bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sedimentary Coastal Cliff Erosion in Greenland
Authors: Luetzenburg G. , Townsend D. , Svennevig K. , Bendixen M. , Bjørk A. A. , Eidam E. F. , Kroon A. 
Published: April 2023

AbstractClimate change will increase the duration of annual sea‐ice‐free periods and shift precipitation patterns across the Arctic. Those factors are likely to increase erosion rates along its coasts. Large parts of the Arctic coast consist of hard rock. However, glacial, deltaic, and coastal sedimentary deposits occur in deglaciated areas and isostatic uplift following glaciations has created beach ridge plains and pocket beaches with coarse soft‐sediment cliffs. Hitherto, very little was known about the spatial distribution, erosion rates, and morphodynamics of soft sediment cliffs along the coast of Greenland. Here, we investigate a 3‐km sedimentary cliff section on the south coast of Qeqertarsuaq (Disko Island). We measured 2D cliff top erosion over 50 years between 1964 and 2014 as well as 3D cliff profile change over 2 years between 2019 and 2021. Morphometric indices of the gravel beach and cliff were calculated based on a series of cross‐shore elevation profiles. Wave run‐up at the beach fronting the cliff was modeled with XBeach‐G for a series of storm events under present day sea‐ice conditions and for a reduced sea‐ice scenario. Cliff top erosion rates varied along the cliff with maximum rates of 0.3 m y−1. The investigated coastal cliff erodes by two coupled processes: (a) precipitation‐driven surface runoff downslope the cliff and (b) wave‐driven erosion at the cliff toe. In a continuously warming climate, this study shows that erosion of soft coastal cliffs in Greenland thus can accelerate due to increased storminess and prolonging open water periods.
Bias Correction and Statistical Modeling of Variable Oceanic Forcing of Greenland Outlet Glaciers
Authors: Verjans Vincent , Robel Alexander , Thompson Andrew F. , Seroussi Helene 
Published: April 2023

AbstractVariability in oceanic conditions directly impacts ice loss from marine outlet glaciers in Greenland, influencing the ice sheet mass balance. Oceanic conditions are available from Atmosphere‐Ocean Global Climate Model (AOGCM) output, but these models require extensive computational resources and lack the fine resolution needed to simulate ocean dynamics on the Greenland continental shelf and close to glacier marine termini. Here, we develop a statistical approach to generate ocean forcing for ice sheet model simulations, which incorporates natural spatiotemporal variability and anthropogenic changes. Starting from raw AOGCM ocean heat content, we apply: (a) a bias‐correction using ocean reanalysis, (b) an extrapolation accounting for on‐shelf ocean dynamics, and (c) stochastic time series models to generate realizations of natural variability. The bias‐correction reduces model errors by ∼25% when compared to independent in‐situ measurements. The bias‐corrected time series are subsequently extrapolated to fjord mouth locations using relations constrained from available high‐resolution regional ocean model results. The stochastic time series models reproduce the spatial correlation, characteristic timescales, and the amplitude of natural variability of bias‐corrected AOGCMs, but at negligible computational expense. We demonstrate the efficiency of this method by generating >6,000 time series of ocean forcing for >200 Greenland marine‐terminating glacier locations until 2100. As our method is computationally efficient and adaptable to any ocean model output and reanalysis product, it provides flexibility in exploring sensitivity to ocean conditions in Greenland ice sheet model simulations. We provide the output and workflow in an open‐source repository, and discuss advantages and future developments for our method.
UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia
Authors: Duployez Nicolas , Vasseur Loïc , Kim Rathana , Largeaud Laëtitia , Passet Marie , L’Haridon Anaïs , Lemaire Pierre , Fenwarth Laurène , Geffroy Sandrine , Helevaut Nathalie , Celli‑Lebras Karine , Adès Lionel , Lebon Delphine , Berthon Céline , Marceau-Renaut Alice , Cheok Meyling , Lambert Juliette , Récher Christian , Raffoux Emmanuel , Micol Jean-Baptiste , Pigneux Arnaud , Gardin Claude , Delabesse Eric , Soulier Jean , Hunault Mathilde , Dombret Hervé , Itzykson Raphael , Clappier Emmanuelle , Preudhomme Claude 
Published: April 2023

AbstractTandem duplications (TDs) of theUBTFgene have been recently described as a recurrent alteration in pediatric acute myeloid leukemia (AML). Here, by screening 1946 newly diagnosed adult AML, we found thatUBTF-TDs occur in about 3% of patients aged 18–60 years, in a mutually exclusive pattern with other known AML subtype-defining alterations. The characteristics of 59 adults withUBTF-TD AML included young age (median 37 years), low bone marrow (BM) blast infiltration (median 25%), and high rates ofWT1mutations (61%),FLT3-ITDs (51%) and trisomy 8 (29%). BM morphology frequently demonstrates dysmyelopoiesis albeit modulated by the co-occurrence ofFLT3-ITD.UBTF-TD patients have lower complete remission (CR) rates (57% after 1 course and 76% after 2 courses of intensive chemotherapy [ICT]) thanUBTF-wild-type patients. In patients enrolled in the ALFA-0702 study (n = 614 patients including 21 withUBTF-TD AML), the 3-year disease-free survival (DFS) and overall survival ofUBTF-TD patients were 42.9% (95%CI: 23.4–78.5%) and 57.1% (95%CI: 39.5–82.8%) and did not significantly differ from those of ELN 2022 intermediate/adverse risk patients. Finally, the study of paired diagnosis and relapsed/refractory AML samples suggests thatWT1-mutated clones are frequently selected under ICT. This study supports the recognition ofUBTF-TD AML as a new AML entity in adults.
Insulin effects on core neurotransmitter pathways involved in schizophrenia neurobiology: a meta-analysis of preclinical studies. Implications for the treatment
Authors: de Bartolomeis Andrea , De Simone Giuseppe , De Prisco Michele , Barone Annarita , Napoli Raffaele , Beguinot Francesco , Billeci Martina , Fornaro Michele 
Published: April 2023

AbstractImpairment of insulin action and metabolic dysregulation have traditionally been associated with schizophrenia, although the molecular basis of such association remains still elusive. The present meta-analysis aims to assess the impact of insulin action manipulations (i.e., hyperinsulinemia, hypoinsulinemia, systemic or brain insulin resistance) on glutamatergic, dopaminergic, γ-aminobutyric acid (GABA)ergic, and serotonergic pathways in the central nervous system. More than one hundred outcomes, including transcript or protein levels, kinetic parameters, and other components of the neurotransmitter pathways, were collected from cultured cells, animals, or humans, and meta-analyzed by applying a random-effects model and adopting Hedges’g to compare means. Two hundred fifteen studies met the inclusion criteria, of which 180 entered the quantitative synthesis. Significant impairments in key regulators of synaptic plasticity processes were detected as the result of insulin handlings. Specifically, protein levels of N-methyl-D-aspartate receptor (NMDAR) subunits including type 2A (NR2A) (Hedges’ g = −0.95, 95%C.I. = −1.50, −0.39; p = 0.001; I2 = 47.46%) and 2B (NR2B) (Hedges’g = −0.69, 95%C.I. = −1.35, −0.02; p = 0.043; I2 = 62.09%), and Postsynaptic density protein 95 (PSD-95) (Hedges’g = −0.91, 95%C.I. = −1.51, −0.32; p = 0.003; I2 = 77.81%) were found reduced in insulin-resistant animal models. Moreover, insulin-resistant animals showed significantly impaired dopamine transporter activity, whereas the dopamine D2 receptor mRNA expression (Hedges’g = 3.259; 95%C.I. = 0.497, 6.020; p = 0.021; I2 = 90.61%) increased under insulin deficiency conditions. Insulin action modulated glutamate and GABA release, as well as several enzymes involved in GABA and serotonin synthesis. These results suggest that brain neurotransmitter systems are susceptible to insulin signaling abnormalities, resembling the discrete psychotic disorders’ neurobiology and possibly contributing to the development of neurobiological hallmarks of treatment-resistant schizophrenia.
Multi-omics signatures in new-onset diabetes predict metabolic response to dietary inulin: findings from an observational study followed by an interventional trial
Authors: Ďásková N. , Modos I. , Krbcová M. , Kuzma M. , Pelantová H. , Hradecký J. , Heczková M. , Bratová M. , Videňská P. , Šplíchalová P. , Králová M. , Heniková M. , Potočková J. , Ouřadová A. , Landberg R. , Kühn T. , Cahová M. , Gojda J. 
Published: April 2023

Abstract
Aim
The metabolic performance of the gut microbiota contributes to the onset of type 2 diabetes. However, targeted dietary interventions are limited by the highly variable inter-individual response. We hypothesized (1) that the composition of the complex gut microbiome and metabolome (MIME) differ across metabolic spectra (lean-obese-diabetes); (2) that specific MIME patterns could explain the differential responses to dietary inulin; and (3) that the response can be predicted based on baseline MIME signature and clinical characteristics.

Method
Forty-nine patients with newly diagnosed pre/diabetes (DM), 66 metabolically healthy overweight/obese (OB), and 32 healthy lean (LH) volunteers were compared in a cross-sectional case-control study integrating clinical variables, dietary intake, gut microbiome, and fecal/serum metabolomes (16 S rRNA sequencing, metabolomics profiling). Subsequently, 27 DM were recruited for a predictive study: 3 months of dietary inulin (10 g/day) intervention.

Results
MIME composition was different between groups. While the DM and LH groups represented opposite poles of the abundance spectrum, OB was closer to DM. Inulin supplementation was associated with an overall improvement in glycemic indices, though the response was very variable, with a shift in microbiome composition toward a more favorable profile and increased serum butyric and propionic acid concentrations. The improved glycemic outcomes of inulin treatment were dependent on better baseline glycemic status and variables related to the gut microbiota, including the abundance of certain bacterial taxa (i.e., Blautia, Eubacterium halii group, Lachnoclostridium, Ruminiclostridium, Dialister, or Phascolarctobacterium), serum concentrations of branched-chain amino acid derivatives and asparagine, and fecal concentrations of indole and several other volatile organic compounds.

Conclusion
We demonstrated that obesity is a stronger determinant of different MIME patterns than impaired glucose metabolism. The large inter-individual variability in the metabolic effects of dietary inulin was explained by differences in baseline glycemic status and MIME signatures. These could be further validated to personalize nutritional interventions in patients with newly diagnosed diabetes.
Technical development and validation of a clinically applicable microenvironment classifier as a biomarker of tumour hypoxia for soft tissue sarcoma
Authors: Forker Laura J. , Bibby Becky , Yang Lingjian , Lane Brian , Irlam Joely , Mistry Hitesh , Khan Mairah , Valentine Helen , Wylie James , Shenjere Patrick , Leahy Michael , Gaunt Piers , Billingham Lucinda , Seddon Beatrice M. , Grimer Rob , Robinson Martin , Choudhury Ananya , West Catharine 
Published: April 2023

Abstract
Background
Soft tissue sarcomas (STS) are rare, heterogeneous tumours and biomarkers are needed to inform management. We previously derived a prognostic tumour microenvironment classifier (24-gene hypoxia signature). Here, we developed/validated an assay for clinical application.

Methods
Technical performance of targeted assays (Taqman low-density array, nanoString) was compared in 28 prospectively collected formalin-fixed, paraffin-embedded (FFPE) biopsies. The nanoString assay was biologically validated by comparing to HIF-1α/CAIX immunohistochemistry (IHC) in clinical samples. The Manchester (n = 165) and VORTEX Phase III trial (n = 203) cohorts were used for clinical validation. The primary outcome was overall survival (OS).

Results
Both assays demonstrated excellent reproducibility. The nanoString assay detected upregulation of the 24-gene signature under hypoxia in vitro, and 16/24 hypoxia genes were upregulated in tumours with high CAIX expression in vivo. Patients with hypoxia-high tumours had worse OS in the Manchester (HR 3.05, 95% CI 1.54–5.19, P = 0.0005) and VORTEX (HR 2.13, 95% CI 1.19–3.77, P = 0.009) cohorts. In the combined cohort, it was independently prognostic for OS (HR 2.24, 95% CI 1.42–3.53, P = 0.00096) and associated with worse local recurrence-free survival (HR 2.17, 95% CI 1.01–4.68, P = 0.04).

Conclusions
This study comprehensively validates a microenvironment classifier befitting FFPE STS biopsies. Future uses include: (1) selecting high-risk patients for perioperative chemotherapy; and (2) biomarker-driven trials of hypoxia-targeted therapies.
Downregulation of the Rho GTPase pathway abrogates resistance to ionizing radiation in wild-type p53 glioblastoma by suppressing DNA repair mechanisms
Authors: Magalhaes Yuli Thamires , Boell Viktor Kalbermatter , Cardella Giovanna Duo , Forti Fabio Luis 
Published: April 2023

AbstractGlioblastoma (GBM), the most common aggressive brain tumor, is characterized by rapid cellular infiltration and is routinely treated with ionizing radiation (IR), but therapeutic resistance inevitably recurs. The actin cytoskeleton of glioblastoma cells provides their high invasiveness, but it remains unclear whether Rho GTPases modulate DNA damage repair and therapeutic sensitivity. Here, we irradiated glioblastoma cells with different p53 status and explored the effects of Rho pathway inhibition to elucidate how actin cytoskeleton disruption affects the DNA damage response and repair pathways. p53-wild-type and p53-mutant cells were subjected to Rho GTPase pathway modulation by treatment with C3 toxin; knockdown of mDia-1, PFN1 and MYPT1; or treatment with F-actin polymerization inhibitors. Rho inhibition increased the sensitivity of glioma cells to IR by increasing the number of DNA double-strand breaks and delaying DNA repair by nonhomologous end-joining in p53-wild-type cells. p53 knockdown reversed this phenotype by reducing p21 expression and Rho signaling activity, whereas reactivation of p53 in p53-mutant cells by treatment with PRIMA-1 reversed these effects. The interdependence between p53 and Rho is based on nuclear p53 translocation facilitated by G-actin and enhanced by IR. Isolated IR-resistant p53-wild-type cells showed an altered morphology and increased stress fiber formation: inhibition of Rho or actin polymerization decreased cell viability in a p53-dependent manner and reversed the resistance phenotype. p53 silencing reversed the Rho inhibition-induced sensitization of IR-resistant cells. Rho inhibition also impaired the repair of IR-damaged DNA in 3D spheroid models. Rho GTPase activity and actin cytoskeleton dynamics are sensitive targets for the reversal of acquired resistance in GBM tumors with wild-type p53.
Higher-order mesoscopic self-assembly of fluorinated surfactants on water surfaces
Authors: Tanaka Motomu , Krafft Marie Pierre , Pasc Andreea 
Published: April 2023

AbstractSurfactants containing fluorocarbon chains have been increasingly studied because they self-assemble into a variety of microscopic and mesoscopic domains and tend to form highly ordered patterns at the air/water interface; these patterns are clearly different from those formed by their hydrocarbon analogs. Focusing on the fluorinated surfactants possessing unique physical characteristics, this review describes the relationship between the line tension and dipole interaction, which is the comprehensive principle governing the pattern formation of two-dimensional self-assemblies. This review further discusses several key experimental and analytical techniques that are useful for characterizing the shape, size, correlation, and viscoelasticity of hierarchical self-assemblies on water surfaces. Finally, several biomedical applications, including biomimetic surface coating, multimodal contrast agents in medical diagnostics, and controlled delivery of gases (O2 and NO) for oxygenation and antimicrobial effects, are introduced to highlight how the unique physicochemical properties of fluorinated self-assemblies can be applied in materials science.
Fabricating higher-order functional DNA origami structures to reveal biological processes at multiple scales
Authors: Zhou Yihao , Dong Jinyi , Wang Qiangbin 
Published: April 2023

AbstractDNA origami technology enables the precise assembly of well-defined two-dimensional and three-dimensional nanostructures with DNA, an inherently biocompatible material. Given their modularity and addressability, DNA origami objects can be used as scaffolds to fabricate larger higher-order structures with other functional biomolecules and engineer these molecules with nanometer precision. Over the past decade, these higher-order functional structures have shown potential as powerful tools to study the function of various bio-objects, revealing the corresponding biological processes, from the single-molecule level to the cell level. To inspire more creative and fantastic research, herein, we highlight seminal works in four emerging areas of bioapplications of higher-order DNA origami structures: (1) assisting in single-molecule studies, including protein structural analysis, biomolecule interaction analysis, and protein functional analysis, (2) manipulating lipid membranes, (3) directing cell behaviors, and (4) delivering drugs as smart nanocarriers. Finally, current challenges and opportunities in the fabrication and application of DNA origami-based functional structures are discussed.
Toward the production of renewable diesel over robust Ni nanoclusters highly dispersed on a two-dimensional zeolite
Authors: Pang Hao , Yang Guoju , Li Lin , Yu Jihong 
Published: April 2023

AbstractDeoxygenation of bioderived lipids into renewable transportation fuels is a promising route to decreasing the dependence on fossil sources. Ni-based catalysts are high performing and cost-effective in deoxygenation reactions but suffer from severe sintering and aggregation. Herein, a ligand-chelating impregnation method was used to prepare highly dispersed Ni nanoclusters on a two-dimensional (2D) ITQ-2 zeolite. Comprehensive characterization was utilized to monitor the changes in the organometallic precursors during activation and to investigate their impact on the dispersion of the Ni nanoclusters on the ITQ-2 zeolite. The high external surface area and abundant surface defects of the 2D support enhanced the dispersion and immobilization of the Ni nanoclusters and outperformed conventional zeolites. The protection of the Ni2+ cations by the organic ligand suppressed the aggregation of Ni species during the activation processes, thereby leading to the formation of uniformly distributed Ni nanoclusters on the ITQ-2 zeolite. Due to the highly dispersed Ni nanoclusters and immobilization on the 2D zeolite, the Ni/ITQ-2-co material prepared by the ligand-chelating impregnation approach showed outstanding activity and stability for conversions of stearic acid or palm oil to diesel range alkanes. This work provides a rational design and precise modulation of metal-based catalysts for the production of renewable diesel.
Single-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers
Authors: Brase Logan , You Shih-Feng , D’Oliveira Albanus Ricardo , Del-Aguila Jorge L. , Dai Yaoyi , Novotny Brenna C. , Soriano-Tarraga Carolina , Dykstra Taitea , Fernandez Maria Victoria , Budde John P. , Bergmann Kristy , Morris John C. , Bateman Randall J. , Perrin Richard J. , McDade Eric , Xiong Chengjie , Goate Alison M. , Farlow Martin ,   Dominantly Inherited Alzheimer Network (DIAN), Sutherland Greg T. , Kipnis Jonathan , Karch Celeste M. , Benitez Bruno A. , Harari Oscar 
Published: April 2023

AbstractGenetic studies of Alzheimer disease (AD) have prioritized variants in genes related to the amyloid cascade, lipid metabolism, and neuroimmune modulation. However, the cell-specific effect of variants in these genes is not fully understood. Here, we perform single-nucleus RNA-sequencing (snRNA-seq) on nearly 300,000 nuclei from the parietal cortex of AD autosomal dominant (APP and PSEN1) and risk-modifying variant (APOE, TREM2 and MS4A) carriers. Within individual cell types, we capture genes commonly dysregulated across variant groups. However, specific transcriptional states are more prevalent within variant carriers. TREM2 oligodendrocytes show a dysregulated autophagy-lysosomal pathway, MS4A microglia have dysregulated complement cascade genes, and APOEε4 inhibitory neurons display signs of ferroptosis. All cell types have enriched states in autosomal dominant carriers. We leverage differential expression and single-nucleus ATAC-seq to map GWAS signals to effector cell types including the NCK2 signal to neurons in addition to the initially proposed microglia. Overall, our results provide insights into the transcriptional diversity resulting from AD genetic architecture and cellular heterogeneity. The data can be explored on the online browser (http://web.hararilab.org/SNARE/).
Microbial biomanufacturing for space-exploration—what to take and when to make
Authors: Averesch Nils J. H. , Berliner Aaron J. , Nangle Shannon N. , Zezulka Spencer , Vengerova Gretchen L. , Ho Davian , Casale Cameran A. , Lehner Benjamin A. E. , Snyder Jessica E. , Clark Kevin B. , Dartnell Lewis R. , Criddle Craig S. , Arkin Adam P. 
Published: April 2023

AbstractAs renewed interest in human space-exploration intensifies, a coherent and modernized strategy for mission design and planning has become increasingly crucial. Biotechnology has emerged as a promising approach to increase resilience, flexibility, and efficiency of missions, by virtue of its ability to effectively utilize in situ resources and reclaim resources from waste streams. Here we outline four primary mission-classes on Moon and Mars that drive a staged and accretive biomanufacturing strategy. Each class requires a unique approach to integrate biomanufacturing into the existing mission-architecture and so faces unique challenges in technology development. These challenges stem directly from the resources available in a given mission-class—the degree to which feedstocks are derived from cargo and in situ resources—and the degree to which loop-closure is necessary. As mission duration and distance from Earth increase, the benefits of specialized, sustainable biomanufacturing processes also increase. Consequentially, we define specific design-scenarios and quantify the usefulness of in-space biomanufacturing, to guide techno-economics of space-missions. Especially materials emerged as a potentially pivotal target for biomanufacturing with large impact on up-mass cost. Subsequently, we outline the processes needed for development, testing, and deployment of requisite technologies. As space-related technology development often does, these advancements are likely to have profound implications for the creation of a resilient circular bioeconomy on Earth.