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Biobanks play a central role in pediatric translational research, which deals primarily with genetic data from sample-based research. However, participation of children in biobanking has received only limited attention in the literature, even though research in general and in clinical trials in particular have a long history in involving minors. So, we resolved to explore specific challenging ethical, legal, and societal issues (ELSI) in the current pediatric biobanking landscape to propose a way forward for biobanking with children as partners in research. Methodologically, we first established the accessibility and utilization of pediatric biobanks, mainly in Europe. This was supported by a literature review related to children's participation, taking into account not only academic papers but also relevant guidelines and best-practices. Our findings are discussed under five themes: general vulnerability; ethical issues-balancing risks and benefits, right to an open future, return of results including secondary findings; legal issues-capacity and legal majority; societal issues-public awareness and empowerment; and responsible research with children. Ultimately, we observed an on-going shift from the parents'/guardians' consent being a sine-qua-non condition to the positive minor's agreement: confirming that the minor is the participant, not the parent(s)/guardian(s). This ethical rethinking is paving the way toward age-appropriate, dynamic and participatory models of involving minors in decision-making. However, we identified a requirement for dynamic tools to assess maturity, a lack of co-produced engagement tools and paucity of shared best practices. We highlight the need to provide empowerment and capability settings to support researchers and biobankers, and back this with practical examples. In conclusion, equipping children and adults with appropriate tools, and ensuring children's participation is at the forefront of responsible pediatric biobanking, is an

In order to investigate the serendipitous find of a gastropod encrusted by the symbiont-bearing colonial coral Oculina patagonica, we examined several specimens of cnidarian-encrusted gastropods, ranging in age from the Pliocene to the Recent, and characterized in detail their sclerobiont cover. The results of our analysis suggest that gastropod shells can be encrusted by symbiont-bearing colonial corals at various times: (1) when the gastropod is alive; (2) when the shell is being used by a secondary inhabitant (e.g., hermit crabs or sipunculid worms); (3) when the shell is discarded but yet to be buried. The relationship between the symbiont-bearing coral and the inhabitant(s) of the encrusted shell is an example of facultative mutualism, i.e., it is non-obligate yet beneficial for both ends as the former obtains the capability to move, and the latter improves the resistance and resilience of its armor, thus obtaining extra protection from predators. Being able to move could prove particularly useful for a symbiont-bearing coral because, in addition to removing the risk of being smothered by sediment, it would also favor the photosynthetic activity of its algal endosymbionts by allowing the coral to be always clean of sedimentary particles. Although the resulting epibiotic association would be limited in size by the ability of either the gastropod or the secondary inhabitant of the shell to move at the seafloor, these small and easy-to-miss benthic islands might become the seeds that allow sessile carbonate producers such as hermatypic colonial corals to colonize unconsolidated substrates.

Near the Fauglia village (Tuscany, Italy), a Calabrian (lower Pleistocene) stratigraphic succession crops out in a sand quarry. This succession is comprised of an alternation of sands and silts featuring an exceptionally preserved Posidonia oceanica meadow (preserving in situ rhyzomes and loose leaves) and an abundant and diverse assemblage of fossil invertebrates that also includes the zooxanthellate coral Cladocora caespitosa. The latter forms a rare example of a Cladocora bank, exhibiting peculiar fossilization modes that range from compound molds to recrystallized corallites, overlain by an oyster reef. Paleoenvironmental considerations, based on a comparison with analogue environments from the present-day Mediterranean region, indicate a shallow-water, protected marine environment characterized through time by a seagrass meadow (ranging in water depth from 10 to 35m), a subsequent coral bank (5 to 20 m water depth), and finally by an oyster reef in water shallower than 5-10 m. Throughout the 6-m-thick stratigraphic section, five taphofacies are recognized, showing different diagenetic signatures. Subsequent stages of aragonite dissolution and calcite re-precipitation are thus hypothesized, revealing a complex and unusual diagenetic history for this remarkable find of exceptionally preserved Pleistocene coral bank and seagrass meadow.

Aetobatus (Myliobatiformes: Aetobatidae) is a living genus of eagle rays that occurs in shal-low-marine, tropical and subtropical environments of the Atlantic, Pacific, and Indian Oceans. Nowa-days, Aetobatus does not inhabit the cool-to warm-temperate European and Mediterranean waters, though it is known from this broad region by virtue of several fossil teeth ranging chronostratigra-phically from the lower Palaeogene to the upper Neogene. The present paper reports on a fossil aeto-batid tooth discovered in mid-Pliocene (upper Zanclean to lower Piacenzian, 3.82-3.19 Ma) marine deposits exposed in the vicinities of Certaldo (Tuscany, Italy) and identified as belonging to †Aetobatus cf. cappettai. This specimen comprises the youngest occurrence of Aetobatus along the coasts of main-land Europe; furthermore, together with previous finds from roughly coeval deposits of Mallorca (Balearic Islands, Spain), it represents the most recent record of this genus in the whole Euro-Mediter-ranean region. In light of the environmental preferences of extant Aetobatus spp., our discovery suggests palaeoenvironmental conditions favourable to the persistence of tropical/subtropical taxa of "Mio-cene survivors" along the Pliocene coasts of Tuscany. In addition, it raises the question of whether or not the Messinian Salinity Crisis really resulted in the complete collapse of the Mediterranean marine biota and in the subsequent recolonisation of the Mediterranean Basin from the adjoining Atlantic waters and/or scattered marginal intrabasinal refugia at the beginning of the Pliocene. The possibility of Aetobatus recolonising the Mediterranean Sea through the Suez Canal in the near future is dis-cussed.

Background: Informed consent forms for clinical research are several and variable at international, national and local levels. According to the literature, they are often unclear and poorly understood by participants. Within the H2020 project CORBEL—Coordinated Research Infrastructures Building Enduring Life-science Services—clinical researchers, researchers in ethical, social, and legal issues, experts in planning and management of clinical studies, clinicians, researchers in citizen involvement and public engagement worked together to provide a minimum set of requirements for informed consent in clinical studies. Methods: The template was based on a literature review including systematic reviews and guidelines searched on PubMed, Embase, Cochrane Library, NICE, SIGN, GIN, and Clearinghouse databases, and on comparison of templates gathered through an extensive search on the websites of research institutes, national and international agencies, and international initiatives. We discussed the draft versions step-by-step and then we referred to it as the “matrix” to underline its modular character and indicate that it allows adaptation to the context in which it will be used. The matrix was revised by representatives of two international patient groups. Results: The matrix covers the process of ensuring that the appropriate information, context and setting are provided so that the participant can give truly informed consent. It addresses the key topics and proposes wording on how to clarify the meaning of placebo and of non-inferiority studies, the importance of individual participants’ data sharing, and the impossibility of knowing in advance how the data might be used in future studies. Finally, it presents general suggestions on wording, format, and length of the information sheet. Conclusions: The matrix underlines the importance of improving the process of communication, its proper conditions (space, time, setting), and addresses the participants’ lack of knowled

Neoadjuvant chemotherapy has been established as the standard of care for HER2-positive breast cancer since it allows cancer down-staging, up to pathological complete response. The standard of care in the neoadjuvant setting for HER2-positive breast cancer is a combination of highly cytotoxic drugs such as anthracyclines and the anti-HER2 monoclonal antibody. Despite this cocktail allows a pathological complete response in up to 50%, their co-administration is strongly limited by intrinsic cardiotoxicity. Therefore, only a sequential administration of anthracyclines and the anti-HER2 treatment is allowed. Here, we propose the anthracycline formulation in H-Ferritin nanocages as promising candidate to solve this unmet clinical need, thanks to its capability to increase anthracyclines efficacy while reducing their cardiotoxicity. Treating a murine model of HER2-positive breast cancer with co-administration of Trastuzumab and H-Ferritin anthracycline nanoformulation, we demonstrate an improved tumor penetration of drugs, leading to increased anticancer efficacy and reduced of cardiotoxicity.

In the Montalto quarry, in the vicinities of Fauglia (Tuscany, Italy), a lower Pleistocene (Calabrian) stratigraphic succession crops out. This succession is characterised by an alternation of sandstones, clayey sandstones and mudstones, featuring abundant fossils of invertebrates and plants. Throughout a 6-m-thick measured stratigraphic section, several different preservation styles can be observed (hence the recognition of different taphofacies) and a complex taphonomic history can be reconstructed. At the base of the section, in massive sandstones, accumulations of disarticulated bivalve shells and bivalve internal moulds are preserved in discontinuous lenses. In the overlying stratum, infaunal molluscs such as Panopea are preserved in life position, as calcite-cemented internal moulds and rare external moulds. Isolated blocks of external moulds of Cladocora caespitosa frames are found in the clayey sandstone above, together with pectinids preserved as original shells. Overlying this unit, a sandy mudstone interval hosts several well-preserved vegetal remains, including a horizon that is rich in exceptionally preserved specimen of Posidonia oceanica with both rhizomes and leaves. In the overlying strata, Cladocora caespitosa occurs as forming a conspicuous coral reef, primarily appearing as isolated blocks consisting of compound moulds and recrystallised corallites developing upwards into a fully developed bioconstruction that is mainly preserved as external moulds. In this unit, bivalves are partially or completely recrystallised, and they also exhibit geopetal structures that testify to at least three stages of mineral precipitation, namely: the cementation of the terrigenous infill; the recrystallization of the aragonitic shell material; and the precipitation of large crystals filling the remaining voids. Microscopic analyses revealed a calcite composition for all these phases. All the materials that were sampled from this unit become luminescent under UV ligh

A new palaeontological geosite has been discovered in the vicinities of Fauglia (Tuscany, Italy), in the Neogene Tora-Fine Basin. Here, an entire coral reef has remained “frozen in time” from Pleistocene times, exhibiting a peculiar fossil preservation. The studied outcrop extends over a 65 m-long artificial cliff where a 4-m-thick stratigraphic section is exposed. The section features an alternation of mudstones, clayey sandstones, and massive sandstones that host a reef of colonies of the Mediterranean scleractinian coral Cladocora caespitosa. The entire reef is covered by a thick layer of sand. The sedimentological features and the macrofossil assemblage suggest positioning of the outcrop in the Morrona Formation, which is locally referred to the early Pleistocene (Calabrian stage). The faunal association of the reef includes several species of echinoids, bivalves, gastropods, scaphopods, crustaceans, and cnidarians. Complex interactions between animals have also been recognized (e.g., corals growing around bivalves and Oichnus traces). Body fossils display a peculiar preservation style. Corals, mollusks and echinoids are mainly comprised of composite molds, inner and outer molds, and pseudomorphs; pristine shells are rare . Bivalves exhibit a geopetal structure that testifies for three stages of mineral precipitation, namely: the cementation of the terrigenous infill; the precipitation of large crystals filling the voids; the re-precipitation of the shell carbonate to form pseudomorphs. Microscope analyses revealed a calcite composition of all these phases. Subsequent stages of dissolution and re-precipitation of calcite are here hypothesized, revealing a complex and unusual diagenetic history for this Pleistocene coral reef.

Well-preserved remains of a Posidonia oceanica meadow have been found in a Lower Pleistocene (Calabrian) succession cropping out near Fauglia (Tuscany, Italy). This paper analyses and describes the benthic foraminiferal community associated with this well-preserved Pleistocene P. oceanica meadow, with the purpose of testing the usefulness of foraminifera as an Indirect Palaeo-Seagrass Indicator (IPSI), providing both qualitative and quantitative parameters to recognize other meadow-related environments where fossil remains of seagrasses are not preserved. Despite being influenced by some diagenetic processes that might have affected the foraminiferal assemblage, the Fauglia succession represents a suitable setting for testing benthic foraminifera as IPSI in a temperate environment. Considering this limitation, together with other ecological constraints such as seawater temperature, this study provides evidence of the high potential of benthic foraminifera as IPSI. Several parameters such as the modified Foraminifera Index (FI’), the “long vs. short life-span index” (ILS), and the presence of permanently attached, encrusting foraminifera were tested. New indexes were also developed, namely the K/R ratio, consisting of the ratio between keeled Elphidium and the sum of rounded elphidiids (e.g., Elphidium translucens, Cribroelphidium, Porosononion) and Haynesina, and the K/REXT ratio, consisting of the ratio between keeled Elphidium and the sum of rounded elphidiids, Haynesina and other related genera that display a rounded periphery (i.e., Astrononion, Melonis, Nonion, Nonionella, Valvulineria). All these indexes were examined, suggesting their potential use for recognizing seagrass-related palaeoenvironments. The K/REXT ratio (and K/R) in association with the presence of permanently attached foraminifera revealed to be the most reliable palaeo-seagrass indicators, suggesting that this combination could be very useful also in other case studies where diagenesis altered

Biobanks have evolved, and their governance procedures have undergone important transformations. Our paper examines this issue by focusing on the perspective of the professionals working in management or scientific roles in research-based biobanks, who have an important impact on shaping these transformations. In particular, it highlights that recent advances in molecular medicine and genomic research have raised a range of ethical, legal and societal implications (ELSI) related to biobank-based research, impacting directly on regulations and local practices of informed consent (IC), private-public partnerships (PPPs), and engagement of participants. In our study, we investigate the ways that these concerns influence biobanking practices and assess the level of satisfaction of the cross-national biobanking research communities with the ELSI related procedures that are currently in place. We conducted an online survey among biobankers and researchers to investigate secondary use of data, informing and/or re-contacting participants, sharing of data with third parties from industry, participant engagement, and collaboration with industrial partners. Findings highlight the need for a more inclusive and transparent biobanking practice where biobanks are seen in a more active role in providing information and communicating with participants; the need to improve the current IC procedures and the role of biobanks in sharing of samples and data with industry partners and different countries, and the need for practical, tangible and hands-on ethical and legal guidance.

[This corrects the article DOI: 10.1371/journal.pone.0221496.].

The known challenge of underutilization of data and biological material from biorepositories as potential resources for medical research has been the focus of discussion for over a decade. Recently developed guidelines for improved data availability and reusability - entitled FAIR Principles (Findability, Accessibility, Interoperability, and Reusability) - are likely to address only parts of the problem. In this article, we argue that biological material and data should be viewed as a unified resource. This approach would facilitate access to complete provenance information, which is a prerequisite for reproducibility and meaningful integration of the data. A unified view also allows for optimization of long-term storage strategies, as demonstrated in the case of biobanks. We propose an extension of the FAIR Principles to include the following additional components: (1) quality aspects related to research reproducibility and meaningful reuse of the data, (2) incentives to stimulate effective enrichment of data sets and biological material collections and its reuse on all levels, and (3) privacy-respecting approaches for working with the human material and data. These FAIR-Health principles should then be applied to both the biological material and data. We also propose the development of common guidelines for cloud architectures, due to the unprecedented growth of volume and breadth of medical data generation, as well as the associated need to process the data efficiently.