bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Spectral Study of the Caloris Basin on Mercury and the Origin of Associated Volcanic Smooth Plains
Authors: Caminiti E. , Doressoundiram A. , Besse S. , Wright J. 
Published: April 2023

AbstractResults from the NASA/MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) mission showed that 27% of Mercury's surface is covered by smooth plains mostly produced by extensive effusive volcanism. The Caloris impact basin is associated with two, mostly volcanic, smooth plains, one in its interior and one surrounding the basin. Previous studies have shown that it is difficult to estimate the relative ages of the interior and exterior plains and to explain their spectral and compositional differences. We perform an exhaustive spectral analysis of the basin based on data obtained by the Mercury Atmospheric and Surface Composition Spectrometer spectrometer onboard MESSENGER between 300 and 1,450 nm with a 5 nm resolution. Unlike previous results based on crater counts, we found that the exterior plains were emplaced before the interior plains although both postdate the formation of the basin. We propose a decrease in the partial melting degree and/or partial melting depth over time to explain the spectral and compositional differences. The study highlights spectrally heterogeneous exterior plains associated with a compositional heterogeneity and the presence of low reflectance material (LRM) deposits. This heterogeneity in the exterior plains could be related to the formation of the basin and asymmetry of the ejecta deposits or to a heterogeneous distribution of LRM present at depths before the formation of the basin.
Fluvial‐Aeolian Interaction and Compositional Variability in the River‐Fed Yarlung Tsangpo Dune System (Southern Tibet)
Authors: Liang Wendong , Hu Xiumian , Garzanti Eduardo , Dong Xiaolong , Zhang Yiqiu 
Published: April 2023

AbstractRiver‐fed dune fields characterized by relatively low quartz content are much more common on Earth than generally assumed, and the aeolian dune field system in the Yarlung Tsangpo (Upper Brahmaputra) river catchment is considered a typical example. As one of the highest‐altitude fluvial‐aeolian systems on Earth, the dune fields in different wide tracts of the Yarlung Tsangpo valley, made of sand entirely blown from the adjacent river bed, provides an excellent natural laboratory in which to investigate the diverse factors controlling textural and compositional changes induced by aeolian processes. To this aim, the textural (grain‐size, roundness) and compositional (petrography, heavy minerals) properties of multiple size classes of fluvial and aeolian sands were quantified. The results show that sediment composition is markedly controlled by grain size, with greater intrasample than intersample variability. Grain‐size controlled compositional differences cannot be exclusively ascribed to hydraulic‐sorting effects. Independent of their density or shape, quartz, sedimentary rock fragments, zircon, apatite, and epidote grains are observed to be on average smaller than feldspars, volcanic rock fragments, and pyroxenes. This indicates that the original size of minerals in source rocks also played a significant role, limiting their availability in finer (e.g., garnet) or coarser (e.g., apatite) classes. In the river‐fed dune system, the lower content of phyllosilicates and higher grain roundness could represent useful criteria to distinguish aeolian from fluvial sand. The efficient aeolian abrasion of river‐fed sediments on the Tibetan Plateau may be an effective mechanism for the production of dust deposited as vast loess covers during the Quaternary.
Paleoceanographic Implications of Diatom Seasonal Laminations in the Upper Miocene Pisco Formation (Ica Desert, Peru) and Their Clues on the Development of the Pisco Fossil‐Lagerstätte
Authors: Gariboldi Karen , Pike Jennifer , Malinverno Elisa , Di Celma Claudio , Gioncada Anna , Bianucci Giovanni 
Published: April 2023

AbstractThe detailed study of diatom laminations conducted by means of backscattered electron imaging serves as tool to unravel details of past ocean dynamics. In this paper we apply this method to the analysis of the diatomites of Cerro Los Quesos, Upper Miocene Pisco Fm, Peru. Numerous studies have been conducted on the Pisco Fm; however, a focus on its paleoceanographic significance is still lacking. In this work, we provide information on the oceanographic setting in the area at the time of diatomites deposition. The high abundance of deep‐living Coscinodiscus laminae, proceeded by either a mixed lamina or a terrigenous one, let us hypothesize a deep position of the thermocline during the deposition of the Pisco diatomites; together with the scarcity of Chaetoceros Hyalochaete spp. resting spores, this evidence confutes the belief that equals high biogenic silica content in marine sediments with enhanced upwelling. Conversely, the depositional setting of the Pisco Fm diatomites is more similar to what is known as “permanent El Niño” (or “El Padre”) state, meaning a constant weakened upwelling (or upwelling of nutrients‐poor waters). Climate modeling warns that an increase in atmospheric CO2 may lead to this mean state in the near future. Thanks to this study we also obtained refined information on the diatomites sedimentations rates. The comparison of the Pisco diatomites sedimentation rates with those of Quaternary diatomites gave strength to the hypothesis that the formation of the vertebrate Lagerstätte may have been enhanced, among others, by the so‐called “impact‐burial” mechanism.
Substantial Upper Plate Faulting Above a Shallow Subduction Megathrust Earthquake: Mechanics and Implications of the Surface Faulting During the 2016 Kaikoura, New Zealand, Earthquake
Authors: Herman M. W. , Furlong K. P. , Benz H. M. 
Published: April 2023

AbstractThe 2016 moment magnitude 7.8 Kaikoura, New Zealand, earthquake occurred at the southern end of the Hikurangi subduction zone where the upper plate above the shallow megathrust is exposed sub‐aerially. As a result, the substantial co‐seismic deformation in the upper plate above the megathrust rupture was observed geologically and geodetically. We explore the relationship between this surface faulting and the subduction megathrust rupture and find that the greatest upper plate fault slip occurred coincident (in time and location) with the megathrust rupture. Models of Coulomb stress change demonstrate that these surface faults become positively loaded as the upper plate rebounds during the megathrust event, favoring fault slip. In addition, during the megathrust rupture these faults terminate against an uncoupled subduction plate interface. We simulate the effects of decoupling at the base of these faults and find that very large fault slip is an expected consequence of this decoupling, allowing near‐complete strain release. In contrast, typical strike‐slip faults, pinned at their base, would have lower amounts of fault slip. These two conditions—increased Coulomb stress and basal decoupling—combine to produce the extreme co‐seismic upper plate faulting observed above the shallow Kaikoura megathrust earthquake. Similar conditions occur in other global subduction zones, but in most subduction zones the region above the coupled megathrust is underwater and poorly observed. Our analysis of the Kaikoura earthquake indicates a need to reevaluate patterns of strain accumulation and release in these regions, rather than assuming simple models of elastic rebound.
AML classification in the year 2023: How to avoid a Babylonian confusion of languages
Authors: Huber Sandra , Baer Constance , Hutter Stephan , Dicker Frank , Meggendorfer Manja , Pohlkamp Christian , Kern Wolfgang , Haferlach Torsten , Haferlach Claudia , Hoermann Gregor 
Published: April 2023

AbstractIn parallel to the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO 2022), an alternative International Consensus Classification (ICC) has been proposed. To evaluate the impact of the new classifications on AML diagnoses and ELN-based risk classification, we analyzed 717 MDS and 734 AML non-therapy-related patients diagnosed according to the revised 4th WHO edition (WHO 2017) by whole genome and transcriptome sequencing. In both new classifications, the purely morphologically defined AML entities decreased from 13% to 5%. Myelodysplasia-related (MR) AML increased from 22% to 28% (WHO 2022) and 26% (ICC). Other genetically-defined AML remained the largest group, and the abandoned AML-RUNX1 was mainly reclassified as AML-MR (WHO 2022: 77%; ICC: 96%). Different inclusion criteria of AML-CEBPA and AML-MR (i.a. exclusion of TP53 mutated cases according to ICC) were associated with differences in overall survival. In conclusion, both classifications focus on more genetics-based definitions with similar basic concepts and a large degree of agreement. The remaining non-comparability (e.g., TP53 mutated AML) needs additional studies to definitely answer open questions on disease categorization in an unbiased way.
Functional roles of SRC signaling in pancreatic cancer: Recent insights provide novel therapeutic opportunities
Authors: Poh Ashleigh R. , Ernst Matthias 
Published: April 2023

AbstractPancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant disease with a 5-year survival rate of <10%. Aberrant activation or elevated expression of the tyrosine kinase c-SRC (SRC) is frequently observed in PDAC and is associated with a poor prognosis. Preclinical studies have revealed a multifaceted role for SRC activation in PDAC, including promoting chronic inflammation, tumor cell proliferation and survival, cancer cell stemness, desmoplasia, hypoxia, angiogenesis, invasion, metastasis, and drug resistance. Strategies to inhibit SRC signaling include suppressing its catalytic activity, inhibiting protein stability, or by interfering with signaling components of the SRC signaling pathway including suppressing protein interactions of SRC. In this review, we discuss the molecular and immunological mechanisms by which aberrant SRC activity promotes PDAC tumorigenesis. We also provide a comprehensive update of SRC inhibitors in the clinic, and discuss the clinical challenges associated with targeting SRC in pancreatic cancer.
The readability of parent information leaflets in paediatric studies
Authors: Nash Elizabeth , Bickerstaff Matthew , Chetwynd Andrew J. , Hawcutt Daniel B. , Oni Louise 
Published: April 2023

AbstractBackgroundPoor literacy can impact achieving optimal health outcomes. The aim of this project was to assess the readability of parent information leaflets (PILs).MethodsA single-centre study using paediatric PILs. Five readability tests were applied (Gunning Fog Index (GFI), Simple Measure of Gobbledygook (SMOG), Flesch Kincaid Grade Level (FKGL), Coleman–Liau Index (CLI) and Automated Readability Index (ARI)). Results were compared to standards and by subtype.ResultsA total of 109 PILs were obtained; mean (±SD) number of characters was 14,365 (±12,055), total words 3066 (±2541), number of sentences 153 (±112), lexical density 49 (±3), number of characters per word 4.7 (±0.1), number of syllables per word 1.6 (±0.1) and number of words per sentence 19.1 (±2.5). The Flesch reading ease score was 51.1 (±5.6), equating to reading age 16–17 years. The mean PIL readability scores were GFI (12.18), SMOG (11.94), FKGL (10.89), CLI (10.08) and ARI (10.1). There were 0 (0%) PILs classed as easy (score <6), 21 (19%) mid-range (6–10) and 88 (81%) were difficult (>10). They were significantly above the recommended reading age (p < 0.0001) and commercial studies were least accessible (p < 0.01).ConclusionExisting PILs are above the national reading level. Researchers should use readability tools to ensure that they are accessible.ImpactPoor literacy is a barrier to accessing research and achieving good health outcomes.Current parent information leaflets are pitched far higher than the national reading age.This study provides data to demonstrate the reading age of a large portfolio of research studies.This work raises awareness of literacy as a barrier to research participation and provides tips on how to improve the readability of patient information leaflets to guide investigators.
In silico enhancer mining reveals SNS-032 and EHMT2 inhibitors as therapeutic candidates in high-grade serous ovarian cancer
Authors: Quintela Marcos , James David W. , Garcia Jetzabel , Edwards Kadie , Margarit Lavinia , Das Nagindra , Lutchman-Singh Kerryn , Beynon Amy L. , Rioja Inmaculada , Prinjha Rab K. , Harker Nicola R. , Gonzalez Deyarina , Steven Conlan R. , Francis Lewis W. 
Published: April 2023

Abstract
Background
Epigenomic dysregulation has been linked to solid tumour malignancies, including ovarian cancers. Profiling of re-programmed enhancer locations associated with disease has the potential to improve stratification and thus therapeutic choices. Ovarian cancers are subdivided into histological subtypes that have significant molecular and clinical differences, with high-grade serous carcinoma representing the most common and aggressive subtype.

Methods
We interrogated the enhancer landscape(s) of normal ovary and subtype-specific ovarian cancer states using publicly available data. With an initial focus on H3K27ac histone mark, we developed a computational pipeline to predict drug compound activity based on epigenomic stratification. Lastly, we substantiated our predictions in vitro using patient-derived clinical samples and cell lines.

Results
Using our in silico approach, we highlighted recurrent and privative enhancer landscapes and identified the differential enrichment of a total of 164 transcription factors involved in 201 protein complexes across the subtypes. We pinpointed SNS-032 and EHMT2 inhibitors BIX-01294 and UNC0646 as therapeutic candidates in high-grade serous carcinoma, as well as probed the efficacy of specific inhibitors in vitro.

Conclusion
Here, we report the first attempt to exploit ovarian cancer epigenomic landscapes for drug discovery. This computational pipeline holds enormous potential for translating epigenomic profiling into therapeutic leads.
A Phase 1/2 trial of SRA737 (a Chk1 inhibitor) administered orally in patients with advanced cancer
Authors: Kristeleit Rebecca , Plummer Ruth , Jones Robert , Carter Louise , Blagden Sarah , Sarker Debashis , Arkenau Tobias , Evans Thomas R. Jeffry , Danson Sarah , Symeonides Stefan N. , Veal Gareth J. , Klencke Barbara J. , Kowalski Mark M. , Banerji Udai 
Published: April 2023

Abstract
Background
This was a first-in-human Phase 1/2 open-label dose-escalation study of the novel checkpoint kinase 1 (Chk1) inhibitor SRA737.

Methods
Patients with advanced solid tumours enrolled in dose-escalation cohorts and received SRA737 monotherapy orally on a continuous daily (QD) dosing schedule in 28-day cycles. Expansion cohorts included up to 20 patients with prospectively selected, pre-specified response predictive biomarkers.

Results
In total, 107 patients were treated at dose levels from 20–1300 mg. The maximum tolerated dose (MTD) of SRA737 was 1000 mg QD, the recommended Phase 2 dose (RP2D) was 800 mg QD. Common toxicities of diarrhoea, nausea and vomiting were generally mild to moderate. Dose-limiting toxicity at daily doses of 1000 and 1300 mg QD SRA737 included gastrointestinal events, neutropenia and thrombocytopenia. Pharmacokinetic analysis at the 800 mg QD dose showed a mean Cmin of 312 ng/mL (546 nM), exceeding levels required to cause growth delay in xenograft models. No partial or complete responses were seen.

Conclusions
SRA737 was well tolerated at doses that achieved preclinically relevant drug concentrations but single agent activity did not warrant further development as monotherapy. Given its mechanism of action resulting in abrogating DNA damage repair, further clinical development of SRA737 should be as combination therapy.

Clinical trial registration
Clinicaltrials.gov NCT02797964.
Clinical biomarker-based biological aging and risk of cancer in the UK Biobank
Authors: Mak Jonathan K. L. , McMurran Christopher E. , Kuja-Halkola Ralf , Hall Per , Czene Kamila , Jylhävä Juulia , Hägg Sara 
Published: April 2023

Abstract
Background
Despite a clear link between aging and cancer, there has been inconclusive evidence on how biological age (BA) may be associated with cancer incidence.

Methods
We studied 308,156 UK Biobank participants with no history of cancer at enrolment. Using 18 age-associated clinical biomarkers, we computed three BA measures (Klemera-Doubal method [KDM], PhenoAge, homeostatic dysregulation [HD]) and assessed their associations with incidence of any cancer and five common cancers (breast, prostate, lung, colorectal, and melanoma) using Cox proportional-hazards models.

Results
A total of 35,426 incident cancers were documented during a median follow-up of 10.9 years. Adjusting for common cancer risk factors, 1-standard deviation (SD) increment in the age-adjusted KDM (hazard ratio = 1.04, 95% confidence interval = 1.03–1.05), age-adjusted PhenoAge (1.09, 1.07–1.10), and HD (1.02, 1.01–1.03) was significantly associated with a higher risk of any cancer. All BA measures were also associated with increased risks of lung and colorectal cancers, but only PhenoAge was associated with breast cancer risk. Furthermore, we observed an inverse association between BA measures and prostate cancer, although it was attenuated after removing glycated hemoglobin and serum glucose from the BA algorithms.

Conclusions
Advanced BA quantified by clinical biomarkers is associated with increased risks of any cancer, lung cancer, and colorectal cancer.
Targeting fatty acid oxidation via Acyl-CoA binding protein hinders glioblastoma invasion
Authors: Duman Ceren , Di Marco Barbara , Nevedomskaya Ekaterina , Ulug Berk , Lesche Ralf , Christian Sven , Alfonso Julieta 
Published: April 2023

AbstractThe diffuse nature of Glioblastoma (GBM) tumors poses a challenge to current therapeutic options. We have previously shown that Acyl-CoA Binding Protein (ACBP, also known as DBI) regulates lipid metabolism in GBM cells, favoring fatty acid oxidation (FAO). Here we show that ACBP downregulation results in wide transcriptional changes affecting invasion-related genes. In vivo experiments using patient-derived xenografts combined with in vitro models demonstrated that ACBP sustains GBM invasion via binding to fatty acyl-CoAs. Blocking FAO mimics ACBPKD-induced immobility, a cellular phenotype that can be rescued by increasing FAO rates. Further investigation into ACBP-downstream pathways served to identify Integrin beta-1, a gene downregulated upon inhibition of either ACBP expression or FAO rates, as a mediator for ACBP’s role in GBM invasion. Altogether, our findings highlight a role for FAO in GBM invasion and reveal ACBP as a therapeutic vulnerability to stall FAO and subsequent cell invasion in GBM tumors.
Therapeutic efficacy of a MMAE-based anti-DR5 drug conjugate Oba01 in preclinical models of pancreatic cancer
Authors: Zheng Chao , Zhou Dongdong , Li Weisong , Duan Yanhui , Xu Minwen , Liu Jie , Cheng Jingpei , Xiao Youban , Xiao Han , Gan Tao , Liang Jianmin , Zheng Dexian , Wang Liefeng , Zhang Shuyong 
Published: April 2023

AbstractPancreatic cancer (PC) is among the most aggressive malignancies associated with a 5-year survival rate of <9%, and the treatment options remain limited. Antibody–drug conjugates (ADCs) are a new class of anticancer agents with superior efficacy and safety profiles. We studied the antitumor activity of Oba01 ADC and the mechanism underlying the targeting of death receptor 5 (DR5) in preclinical PC models. Our data revealed that DR5 was highly expressed on the plasma membrane of PC cells and Oba01 showed potent in vitro antitumor activity in a panel of human DR5-positive PC cell lines. DR5 was readily cleaved by lysosomal proteases after receptor-mediated internalization. Monomethyl auristatin E (MMAE) was then released into the cytosol to induce G2/M-phase growth arrest, cell death via apoptosis induction, and the bystander effect. Furthermore, Oba01 mediated cell death via antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. For improved potency, we investigated the synergetic effect of Oba01 in combination with approved drugs. Oba01 combined with gemcitabine showed better antiproliferative activity than either standalone treatment. In cell- and patient-derived xenografts, Oba01 showed excellent tumoricidal activity in mono- or combinational therapy. Thus, Oba01 may provide a novel biotherapeutic approach and a scientific basis for clinical trials in DR5-expressing patients with PC.
Positive feedback induces switch between distributive and processive phosphorylation of Hog1
Authors: Mosbacher Maximilian , Lee Sung Sik , Yaakov Gilad , Nadal-Ribelles Mariona , de Nadal Eulàlia , van Drogen Frank , Posas Francesc , Peter Matthias , Claassen Manfred 
Published: April 2023

AbstractCellular decision making often builds on ultrasensitive MAPK pathways. The phosphorylation mechanism of MAP kinase has so far been described as either distributive or processive, with distributive mechanisms generating ultrasensitivity in theoretical analyses. However, the in vivo mechanism of MAP kinase phosphorylation and its activation dynamics remain unclear. Here, we characterize the regulation of the MAP kinase Hog1 in Saccharomyces cerevisiae via topologically different ODE models, parameterized on multimodal activation data. Interestingly, our best fitting model switches between distributive and processive phosphorylation behavior regulated via a positive feedback loop composed of an affinity and a catalytic component targeting the MAP kinase-kinase Pbs2. Indeed, we show that Hog1 directly phosphorylates Pbs2 on serine 248 (S248), that cells expressing a non-phosphorylatable (S248A) or phosphomimetic (S248E) mutant show behavior that is consistent with simulations of disrupted or constitutively active affinity feedback and that Pbs2-S248E shows significantly increased affinity to Hog1 in vitro. Simulations further suggest that this mixed Hog1 activation mechanism is required for full sensitivity to stimuli and to ensure robustness to different perturbations.
Interfacial engineering of ferromagnetism in wafer-scale van der Waals Fe4GeTe2 far above room temperature
Authors: Wang Hangtian , Lu Haichang , Guo Zongxia , Li Ang , Wu Peichen , Li Jing , Xie Weiran , Sun Zhimei , Li Peng , Damas Héloïse , Friedel Anna Maria , Migot Sylvie , Ghanbaja Jaafar , Moreau Luc , Fagot-Revurat Yannick , Petit-Watelot Sébastien , Hauet Thomas , Robertson John , Mangin Stéphane , Zhao Weisheng , Nie Tianxiao 
Published: April 2023

AbstractDespite recent advances in exfoliated vdW ferromagnets, the widespread application of 2D magnetism requires a Curie temperature (Tc) above room temperature as well as a stable and controllable magnetic anisotropy. Here we demonstrate a large-scale iron-based vdW material Fe4GeTe2 with the Tc reaching ~530 K. We confirmed the high-temperature ferromagnetism by multiple characterizations. Theoretical calculations suggested that the interface-induced right shift of the localized states for unpaired Fe d electrons is the reason for the enhanced Tc, which was confirmed by ultraviolet photoelectron spectroscopy. Moreover, by precisely tailoring Fe concentration we achieved arbitrary control of magnetic anisotropy between out-of-plane and in-plane without inducing any phase disorders. Our finding sheds light on the high potential of Fe4GeTe2 in spintronics, which may open opportunities for room-temperature application of all-vdW spintronic devices.