bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial Machine Learning for Exploring the Variability in Low Height‐For‐Age From Socioeconomic, Agroecological, and Climate Features in the Northern Province of Rwanda
Authors: Nduwayezu Gilbert , Kagoyire Clarisse , Zhao Pengxiang , Eklund Lina , Pilesjo Petter , Bizimana Jean Pierre , Mansourian Ali 
Published: September 2024

AbstractChildhood stunting is a serious public health concern in Rwanda. Although stunting causes have been documented, we still lack a more in‐depth understanding of their local factors at a more detailed geographic level. We cross‐sectionally examined 615 height‐for‐age prevalence observations in the Northern Province of Rwanda, linked with their related covariates, to explore the spatial heterogeneity in the low height‐for‐age prevalence by fitting linear and non‐linear spatial regression models and explainable machine learning. Specifically, complemented with generalized additive models, we fitted the ordinary least squares (OLS), a standard geographically weighted regression (GWR), and multiscale geographically weighted regression (MGWR) models to characterize the imbalanced distribution of stunting risk factors and uncover the nonlinear effect of significant predictors, explaining the height‐for‐age variations. The results reveal that 27% of the children measured were stunted, and that likelihood was found to be higher in the districts of Musanze, Gakenke, and Gicumbi. The local MGWR model outperformed the ordinary GWR and OLS, with coefficients of determination of 0.89, 0.84, and 0.25, respectively. At specific ranges, the study shows that height‐for‐age decreases with an increase in the number of days a child was left alone, elevation, and rainfall. In contrast, land surface temperature is positively associated with height‐for‐age. However, variables like the normalized difference vegetation index, slope, soil fertility, and urbanicity exhibited bell‐shaped and U‐shaped non‐linear associations with the height‐for‐age prevalence. Identifying areas with the highest rates of stunting will help determine the most effective measures for reducing the burden of undernutrition.
Two‐Step Electron Acceleration During a Flux Rope Crossing of Earth's Bow Shock
Authors: Hu D. K. , Liu Y. Y. , Cao J. B. , Liu C. M. 
Published: September 2024

AbstractThe generation of cosmic ray particles with ultra‐relativistic energies is a crucial issue in astrophysical and space physics. Shocks have been acknowledged as efficient accelerators in the universe which can produce energetic particles through a variety of mechanisms, such as diffusive shock acceleration (DSA), shock surfing acceleration (SSA) and shock drift acceleration (SDA). Using the data set obtained by the Magnetospheric Multiscale mission, we report an unusually sharp enhancement of energetic electron flux in the upstream region of Earth's bow shock, associated with a bipolar variation of the interplanetary magnetic field. To explain these observations, we propose a two‐step acceleration scenario where electrons trapped in a flux rope (FR) first undergo head‐on collisions and are further accelerated by FR contraction as the FR crosses the shock. Such a scenario can well explain the spacecraft observations. This work can improve our understanding of particle acceleration processes at shocks.
B4GALT1-dependent galectin-8 binding with TGF-β receptor suppresses colorectal cancer progression and metastasis
Authors: Hsu Tzu-Hui , Chang Yu-Chan , Lee Yi-Yuan , Chen Chi-Long , Hsiao Michael , Lin Fan-Ru , Chen Li-Han , Lin Chun-Hung , Angata Takashi , Liu Fu-Tong , Lin Kuo-I 
Published: September 2024

AbstractTransforming growth factor (TGF)-β signaling is critical for epithelial-mesenchymal transition (EMT) and colorectal cancer (CRC) metastasis. Disruption of Smad-depednent TGF-β signaling has been shown in CRC cells. However, TGF-β receptor remains expressed on CRC cells. Here, we investigated whether the cooperation between tumor-associated N-glycosylation and a glycan-binding protein modulated the TGF-β-driven signaling and metastasis of CRC. We showed that galectin-8, a galactose-binding lectin, hampered TGF-β-induced EMT by interacting with the type II TGF-β receptor and competing with TGF-β binding. Depletion of galectin-8 promoted the migration of CRC cells by increasing TGF-β-receptor-mediated RAS and Src signaling, which was attenuated after recombinant galectin-8 treatment. Treatment with recombinant galectin-8 also induces JNK-dependent apoptosis in CRC cells. The anti-migratory effect of galectin-8 depended on β4-galactosyltransferase-I (B4GALT1), an enzyme involved in N-glycan synthesis. Increased B4GALT1 expression was observed in clinical CRC samples. Depletion of B4GALT1 reduced the metastatic potential of CRC cells. Furthermore, inducible expression of galectin-8 attenuated tumor development and metastasis of CRC cells in an intra-splenic injection model. Our results thus demonstrate that galectin-8 alters non-canonical TGF-β response in CRC cells and suppresses CRC progression.
TBC1 domain-containing proteins are frequently involved in triple-negative breast cancers in connection with the induction of a glycolytic phenotype
Authors: Lupi Mariadomenica , Avanzato Daniele , Confalonieri Stefano , Martino Flavia , Pennisi Rosa , Pupo Emanuela , Audrito Valentina , Freddi Stefano , Bertalot Giovanni , Montani Francesca , Matoskova Bronislava , Sigismund Sara , Di Fiore Pier Paolo , Lanzetti Letizia 
Published: September 2024

AbstractMetabolic plasticity is a hallmark of cancer, and metabolic alterations represent a promising therapeutic target. Since cellular metabolism is controlled by membrane traffic at multiple levels, we investigated the involvement of TBC1 domain-containing proteins (TBC1Ds) in the regulation of cancer metabolism. These proteins are characterized by the presence of a RAB-GAP domain, the TBC1 domain, and typically function as attenuators of RABs, the master switches of membrane traffic. However, a number of TBC1Ds harbor mutations in their catalytic residues, predicting biological functions different from direct regulation of RAB activities. Herein, we report that several genes encoding for TBC1Ds are expressed at higher levels in triple-negative breast cancers (TNBC) vs. other subtypes of breast cancers (BC), and predict prognosis. Orthogonal transcriptomics/metabolomics analysis revealed that the expression of prognostic TBC1Ds correlates with elevated glycolytic metabolism in BC cell lines. In-depth investigations of the three top hits from the previous analyses (TBC1D31, TBC1D22B and TBC1D7) revealed that their elevated expression is causal in determining a glycolytic phenotype in TNBC cell lines. We further showed that the impact of TBC1D7 on glycolytic metabolism of BC cells is independent of its known participation in the TSC1/TSC2 complex and consequent downregulation of mTORC1 activity. Since TBC1D7 behaves as an independent prognostic biomarker in TNBC, it could be used to distinguish good prognosis patients who could be spared aggressive therapy from those with a poor prognosis who might benefit from anti-glycolytic targeted therapies. Together, our results highlight how TBC1Ds connect disease aggressiveness with metabolic alterations in TNBC. Given the high level of heterogeneity among this BC subtype, TBC1Ds could represent important tools in predicting prognosis and guiding therapy decision-making.
Large-scale analysis of whole genome sequencing data from formalin-fixed paraffin-embedded cancer specimens demonstrates preservation of clinical utility
Authors: Basyuni Shadi , Heskin Laura , Degasperi Andrea , Black Daniella , Koh Gene C. C. , Chmelova Lucia , Rinaldi Giuseppe , Bell Steven , Grybowicz Louise , Elgar Greg , Memari Yasin , Robbe Pauline , Kingsbury Zoya , Caldas Carlos , Abraham Jean , Schuh Anna , Jones Louise ,   PARTNER Trial Group,   Personalised Breast Cancer Program Group, Tischkowitz Marc , Brown Matthew A. , Davies Helen R. , Nik-Zainal Serena 
Published: September 2024

AbstractWhole genome sequencing (WGS) provides comprehensive, individualised cancer genomic information. However, routine tumour biopsies are formalin-fixed and paraffin-embedded (FFPE), damaging DNA, historically limiting their use in WGS. Here we analyse FFPE cancer WGS datasets from England’s 100,000 Genomes Project, comparing 578 FFPE samples with 11,014 fresh frozen (FF) samples across multiple tumour types. We use an approach that characterises rather than discards artefacts. We identify three artefactual signatures, including one known (SBS57) and two previously uncharacterised (SBS FFPE, ID FFPE), and develop an “FFPEImpact” score that quantifies sample artefacts. Despite inferior sequencing quality, FFPE-derived data identifies clinically-actionable variants, mutational signatures and permits algorithmic stratification. Matched FF/FFPE validation cohorts shows good concordance while acknowledging SBS, ID and copy-number artefacts. While FF-derived WGS data remains the gold standard, FFPE-samples can be used for WGS if required, using analytical advancements developed here, potentially democratising whole cancer genomics to many.
DNA methylation controls stemness of astrocytes in health and ischaemia
Authors: Kremer Lukas P. M. , Cerrizuela Santiago , El-Sammak Hadil , Al Shukairi Mohammad Eid , Ellinger Tobias , Straub Jannes , Korkmaz Aylin , Volk Katrin , Brunken Jan , Kleber Susanne , Anders Simon , Martin-Villalba Ana 
Published: September 2024

AbstractAstrocytes are the most abundant cell type in the mammalian brain and provide structural and metabolic support to neurons, regulate synapses and become reactive after injury and disease. However, a small subset of astrocytes settles in specialized areas of the adult brain where these astrocytes instead actively generate differentiated neuronal and glial progeny and are therefore referred to as neural stem cells1–3. Common parenchymal astrocytes and quiescent neural stem cells share similar transcriptomes despite their very distinct functions4–6. Thus, how stem cell activity is molecularly encoded remains unknown. Here we examine the transcriptome, chromatin accessibility and methylome of neural stem cells and their progeny, and of astrocytes from the striatum and cortex in the healthy and ischaemic adult mouse brain. We identify distinct methylation profiles associated with either astrocyte or stem cell function. Stem cell function is mediated by methylation of astrocyte genes and demethylation of stem cell genes that are expressed later. Ischaemic injury to the brain induces gain of stemness in striatal astrocytes7. We show that this response involves reprogramming the astrocyte methylome to a stem cell methylome and is absent if the de novo methyltransferase DNMT3A is missing. Overall, we unveil DNA methylation as a promising target for regenerative medicine.
Mapping glycoprotein structure reveals Flaviviridae evolutionary history
Authors: Mifsud Jonathon C. O. , Lytras Spyros , Oliver Michael R. , Toon Kamilla , Costa Vincenzo A. , Holmes Edward C. , Grove Joe 
Published: September 2024

AbstractViral glycoproteins drive membrane fusion in enveloped viruses and determine host range, tissue tropism and pathogenesis1. Despite their importance, there is a fragmentary understanding of glycoproteins within the Flaviviridae2, a large virus family that include pathogens such as hepatitis C, dengue and Zika viruses, and numerous other human, animal and emergent viruses. For many flaviviruses the glycoproteins have not yet been identified, for others, such as the hepaciviruses, the molecular mechanisms of membrane fusion remain uncharacterized3. Here we combine phylogenetic analyses with protein structure prediction to survey glycoproteins across the entire Flaviviridae. We find class II fusion systems, homologous to the Orthoflavivirus E glycoprotein in most species, including highly divergent jingmenviruses and large genome flaviviruses. However, the E1E2 glycoproteins of the hepaciviruses, pegiviruses and pestiviruses are structurally distinct, may represent a novel class of fusion mechanism, and are strictly associated with infection of vertebrate hosts. By mapping glycoprotein distribution onto the underlying phylogeny, we reveal a complex evolutionary history marked by the capture of bacterial genes and potentially inter-genus recombination. These insights, made possible through protein structure prediction, refine our understanding of viral fusion mechanisms and reveal the events that have shaped the diverse virology and ecology of the Flaviviridae.
Recurrent evolution and selection shape structural diversity at the amylase locus
Authors: Bolognini Davide , Halgren Alma , Lou Runyang Nicolas , Raveane Alessandro , Rocha Joana L. , Guarracino Andrea , Soranzo Nicole , Chin Chen-Shan , Garrison Erik , Sudmant Peter H. 
Published: September 2024

AbstractThe adoption of agriculture triggered a rapid shift towards starch-rich diets in human populations1. Amylase genes facilitate starch digestion, and increased amylase copy number has been observed in some modern human populations with high-starch intake2, although evidence of recent selection is lacking3,4. Here, using 94 long-read haplotype-resolved assemblies and short-read data from approximately 5,600 contemporary and ancient humans, we resolve the diversity and evolutionary history of structural variation at the amylase locus. We find that amylase genes have higher copy numbers in agricultural populations than in fishing, hunting and pastoral populations. We identify 28 distinct amylase structural architectures and demonstrate that nearly identical structures have arisen recurrently on different haplotype backgrounds throughout recent human history. AMY1 and AMY2A genes each underwent multiple duplication/deletion events with mutation rates up to more than 10,000-fold the single-nucleotide polymorphism mutation rate, whereas AMY2B gene duplications share a single origin. Using a pangenome-based approach, we infer structural haplotypes across thousands of humans identifying extensively duplicated haplotypes at higher frequency in modern agricultural populations. Leveraging 533 ancient human genomes, we find that duplication-containing haplotypes (with more gene copies than the ancestral haplotype) have rapidly increased in frequency over the past 12,000 years in West Eurasians, suggestive of positive selection. Together, our study highlights the potential effects of the agricultural revolution on human genomes and the importance of structural variation in human adaptation.
The Therapeutic Potential of Gold Complexes
Authors: Wani Waseem A , Alajmi Mohamed F , Hussain Afzal , Wani Irshad Ahmad 
Published: September 2024

Globally, millions of deaths are reported annually due to cancers, bacterial, fungal, viral and parasitic diseases, diabetes and inflammatory conditions. Metal complexes have been extensively developed and tested for anticancer, antibacterial, antifungal, antiviral, antiparasitic, antidiabetic and anti-inflammatory properties. It is quite encouraging to learn that quite a lot of metal complexes with interesting therapeutic properties have been developed.
This concise book reviews the recent advances made in the development of gold complexes as therapeutics, highlighting the different ligand architectures that have been used for their development. The mechanisms of therapeutic action, the development of nanodrugs and the toxicity issues of gold complexes are all discussed in detail. Finally, the book reflects on the future research and development in gold complexes as therapeutic agents. Postgraduates and researchers in drug discovery and development interested in metal-based therapeutics and biomedical applications of gold will find this book enlightening.
CADGen: Computer‐aided design sequence construction with a guided codebook learning
Authors: Zhou Shengdi , Zan Xiaoqiang , Li Zhuqing , Zhou Bin 
Published: September 2024

AbstractComputer‐aided design (CAD) software continues to be a crucial tool in digital twin application and manufacturing, facilitating the design of various products. We present a novel CAD generation method, an agent that constructs the CAD sequences containing the sketch‐and‐extrude modelling operations efficiently and with high quality. Starting from the sketch and extrusion operation sequences, we utilise the transformer encoder to encode them into different disentangled codebooks to represent their distribution properties while considering their correlations. Then, a combination of auto‐regressive and non‐autoregressive samplers is trained to sample the code for CAD sequence construction. Extensive experiments demonstrate that our model generates diverse and high‐quality CAD models. We also show some cases of real digital twin applications and indicate that our generated model can be used as the data source for the digital twin platform, exhibiting designers' potential.
Inaugural editorial‐Digital Twins and Applications
Authors: Sun Youxian , Wang Wenhai , Yang Qiang , Zhang Yinan 
Published: September 2024

AbstractAcademician of the CAE member Youxian Sun from Zhejiang University initiated Digital Twins and Applications (ISSN 2995‐2182). It is published by Zhejiang University Press and the Institution of Engineering and Technology and sponsored by Zhejiang University. Digital Twins and Applications aim to provide a specialised platform for researchers, practitioners, and industry experts to publish high‐quality, state‐of‐the‐art research on digital twin technologies and their applications.
Availability evaluation and optimisation of advanced receiver autonomous integrity monitoring fault detection and exclusion considering temporal correlations
Authors: Du Jingtian , Fang Kun , Wang Zhipeng , Zhu Yanbo 
Published: September 2024

AbstractThe Advanced Receiver Autonomous Integrity Monitoring (ARAIM) provides an Aircraft‐Based Augmentation System function for aircraft Global Navigation Satellite System equipment. Currently, the consideration of temporal correlations of test statistics is an important update to the ARAIM baseline algorithm. However, due to the tight budgets of integrity and continuity, the updated ARAIM Fault Detection and Exclusion (FDE) is not satisfactory in availability coverage. The baseline algorithm is based on equal allocation of integrity and continuity, which causes ARAIM to be susceptible to faults and satellite outages. An availability optimisation of ARAIM FDE based on dynamic budget allocation is proposed, aiming to make full use of the prior knowledge provided by the Integrity Support Message (ISM). The contribution of each solution separation test in the ARAIM FDE to the total continuity and integrity risks is estimated, and the continuity and integrity allocation constraints are obtained. The impacts of faults and satellite outages on availability are analysed, and a predictive Protection Level (PL) for ARAIM FDE is proposed for use as an objective function for optimising risk allocation. Then, a risk allocation method based on the multiplier penalty function method is proposed. The performances of the baseline algorithm and the proposed method under the maximum Number of Effective Samples are simulated. For dual‐constellation H‐ARAIM, the optimised Horizontal PL (HPL) is 40% lower than that of the baseline algorithm on average, and the average number of critical satellites supporting RNP 0.3 is less than 1 worldwide. For the three‐constellation V‐ARIAM, the optimised HPL is 27% lower than that of the baseline algorithm on average, and the optimised Vertical PL (VPL) is 18% lower. The proposed method has high availability coverage and can better respond to the requirements for high‐performance navigation services.
Unveiling accretion in the massive young stellar object G033.3891
Authors: Koumpia E. , Sun D. , Koutoulaki M. , Ilee J. D. , de Wit W.-J. , Oudmaijer R. D. , Frost A. J. 
Published: September 2024

Context. The inner parts of the hot discs surrounding massive young stellar objects (MYSOs) are still barely explored due to observational limitations in terms of angular resolution, scarcity of diagnostic lines, and the embedded and rare nature of these targets.
Aims. We present the first K-band spectro-interferometric observations towards the MYSO G033.3891, which based on former kinematic evidence via the CO bandhead emission is known to host an accreting disc.
Methods. Using the high spectral resolution mode (R∼4000) of the GRAVITY/VLTI, we spatially resolved the emission of the inner dusty disc and the crucial gaseous interface between the star and the dusty disc. Using detailed modelling on the K-band dust continuum and tracers known to be associated with the ionised and molecular gaseous interface (Brγ, CO), we report on the smallest scales of accretion and ejection.
Results. The new observations in combination with our geometric and kinematic models employed to fit former high spectral resolution observations on the source (R∼30 000; CRIRES/VLTI) allowed us to constrain the size of the inner gaseous disc both spatially and kinematically via the CO overtone emission at only 2 au. Our models reveal that both Brγ and CO emissions are located well within the dust sublimation radius (5 au) as traced by the hot 2.2 µm dust continuum.
Conclusions. Our paper provides the first case study where the tiniest scales of gaseous accretion around the MYSO G033.3891 are probed both kinematically and spatially via the CO bandhead emission. This analysis of G033.3891 stands as only the second instance of such an investigation within MYSOs, underscoring the gradual accumulation of knowledge regarding how massive young stars gain their mass while further solidifying the disc nature of accretion at the smallest scales of MYSOs.
Derivation of a generalized Kappa distribution from the scaling properties of solar wind magnetic field fluctuations at kinetic scales
Authors: Belardinelli Daniele , Benella Simone , Stumpo Mirko , Consolini Giuseppe 
Published: September 2024

Context. Kinetic-scale dynamics in weakly collisional space plasmas usually exhibits a self-similar statistics of magnetic field fluctuations. This implies the existence of an invariant probability density function (master curve).
Aims. We provide an analytical derivation of the master curve by assuming that perpendicular fluctuations can be modeled through a scale-dependent Langevin equation.
Methods. In our model, magnetic field fluctuations are the stochastic variable, and their scale-to-scale evolution is assumed to be a Langevin process. We propose a formal derivation of the master curve describing the statistics of the fluctuations at kinetic scales. The model predictions were tested on independent data samples of the fast solar wind measured near the Sun by Parker Solar Probe and near the Earth by Cluster.
Results. The master curve is a generalization of the Kappa distribution with two parameters: One parameter regulates the tails, and the other controls the asymmetry. The model predictions match the spacecraft observations up to 5σ and even beyond in the case of perpendicular magnetic field fluctuations.