Personalized medicine beyond genomics: alternative futures in big data-proteomics, environtome and the social proteome.

No field in science and medicine today remains untouched by Big Data, and psychiatry is no exception. Proteomics is a Big Data technology and a next generation biomarker, supporting novel system diagnostics and therapeutics in psychiatry. Proteomics technology is, in fact, much older than genomics and dates to the 1970s, well before the launch of the international Human Genome Project. While the genome has long been framed as the master or "elite" executive molecule in cell biology, the proteome by contrast is humble. Yet the proteome is critical for life-it ensures the daily functioning of cells and whole organisms. In short, proteins are the blue-collar workers of biology, the down-to-earth molecules that we cannot live without. Since 2010, proteomics has found renewed meaning and international attention with the launch of the Human Proteome Project and the growing interest in Big Data technologies such as proteomics. This article presents an interdisciplinary technology foresight analysis and conceptualizes the terms "environtome" and "social proteome". We define "environtome" as the entire complement of elements external to the human host, from microbiome, ambient temperature and weather conditions to government innovation policies, stock market dynamics, human values, political power and social norms that collectively shape the human host spatially and temporally. The "social proteome" is the subset of the environtome that influences the transition of proteomics technology to innovative applications in society. The social proteome encompasses, for example, new reimbursement schemes and business innovation models for proteomics diagnostics that depart from the "once-a-life-time" genotypic tests and the anticipated hype attendant to context and time sensitive proteomics tests. Building on the "nesting principle" for governance of complex systems as discussed by Elinor Ostrom, we propose here a 3-tiered organizational architecture for Big Data science such as proteomics. The proposed nested governance structure is comprised of (a) scientists, (b) ethicists, and (c) scholars in the nascent field of "ethics-of-ethics", and aims to cultivate a robust social proteome for personalized medicine. Ostrom often noted that such nested governance designs offer assurance that political power embedded in innovation processes is distributed evenly and is not concentrated disproportionately in a single overbearing stakeholder or person. We agree with this assessment and conclude by underscoring the synergistic value of social and biological proteomes to realize the full potentials of proteomics science for personalized medicine in psychiatry in the present era of Big Data.

Global Governance for Personalized Medicine, Politics of Uncertainty, and Pierre Bourdieu.

How we choose to respond to uncertainty matters for robust and responsible science. New laws and consensus reports are popular instruments for global governance of emerging technology and attendant uncertainty. However, the sociologist Pierre Bourdieu noted that "[t]he judicial situation operates like a neutral space that neutralizes the stakes in any conflict through the de-realization and distancing implicit in the conversion of a direct struggle between parties into a dialogue between mediators." Put in other words, while law and legal modes of reasoning are certainly useful for conflict resolution and closure, their overprivileging in emerging technology and uncertainty governance can potentially bring about depoliticization by transforming the struggles and dissent necessary for democratic governance into a "dialogue between mediators." Hence, the critical sociological gaze offered by Bourdieu is particularly relevant for democratization of global governance of multiomics technologies and timely with the current uptake of personalized medicine. For example, in May 2023, the Romanian government introduced a law to give patients the right to personalized medicine. Personalized medicine is related to the larger umbrella concept and field of theranostics, the fusion of therapeutics and diagnostics. It is therefore timely to reflect on a "right for theranostics in planetary health," considering the potential for future pandemics and ecological crises in the 21st century. Rather than forcing consensus or convergence in an innovation ecosystem, dissent grounded in rigorous political theory, sociology of law and critical legal studies can strengthen democratization and global governance for personalized medicine and multiomics technologies.

Taking Political Determinants of Planetary Health Seriously: Expanding from P4 to P5 Medicine.

Predictive, Personalized, Preventive, and Participatory (P4) Medicine is embedded in the precision medicine conceptual framework to achieve the overarching goal of "the right drug, for the right patient, at the right dose, and at the right time." Science cultures and political determinants of health have normative and instrumental impacts on P4 medicine. Yet, since the age of Enlightenment in the 17th century, science and economics have been disarticulated from politics along the lines of classical liberalism, and with an ahistorical approach that continues into the 21st century. The consequence of this liberal disarticulation is that science is falsely and narrowly understood as an invariably technocratic and objective field. In the aftermath of the Covid-19 pandemic, it is clearer that political determinants of health are the causes-of-causes for disease and health. I propose that we need P5 medicine with a fifth P, political determinants of planetary health. The new "P" can engage not only with instrumental aspects of P4 medicine research and clinical implementation but also with the structural factors that are an integral part of the politics of the P4 medicine. For example, the living legacies of colonialism contribute to the unequal relationships in trade, labor, provision, and production of materials among nation-states and between the Global South and the Global North and shape the class struggles in contemporary society, science, and medicine. A decolonial politics of care in which the political determinants of planetary health are taken seriously is therefore crucial and relevant to building a robust, ethical, responsible, and just P5 medicine in the 21st century.

Technological Encounters in a Knowledge Economy: An Epistemic X-Ray.

Climate emergency is a planetary health and systems science challenge because human health, nonhuman animal health, and the health of the planetary ecosystems are coproduced and interdependent. Yet, we live in a time when climate emergency is tackled by platitudes and weak reforms instead of structural and systems changes, and with tools of the very same systems and metanarratives, for example, infinite growth at all costs, that are causing climate change in the first place. Seeking solutions to problems from within the knowledge frames and metanarratives that are causing the problems reproduces the same problems across time and geographies. This article examines and underlines the importance of an epistemological gaze on knowledge economy, an epistemological X-ray, as another solution in the toolbox of decolonial and other social justice struggles in an era of climate emergency. Epistemology questions and excavates the metanarratives embedded in knowledge forms that are popular, dominant, and hegemonic as well as knowledges that are silent, omitted, or erased. In this sense, epistemology does not take the "archives" of data and knowledge for granted but asks questions such as who, when, how, and with what and whose funding the archive was built, and what is included and left out? Epistemological choices made by innovators, funders, and knowledge actors often remain opaque in knowledge economies. Epistemology research is crucial for science and innovations to be responsive to planetary society and climate emergency and mindful of the social, political, neocolonial, and historical contexts of science and technology in the 21st century.

Feminism Is for Everyone: Scientists, Too.

Critically informed engagement in politics and the knowledge of social theory help democratize knowledge production, and redress power asymmetries in science and society. A feminist lens is one of the many ways in which power asymmetries in science can be critically unpacked and interrupted. There are many strands of feminism and feminist theory that differ in their approaches to resist patriarchy and injustices in science and society. As an example, I adopt here the definition of feminism of the late cultural critic bell hooks because her works underscore that feminism is an intersectional liberatory methodology for everyone to resist multiple forms of oppression simultaneously. Queer theory is a strand of social theory that came to prominence since the 1990s in particular. Queer feminism continues to shape feminist writing on science cultures and the knowledge-based innovations contemporary science strives to accomplish. Systems science brings about systems thinking, and that includes rethinking science as culture beyond a narrow realm of technology, and being cognizant of the broader social, feminist, queer, and political contexts of science around the world.

Ketoconazole-associated preferential increase in dopamine D2 receptor occupancy in striatum compared to pituitary in vivo: role for drug transporters?

Membrane transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are efflux pumps that remove drugs from the brain back to the peripheral blood compartment, serving as a functional component of the blood-brain barrier (BBB). We report here that coadministration of the P-gp and BCRP inhibitor ketoconazole with risperidone may preferentially increase D2 receptor occupancy in the striatum compared to pituitary. Four male patients with schizophrenia or schizoaffective disorder who had received at least 4 prior injections of the long-acting risperidone at a stable dose of 25 to 50 mg participated in this positron emission tomography study. Multiple-dose ketoconazole coadministration reduced the P-gp activity as shown by fexofenadine oral challenge. Importantly, we found a strong statistical trend in this sample of 4 subjects who consistently showed a decrease in striatal fluorine 18 (F)-fallypride binding (an indication of increased D2 receptor occupancy) after ketoconazole coadministration (P = 0.057), whereas the pituitary (a region that lies outside the BBB) F-fallypride binding did not change (P = 0.99). These observations warrant further research with selective drug transporter inhibitors. We suggest that in neuroimaging studies, the pituitary drug occupancy can serve as a useful new "positive control" to evaluate whether drug occupancy is preferentially increased in brain regions that fall inside the BBB after cotreatment with P-gp and BCRP inhibitors. This is a noteworthy study design consideration regarding the future clinical testing of novel adjunct interventions aimed at modulating membrane transporter function at the BBB, with the goal of augmenting drug access into the brain compartment, particularly in treatment-resistant psychiatric illness.

Decolonizing Knowledge Upstream: New Ways to Deconstruct and Fight Disinformation in an Era of COVID-19, Extreme Digital Transformation, and Climate Emergency.

Lies and disinformation have always existed throughout human history. However, disinformation has become a "pandemic within a pandemic" with convergence of COVID-19 and digital transformation of health care, climate emergency, and pervasive human-computer interaction in all facets of life. We are living through an era of post-truth. New approaches to fight disinformation are urgently needed and of paramount importance for systems science and planetary health. In this study, we discuss the ways in which extractive and entrenched epistemologies such as technocracy and neoliberalism co-produce disinformation. We draw from the works of David Collingridge in technology entrenchment and the literature on digital health, international affairs, climate emergency, degrowth, and decolonializing methodologies. We expand the vocabulary on and interventions against disinformation, and propose the following: (1) rapid epistemic disobedience as a critical governance tool to resist the cultural hegemony of neoliberalism and its master narrative infinite growth that is damaging the planetary ecosystems, while creating echo chambers overflowing with disinformation, and (2) a two-tiered taxonomy of reflexivity, a state of self-cognizance by knowledge actors, for example, scientists, engineers, and physicians (type 1 reflexivity), as well as by chroniclers of former actors, for example, civil society organizations, journalists, social sciences, and humanities scholars (type 2 reflexivity). This article takes seriously the role of master narratives in quotidian life in production of disinformation and ecological breakdown. The infinite growth narrative does not ask critical questions such as "growth in what, at what costs to society and environment?," and is a dangerous game of brinkmanship that has been testing the planetary ecological boundaries and putting at risk the veracity of knowledge. There is a need for scholars and systems scientists who break ranks with entrenched narratives that pose existential threats to planetary sustainability and are harmful to knowledge veracity. Scholars who resist the obvious recklessness and juggernaut of the pursuit of neoliberal infinite growth would be rooting for living responsibly and in solidarity on a planet with finite resources. The interventions proposed in this study, rapid epistemic disobedience and the expanded reflexivity taxonomy, can advance progressive policies for a good life for all within planetary boundaries, and decolonize knowledge from disinformation in ways that are necessarily upstream, radical, rapid, and emancipatory.

Disinformation as COVID-19's Twin Pandemic: False Equivalences, Entrenched Epistemologies, and Causes-of-Causes.

We are currently facing and traversing in the thick of a twin pandemic: coronavirus disease 2019 (COVID-19) and disinformation. Disinformation is false information created and spread deliberately with the intention to mislead public opinion, obscure truths, and undermine trust in knowledge. The digital age we live in is quite different than the printing revolution and invention of the oil-based ink printing press centuries ago. Digital technologies can spread and repeat disinformation at extremely high speeds, while anyone, a qualified expert or not, and with internet access, can become an author. To fight disinformation, we ought to dismantle the entrenched and extractive epistemologies that act as upstream drivers and sites of disinformation production. Epistemology refers to the value-laden knowledge frames, overarching master narratives, and storylines, in which knowledge is produced. If the epistemologies in which we generate knowledge are false, then the knowledge products will be laden with disinformation. Moreover, the harms caused by disinformation can extend well beyond the immediate knowledge domain where disinformation has originated. This occurs when "false equivalence" is used as a form of rhetoric. False equivalence is a type of flawed sense making where equal weight is given to arguments with concrete material evidence, and those that are conjecture, untrue, or unjust. This article presents an analysis of the disinformation pandemic attendant to COVID-19, with an eye to its causes-of-causes: unchecked extractive epistemologies (e.g., technocracy), and the practice of false equivalence in pandemic discourses. We argue that holding the political agency of master narratives to account is essential (1) to fight the disinformation pandemic and (2) for prefigurative politics to build egalitarian and democratic societies in place of the instrumental/transactional relationships that typify the contemporary nation states and the neoliberal university whose ossified rituals lack the normative capacities for critical governance in a time of converging social, digital, and ecological crises. For liberation from disinformation, we should start with liberation from entrenched extractive epistemologies in science and society.

Narrative Metadata: Leaving the War Metaphor Behind and Unpacking the Control Tactics of Biopower in COVID-19.

Narratives are a veritable type of metadata. Narratives are power-laden storylines that conjure up emotions and enact value systems that markedly affect scientific practices, and to what ends, and for whom science and health innovations are made available. Narratives, if they are left unchecked, can undermine critical thinking and the agency of publics, threatening the possibilities for robust, responsible, relevant, and democratic science. One such narrative, a sociotechnical metadata in its own right, and of immense relevance in the current historical moment of the pandemic, is the uncritical use of the war and other military metaphors in COVID-19 science and planetary health interventions. In October 2022 issue of OMICS, Ebru Yetiskin adopts a biophilosophical transdisciplinary approach and feminist versions of science and technology studies to examine the ways in which the war discourse and other military metaphors have been deployed for the sake of biopower during COVID-19. In this article, we discuss the need to critically unpack the narrative metadata to leave the war metaphor behind, and hold to account the control tactics of biopower embedded in the COVID-19 pandemic.

The positive effect of black seed (Nigella sativa L.) essential oil on thyroid hormones in rats with hypothyroidism and hyperthyroidism.

In our study, the effect of essential oil obtained from Nigella sativa L. (NSE) on thyroid hormones and antioxidant balance in hypothyroidism (HT) and hyperthyroidism (HP) models induced by propylthiouracil(PTU) and L-thyroxine(LT4 ), respectively, in rats were investigated for 4 weeks. NSE was administered by gastric gavage at a dose of 200 mg/kg body weight. In this study, 48 male Wistar albino rats with an average weight of 180-290 g and age 5-6 months were divided into eight groups, as follows: groups with HT, (1) control, (2) HT, (3) NSE, and (4) HT + NSE; groups with HP, (1) control, (2) HP, (3), and NSE (4) HP + NSE. As a result, we found that NSE administration increased total triiodothyronine (TT3 ) and decreased nitric oxide in HT + NSE. Besides, it decreased TT3 in HP + NSE and increased total antioxidant capacity. Our findings suggest that NSE may have beneficial effects on thyroid gland abnormalities owing to its antioxidant properties. PRACTICAL APPLICATIONS: Essential oils derived from Nigella sativa L. seed contain many bioactive substances such as thymoquinone and cymene. This paper emphasizes the effect of NSE on thyroid hormone abnormalities and negative oxidative state that occurs in HT and HP models. The present study provides evidence of a positive effect of NSE particularly on TT3 levels in the HT and HP models. It can therefore be assumed that NSE could be used as a supportive natural alternative source to improve thyroid hormone levels and relieve increased oxidative stress.

Digital Is Political: Why We Need a Feminist Conceptual Lens on Determinants of Digital Health.

Digital health is a rapidly emerging field that offers several promising potentials: health care delivery remotely, in urban and rural areas, in any time zone, and in times of pandemics and ecological crises. Digital health encompasses electronic health, computing science, big data, artificial intelligence, and the Internet of Things, to name but a few technical components. Digital health is part of a vision for systems medicine. The advances in digital health have been, however, uneven and highly variable across communities, countries, medical specialties, and societal contexts. This article critically examines the determinants of digital health (DDH). DDH describes and critically responds to inequities and differences in digital health theory and practice across people, places, spaces, and time. DDH is not limited to studying variability in design and access to digital technologies. DDH is situated within a larger context of the political determinants of health. Hence, this article presents an analysis of DDH, as seen through political science, and the feminist studies of technology and society. A feminist lens would strengthen systems-driven, historically and critically informed governance for DDH. This would be a timely antidote against unchecked destructive/extractive governance narratives (e.g., technocracy and patriarchy) that produce and reproduce the health inequities. Moreover, feminist framing of DDH can help cultivate epistemic competence to detect and reject false equivalences in how we understand the emerging digital world(s). False equivalence, very common in the current pandemic and post-truth era, is a type of flawed reasoning in decision-making where equal weight is given to arguments with concrete material evidence, and those that are conjecture, untrue, or unjust. A feminist conceptual lens on DDH would help remedy what I refer to in this article as "the normative deficits" in science and technology policy that became endemic with the rise of neoliberal governance since the 1980s in particular. In this context, it is helpful to recall the feminist writer Ursula K. Le Guin. Le Guin posed "what if?" questions, to break free from oppressive narratives such as patriarchy and re-imagine technology futures. It is time to envision an emancipated, equitable, and more democratic world by asking "what if we lived in a feminist world?" That would be truly awesome, for everyone, women and men, children, youth, and future generations, to steer digital technologies and the new field of DDH toward broadly relevant, ethical, experiential, democratic, and socially responsive health outcomes.

Rethinking Clinical Trials and Personalized Medicine with Placebogenomics and Placebo Dose.

Pharmacogenomics, nutrigenomics, vaccinomics, and the nascent field of plant omics are examples of variability science. They are embedded within an overarching framework of personalized medicine. Across these public health specialties, the significance and biology of the placebo response have been historically neglected. A placebo is any substance such as a sugar pill administered in the guise of medication, but one that does not have pharmacological activity. Placebos do have clinical effects, however, that can be substantive in magnitude and vary markedly from person-to-person depending, for example, on the type of disease, symptoms, or clinical trial design. Research over the past several decades attests to a genuine neurobiological basis for placebo effects. All drugs have placebo components that contribute to their overall treatment effect. Placebos are used in clinical trials as control groups to ascertain the net pharmacological effect of a drug candidate. Not only less well known but also relevant to rational therapeutics and personalized medicine is the nocebo. A nocebo effect occurs when an inert substance is administered in a context that induces negative expectations, worsening patients' symptoms. With the COVID-19 pandemic, there are high public expectations for new vaccines and medicines to end the contagion, while at the same time antiscience, post-truth, and antivaccine movements are worrisomely on the rise. These social movements, changes in public health cultures, and conditioned behavioral responses can trigger both placebo and nocebo effects. Hence, in clinical trials, forecasting and explaining placebo and nocebo variability are more important than ever for robust science and personalized health care. Against this overarching context, this article provides (1) a brief history of placebo and (2) a discussion on biology, mechanisms, and variability of placebo effects, and (3) discusses three emerging new concepts: placebogenomics, nocebogenomics, and augmented placebo, that is, the notion of a "placebo dose." We conclude with a roadmap for placebogenomics, its synergies with the nascent field of social pharmacology, and the ways in which a new taxonomy of drug and placebo variability can be anticipated in the next decade.

Thanatechnology and the Living Dead: New Concepts in Digital Transformation and Human-Computer Interaction.

In a digital society, shall we be the authors of our own experience, not only during our lifetime but also after we die? We ask this question because dying and bereavement have become even harder, and much less private, in the digital age. New big data-driven digital industries and technologies are on the rise, with promises of interactive 3D avatars and storage of digital memories of the deceased, so they can continue to exist online as the "living dead" in a digital afterlife. Famous rock and roll icons like Roy Orbison, Frank Zappa, Ronnie James Dio, and Amy Winehouse have famously been turned into holograms that can once again give "live" performances on the touring circuit, often pulling in large audiences. Death studies, dying, and grief have become virtual in the 21st century. We live in truly unprecedented times for human-computer interactions. Thanatology is the scientific study of death, dying, loss, and grief. In contrast to the biological study of biological aging (cellular senescence) and programmed cell death (apoptosis), thanatology employs multiple professional lenses, medical, psychological, physical, spiritual, ethical, descriptive, and normative. In 1997, Carla Sofka introduced the term thanatechnology as "technological mechanisms such as interactive videodiscs and computer programs that are used to access information or aid in learning about thanatology topics." Onward to 2021, the advent of social media, the Internet of Things, and sensors that digitize and archive nearly every human movement and experience are taking thanatechnology, and by extension, digital transformation, to new heights. For example, what happens to digital remains of persons once they cease to exist physically? This article offers a critical study and snapshot of this nascent field, and the "un-disciplinary" sociotechnical issues digital thanatechnologies raise in relation to big data. We also discuss how best to critically govern this new frontier in systems science and the digital society. We suggest that new policy narratives such as (1) the right to nonparticipation in relation to information and communication technologies and (2) the planetary public goods deserve further attention to democratize thanatechnology and big data. To the extent that systems science often depends on data from online platforms, for example, in times of pandemics and ecological crises, "critical thanatechnology studies," introduced in this article, is a timely and essential field of scholarship with broad importance for systems science and planetary health.

Ethnocultural community leaders' views and perceptions on biobanks and population specific genomic research: a qualitative research study.

Substantial investments were made in population based biobanks over the past decade. Ethnocultural community members are both sponsors and beneficiaries of biobanks. In addition, the success of biobank projects depends on community support and participation. Yet there are few empirical data on views, perceptions and interests of ethnocultural communities on biobanks. This silent gap in genomics, ethics and policy literatures has to be addressed. We conducted a qualitative research study with in-depth interviews of ethnocultural community leaders (e.g., members of the Canadian Parliament, school commissioners) on their perspectives concerning population specific genomics research and biobanks. An equal partnership model where public is not only informed, but also involved in decision-making processes was perceived as an essential democratic requisite. These empirical data on ethnocultural community leaders' views, interests and perceptions identify several key socio-cultural and ethical factors that can be decisive for effective and sustainable community involvement in biobanks.