Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group

Purpose: Many different treatments are suggested by guidelines to treat grade 1−2 (G1−G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1−G2 NET. Methods: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation. Results: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1–G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03). Conclusions: SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1−G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy

DigiArt: towards a virtualization of Cultural Heritage

DigiArt is a Europe-wide project aimed at providing a new, cost efficient solution to the capture, processing and display of cultural artefacts. The project will change the ways in which the public interact with cultural objects and spaces in a dramatic way. This project is unique in its collaborative approach: cultural heritage professionals working directly with electrical, mechanical, optical and software engineers to develop a solution to current issues faced by the museum sector. The innovations created by the engineers are driven by the demand of the cultural heritage sector. The diversity of the objects and spaces of the three test museums are challenging the engineers to provide a tool useful for a broad variety of indoor and outdoor museums in the future. This goes from using Unmanned Aerial Vehicle (UAVs or drones) to fly and record large sites, to using scanners to record fine jewellery. As a case study, we present here the use-case of Scladina Cave. At the end of the project, the Scladina Cave Archaeological Centre will offer two different visitor experiences. The first uses virtual reality, which will be available anytime, anywhere, to anyone with an internet connected device. The second will use augmented reality technologies within the cave site. The augmented reality visit of the cave will enhance the tour of Scladina by offering visits that would not be possible where it not for the augmented reality, where 3D objects and animations will contribute to offer a new 3D-immersive experience

Preliminary reports on the 2016-2017 excavation of the Neolithic ossuary and terrace

This article reports on the first three systematic excavation seasons at the Neolithic ossuary of Grotte de La Faucille, Belgium. The site was dated on human bone to 4266 ± 40 14C BP (3011-2702 cal BC; 2 sigma), corresponding to the transition from the late to the final Neolithic. The area excavated to date is clearly reworked and the individuals are distributed across the site. Further excavation will focus on the inferior levels at the entrance and inside the cave. This report presents the preliminary analysis of the anthropological and archaeological evidence recorded to date. Five archaeological artefacts were discovered made on bone, tooth and flint. The site has produced skeletal and dental remains of at least 12 humans (MNI 6 juveniles and 6 adults) as well as a number of bone and lithic artefacts. The skeletal remains are fragmentary and some elements, such as the cranium, are highly underrepresented given the number of individuals. The potential to find the remainder of at least 12 individuals is promising and continued excavation may result in one of the largest recent excavation of a multiple Neolithic burial site of the 21st century. The results presented here and ongoing analysis have the potential to significantly expand our understanding of the mortuary behaviours, or variation in behaviours, of the Belgian Neolithic and contribute further to the lively debate on the spread of the Neolithic

Neurodevelopmental Disorders and Suicide: A Narrative Review

Specific risk factors for self-harm and suicide in children and adolescents with neurodevelopmental disorders (NDD) may differ from those in the general population within this age range. In the present review paper, we conducted a narrative analysis of the literature, aiming to establish a connection between suicide and affective disorders in children and adolescents with NDD. Emotion dysregulation (ED) as an individual factor and adverse childhood experiences (ACE) as environmental factors are discussed as risk factors for suicidality in all individuals with NDD. We propose a theoretical model in which ED and ACE can directly lead to self-harm or suicide, directly or indirectly by interacting with depressive spectrum disorders. Additionally, we suggest that specific risk factors are more frequently associated with each of the neurodevelopmental disorders listed in the DSM-V. This review underlines the key points useful to improve the knowledge of the trajectory leading to suicide risk in NDDs with the purpose to facilitate the early identification of the suicide risk

Temporal variation in cave bear (Ursus spelaeus) dentition: The stratigraphic sequence of Scladina Cave, Belgium

© 2018 Elsevier Ltd The supposed herbivorous cave bear (Ursus spelaeus) occupied Europe throughout the Quaternary. Being subject to large spatial variation has led to the intensive study on its geographical polymorphism, generating debates on sub-speciation. However, temporal morphological information on the species is somewhat lacking. Here, we apply geometric morphometrics (GMM) technique to investigate temporal morphological variation in molar size and shape of Ursus spelaeus from different chronostratigraphic sediment units in a geographically confined site (Scladina Cave, Belgium), covering approximately 100,000 years. Our findings show significant morphological variation between groups analysed in both size and shape. M2 shows a chronological size increase with PCA plots visually expressing differences in all groups, relating to a buccolingual expansion and an increase of the talon masticatory platform through time. Reduction in the M1 is also shown, possibly to maintain biomechanical performance of dentition for effective mastication, more so in groups relating to the latter stages of the Quaternary. Findings suggest a rapid response to climatic factors constraining consumable food sources, with GMM offering a promising analytical approach in understanding the palaeobiology, palaeoecology and morphological variation in extinct and extant fossil mammals

Mandibular ecomorphology in the genus ursus (Ursidae, Carnivora): relevance for the palaeoecological adaptations of cave bears (U. spelaeus) from Scladina cave

Considerable morphological and ecological diversity has been found in extinct and extant members of the bear genus, Ursus, and appears to be key in explaining how they have thrived across vast ecological gradients. One example is the cave bear Ursus spelaeus. We applied 2D geometric morphometric techniques to describe morphological changes in the mandibles of extant Ursus species to further interpret the palaeoecology of U. spelaeus. Ursus species were discriminated using their mandibular morphology, which showed intra and interspecific shape variation that was indirectly linked to climatic adaptations through dietary variation. Mandibles of bears that inhabit colder, drier and more seasonal environments were generally slender with large diastema and a dorsoventrally smaller ramus. In contrast, species from warmer environments with higher levels of precipitation were found to have a dorsoventrally taller ramus (relative to the corpus). Discriminant function analyses of the morphology of U. spelaeus suggested adaptations to a series of fluctuating environments through time, helping to assess previously proposed Marine Isotope Stages for sedimentary deposits in Scladina Cave. Our geometric morphometrics analyses of bear mandibular ecomorphology demonstrates how geometric morphometrics provides a valuable tool to enhance paleoenvironmental reconstructions within deposits of the same fossil site

Recapitulating thyroid cancer histotypes through engineering embryonic stem cells

Thyroid carcinoma (TC) is the most common malignancy of endocrine organs. The cell subpopulation in the lineage hierarchy that serves as cell of origin for the different TC histotypes is unknown. Human embryonic stem cells (hESCs) with appropriate in vitro stimulation undergo sequential differentiation into thyroid progenitor cells (TPCs-day 22), which maturate into thyrocytes (day 30). Here, we create follicular cell-derived TCs of all the different histotypes based on specific genomic alterations delivered by CRISPR-Cas9 in hESC-derived TPCs. Specifically, TPCs harboring BRAFV600E or NRASQ61R mutations generate papillary or follicular TC, respectively, whereas addition of TP53R248Q generate undifferentiated TCs. Of note, TCs arise by engineering TPCs, whereas mature thyrocytes have a very limited tumorigenic capacity. The same mutations result in teratocarcinomas when delivered in early differentiating hESCs. Tissue Inhibitor of Metalloproteinase 1 (TIMP1)/Matrix metallopeptidase 9 (MMP9)/Cluster of differentiation 44 (CD44) ternary complex, in cooperation with Kisspeptin receptor (KISS1R), is involved in TC initiation and progression. Increasing radioiodine uptake, KISS1R and TIMP1 targeting may represent a therapeutic adjuvant option for undifferentiated TCs

Earliest evidence of Neanderthal multifunctional bone tool production from cave lion (Panthera spelaea) remains

Throughout history, humans have had a complex relationship with lions, both reverencing and fearing them. Interactions between Neanderthals and cave lions (Panthera spelaea) remain poorly documented due to the scarcity of direct evidence. This study examines the selective use of cave lion bones by Neanderthals to determine whether this behaviour was driven by practical, functional, or symbolic factors, through a detailed zooarchaeological analysis. Previous studies highlighted Neanderthals’ skinning and butchering of cave lions, yet new discoveries at Scladina Cave (Belgium) offer deeper insights into this relationship. Dated to the end of the Saalian, the faunal assemblage provides the earliest evidence of bone tools crafted from cave lion remains. A tibia was deliberately processed into multifunctional tools, initially serving as an intermediate tool before being repurposed as retouchers. Proteomic analysis applied on the remains, confirmed the specific identification. These findings reveal that Neanderthals not only competed with but actively utilized cave lions for practical purposes, indicating complex ecological and behavioral interactions. Relationships between pre-humans and large predators, rooted in the Middle Pleistocene, suggest a strategic exploitation of carnivore remains. However, opportunistic procurement cannot be entirely ruled out as a potential factor influencing animal choice in tool production. The intentional transformation of lion bones into functional tools highlights Neanderthals’ cognitive skills, adaptability, and capacity for resource utilization beyond their immediate survival needs

Towards a Decision Support Tool for Assessing, Managing and Mitigating Seismic Risk of Electric Power Networks

Recent seismic event worldwide proved how fragile the electric power system can be to seismic events. Decision Support Systems (DSSs) could have a critical role in assessing the seismic risk of electric power networks and in enabling asset managers to test the effectiveness of alternative mitigation strategies and investments on resilience. This paper exemplifies the potentialities of CIPCast, a DSS recently created in the framework of the EU-funded project CIPRNet, to perform such tasks. CIPCast enables to perform risk assessment for Critical Infrastructures (CI) when subjected to different natural hazards, including earthquakes. An ad-hoc customization of CIPCast for the seismic risk analysis and management of electric power networks is featured in this paper. The international literature describes effective and sound efforts towards the creation of software platforms and frameworks for the assessment of seismic risk of electric power networks. None of them, unfortunately, achieved the goal of creating a user-friendly and ready available DDS to be used by asset managers, local authorities and civil protection departments. Towards that and building on the international literature, the paper describes metrics and methods to be integrated within CIPCast for assessing the earthquake-induced physical and functional impacts of the electric power network at component and system level. The paper describes also how CIPCast can inform the service restoration process