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Abstract Background The modular approach to analysis of genetically modified organisms (GMOs) relies on the independence of the modules combined (i.e. DNA extraction and GM quantification). The validity of this assumption has to be proved on the basis of specific performance criteria. Results An experiment was conducted using, as a reference, the validated quantitative real-time polymerase chain reaction (PCR) module for detection of glyphosate-tolerant Roundup Ready® GM soybean (RRS). Different DNA extraction modules (CTAB, Wizard and Dellaporta), were used to extract DNA from different food/feed matrices (feed, biscuit and certified reference material [CRM 1%]) containing the target of the real-time PCR module used for validation. Purity and structural integrity (absence of inhibition) were used as basic criteria that a DNA extraction module must satisfy in order to provide suitable template DNA for quantitative real-time (RT) PCR-based GMO analysis. When performance criteria were applied (removal of non-compliant DNA extracts), the independence of GMO quantification from the extraction method and matrix was statistically proved, except in the case of Wizard applied to biscuit. A fuzzy logic-based procedure also confirmed the relatively poor performance of the Wizard/biscuit combination. Conclusions For RRS, this study recognises that modularity can be generally accepted, with the limitation of avoiding combining highly processed material (i.e. biscuit) with a magnetic-beads system (i.e. Wizard).

The aim of this study was to develop a sampling procedure to quantify genetically-modified Round-up Ready (GM RR) soybeans in a lot. Seven lots (35 kg each) fortified with three different percentages of GM RR soybeans (4 lots at 1%, 2 lots at 10%, and 1 lot at 5%) were prepared. Four sampling procedures were carried out on each lot. Different numbers and sizes of increment samples were collected from the lots tested and prepared by homogenising the sample with water. Separate analyses were carried out using quantitative Real Time PCR of split aliquots. The sampling procedures that used ten increment samples provided the best results, in terms of precision and accuracy. [ABSTRACT FROM AUTHOR]

Objective. Measures of functional connectivity (FC) can elucidate which cortical regions work together in order to complete a variety of behavioral tasks. This study's primary objective was to expand a previously published model of measuring FC to include multiple subjects and several regions of interest. While FC has been more extensively investigated in vision and other sensorimotor tasks, it is not as well understood in audition. The secondary objective of this study was to investigate how auditory regions are functionally connected to other cortical regions when attention is directed to different distinct auditory stimuli. Approach. This study implements a linear dynamic system (LDS) to measure the structured time-lagged dependence across several cortical regions in order to estimate their FC during a dual-stream auditory attention task. Results. The model's output shows consistent functionally connected regions across different listening conditions, indicative of an auditory attention network that engages regardless of endogenous switching of attention or different auditory cues being attended. Significance. The LDS implemented in this study implements a multivariate autoregression to infer FC across cortical regions during an auditory attention task. This study shows how a first-order autoregressive function can reliably measure functional connectivity from M/EEG data. Additionally, the study shows how auditory regions engage with the supramodal attention network outlined in the visual attention literature., (© 2024 IOP Publishing Ltd.)

Sodium plays a key role in the regulation of water balance and is also important in food formulation due to its contribution to the taste and use in the preservation of many foods. Excessive intake of any essential nutrient is problematic and this seems to be particularly the case for sodium since a high intake makes it the nutrient most strongly associated with mortality. Sodium intake has been the object of recommendations by public health agencies such as the WHO and this has resulted in efforts by the food industry to reduce the sodium content of packaged foods, although there is still room for improvement. The recent literature also emphasizes the need for other strategies, e.g., regulations and education, to promote adequate sodium intake. In the present paper, we also describe the potential benefits of a global healthy lifestyle that considers healthy eating but also physical activity habits that improve body functionality and may help to attenuate the detrimental effects of high sodium intake on body composition and cardiometabolic health. In conclusion, a reduction in sodium intake, an improvement in body functioning, and educational interventions promoting healthy eating behaviours seem to be essential for the optimal regulation of sodium balance.

Background: Over the last decade, the return of results (ROR) in precision medicine research (PMR) has become increasingly routine. Calls for individual rights to research results have extended the "duty to report" from clinically useful genetic information to traits and ancestry results. ROR has thus been reframed as inherently beneficial to research participants, without a needed focus on who benefits and how. This paper addresses this gap, particularly in the context of PMR aimed at increasing participant diversity, by providing investigator and researcher perspectives on and questions about the assumed value of ROR in PMR., Methods: Semi-structured interviews with a purposive sample of investigators and researchers across federally funded PMR studies in three national consortia, as well as observations of study activities, focused on how PM researchers conceptualize diversity and implement inclusive practices across research stages, including navigating ROR., Results: Interviewees (1) validated the value of ROR as a benefit of PMR, while others (2) questioned the benefit of clinically actionable results to individuals in the absence of sufficient resources for translating findings into health care for diverse and disadvantaged populations; (3) expressed uncertainties in applying the presumed value of ROR as a benefit for non- clinical results; and (4) and debated when the promise of the value of ROR may undermine trust in PMR, and divert efforts to return value beyond ROR., Conclusions: Conceptualizations of diversity and inclusion among PM researchers and investigators raise unique ethical questions where unexamined assumptions of the value of ROR inform study recruitment efforts to enroll minoritized and under-represented populations. A lack of consideration for resources and infrastructure necessary to translate ROR into actionable information may hinder trustworthy community-research relationships. Thus, we argue for a more intentional interrogation of ROR practices as an offer of benefit and for whom.

Given the aging of general population, very elderly females with Takotsubo syndrome (TTS) are not rarely encountered in clinical practice. Although coronary angiography with left ventriculography is the gold standard diagnostic tool to exclude or confirm TTS, currently, this invasive procedure is less frequently performed in older patients with several comorbidities, such as renal failure, anemia, infections, neurological disorders, malignancy, and severe frailty. In these patients, a "presumed" TTS is diagnosed on the basis of clinical presentation, electrocardiogram, cardiac biomarkers, and echocardiographic findings without coronary angiography. While, in younger patients, TTS is generally a benign condition, in very elderly females, it is associated with higher in-hospital mortality and poor prognosis. Herein, we present four cases of ultra-octogenarian females diagnosed with "presumed TTS", who did not undergo coronary angiography due to severe frailty and multiple comorbidities and who exhibited poor outcome. This could arise the question if an early more aggressive approach could have changed final results. Probably, the solution could only be a personalized decision deriving from a profound and detailed discussion of each case through a multidisciplinary team approach., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: In the wake of mandates for biomedical research to increase participation by members of historically underrepresented populations, community engagement (CE) has emerged as a key intervention to help achieve this goal., Methods: Using interviews, observations, and document analysis, we examine how stakeholders in precision medicine research understand and seek to put into practice ideas about who to engage, how engagement should be conducted, and what engagement is for., Results: We find that ad hoc, opportunistic, and instrumental approaches to CE exacted significant consequences for the time and resources devoted to engagement and the ultimate impacts it has on research. Critical differences emerged when engagement and research decisionmaking were integrated with each other versus occurring in parallel, separate parts of the study organization, and whether community members had the ability to determine which issues would be brought to them for consideration or to revise or even veto proposals made upstream based on criteria that mattered to them. CE was understood to have a range of purposes, from instrumentally facilitating recruitment and data collection, to advancing community priorities and concerns, to furthering long-term investments in relationships with and changes in communities. These choices about who to engage, what engagement activities to support, how to solicit and integrate community input into the workflow of the study, and what CE was for were often conditioned upon preexisting perceptions and upstream decisions about study goals, competing priorities, and resource availability., Conclusions: Upstream choices about CE and constraints of time and resources cascade into tradeoffs that often culminated in "pantomime community engagement." This approach can create downstream costs when engagement is experienced as improvised and sporadic. Transformations are needed for CE to be seen as a necessary scientific investment and part of the scientific process.

Introduction: Federal agencies have instituted guidelines to prioritize the enrollment and retention of diverse participants in precision medicine research (PMR). Prior studies examining participation of minoritized communities have shown that potential benefits represent a key determinant. Human subject research guidance, however, conceptualizes potential benefits narrowly, emphasizing generalized advances in medical knowledge. Further, few studies have provided qualitative data that critically examine how the concept of "benefit" is interpreted or challenged in the context of research practice. This paper examines the experiences of PMR investigators and frontline research staff to understand how standard approaches to benefit are received, contested, and negotiated "on the ground.", Methods: Findings are drawn from a qualitative project conducted across five US-based, federally funded PMR studies. Data collection included 125 in-depth interviews with a purposive sample of investigators, research staff, community advisory board members, and NIH program officers associated with these PMR studies., Results: Researchers report that the standard approach to benefit - which relies on the premise of altruism and the promise of incrementally advancing scientific knowledge - is frequently contested. Researchers experience moral distress over the unmet clinical, psychosocial, and material needs within the communities they are engaging. Many believe the broader research enterprise has a responsibility to better address these needs., Conclusion: Researchers frequently take issue with and sometimes negotiate what is owed to participants and to their communities in exchange for the data they provide. These experiences of moral distress and these improvisations warrant systematic redress, not by individual researchers but by the broader research ethics infrastructure., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Scientists have identified a "diversity gap" in genetic samples and health data, which have been drawn predominantly from individuals of European ancestry, as posing an existential threat to the promise of precision medicine. Inadequate inclusion as articulated by scientists, policymakers, and ethicists has prompted large-scale initiatives aimed at recruiting populations historically underrepresented in biomedical research. Despite explicit calls to increase diversity, the meaning of diversity - which dimensions matter for what outcomes and why - remain strikingly imprecise. Drawing on our document review and qualitative data from observations and interviews of funders and research teams involved in five precision medicine research (PMR) projects, we note that calls for increasing diversity often focus on "representation" as the goal of recruitment. The language of representation is used flexibly to refer to two objectives: achieving sufficient genetic variation across populations and including historically disenfranchised groups in research. We argue that these dual understandings of representation are more than rhetorical slippage, but rather allow for the contemporary collection of samples and data from marginalized populations to stand in as correcting historical exclusion of social groups towards addressing health inequity. We trace the unresolved historical debates over how and to what extent researchers should procure diversity in PMR and how they contributed to ongoing uncertainty about what axes of diversity matter and why. We argue that ambiguity in the meaning of representation at the outset of a study contributes to a lack of clear conceptualization of diversity downstream throughout subsequent phases of the study., (Copyright ©2022, Yale Journal of Biology and Medicine.)

US funding agencies have begun to institutionalize expectations that biomedical studies achieve defined thresholds for diversity among research participants, including in precision medicine research (PMR). In this paper, we examine how practices of recruitment have unfolded in the wake of these diversity mandates. We find that a very common approach to seeking diverse participants leverages understandings of spatial, geographic, and site diversity as proxies and access points for participant diversity. That is, PMR investigators recruit from a diverse sampling of geographic areas, neighborhoods, sites, and institutional settings as both opportunistic but also meaningful ways to "bake in" participant diversity. In this way, logics of geographic and institutional diversity shift the question from who to recruit, to where. However, despite seeing geographic and site diversity as social and scientific 'goods' in the abstract and as key to getting diverse participants, PMR teams told us that working with diverse sites was often difficult in practice due to constraints in funding, time, and personnel, and inadequate research infrastructures and capacity. Thus, the ways in which these geographic and institutional diversity strategies were implemented resulted ultimately in limiting the meaningful inclusion of populations and organizations that had not previously participated in biomedical research and reproduced the inclusion of institutions that are already represented. These prevailing assumptions about and practices of "baked-in" diversity in fact exacerbate and produce other forms of inequity, in research capacity and research representation. These findings underscore how structural inequities in research resources must be addressed for diversity to be achieved in both research sites and research participants., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

While most classical approaches to Granger causality detection assume linear dynamics, many interactions in real-world applications, like neuroscience and genomics, are inherently nonlinear. In these cases, using linear models may lead to inconsistent estimation of Granger causal interactions. We propose a class of nonlinear methods by applying structured multilayer perceptrons (MLPs) or recurrent neural networks (RNNs) combined with sparsity-inducing penalties on the weights. By encouraging specific sets of weights to be zero-in particular, through the use of convex group-lasso penalties-we can extract the Granger causal structure. To further contrast with traditional approaches, our framework naturally enables us to efficiently capture long-range dependencies between series either via our RNNs or through an automatic lag selection in the MLP. We show that our neural Granger causality methods outperform state-of-the-art nonlinear Granger causality methods on the DREAM3 challenge data. This data consists of nonlinear gene expression and regulation time courses with only a limited number of time points. The successes we show in this challenging dataset provide a powerful example of how deep learning can be useful in cases that go beyond prediction on large datasets. We likewise illustrate our methods in detecting nonlinear interactions in a human motion capture dataset.

Purpose: To identify meanings of and challenges to enacting equitable diversification of genomics research, and specifically precision medicine research (PMR), teams., Methods: We conducted in-depth interviews with 102 individuals involved in three U.S.-based precision medicine research consortia and conducted over 400 observation hours of their working group meetings, consortium-wide meetings, and conference presentations. We also reviewed published reports on genomic workforce diversity (WFD), particularly those relevant to the PMR community., Results: Our study finds that many PMR teams encounter challenges as they strive to achieve equitable diversification on scientific teams. Interviewees articulated that underrepresented team members were often hired to increase the study's capacity to recruit diverse research participants, but are limited to on-the-ground staff positions with little influence over study design. We find existing hierarchies and power structures in the academic research ecosystem compound challenges for equitable diversification., Conclusion: Our results suggest that meaningful diversification of PMR teams will only be possible when team equity is prioritized as a core value in academic research communities., Competing Interests: The authors have declared that no competing interests exist.