Contractual Mechanisms for Securing the Public Interest in Data Sharing in Public-Private Health Research Partnerships

Public private partnerships (PPPs) are increasingly common in health research, with large European investment over the last 20 years and renewed focus in the wake of the global health crisis COVID-19. PPPs have been used for health research that seeks to collect, analyse and share personal data from research participants, often on the basis of informed or broad consent. PPPs are underpinned by contracts, both to govern the use of data and samples necessary for health research, and to govern the agreement between the public and private contracting parties of a project. This raises the question of how far contracts adequately protect public interests, for example in privacy and data protection when patient data are exposed to a broader range of potential uses from the private sector. A core principle of contract law is that you cannot contract for unlawful activity. As such, contracts could be void if their design or performance entails a breach of statute or common law, for example data protection and privacy laws or the common law duty of confidentiality. This paper analyses the implications of this general principle of illegality for contracts underpinning PPPs in health research, particularly to understand the extent to which it could operate to protect the public interest as conceived by privacy and data protection law. The paper will show how this heavily policy-driven doctrine has scope to ensure that contracts and contract terms that are contrary to public policy are void or unenforceable which, in the context of PPPs using personal information for health innovation and research, is a welcome, though limited, accountability mechanism in private law that could operate to serve the public interest

Immune-Boosting Functional Foods: A Potential Remedy for Chinese Consumers Living Under Polluted Air

The deterioration of air quality in China has resulted in many people looking for remedies to counteract the impact that air pollution is perceived to be having on their health. As the importance of diet on immune health is becoming increasingly well recognised, a narrative literature review was undertaken to elucidate Chinese consumers’ acceptance of functional food products designed to help the immune system recover from pollution-driven impact and to assess their market potential. Consumers’ attitude towards immune-boosting functional foods were mainly positive, with scientific validation being important in determining the credibility of a product. This was despite the fact that the effectiveness of the functional food products currently in the market that purported to be remedies for pollution-driven impacts on the lung did not appear to be supported by scientific evidence. Numerous studies have reported functional foods could provide a wide range of benefits to immune health, including helping pollution-driven immune issues. This review highlights the market demand for effective and scientifically-proven functional food products that help Chinese consumers’ immune system recover from the impact of air pollution

Parental Involvement Among Collegiate Student-Athletes: An Analysis Across NCAA Divisions

Despite emerging evidence of a link between parental involvement and student-athletes’ (SA) experiences, and the desire for educational programming for parents of these SAs, previous research has been limited to the Division I level. This has prevented the ability to inform, develop, and deliver parent programming across the NCAA’s diverse membership. The present study was designed to descriptively assess SA reports of parental involvement (i.e., support, contact, academic engagement, athletic engagement) across NCAA Division I, II, and III member institutions and examine the potential impact of this involvement on SAs’ experiences (i.e., academic self-efficacy, athletic satisfaction, well-being, individuation). Participants were 455 SAs (53% female; 81% Caucasian; Mage = 19.81, SD = 1.65) from DI (30%), DII (37%), and DIII (33%) institutions, who completed an online survey with items assessing parental involvement and SA experiences. Regarding academic classification, 32% were freshmen, 24% sophomores, 22% juniors, and 22% seniors. Results provide novel evidence for an absence of division-wide differences in average levels of involvement and no variability in links between involvement and SA experiences across divisions. Results complement and extend previous research by offering a clearer understanding of differential associations between involvement and SAs’ experiences regardless of division, notably that involvement bolstered well-being but also strongly detracted from individuation. Findings highlight the importance of developing programs to promote positive and developmentally-appropriate parental involvement across the spectrum of intercollegiate athletics, especially given the absence of evidence-based resources presently offered by the NCAA

Chinese consumers’ perceptions of immune health and immune-boosting remedies including functional foods

To facilitate the successful design of functional foods designed to boost immunity and to guide the successful promotion of such products, to Chinese consumers, fundamental knowledge is required on how consumers perceive the concept of immunity, the steps they take to improve their immunity and what their general attitudes are toward new functional food products. To explore these issues, focus groups (n = 4) and in-home semi-structured interviews (n = 12) were conducted in Shanghai. Immunity was understood to be the defense system that protects the body, with perceived causes for poor immunity including irregular lifestyles, polluted air, and increased age. Participants believed that immunity could be changed by modifying their diet with either conventional or functional foods (including TCM-based foods), supplements (TCM or non-TCM containing), TCM medical gels, TCM patent medicine, and Western medicine all playing varying roles at enhancing immunity and protecting health at different stages of wellbeing

KSHV LANA acetylation-selective acidic domain reader sequence mediates virus persistence

Viruses modulate biochemical cellular pathways to permit infection. A recently described mechanism mediates selective protein interactions between acidic domain readers and unacetylated, lysine-rich regions, opposite of bromodomain function. Kaposi´s sarcoma (KS)-associated herpesvirus (KSHV) is tightly linked with KS, primary effusion lymphoma, and multicentric Castleman’s disease. KSHV latently infects cells, and its genome persists as a multicopy, extrachromosomal episome. During latency, KSHV expresses a small subset of genes, including the latency-associated nuclear antigen (LANA), which mediates viral episome persistence. Here we show that LANA contains two tandem, partially overlapping, acidic domain sequences homologous to the SET oncoprotein acidic domain reader. This domain selectively interacts with unacetylated p53, as evidenced by reduced LANA interaction after overexpression of CBP, which acetylates p53, or with an acetylation mimicking carboxyl-terminal domain p53 mutant. Conversely, the interaction of LANA with an acetylation-deficient p53 mutant is enhanced. Significantly, KSHV LANA mutants lacking the acidic domain reader sequence are deficient for establishment of latency and persistent infection. This deficiency was confirmed under physiological conditions, on infection of mice with a murine gammaherpesvirus 68 chimera expressing LANA, where the virus was highly deficient in establishing latent infection in germinal center B cells. Therefore, LANA’s acidic domain reader is critical for viral latency. These results implicate an acetylation-dependent mechanism mediating KSHV persistence and expand the role of acidic domain readers.info:eu-repo/semantics/publishedVersio

Cross-species conservation of episome maintenance provides a basis for in vivo investigation of Kaposi's sarcoma herpesvirus LANA

Copyright: © 2017 Habison et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Many pathogens, including Kaposi's sarcoma herpesvirus (KSHV), lack tractable small animal models. KSHV persists as a multi-copy, nuclear episome in latently infected cells. KSHV latency-associated nuclear antigen (kLANA) binds viral terminal repeat (kTR) DNA to mediate episome persistence. Model pathogen murine gammaherpesvirus 68 (MHV68) mLANA acts analogously on mTR DNA. kLANA and mLANA differ substantially in size and kTR and mTR show little sequence conservation. Here, we find kLANA and mLANA act reciprocally to mediate episome persistence of TR DNA. Further, kLANA rescued mLANA deficient MHV68, enabling a chimeric virus to establish latent infection in vivo in germinal center B cells. The level of chimeric virus in vivo latency was moderately reduced compared to WT infection, but WT or chimeric MHV68 infected cells had similar viral genome copy numbers as assessed by immunofluorescence of LANA intranuclear dots or qPCR. Thus, despite more than 60 Ma of evolutionary divergence, mLANA and kLANA act reciprocally on TR DNA, and kLANA functionally substitutes for mLANA, allowing kLANA investigation in vivo. Analogous chimeras may allow in vivo investigation of genes of other human pathogens.This work was supported in part by National Institutes of Health grants CA082036 (NCI), DE025208, and DE024971 (both NIDCR), to KMK, FCT PTDC/IMI-MIC/0980/2014 to JPS, FCT Harvard Medical School Portugal Program in Translational Research (HMSP-ICT/0021/2010) to JPS, KMK, CEM, Instituto de Medicina Molecular Directors Fund to JPS, and iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344) FCT/FEDER (PT2020 Partnership Agreement) to CEM. M.P.M is supported by a fellowship from Fundação para a Ciência e Tecnologia (FCT), Portugal.info:eu-repo/semantics/publishedVersio

Biomodifying the ‘Natural’: from adaptive regulation to adaptive societal governance

Biomodifying technologies—such as gene editing, induced pluripotent stem cells and bioprinting— are being developed for a wide range of applications, from pest control to lab-grown meat. In medicine, regulators have responded to the challenge of evaluating modified ‘natural’ material as a therapeutic ‘product’ by introducing more flexible assessment schemes. Attempts have also been made to engage stakeholders across the globe on the acceptable parameters for these technologies, particularly in the case of gene editing. Regulatory flexibility and stakeholder engagement are important, but a broader perspective is also needed to respond to the potential disruption of biomodification. Our case-study technologies problematize basic ideas — such as ‘nature,’ ‘product’ and ‘donation’— that underpin the legal categories used to regulate biotechnology. Where such foundational concepts are rendered uncertain, a socially responsive and sustainable solution would involve exploring evolutions in these concepts across different societies. We suggest that the global observatory model is a good starting point for this ‘Adaptive Societal Governance’ approach, in which a self-organising network of scholars and interested parties could carry out the multi-modal (meta)analyses needed to understand societal constructions of ideas inherent to our understanding of ‘life.

cAMP/CREB-regulated LINC00473 marks LKB1-inactivated lung cancer and mediates tumor growth

The LKB1 tumor suppressor gene is frequently mutated and inactivated in non–small cell lung cancer (NSCLC). Loss of LKB1 promotes cancer progression and influences therapeutic responses in preclinical studies; however, specific targeted therapies for lung cancer with LKB1 inactivation are currently unavailable. Here, we have identified a long noncoding RNA (lncRNA) signature that is associated with the loss of LKB1 function. We discovered that LINC00473 is consistently the most highly induced gene in LKB1-inactivated human primary NSCLC samples and derived cell lines. Elevated LINC00473 expression correlated with poor prognosis, and sustained LINC00473 expression was required for the growth and survival of LKB1-inactivated NSCLC cells. Mechanistically, LINC00473 was induced by LKB1 inactivation and subsequent cyclic AMP–responsive element–binding protein (CREB)/CREB-regulated transcription coactivator (CRTC) activation. We determined that LINC00473 is a nuclear lncRNA and interacts with NONO, a component of the cAMP signaling pathway, thereby facilitating CRTC/CREB-mediated transcription. Collectively, our study demonstrates that LINC00473 expression potentially serves as a robust biomarker for tumor LKB1 functional status that can be integrated into clinical trials for patient selection and treatment evaluation, and implicates LINC00473 as a therapeutic target for LKB1-inactivated NSCLC

Phase I, Dose-Escalation, Two-Part Trial of the PARP Inhibitor Talazoparib in Patients with Advanced Germline BRCA1/2 Mutations and Selected Sporadic Cancers

Talazoparib inhibits PARP catalytic activity, trapping PARP1 on damaged DNA and causing cell death in BRCA1/2-mutated cells. We evaluated talazoparib therapy in this two-part, phase I, first-in-human trial. Antitumor activity, MTD, pharmacokinetics, and pharmacodynamics of once-daily talazoparib were determined in an open-label, multicenter, dose-escalation study (NCT01286987). The MTD was 1.0 mg/day, with an elimination half-life of 50 hours. Treatment-related adverse events included fatigue (26/71 patients; 37%) and anemia (25/71 patients; 35%). Grade 3 to 4 adverse events included anemia (17/71 patients; 24%) and thrombocytopenia (13/71 patients; 18%). Sustained PARP inhibition was observed at doses ≥0.60 mg/day. At 1.0 mg/day, confirmed responses were observed in 7 of 14 (50%) and 5 of 12 (42%) patients with BRCA mutation–associated breast and ovarian cancers, respectively, and in patients with pancreatic and small cell lung cancer. Talazoparib demonstrated single-agent antitumor activity and was well tolerated in patients at the recommended dose of 1.0 mg/day

Therapeutic Vaccination With Recombinant Adenovirus Reduces Splenic Parasite Burden in Experimental Visceral Leishmaniasis

Therapeutic vaccines, when used alone or in combination therapy with antileishmanial drugs, may have an important place in the control of a variety of forms of human leishmaniasis. Here, we describe the development of an adenovirus-based vaccine (Ad5-KH) comprising a synthetic haspb gene linked to a kmp11 gene via a viral 2A sequence. In nonvaccinated Leishmania donovani–infected BALB/c mice, HASPB- and KMP11-specific CD8+ T cell responses were undetectable, although IgG1 and IgG2a antibodies were evident. After therapeutic vaccination, antibody responses were boosted, and IFNγ+CD8+ T cell responses, particularly to HASPB, became apparent. A single vaccination with Ad5-KH inhibited splenic parasite growth by ∼66%, a level of efficacy comparable to that observed in early stage testing of clinically approved antileishmanial drugs in this model. These studies indicate the usefulness of adenoviral vectors to deliver leishmanial antigens in a potent and host protective manner to animals with existing L. donovani infection