic output.

The number of biobanks, in particular hospital-integrated tumor biobanks (HITB), is increasing all around the world. This is the consequence of an increase in the need for human biological resources for scientific projects and more specifically, for translational and clinical research. The robustness and reproducibility of the results obtained depend greatly on the quality of the biospecimens and the associated clinical data. They also depend on the number of patients studied and on the expertise of the biobank that supplied the biospecimens. The quality of a research biobank is undoubtedly reflected in the number and overall quality of the research projects conducted with biospecimens provided by the biobank. Since the quality of a research project can be measured from the impact factor of resulting publications, this also provides some indication of the quality of a research biobank. It is necessary for the biobank community to define "surrogate" quality indicators, and to establish systems of evaluation in relation to current and future resource requirements. These indicators will help in the realistic assessment of biobanks by institutions and funding bodies, and they will help biobanks demonstrate their value, raise their quality standards, and compete for funding. Given that biobanks are expensive structures to maintain, funding issues are particularly important, especially in the current economic climate. Use of performance indicators may also contribute to the development of a biobank impact factor or "bioresource research impact factor" (BRIF). Here we review four major categories of indicators that appear to be useful for the evaluation of a(m) HITB (quality, activity, scientific productivity, and "visibility"). In addition, we propose a scoring system to measure the chosen indicators.

Quantifying the use of bioresources for promoting their sharing in scientific research.

An increasing portion of biomedical research relies on the use of biobanks and databases. Sharing of such resources is essential for optimizing knowledge production. A major obstacle for sharing bioresources is the lack of recognition for the efforts involved in establishing, maintaining and sharing them, due to, in particular, the absence of adequate tools. Increasing demands on biobanks and databases to improve access should be complemented with efforts of end-users to recognize and acknowledge these resources. An appropriate set of tools must be developed and implemented to measure this impact.To address this issue we propose to measure the use in research of such bioresources as a value of their impact, leading to create an indicator: Bioresource Research Impact Factor (BRIF). Key elements to be assessed are: defining obstacles to sharing samples and data, choosing adequate identifier for bioresources, identifying and weighing parameters to be considered in the metrics, analyzing the role of journal guidelines and policies for resource citing and referencing, assessing policies for resource access and sharing and their influence on bioresource use. This work allows us to propose a framework and foundations for the operational development of BRIF that still requires input from stakeholders within the biomedical community.

Shift work and metabolic syndrome: respective impacts of job strain, physical activity, and dietary rhythms.

The impact of shift work on cardiovascular disease (CVD) risk factors and metabolic syndrome are not yet completely understood. The objectives of this study were to evaluate the impact of shift work on metabolic syndrome according to two different definitions in a population of strictly rotating shift workers (3x8 h) compared to paired counterparts working only day hours, and to study whether shift work itself is a determinant of metabolic syndrome after taking into account a large panel of confusing factors. We conducted a cross-sectional study comparing 98 strictly rotating shift workers to 100 regular day-workers (all subjects had a long experience of their working rhythms) within the same petrochemical plant. Clinical, behavioral, occupational, and biological data were collected, and a detailed nutritional investigation was done. Shift and day workers were comparable in terms of major CVD factors, and both had a 10 yr Framingham risk scoring of 11%. Shift workers reported an increased job strain and higher total and at-work physical activity. Alterations in metabolic parameters were evident with a rise in triglycerides, free fatty acids, and gamma glutamyl transpeptidase and lower HDL-cholesterol. Multiple logistic regression analysis demonstrated that shift work was associated with occurrence of metabolic syndrome, as defined by the National Cholesterol Education Program-ATPIII criteria, OR: 2.38 (1.13-4.98), but not using the more recent score from the International Diabetes Federation, which gives a major emphasis on abdominal obesity. Total energy intake and contributions of the major nutrients did not differ between the two groups, with the notable exception of saturated lipids (+10% in shift workers). Meal distribution was clearly different: energy intake was more fractionated within the day, with a lesser contribution of breakfast and lunch but with increased intakes during intermediate light meals, particularly in the afternoon and night. Multivariate analyses were performed to test for the influence of dietary rhythms on the development of an NCEP-ATPIII metabolic syndrome. Dietary intakes at breakfast and during intermediate light meals appear to be "protective" against metabolic syndrome, while a high load at dinner favors its occurrence. A high intake at lunch is particularly deleterious to shift workers. However, in all tested models, shift work remained significantly associated with metabolic syndrome, after taking into account potential covariates like job strain, physical activity, quantitative dietary parameters, and meal distribution. A specific follow-up of shift workers should be recommended to occupational physicians.

Hepatic lipase: structure/function relationship, synthesis, and regulation.

Hepatic lipase (HL) is a lipolytic enzyme, synthesized by hepatocytes and found localized at the surface of liver sinusoid capillaries. In humans, the enzyme is mostly bound onto heparan-sulfate proteoglycans at the surface of hepatocytes and also of sinusoid endothelial cells. HL shares a number of functional domains with lipoprotein lipase and with other members of the lipase gene family. It is a secreted glycoprotein, and remodelling of the N-linked oligosaccharides appears to be crucial for the secretion process, rather than for the acquisition of the catalytic activity. HL is also present in adrenals and ovaries, where it might promote delivery of lipoprotein cholesterol for steroidogenesis. However, evidence of a local synthesis is still controversial. HL activity is fairly regulated according to the cell cholesterol content and to the hormonal status. Coordinate regulations have been reported for both HL and the scavenger-receptor B-I, suggesting complementary roles in cholesterol metabolism. However, genetic variants largely contribute to HL variability and their possible impact in the development of a dyslipidemic phenotype, or in a context of insulin-resistance, is discussed.

Secreted apolipoprotein E reduces macrophage-mediated LDL oxidation in an isoform-dependent way.

As an inflammatory cell, the macrophage produces various oxidizing agents, such as free radical species. These can modify LDL as a secondary effect and doing so may favor atherogenic processes. Any molecule able to counteract these reactions would be of much benefit, especially if secreted by the macrophage itself at the lesion site. Such is the case for apolipoprotein E (apoE), which has been shown to exert antioxidant properties in some studies, mostly in relation to Alzheimer's disease. In this study, we assessed the antioxidant potential of the various isoforms of apoE (E2, E3, and E4) using a metal-induced LDL oxidation system with exogenous recombinant apoE and an in vitro model of macrophage-mediated LDL oxidation. We found that all three isoforms had an antioxidant capacity. However, whereas apoE2 was the most protective isoform in the cell-free system, the opposite was observed in apoE-transfected J774 macrophages. In the latter model, cellular cholesterol efflux was found to be more important with apoE2, possibly explaining the larger quantity of oxidative indices observed in the medium. It is proposed that the antioxidant property of apoE results from a balance between direct apoE antioxidant capacities, such as the ability to trap free radicals, and potentially pro-oxidative indirect events associated with cholesterol efflux from cells. Our observations add to the therapeutic potential of apoE. However, they also suggest the need for more experiments in order to achieve careful selection of the apoE isoform to be targeted, especially in the perspective of apoE transgene use.