bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Geographical Analysis of Access to Trauma Centers from US National Parks in 2018
Authors: Lu Lily Y. , Robichaud Sabrina N. , Boggs Krislyn M. , Bedell Brandon R. , Cash Rebecca E. , Sullivan Ashley F. , Harris N. Stuart , Camargo Carlos A. 
Published: October 2022

AbstractIntroduction:Millions of people visit US national parks annually to engage in recreational wilderness activities, which can occasionally result in traumatic injuries that require timely, high-level care. However, no study to date has specifically examined timely access to trauma centers from national parks. This study aimed to examine the accessibility of trauma care from national parks by calculating the travel time by ground and air from each park to its nearest trauma center. Using these calculations, the percentage of parks by census region with timely access to a trauma center was determined.Methods:This was a cross-sectional study analyzing travel times by ground and air transport between national parks and their closest adult advanced trauma center (ATC) in 2018. A list of parks was compiled from the National Parks Service (NPS) website, and the location of trauma centers from the 2018 National Emergency Department Inventory (NEDI)-USA database. Ground and air transport times were calculated using Google Maps and ArcGIS, with medians and interquartile ranges reported by US census region. Percentage of parks by region with timely trauma center access—defined as access within 60 minutes of travel time—were determined based on these calculated travel times.Results:In 2018, 83% of national parks had access to an adult ATC within 60 minutes of air travel, while only 26% had timely access by ground. Trauma center access varied by region, with median travel times highest in the West for both air and ground transport. At a national level, national parks were unequally distributed, with the West housing the most parks of all regions.Conclusion:While most national parks had timely access to a trauma center by air travel, significant gaps in access remain for ground, the extent of which varies greatly by region. To improve the accessibility of trauma center expertise from national parks, the study highlights the potential that increased implementation of trauma telehealth in emergency departments (EDs) may have in bridging these gaps.
Population-level salt intake in the WHO European Region in 2022: a systematic review
Authors: Kwong Edwin Jit Leung , Whiting Stephen , Bunge Anne Charlotte , Leven Yana , Breda Joao , Rakovac Ivo , Cappuccio Francesco Paolo , Wickramasinghe Kremlin 
Published: October 2022

AbstractObjective:The WHO recommends that adults consume less than 5 g of salt per day to reduce the risk of CVD. This study aims to examine the average population daily salt intake in the fifty-three Member States of the WHO European Region.Design:A systematic review was conducted to examine the most up-to-date salt intake data for adults published between 2000 and 2022. Data were obtained from peer-reviewed and grey literature, WHO surveys and studies, as well as from national and global experts.Setting:The fifty-three Member States of the WHO European Region.Participants:People aged 12 years or more.Results:We identified fifty studies published between 2010 and 2021. Most countries in the WHO European Region (n 52, 98 %) reported salt intake above WHO recommended maximum levels. In almost all countries (n 52, 98 %), men consume more salt than women, ranging between 5·39 and 18·51 g for men and 4·27 and 16·14 g for women. Generally, Western and Northern European countries have the lowest average salt intake, whilst Eastern European and Central Asian countries have the highest average. Forty-two percentage of the fifty-three countries (n 22) measured salt intake using 24 h urinary collection, considered the gold standard method.Conclusions:This study found that salt intakes in the WHO European Region are significantly above WHO recommended levels. Most Member States of the Region have conducted some form of population salt intake. However, methodologies to estimate salt intake are highly disparate and underestimations are very likely.
A simple approach to estimate long-term interest rates
Authors: Driessen Joost , Nijman Theo E. , Simon Zorka 
Published: October 2022

AbstractWe propose an easy to implement yield curve extrapolation method to determine long-term interest rates suitable for regulatory valuation. We empirically evaluate this approach for the German nominal bond market, by estimating the model on bonds with maturities up to 20 years and assessing the out-of-sample performance for bonds with maturities beyond 20 years. Even though observed long-term yields are somewhat lower than the predicted yields, the method performs quite well empirically given its simplicity. We perform a case study on pension fund liability valuation and show that our proposed method would have a substantial impact on liability values.
Climate Change Impacts Can Be Differentially Perceived Across Time Scales: A Study Among the Tuareg of the Algerian Sahara
Authors: Miara M. D. , Negadi M. , Tabak S. , Bendif H. , Dahmani W. , Ait Hammou M. , Sahnoun T. , Snorek J. , Porcher V. , Reyes‐García V. , Teixidor‐Toneu I. 
Published: October 2022

AbstractAs an Indigenous community of Algeria and the broader Sahel, the Tuareg hold unique ecological knowledge, which might contribute to broader models of place‐based climate change impacts. Between January and April 2019, we carried out semi‐structured interviews (N = 23) and focus group discussions (N = 3) in five villages of the province of Illizi, Algeria, to document the local Tuareg community's timeline and ecological calendar, both of which are instruments used to understand place‐based reports of climate change impacts. The livelihoods of the Tuareg of Illizi are finely tuned to climate variability as reflected in changes reported in the cadence of events in their ecological calendar (marked by cyclical climatic and religious events). Participants reported rain and temperature irregularities and severe drought events, which have impacted their pastoral and semi‐pastoral livelihoods. These reports are aligned with scientifically measured climate observations and predictions. Paradoxically, although participants recall with detail the climatic disasters that happened in the region over the last century, the Tuareg do not explicitly report decadal trends in the frequency of extreme events. The differential perception of climate change impacts across scales can have important implications for undertaking climate change adaptation measures.
Use of Machine Learning to Estimate Statistics of the Posterior Distribution in Probabilistic Inverse Problems—An Application to Airborne EM Data
Authors: Hansen T. M. , Finlay C. C. 
Published: October 2022

AbstractThe solution to a probabilistic inverse problem is the posterior probability distribution for which a full analytic expression is rarely possible. Sampling methods are therefore often used to generate a sample from the posterior. Decision‐makers may be interested in the probability of features related to model parameters (e.g., existence of pollution or the cumulative clay thickness) rather than the individual realizations themselves. Such features and their associated uncertainty, are simple to compute once a sample from the posterior distribution has been generated. However, sampling methods are often associated with high computational costs, especially when the prior and posterior distribution is non‐trivial (non‐Gaussian), and when the inverse problem is non‐linear. Here we demonstrate how to use a neural network to directly estimate posterior statistics of continuous or discrete features of the posterior distribution. The method is illustrated on a probabilistic inversion of airborne EM data from Morrill Nebraska, where the forward problem is nonlinear and the prior information is non‐Gaussian. Once trained the application of the network is fast, with results similar to those obtained using much slower sampling methods.
Assimilation of Remotely Sensed Leaf Area Index Enhances the Estimation of Anthropogenic Irrigation Water Use
Authors: Nie Wanshu , Kumar Sujay V. , Peters‐Lidard Christa D. , Zaitchik Benjamin F. , Arsenault Kristi R. , Bindlish Rajat , Liu Pang‐Wei 
Published: October 2022

AbstractRepresentation of irrigation in Earth System Models has advanced over the past decade, yet large uncertainties persist in the effective simulation of irrigation practices, particularly over locations where the on‐ground practices and climate impacts are less reliably known. Here we investigate the utility of assimilating remotely sensed vegetation data for improving irrigation water use and associated fluxes within a land surface model. We show that assimilating optical sensor‐based leaf area index estimates significantly improves the simulation of irrigation water use when compared to the USGS ground reports. For heavily irrigated areas, assimilation improves the evaporative fluxes and gross primary production (GPP) simulations, with the median correlation increasing by 0.1–1.1 and 0.3–0.6, respectively, as compared to the reference datasets. Further, bias improvements in the range of 14–35 mm mo−1 and 10–82 g m−2 mo−1 are obtained in evaporative fluxes and GPP as a result of incorporating vegetation constraints, respectively. These results demonstrate that the use of remotely sensed vegetation data is an effective, observation‐informed, globally applicable approach for simulating irrigation and characterizing its impacts on water and carbon states.
METTL3 mediates chemoresistance by enhancing AML homing and engraftment via ITGA4
Authors: Li Mingying , Ye Jingjing , Xia Yuan , Li Meng , Li Guosheng , Hu Xiang , Su Xiuhua , Wang Dongmei , Zhao Xin , Lu Fei , Li Jingxin , Ma Daoxin , Sun Tao , Ji Chunyan 
Published: October 2022

AbstractChemoresistant leukemia relapse is one of the most common causes of death for acute myeloid leukemia (AML) patients and the homing/engraftment in bone marrow (BM) are crucial steps for AML cells to acquire chemoresistance by interacting with stromal cell components. No crosstalk between m6A modification and homing/engraftment has been reported. Here, we performed comprehensive high-throughput analyses, including RNA sequencing of CR (complete remission) and relapsed AML patients, and reverse-phase protein arrays of chemoresistant cells to identify METTL3 as a key player regulating AML chemoresistance. Then, METTL3-mediated m6A modification was proved to induce the chemoresistance in vitro and in vivo. Furthermore, AML homing/engraftment was discovered being enhanced by upregulated-METTL3 in chemoresistant cells. And the homing/engraftment and drug-resistance associated phenotypes of chemoresistant cells could be reversed by a METTL3 inhibitor. Mechanistically, METTL3 extended the half-life of ITGA4 mRNA by m6A methylation, and then, increased expression of ITGA4 protein to enhance homing/engraftment of AML cells. The results provide insights into the function of m6A modification on the interaction between AML cells and BM niches and clarify the relationship between METTL3 and AML homing/engraftment, suggesting a therapeutic strategy for the treatment of refractory/relapsed AML with METTL3 inhibitors.
Central nervous system involvement in childhood acute lymphoblastic leukemia: challenges and solutions
Authors: Thastrup Maria , Duguid Alasdair , Mirian Christian , Schmiegelow Kjeld , Halsey Christina 
Published: October 2022

AbstractDelivery of effective anti-leukemic agents to the central nervous system (CNS) is considered essential for cure of childhood acute lymphoblastic leukemia. Current CNS-directed therapy comprises systemic therapy with good CNS-penetration accompanied by repeated intrathecal treatments up to 26 times over 2–3 years. This approach prevents most CNS relapses, but is associated with significant short and long term neurotoxicity. Despite this burdensome therapy, there have been no new drugs licensed for CNS-leukemia since the 1960s, when very limited anti-leukemic agents were available and there was no mechanistic understanding of leukemia survival in the CNS. Another major barrier to improved treatment is that we cannot accurately identify children at risk of CNS relapse, or monitor response to treatment, due to a lack of sensitive biomarkers. A paradigm shift in treating the CNS is needed. The challenges are clear – we cannot measure CNS leukemic load, trials have been unable to establish the most effective CNS treatment regimens, and non-toxic approaches for relapsed, refractory, or intolerant patients are lacking. In this review we discuss these challenges and highlight research advances aiming to provide solutions. Unlocking the potential of risk-adapted non-toxic CNS-directed therapy requires; (1) discovery of robust diagnostic, prognostic and response biomarkers for CNS-leukemia, (2) identification of novel therapeutic targets combined with associated investment in drug development and early-phase trials and (3) engineering of immunotherapies to overcome the unique challenges of the CNS microenvironment. Fortunately, research into CNS-ALL is now making progress in addressing these unmet needs: biomarkers, such as CSF-flow cytometry, are now being tested in prospective trials, novel drugs are being tested in Phase I/II trials, and immunotherapies are increasingly available to patients with CNS relapses. The future is hopeful for improved management of the CNS over the next decade.
Zymosan-A promotes the regeneration of intestinal stem cells by upregulating ASCL2
Authors: Du Jicong , Fang Lan , Zhao Jianpeng , Yu Yike , Feng Zhenlan , Wang Yuedong , Cheng Ying , Li Bailong , Gao Fu , Liu Cong 
Published: October 2022

AbstractIntestinal stem cells (ISCs) are responsible for intestinal tissue homeostasis and are important for the regeneration of the damaged intestinal epithelia. Through the establishment of ionizing radiation (IR) induced intestinal injury model, we found that a TLR2 agonist, Zymosan-A, promoted the regeneration of ISCs in vivo and in vitro. Zymosan-A improved the survival of abdominal irradiated mice (81.82% of mice in the treated group vs. 30% of mice in the PBS group), inhibited the radiation damage of intestinal tissue, increased the survival rate of intestinal crypts and the number of ISCs after lethal IR in vivo. Through organoid experiments, we found that Zymosan-A promoted the proliferation and differentiation of ISCs after IR. Remarkably, the results of RNA sequencing and Western Blot (WB) showed that Zymosan-A reduced IR-induced intestinal injury via TLR2 signaling pathway and Wnt signaling pathway and Zymosan-A had no radioprotection on TLR2 KO mice, suggesting that Zymosan-A may play a radioprotective role by targeting TLR2. Moreover, our results revealed that Zymosan-A increased ASCL2, a transcription factor of ISCs, playing a core role in the process of Zymosan-A against IR-induced intestinal injury and likely contributing to the survival of intestinal organoids post-radiation. In conclusion, we demonstrated that Zymosan-A promotes the regeneration of ISCs by upregulating ASCL2.
Atomic resolution protein allostery from the multi-state structure of a PDZ domain
Authors: Ashkinadze Dzmitry , Kadavath Harindranath , Pokharna Aditya , Chi Celestine N. , Friedmann Michael , Strotz Dean , Kumari Pratibha , Minges Martina , Cadalbert Riccardo , Königl Stefan , Güntert Peter , Vögeli Beat , Riek Roland 
Published: October 2022

AbstractRecent methodological advances in solution NMR allow the determination of multi-state protein structures and provide insights into structurally and dynamically correlated protein sites at atomic resolution. This is demonstrated in the present work for the well-studied PDZ2 domain of protein human tyrosine phosphatase 1E for which protein allostery had been predicted. Two-state protein structures were calculated for both the free form and in complex with the RA-GEF2 peptide using the exact nuclear Overhauser effect (eNOE) method. In the apo protein, an allosteric conformational selection step comprising almost 60% of the domain was detected with an “open” ligand welcoming state and a “closed” state that obstructs the binding site by changing the distance between the β-sheet 2, α-helix 2, and sidechains of residues Lys38 and Lys72. The observed induced fit-type apo-holo structural rearrangements are in line with the previously published evolution-based analysis covering ~25% of the domain with only a partial overlap with the protein allostery of the open form. These presented structural studies highlight the presence of a dedicated highly optimized and complex dynamic interplay of the PDZ2 domain owed by the structure-dynamics landscape.
Viral transduction of primary human lymphoma B cells reveals mechanisms of NOTCH-mediated immune escape
Authors: Mangolini Maurizio , Maiques-Diaz Alba , Charalampopoulou Stella , Gerhard-Hartmann Elena , Bloehdorn Johannes , Moore Andrew , Giachetti Giorgia , Lu Junyan , Roamio Franklin Valar Nila , Chilamakuri Chandra Sekkar Reddy , Moutsopoulos Ilias , Rosenwald Andreas , Stilgenbauer Stephan , Zenz Thorsten , Mohorianu Irina , D’Santos Clive , Deaglio Silvia , Hodson Daniel J. , Martin-Subero Jose I. , Ringshausen Ingo 
Published: October 2022

AbstractHotspot mutations in the PEST-domain of NOTCH1 and NOTCH2 are recurrently identified in B cell malignancies. To address how NOTCH-mutations contribute to a dismal prognosis, we have generated isogenic primary human tumor cells from patients with Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), differing only in their expression of the intracellular domain (ICD) of NOTCH1 or NOTCH2. Our data demonstrate that both NOTCH-paralogs facilitate immune-escape of malignant B cells by up-regulating PD-L1, partly dependent on autocrine interferon-γ signaling. In addition, NOTCH-activation causes silencing of the entire HLA-class II locus via epigenetic regulation of the transcriptional co-activator CIITA. Notably, while NOTCH1 and NOTCH2 govern similar transcriptional programs, disease-specific differences in their expression levels can favor paralog-specific selection. Importantly, NOTCH-ICD also strongly down-regulates the expression of CD19, possibly limiting the effectiveness of immune-therapies. These NOTCH-mediated immune escape mechanisms are associated with the expansion of exhausted CD8+ T cells in vivo.
Systems-biology analysis of rheumatoid arthritis fibroblast-like synoviocytes implicates cell line-specific transcription factor function
Authors: Ainsworth Richard I. , Hammaker Deepa , Nygaard Gyrid , Ansalone Cecilia , Machado Camilla , Zhang Kai , Zheng Lina , Carrillo Lucy , Wildberg Andre , Kuhs Amanda , Svensson Mattias N. D. , Boyle David L. , Firestein Gary S. , Wang Wei 
Published: October 2022

AbstractRheumatoid arthritis (RA) is an immune-mediated disease affecting diarthrodial joints that remains an unmet medical need despite improved therapy. This limitation likely reflects the diversity of pathogenic pathways in RA, with individual patients demonstrating variable responses to targeted therapies. Better understanding of RA pathogenesis would be aided by a more complete characterization of the disease. To tackle this challenge, we develop and apply a systems biology approach to identify important transcription factors (TFs) in individual RA fibroblast-like synoviocyte (FLS) cell lines by integrating transcriptomic and epigenomic information. Based on the relative importance of the identified TFs, we stratify the RA FLS cell lines into two subtypes with distinct phenotypes and predicted active pathways. We biologically validate these predictions for the top subtype-specific TF RARα and demonstrate differential regulation of TGFβ signaling in the two subtypes. This study characterizes clusters of RA cell lines with distinctive TF biology by integrating transcriptomic and epigenomic data, which could pave the way towards a greater understanding of disease heterogeneity.
Tumor-produced and aging-associated oncometabolite methylmalonic acid promotes cancer-associated fibroblast activation to drive metastatic progression
Authors: Li Zhongchi , Low Vivien , Luga Valbona , Sun Janet , Earlie Ethan , Parang Bobak , Shobana Ganesh Kripa , Cho Sungyun , Endress Jennifer , Schild Tanya , Hu Mengying , Lyden David , Jin Wenbing , Guo Chunjun , Dephoure Noah , Cantley Lewis C. , Laughney Ashley M. , Blenis John 
Published: October 2022

AbstractThe systemic metabolic shifts that occur during aging and the local metabolic alterations of a tumor, its stroma and their communication cooperate to establish a unique tumor microenvironment (TME) fostering cancer progression. Here, we show that methylmalonic acid (MMA), an aging-increased oncometabolite also produced by aggressive cancer cells, activates fibroblasts in the TME, which reciprocally secrete IL-6 loaded extracellular vesicles (EVs) that drive cancer progression, drug resistance and metastasis. The cancer-associated fibroblast (CAF)-released EV cargo is modified as a result of reactive oxygen species (ROS) generation and activation of the canonical and noncanonical TGFβ signaling pathways. EV-associated IL-6 functions as a stroma-tumor messenger, activating the JAK/STAT3 and TGFβ signaling pathways in tumor cells and promoting pro-aggressive behaviors. Our findings define the role of MMA in CAF activation to drive metastatic reprogramming, unveiling potential therapeutic avenues to target MMA at the nexus of aging, the tumor microenvironment and metastasis.
Low-bias photoelectrochemical water splitting via mediating trap states and small polaron hopping
Authors: Wu Hao , Zhang Lei , Du Aijun , Irani Rowshanak , van de Krol Roel , Abdi Fatwa F. , Ng Yun Hau 
Published: October 2022

AbstractMetal oxides are promising for photoelectrochemical (PEC) water splitting due to their robustness and low cost. However, poor charge carrier transport impedes their activity, particularly at low-bias voltage. Here we demonstrate the unusual effectiveness of phosphorus doping into bismuth vanadate (BiVO4) photoanode for efficient low-bias PEC water splitting. The resulting BiVO4 photoanode shows a separation efficiency of 80% and 99% at potentials as low as 0.6 and 1.0 VRHE, respectively. Theoretical simulation and experimental analysis collectively verify that the record performance originates from the unique phosphorus-doped BiVO4 configuration with concurrently mediated carrier density, trap states, and small polaron hopping. With NiFeOx cocatalyst, the BiVO4 photoanode achieves an applied bias photon-to-current efficiency of 2.21% at 0.6 VRHE. The mechanistic understanding of the enhancement of BiVO4 properties provides key insights in trap state passivation and polaron hopping for most photoactive metal oxides.