bluuebunny/crossref_metadata_2025_split huggingface dataset:
Research protocol for an observational health data analysis to assess the applicability of randomized controlled trials focusing on newly diagnosed metastatic prostate cancer using real-world data: PIONEER IMI’s “big data for better outcomes” program
Authors: Gandaglia Giorgio , Pellegrino Francesco , De Meulder Bertrand , Hijazy Ayman , Abbott Thomas , Golozar Asieh , Nicoletti Rossella , Gomez-Rivas Juan , Steinbeisser Carl , Evans-Axelsson Susan , Briganti Alberto , N’Dow James 
Published: April 2024

Background:
Metastatic prostate cancer (PCa) constitutes ~5% of all new PCa diagnoses in Western countries. For most cases, primary consideration should be given to systemic therapies as the first-line approach based on evidence from randomized controlled trials (RCTs). Despite the importance of RCTs as the pinnacle of evidence in modern medicine, concerns have been raised about their applicability to real-life scenarios. These trials often feature participants who are younger with better performance statuses and prognoses compared to their real-world counterparts. The PIONEER project falls under the Innovative Medicine Initiative’s (IMI) “Big Data for Better Outcomes” initiative, aimed at revolutionizing PCa care in Europe. The central focus lies in improving cancer-related outcomes, enhancing health system efficiency, and elevating the quality of health and social care. This study endeavours to evaluate the generalizability of RCT findings concerning newly diagnosed metastatic PCa.

Methods:
A systematic review of the literature will be conducted to compile patient characteristics from RCTs addressing this subject within the past decade. To create a real-world benchmark, patients with recently diagnosed metastatic PCa from a network of population-based databases will serve as a comparison group. The objective is to assess the applicability of RCT results in two ways. First, a comparison will be made between the characteristics of patients with newly diagnosed metastatic PCa enroled in RCTs and those with the same condition included in our databases which might represent the real-world setting. Second, an evaluation will be undertaken to determine the proportion of real-world patients with newly diagnosed metastatic PCa who meet the criteria for RCT enrolment. This study will rely on extensive observational data, primarily sourced from population-based registries, electronic health records, and insurance claims data. The study cohort is established upon routinely gathered healthcare data, meticulously mapped to the Observational Medical Outcomes Partnership Common Data Model.
Scaling approaches and macroecology provide a foundation for assessing ecological resilience in the Anthropocene
Authors: Enquist Brian J. , Erwin Doug , Savage Van , Marquet Pablo A. 
Published: April 2024

In the Anthropocene, intensifying ecological disturbances pose significant challenges to our predictive capabilities for ecosystem responses. Macroecology—which focuses on emergent statistical patterns in ecological systems—unveils consistent regularities in the organization of biodiversity and ecosystems. These regularities appear in terms of abundance, body size, geographical range, species interaction networks, or the flux of matter and energy. This paper argues for moving beyond qualitative resilience metaphors, such as the ‘ball and cup’, towards a more quantitative macroecological framework. We suggest a conceptual and theoretical basis for ecological resilience that integrates macroecology with a stochastic diffusion approximation constrained by principles of biological symmetry. This approach provides an alternative novel framework for studying ecological resilience in the Anthropocene. We demonstrate how our framework can effectively quantify the impacts of major disturbances and their extensive ecological ramifications. We further show how biological scaling insights can help quantify the consequences of major disturbances, emphasizing their cascading ecological impacts. The nature of these impacts prompts a re-evaluation of our understanding of resilience. Emphasis on regularities of ecological assemblages can help illuminate resilience dynamics and offer a novel basis to predict and manage the impacts of disturbance in the Anthropocene more efficiently.This article is part of the theme issue ‘Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere’.
The human side of biodiversity: coevolution of the human niche, palaeo-synanthropy and ecosystem complexity in the deep human past
Authors: Hussain Shumon T. , Baumann Chris 
Published: April 2024

Today's biodiversity crisis fundamentally threatens the habitability of the planet, thus ranking among the primary human challenges of our time. Much emphasis is currently placed on the loss of biodiversity in the Anthropocene, yet these debates often portray biodiversity as a purely natural phenomenon without much consideration of its human dimensions and frequently lack long-term vistas. This paper offers a deep-time perspective on the key role of the evolving human niche in ecosystem functioning and biodiversity dynamics. We summarize research on past hunter–gatherer ecosystem contributions and argue that human–environment feedback systems with important biodiversity consequences are probably a recurrent feature of the Late Pleistocene, perhaps with even deeper roots. We update current understandings of the human niche in this light and suggest that the formation of palaeo-synanthropic niches in other animals proffers a powerful model system to investigate recursive interactions of foragers and ecosystems. Archaeology holds important knowledge here and shows that ecosystem contributions vary greatly in relation to different human lifeways, some of which are lost today. We therefore recommend paying more attention to the intricate relationship between biodiversity and cultural diversity, contending that promotion of the former depends on fostering the latter.
This article is part of the theme issue ‘Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere’.
Unravelling the functional and phylogenetic dimensions of novel ecosystem assemblages
Authors: Ordonez Alejandro , Gill Jacquelyn L. 
Published: April 2024

Human activities are causing taxonomic rearrangements across ecosystems that often result in the emergence of novel communities (assemblies with no historical representative). It is commonly assumed that these changes in the taxonomic makeup of ecosystems also inevitably lead to changes in other aspects of biodiversity, namely functional and phylogenetic diversity. However, this assumption is not always valid, as the changes in functional and phylogenetic composition resulting from taxonomic shifts depend on the level of redundancy in the evaluated community. Therefore, we need improved theoretical frameworks to predict when we can expect coordinated or decoupled responses among these three facets of biodiversity. To advance this understanding, we discuss the conceptual and methodological issues that complicate establishing a link between taxonomic rearrangements driven by human activities and the associated functional and phylogenetic changes. Here, we show that is crucial to consider the expected changes in functional and phylogenetic composition as communities are reshaped owing to human drivers of biodiversity loss to forecast the impacts of novel assemblages on ecosystem functions and the services they provide to humanity.
This article is part of the theme issue ‘Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere’.
A robust brain network for sustained attention from adolescence to adulthood that predicts later substance use
Authors: Weng Yihe , Kruschwitz Johann , Rueda-Delgado Laura M. , Ruddy Kathy , Boyle Rory , Franzen Luisa , Serin Emin , Nweze Tochukwu , Hanson Jamie , Smyth Alannah , Farnan Tom , Banaschewski Tobias , Bokde Arun L.W. , Desrivières Sylvane , Flor Herta , Grigis Antoine , Garavan Hugh , Gowland Penny , Heinz Andreas , Brühl Rüdiger , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Artiges Eric , McGrath Jane , Nees Frauke , Papadopoulos Orfanos Dimitri , Paus Tomáš , Poustka Luise , Holz Nathalie , Fröhner Juliane H. , Smolka Michael N. , Vaidya Nilakshi , Schumann Gunter , Walter Henrik , Whelan Robert ,   IMAGEN Consortium
Published: April 2024

AbstractSubstance use, including cigarettes and cannabis, is associated with poorer sustained attention in late adolescence and early adulthood. Previous studies were predominantly cross-sectional or under-powered and could not indicate if impairment in sustained attention was a predictor of substance-use or a marker of the inclination to engage in such behaviour. This study explored the relationship between sustained attention and substance use across a longitudinal span from ages 14 to 23 in over 1,000 participants. Behaviours and brain connectivity associated with diminished sustained attention at age 14 predicted subsequent increases in cannabis and cigarette smoking, establishing sustained attention as a robust biomarker for vulnerability to substance use. Individual differences in network strength relevant to sustained attention were preserved across developmental stages and sustained attention networks generalized to participants in an external dataset. In summary, brain networks of sustained attention are robust, consistent, and able to predict aspects of later substance use.TeaserA robust brain network for sustained attention at age 14 predicts cigarette and cannabis use from ages 14 to 23.
The “abominable mystery” of Schenck: the polymorphism ofSerjania piscatoriaand its implications for the evolution of vascular variants in Paullinieae (Sapindaceae)
Authors: Marques Natália F. , Cunha Neto Israel L. , Brito Lilian A. , Somner Genise V. 
Published: April 2024

ABSTRACTSerjaniais the only genus of Paullinieae that exhibits all types of vascular variants in stems and includesS. piscatoriawith a complex vascular structure that has intrigued botanists for centuries. Here, we analyzed the stem development ofS. piscatoriain an evolutionary context and determined its phylogenetic position within the genus. We studied four individuals using standardized anatomical techniques and employed DNA sequencing and phylogenetic analysis to determine the species’ phylogenetic position. Additionally, we employed ancestral state reconstruction to explore the pattern of evolution of vascular variants. We find that the stem development inS. piscatoriais determined by various ontogenetic processes that result in vascular variants that occur through modifications during primary and/or secondary growth, or ectopic cambia formation. These various patterns are classified into distinct categories of vascular variants, highlighting the lability of vascular meristems and the polymorphism within the species, which manifests across different individuals.Serjania piscatoriabelongs to a clade composed of species with compound stems, from which the fissured stems observed in the species would have evolved. The findings provide evidence for the diverse stem vasculature inSerjania, and the importance of studying vascular variant diversity from a developmental and evolutionary perspective.
DNA replication in primary hepatocytes without the six-subunit ORC
Authors: Przanowska Róża K. , Chen Yuechuan , Uchida Takayuki-Okano , Shibata Etsuko , Hao Xiaoxiao , Rueda Isaac Segura , Jensen Kate , Przanowski Piotr , Trimboli Anthony , Shibata Yoshiyuki , Leone Gustavo , Dutta Anindya 
Published: April 2024

ABSTRACTThe six subunit ORC is essential for initiation of DNA replication in eukaryotes. Cancer cell-lines in culture can survive and replicate DNA replication after genetic inactivation of individual ORC subunits, ORC1, ORC2 or ORC5. In primary cells, ORC1 was dispensable in the mouse liver for endo-reduplication, but this could be explained by the ORC1 homolog, CDC6, substituting for ORC1 to restore functional ORC. Here, we have created mice with a conditional deletion of ORC2, which does not have a homolog. Although mouse embryo fibroblasts require ORC2 for proliferation, mouse hepatocytes synthesize DNA in cell culture and endo-reduplicatein vivowithout ORC2. Mouse livers endo-reduplicate after simultaneous deletion of ORC1 and ORC2 both during normal development and after partial hepatectomy. Since endo-reduplication initiates DNA synthesis like normal S phase replication these results unequivocally indicate that primary cells, like cancer cell lines, can load MCM2-7 and initiate replication without ORC.
NovoLign: metaproteomics by sequence alignment
Authors: Kleikamp Hugo B.C. , van der Zwaan Ramon , van Valderen Ramon , van Ede Jitske M. , Pronk Mario , Schaasberg Pim , Allaart Maximilienne T. , van Loosdrecht Mark C.M. , Pabst Martin 
Published: April 2024

ABSTRACTTremendous advances in mass spectrometric and bioinformatic approaches have expanded proteomics into the field of microbial ecology. The commonly used spectral annotation method for metaproteomics data relies on database searching, which requires sample-specific databases obtained from whole metagenome sequencing experiments. However, creating these databases is complex, time-consuming, and prone to errors, potentially biasing experimental outcomes and conclusions. This asks for alternative approaches that can provide rapid and orthogonal insights into metaproteomics data. Here we present NovoLign, ade novometaproteomics pipeline that performs sequence alignment ofde novosequences from complete metaproteomics experiments. The pipeline enables rapid taxonomic profiling of complex communities and evaluates the taxonomic coverage of metaproteomics outcomes obtained from database searches. Furthermore, the NovoLign pipeline supports the creation of reference sequence databases for database searching to ensure comprehensive coverage. The NovoLign pipeline is publicly available via:https://github.com/hbckleikamp/NovoLign.
To be browsed or not to be browsed: differences in nutritional characteristics of blackthornPrunus spinosasubject to the long-term pressure of herbivores
Authors: Facciolati Veronica , Zarek Marcin , Błońska Ewa , Lasota Jarosław , Orman Olga , Ciach Michał 
Published: April 2024

AbstractThe impact of ungulates on temperate forest vegetation has been investigated for a long time. Numerous studies on food selection have identified the palatable plant species preferred by large European herbivores. However, intra-specific food selection and the question why particular plants of a given species are ignored during foraging have been neglected in the literature. In central Europe, BlackthornsPrunus spinosagrowing in abandoned pastures are an important component of the red deer’sCervus elaphusdiet. In areas densely populated by deer, annual shoot browsing produces dwarf shrubby forms of blackthorns. However, some blackthorns are not browsed by ungulates and tend to adopt a tree-like form. The existence of distinct, browsing-dependent growth forms of blackthorns raises the question of inter-individual differences in the nutritional composition of plants. Based on factor analysis, we discovered differences in nutritional composition between browsed and unbrowsed blackthorns that might explain the individual plant-related drivers of red deer food preferences. The leaves of browsed blackthorns contained higher concentrations of C, N, P and Cu but lower levels of Ca and Mg than unbrowsed ones. Moreover, browsed blackthorns had a higher water content and higher concentrations of insoluble proteins, chlorophylls and carotenoids. We highlight the fact that the nutritional characteristics of an individual plant may explain the observed food selection pattern, leading to the unhindered growth of a fraction of the blackthorn population, in spite of severe pressure on the part of ungulate herbivores. The results of this study underline the important role of herbivores in the dynamics of plant communities, in which ungulates may mediate the persistence of certain individuals of a given species.HighlightsBrowsing by ungulates leads to the formation of dwarf shrubby forms in blackthornsSome blackthorns are unbrowsed and adopt a tree-like formBrowsed blackthorns differ in chemical composition from unbrowsed onesThe nutritional profile of a given plant may influence food selection by ungulates
Influence of Incorporating Full-Fat Black Soldier Fly Larvae Meal (BSFLM) in Meat Type Chicken Diets on the Lower Gut Short Chain Fatty Acids profile, Gut Morphology and Intestinal Lesion Score
Authors: Bhattacharyya Jayanta , Chatterjee PareshNath , Chatterjee Jayanta Kumar , Pal Aruna 
Published: April 2024

ABSTRACTThough protein demand is increasing day by day but the animal protein industry on a global scale is facing the biggest challenge of replacing antibiotic growth promoters (AGP) to raise broiler chickens. Using AGP is a long-standing practice to include in poultry diets for improving the intestinal health and subsequent performance of the broiler chicken. Due to increased restrictions and bans on the usage of antibiotics, the poultry-producing community is in search of a suitable and sustainable alternative to AGPs. The present study was aimed at to evaluate and analyte the potential impacts and consequences associated with the inclusion of black soldier fly larvae meal (BSFLM) in a commercially available meat type chicken when compared to diets that either contained or lacked the presence of antibiotic growth promoters, specifically enramycin at a concentration of 8% and chlortetracycline at a concentration of 15%. Our study also assessed the influence of inclusion of BSFLM on cecal short chain fatty acids (SCFAs), and the gut health. 180 male day-old Vencobb430Y chicks (mean BW 42.52 g) (P > 0.05) were randomly allocated into isonitrogenous and isoenergetic dietary treatments in three equal groups. BSFLM group has exhibited significant higher concentration of short chain fatty acids in cecum like acetate, isobutyrate, butyrate, and total SCFAs compared to both the AGP and CONTROL groups (P<0.05). The villi height of duodenum and jejunum remained significantly higher in BSFLM supplemented birds as compared to the AGP group (P<0.05). From the analysis of frequency plots depicting the severity of intestinal lesions, it was observed that the presence of serosa and mucosa congestion in the anterior sections of the gastrointestinal tract was within the expected range for both the CONTROL and AGP groups, thus indicating that this particular physiological condition can be considered as normal in these experimental groups. In the duodenal part, incorporating BSFL meal showed significantly higher villi height and crypt depth compared with CONTROL and AGP (P<0.05). Inclusion of full-fat BSF has improved overall intestinal health and lower lesion scores compared to the CONTROL and AGP groups. The present investigation explored thepotential of incorporating full-fat black soldier fly larvae (BSFL) meal into the dietary regimens of broilers for sgnificantly bolstering the health and functionality of their gastrointestinal tract, particularly in instances where the inclusion of antimicrobial growth promoters (AGP) is deliberately omitted from said diets.
Protoxylem microtubule patterning requires ROP pattern co-alignment, realistic microtubule-based nucleation, and moderate microtubule flexibility
Authors: Jacobs Bas , Saltini Marco , Molenaar Jaap , Filion Laura , Deinum Eva E. 
Published: April 2024

AbstractThe development of the water transporting xylem tissue in plants involves an intricate interplay of Rho-of-Plants (ROP) proteins and cortical microtubules to generate highly functional secondary cell wall patterns, such as the ringed or spiral patterns in early-developing protoxylem. We study the requirements of protoxylem microtubule band formation with simulations in CorticalSim, extended to include finite microtubule persistence length and a novel algorithm for microtubule-based nucleation. We find that microtubule flexibility is required to facilitate pattern formation for all realistic degrees of mismatch between array and pattern orientation. At the same time, flexibility leads to more density loss, both from collisions and the microtubule-hostile gap regions, making it harder to maintain microtubule bands. Microtubule-dependent nucleation helps to counteract this effect by gradually shifting nucleation from the gap regions to the bands as microtubules disappear from the gaps. Our results reveal the main mechanisms required for efficient protoxylem band formation.
Interleukin-6 induces nascent protein synthesis in human DRG nociceptors via MNK-eIF4E signaling
Authors: Mitchell Molly E. , Torrijos Gema , Cook Lauren F. , Mwirigi Juliet M. , He Lucy , Shiers Stephanie , Price Theodore J. 
Published: April 2024

ABSTRACTPlasticity of dorsal root ganglion (DRG) nociceptors in the peripheral nervous system requires new protein synthesis. This plasticity is believed to be responsible for the physiological changes seen in DRG nociceptors in animal models of chronic pain. Experiments in human DRG (hDRG) neurons also support this hypothesis, but a direct observation of nascent protein synthesis in response to a pain promoting substance, like interleukin-6 (IL-6), has not been measured in these neurons. To fill this gap in knowledge, we used acutely prepared human DRG explants from organ donors. These explants provide a physiologically relevant microenvironment, closer toin vivoconditions, allowing for the examination of functional alterations in DRG neurons reflective of human neuropathophysiology. Using this newly developed assay, we demonstrate upregulation of the target of the MNK1/2 kinases, phosphorylated eIF4E (p-eIF4E), and nascently synthesized proteins in a substantial subset of hDRG neurons following exposure to IL-6. To pinpoint the specific molecular mechanisms driving this IL-6- driven increase in nascent proteins, we used the specific MNK1/2 inhibitor eFT508. Treatment with eFT508 resulted in the inhibition of IL-6-induced increases in p-eIF4E and nascent proteins. Additionally, using TRPV1 as a marker for nociceptors, we found that these effects occurred in a large number of human nociceptors. Our findings provide clear evidence that IL-6 drives nascent protein synthesis in human TRPV1+ nociceptors via MNK1/2-eIF4E signaling. The work links animal findings to human nociception, creates a framework for additional hDRG signaling experiments, and substantiates the continued development of MNK inhibitors for pain.