bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early progressive mobility to improve neurodevelopment of infants with severe bronchopulmonary dysplasia at a level IV neonatal intensive care unit: a prospective cohort study
Authors: Morris Heidi , Nilan Kathleen , Burkhardt Meghan , Wood Audrey , Passarella Molly , Gibbs Kathleen , DeMauro Sara B. 
Published: November 2024

Abstract
Objective
To measure the feasibility of early progressive mobility (EPM) in intubated infants with severe bronchopulmonary dysplasia (BPD) and compare neurodevelopmental skill acquisition of these infants before and after implementation of a clinical EPM program.

Study design
Single-center pre-post intervention prospective cohort study in a level IV Neonatal Intensive Care Unit (NICU) from 2019–2022. Bivariate tests compared EPM interventions and results of serial Test of Infant Motor Performance (TIMP) assessments in 32 intubated infants with severe BPD cared for during two epochs, before and after NICU-wide EPM implementation.

Results
Infants in epoch 2 experienced significantly more EPM interventions than infants in epoch 1. Infants in epoch 2 also had more advanced motor skills on the TIMP than infants in epoch 1. There were no unplanned extubations.

Conclusions
We demonstrated successful implementation of EPM in this high-risk population with evidence of beneficial impacts on early motor development.
A CADASIL NOTCH3 mutation leads to clonal hematopoiesis and expansion of Dnmt3a-R878H hematopoietic clones
Authors: Sánchez-Lanzas Raúl , Barclay Justin , Hardas Alexandros , Kalampalika Foteini , Jiménez-Pompa Amanda , Gallipoli Paolo , Ganuza Miguel 
Published: November 2024

Abstract
Clonal hematopoiesis (CH) is nearly universal in the elderly. The molecular and cellular mechanisms driving CH and the clinical consequences of carrying clonally derived mutant mature blood cells are poorly understood. We recently identified a C223Y mutation in the extracellular domain (ECD) of NOTCH3 as a putative CH driver in mice. Provocatively, germline NOTCH3 ECD mutations perturbing cysteine numbers cause Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a type of vascular dementia, suggesting an unexpected link between CADASIL and CH. Here, we formally demonstrated that mouse hematopoietic stem and progenitor cells (HSPCs) expressing CADASIL-related NOTCH3

C455R
exhibit a proliferative advantage resulting in robust cellular expansion in vivo and in vitro. Co-expression of NOTCH3

C455R
and Dnmt3a

R878H
, homologous to a frequent human CH mutation, increased the fitness of NOTCH3

C455R
HSPCs, demonstrating their functional cooperation. Surprisingly, the presence of NOTCH3

C455R
hematopoietic cells supported the expansion of Dnmt3a

R878H
HSPCs in a non-cell autonomous fashion in vivo, strongly suggesting that CADASIL patients and asymptomatic carriers can be highly predisposed to DNMT3A

R882H
-driven CH. Considering that CADASIL-related NOTCH3 mutations are more frequent in the general population than anticipated (~1 carrier in 400 people), the effect of these NOTCH3 mutations on CH development should be considered.
Defect-insensitive cylindrical surface lattice resonance array and its batch replication for enhanced immunoassay
Authors: Zhou Bin , Hu Chao , Li Haoyang , Ye Xiangyi , Wen Baohua , Zhou Zhangkai , Cai Jingxuan , Zhou Jianhua 
Published: November 2024

AbstractSurface lattice resonances (SLR) have been demonstrated to enhance the sensitivity and reduce the full width at half maximum (FWHM) of the plasmonic resonances. However, their widespread application in immunoassays has been hindered by limitations of high structural defect sensitivity and fabrication costs. Here, we design a novel three-layer cylindrical SLR array that exhibits high tolerance against structural defects, which would facilitate straightforward fabrication. By integrating metal evaporation and nanoimprint lithography, we demonstrate the replication of the SLR array with exceptional quality. Theoretical simulations indicate that the resonance dips of these arrays exhibit are not sensitive to various structural defects. The experimental results reveal that the FWHM of these arrays can be as low as 5.1 nm while maintaining robust resonance characteristics. Furthermore, we demonstrated the high spectral sensitivity of the SLR array, which enabled the detection of immunoglobulin G (IgG) at concentrations as low as 609 pg/mL. These findings emphasize the potential of the defect-insensitive SLR array as a highly scalable immunoassay platform with exceptional performance.
The abscopal effects of sonodynamic therapy in cancer
Authors: Collins Victoria G. , Hutton Dana , Hossain-Ibrahim Kismet , Joseph James , Banerjee Sourav 
Published: November 2024

AbstractThe abscopal effect is a phenomenon wherein localised therapy on the primary tumour leads to regression of distal metastatic growths. Interestingly, various pre-clinical studies utilising sonodynamic therapy (SDT) have reported significant abscopal effects, however, the mechanism remains largely enigmatic. SDT is an emerging non-invasive cancer treatment that uses focussed ultrasound (FUS) and a sonosensitiser to induce tumour cell death. To expand our understanding of abscopal effects of SDT, we have summarised the preclinical studies that have found SDT-induced abscopal responses across various cancer models, using diverse combination strategies with nanomaterials, microbubbles, chemotherapy, and immune checkpoint inhibitors. Additionally, we shed light on the molecular and immunological mechanisms underpinning SDT-induced primary and metastatic tumour cell death, as well as the role and efficacy of different sonosensitisers. Notably, the observed abscopal effects underscore the need for continued investigation into the SDT-induced ‘vaccine-effect’ as a potential strategy for enhancing systemic anti-tumour immunity and combating metastatic disease. The results of the first SDT human clinical trials are much awaited and are hoped to enable the further evaluation of the safety and efficacy of SDT, paving the way for future studies specifically designed to explore the potential of translating SDT-induced abscopal effects into clinical reality.
An increase of lysosomes through EGF-triggered endocytosis attenuated zinc-mediated lysosomal membrane permeabilization and neuronal cell death
Authors: Eom Jae-Won , Lee Jin-Yeon , Kwon Yeabin , Kim Yang-Hee 
Published: November 2024

AbstractIn the context of acute brain injuries, where zinc neurotoxicity and oxidative stress are acknowledged contributors to neuronal damage, we investigated the pivotal role of lysosomes as a potential protective mechanism. Our research commenced with an exploration of epidermal growth factor (EGF) and its impact on lysosomal dynamics, particularly its neuroprotective potential against zinc-induced cytotoxicity. Using primary mouse cerebrocortical cultures, we observed the rapid induction of EGFR endocytosis triggered by EGF, resulting in a transient increase in lysosomal vesicles. Furthermore, EGF stimulated lysosomal biogenesis, evident through elevated expression of lysosomal-associated membrane protein 1 (LAMP-1) and the induction and activation of prominent lysosomal proteases, particularly cathepsin B (CTSB). This process of EGFR endocytosis was found to promote lysosomal augmentation, thus conferring protection against zinc-induced lysosomal membrane permeabilization (LMP) and subsequent neuronal death. Notably, the neuroprotective effects and lysosomal enhancement induced by EGF were almost completely reversed by the inhibition of clathrin-mediated and caveolin-mediated endocytosis pathways, along with the disruption of retrograde trafficking. Furthermore, tyrosine kinase inhibition of EGFR nullified EGFR endocytosis, resulting in the abrogation of EGF-induced lysosomal upregulation and neuroprotection. An intriguing aspect of our study is the successful replication of EGF’s neuroprotective effects through the overexpression of LAMP-1, which significantly reduced zinc-induced LMP and cell death, demonstrated in both primary mouse cerebrocortical neuronal cultures and human embryonic kidney (HEK) cells. Our research extended beyond zinc-induced neurotoxicity, as we observed EGF’s protective effects against other oxidative stressors linked to intracellular zinc release, including hydrogen peroxide (H2O2) and 1-methyl-4-phenylpyridinium ion (MPP+). Collectively, our findings unveil the intricate interplay between EGF-triggered EGFR endocytosis, lysosomal upregulation, an increase in the regulatory capacity for zinc homeostasis, and the subsequent alleviation of zinc-induced neurotoxicity. These results present promising avenues for therapeutic interventions to enhance neuroprotection by targeting lysosomal augmentation.
STING orchestrates microglia polarization via interaction with LC3 in autophagy after ischemia
Authors: Kong Lingqi , Xu Pengfei , Shen Nan , Li Wenyu , Li Rui , Tao Chunrong , Wang Guoping , Zhang Yan , Sun Wen , Hu Wei , Liu Xinfeng 
Published: November 2024

AbstractAutophagy has both protective and pathogenetic effects on injury caused by cerebral ischemia/reperfusion (I/R). Our previous research has indicated that stimulator of interferon genes (STING) could orchestrate microglia polarization following middle cerebral artery occlusion. However, it remains largely unexplored whether STING balances microglial polarization by regulating autophagy in brain I/R injury. Here, STING was observed to show an up-regulation in the microglia from mice subjected to experimental ischemic stroke. Strikingly, the deletion of STING led to the significant skewness of microglia activated by ischemia from a pro- to anti-inflammatory state and substantially alleviated ischemia-induced infarction and neuronal injury. In addition, STING-null mice can restore long-term neurobehavioral function. Then, the crosstalk between neuroinflammation and microglia autophagy was analyzed. The differential activity of autophagy in wild-type and STING-knockout (KO) mice or primary microglia was largely reversed when STING was restored in microglia. Irritating autophagy by rapamycin skewed the anti‑inflammatory state induced by STING-KO to a pro‑inflammatory state in microglia. Furthermore, microtubule-associated protein light-chain-3 (LC3) was identified as the key factor in the STING regulation of autophagy by glutathione-S-transferase (GST) pull-down analysis. Mechanically, STING can directly interact with LC3 through the STING transmembrane domain (1-139aa). Herein, current data determine the pivotal role of autophagy, specifically via LC3 protein, in the regulation of microglial phenotypic transformation by STING. These findings may provide a possible treatment target for delaying the progression of ischemic stroke.
Effect of genetically predicted sclerostin on cardiovascular biomarkers, risk factors, and disease outcomes
Authors: Alcalde-Herraiz Marta , Xie JunQing , Newby Danielle , Prats Clara , Gill Dipender , Gordillo-Marañón María , Prieto-Alhambra Daniel , Català Martí , Prats-Uribe Albert 
Published: November 2024

AbstractSclerostin inhibitors protect against osteoporotic fractures, but their cardiovascular safety remains unclear. We conducted a cis-Mendelian randomisation analysis to estimate the causal effect of sclerostin levels on cardiovascular risk factors. We meta-analysed three GWAS of sclerostin levels including 49,568 Europeans and selected 2 SNPs to be used as instruments. We included heel bone mineral density and hip fracture risk as positive control outcomes. Public GWAS and UK Biobank patient-level data were used for the study outcomes, which include cardiovascular events, risk factors, and biomarkers. Lower sclerostin levels were associated with higher bone mineral density and 85% reduction in hip fracture risk. However, genetically predicted lower sclerostin levels led to 25–85% excess coronary artery disease risk, 40% to 60% increased risk of type 2 diabetes, and worse cardiovascular biomarkers values, including higher triglycerides, and decreased HDL cholesterol levels. Results also suggest a potential (but borderline) association with increased risk of myocardial infarction. Our study provides genetic evidence of a causal relationship between reduced levels of sclerostin and improved bone health and fracture protection, but increased risk of cardiovascular events and risk factors.
Data-driven design of novel lightweight refractory high-entropy alloys with superb hardness and corrosion resistance
Authors: Gao Tianchuang , Gao Jianbao , Yang Shenglan , Zhang Lijun 
Published: November 2024

AbstractLightweight refractory high-entropy alloys (LW-RHEAs) hold significant potential in the fields of aviation, aerospace, and nuclear energy due to their low density, high strength, high hardness, and corrosion resistance. However, the enormous composition space has severely hindered the development of novel LW-RHEAs with excellent comprehensive performance. In this paper, an machine learning (ML)-based alloy design strategy combined with a multi-objective optimization method was proposed and applied for a rational design of Al-Nb-Ti-V-Zr-Cr-Mo-Hf LW-RHEAs. The quantitative relation of “composition-structure-property” was first established by ML modeling. Then, feature analysis reveals that Cr content greater than 12 at.% is a key criterion for alloys with high corrosion resistance. The phase structure, density, melting point, hardness and corrosion resistance of the alloys were screened layer by layer, and finally, three LW-RHEAs with superb hard and corrosion resistance were successfully designed. Key experimental validation indicates that three target alloys have densities around 6.5 g/cm3, and all alloys are disordered bcc_A2 single-phase with the highest hardness of 593 HV and the largest pitting potential of 2.5 VSCE, which far exceeds all the literature reports. The successful demonstration in this paper clearly demonstrates that the present design strategy driven by the ML technique should be generally applicable to other RHEA systems.
Systematic screening of 42 vancomycin-resistant Enterococcus faecium strains for resistance, biofilm, and desiccation in simulated microgravity
Authors: Arndt Franca , Siems Katharina , Walker Sarah V. , Bryan Noelle C. , Leuko Stefan , Moeller Ralf , Boschert Alessa L. 
Published: November 2024

AbstractVancomycin-resistant Enterococcus faecium (VRE) presents significant challenges in healthcare, particularly for hospitalized and immunocompromised patients, including astronauts with dysregulated immune function. We investigated 42 clinical E. faecium isolates in simulated microgravity (sim. µg) using a 2-D Clinostat, with standard gravity conditions (1 g) as a control. Isolates were tested against 22 antibiotics and characterized for biofilm formation and desiccation tolerance. Results showed varied responses in minimum inhibitory concentration (MIC) values for seven antibiotics after sim. µg exposure. Additionally, 55% of isolates showed a trend of increased biofilm production, and 59% improved desiccation tolerance. This investigation provides initial insights into E. faecium’s changes in response to simulated spaceflight, revealing shifts in antibiotic resistance, biofilm formation, and desiccation tolerance. The observed adaptability emphasizes the need to further understand VRE’s resilience to microgravity, which is crucial for preventing infections and ensuring crew health on future long-duration space missions.
Plasmodium vivax antigen candidate prediction improves with the addition of Plasmodium falciparum data
Authors: Chou Renee Ti , Ouattara Amed , Takala-Harrison Shannon , Cummings Michael P. 
Published: November 2024

AbstractIntensive malaria control and elimination efforts have led to substantial reductions in malaria incidence over the past two decades. However, the reduction in Plasmodium falciparum malaria cases has led to a species shift in some geographic areas, with P. vivax predominating in many areas outside of Africa. Despite its wide geographic distribution, P. vivax vaccine development has lagged far behind that for P. falciparum, in part due to the inability to cultivate P. vivax in vitro, hindering traditional approaches for antigen identification. In a prior study, we have used a positive-unlabeled random forest (PURF) machine learning approach to identify P. falciparum antigens based on features of known antigens for consideration in vaccine development efforts. Here we integrate systems data from P. falciparum (the better-studied species) to improve PURF models to predict potential P. vivax vaccine antigen candidates. We further show that inclusion of known antigens from the other species is critical for model performance, but the inclusion of only the unlabeled proteins from the other species can result in misdirection of the model toward predictors of species classification, rather than antigen identification. Beyond malaria, incorporating antigens from a closely related species may aid in vaccine development for emerging pathogens having few or no known antigens.
Cretaceous bird from Brazil informs the evolution of the avian skull and brain
Authors: Chiappe Luis M. , Navalón Guillermo , Martinelli Agustín G. , Carvalho Ismar de Souza , Miloni Santucci Rodrigo , Wu Yun-Hsin , Field Daniel J. 
Published: November 2024

AbstractA dearth of Mesozoic-aged, three-dimensional fossils hinders understanding of the origin of the distinctive skull and brain of modern (crown) birds1. Here we report Navaornis hestiae gen. et sp. nov., an exquisitely preserved fossil species from the Late Cretaceous of Brazil. The skull of Navaornis is toothless and large-eyed, with a vaulted cranium closely resembling the condition in crown birds; however, phylogenetic analyses recover Navaornis in Enantiornithes, a highly diverse clade of Mesozoic stem birds. Despite an overall geometry quantitatively indistinguishable from crown birds, the skull of Navaornis retains numerous plesiomorphies including a maxilla-dominated rostrum, an akinetic palate, a diapsid temporal configuration, a small cerebellum and a weakly expanded telencephalon. These archaic neurocranial traits are combined with a crown bird-like degree of brain flexion and a bony labyrinth comparable in shape to those of many crown birds but substantially larger. Altogether, the emergent cranial geometry of Navaornis shows an unprecedented degree of similarity between crown birds and enantiornithines, groups last sharing a common ancestor more than 130 million years ago2. Navaornis provides long-sought insight into the detailed cranial and endocranial morphology of stem birds phylogenetically crownward of Archaeopteryx, clarifying the pattern and timing by which the distinctive neuroanatomy of living birds was assembled.
Fluorspar to fluorochemicals upon low-temperature activation in water
Authors: Klose Immo , Patel Calum , Mondal Anirban , Schwarz Andrew , Pupo Gabriele , Gouverneur Véronique 
Published: November 2024

AbstractThe dangerous chemical hydrogen fluoride sits at the apex of the fluorochemical industry, but the substantial hazards linked to its production under harsh conditions (above 300 degrees Celsius) and transport are typically contracted to specialists. All fluorochemicals for applications, including refrigeration, electric transportation, agrochemicals and pharmaceuticals, are prepared from fluorspar (CaF2) through a procedure that generates highly dangerous hydrogen fluoride1–5. Here we report a mild method to obtain fluorochemicals directly from fluorspar, bypassing the necessity to manufacture hydrogen fluoride. Acid-grade fluorspar (more than 97 per cent CaF2) is treated with the fluorophilic Lewis acid boric acid (B(OH)3) or silicon dioxide (SiO2), in the presence of oxalic acid, a Brønsted acid that is highly effective for Ca2+ sequestration. This scalable process carried out in water at low temperature (below 50 degrees Celsius) enables access to widely used fluorochemicals, including tetrafluoroboric acid, alkali metal fluorides, tetraalkylammonium fluorides and fluoro(hetero)arenes. The replacement of oxalic acid with sulfuric acid gave comparable results for B(OH)3, but was not as effective when the fluorophilic Lewis acid was SiO2. A similar process also works with the lower-purity metspar. The production of fluorochemicals directly from fluorspar offers the possibility of decentralized manufacturing—an attractive model for the fluorochemical industry. With the renewed interest in innovative methods to synthesize oxalic acid via carbon dioxide capture and biomass6,7, and the challenges posed by our dependence on fossil fuels for sulfur and therefore sulfuric acid supply8,9, our technology may represent a departure towards a sustainable fluorochemical industry.
Adult skull bone marrow is an expanding and resilient haematopoietic reservoir
Authors: Koh Bong Ihn , Mohanakrishnan Vishal , Jeong Hyun-Woo , Park Hongryeol , Kruse Kai , Choi Young Jun , Nieminen-Kelhä Melina , Kumar Rahul , Pereira Raquel S. , Adams Susanne , Lee Hyuek Jong , Bixel M. Gabriele , Vajkoczy Peter , Krause Daniela S. , Adams Ralf H. 
Published: November 2024

AbstractThe bone marrow microenvironment is a critical regulator of haematopoietic stem cell self-renewal and fate1. Although it is appreciated that ageing, chronic inflammation and other insults compromise bone marrow function and thereby negatively affect haematopoiesis2, it is not known whether different bone compartments exhibit distinct microenvironmental properties and functional resilience. Here we use imaging, pharmacological approaches and mouse genetics to uncover specialized properties of bone marrow in adult and ageing skull. Specifically, we show that the skull bone marrow undergoes lifelong expansion involving vascular growth, which results in an increasing contribution to total haematopoietic output. Furthermore, skull is largely protected against major hallmarks of ageing, including upregulation of pro-inflammatory cytokines, adipogenesis and loss of vascular integrity. Conspicuous rapid and dynamic changes to the skull vasculature and bone marrow are induced by physiological alterations, namely pregnancy, but also pathological challenges, such as stroke and experimental chronic myeloid leukaemia. These responses are highly distinct from femur, the most extensively studied bone marrow compartment. We propose that skull harbours a protected and dynamically expanding bone marrow microenvironment, which is relevant for experimental studies and, potentially, for clinical treatments in humans.