bluuebunny/crossref_metadata_2025_split huggingface dataset:
Navigating the complex terrain of healthcare systems in Sub-Saharan Africa: challenges and opportunities for progress
Authors: Agyei Eunice , Kumah Emmanuel 
Published: June 2024

AbstractSub-Saharan Africa (SSA) faces a complex healthcare landscape characterized by a multitude of challenges and opportunities. This paper delves into the pressing issues confronting SSA’s healthcare systems and presents a roadmap for sustainable improvement. The region grapples with a disproportionate burden of infectious diseases, such as HIV/AIDS, tuberculosis, and malaria, alongside a rising prevalence of non-communicable diseases. A severe shortage of trained healthcare professionals, urban–rural healthcare disparities, and financial barriers further compound the situation. However, amid these challenges lie significant opportunities for progress. Three key pillars for transforming healthcare in SSA are highlighted: strengthening healthcare financing, improving governance and policy frameworks, and enhancing healthcare infrastructure and technology. SSA stands at a crossroads in its pursuit of improved healthcare systems and overall well-being. Addressing these opportunities through the joint efforts of governments, international organizations, and communities can create an accessible, accountable, and technologically advanced healthcare system. Investments made today will yield substantial dividends in terms of improved health outcomes, economic growth, and societal development. SSA has the potential to transform its healthcare landscape and embark on a path towards a healthier and more prosperous future.
Predicting Flood Event Class Using a Novel Class Membership Function and Hydrological Modeling
Authors: Zhang Yongyong , Zhang Yongqiang , Zhai Xiaoyan , Xia Jun , Tang Qiuhong , Zhao Tongtiegang , Wang Wei 
Published: June 2024

AbstractPredicting flood event classes aids in the comprehensive investigation of flood behavior dynamics and supports flood early warning and emergency plan development. Existing studies have mainly focused on historical flood event classification and the prediction of flood hydrographs or certain metrics (e.g., magnitude and timing) but have not focused on predicting flood event classes. Our study proposes a new approach for predicting flood event classes based on the class membership functions of flood regime metrics and hydrological modeling. The approach is validated using 1446 unimpacted flood events in 68 headstream catchments widely distributed across China. The new approach performs well, with class hit rates of 68.3% ± 0.4% for all events; 65.8% ± 0.6%, 56.8% ± 0.9%, and 69.5% ± 0.9% for the small, moderate and high spike flood event classes, respectively; and 82.5% ± 1.2% and 75.4% ± 1.1% for the moderate and high dumpy flood event classes, respectively. Furthermore, it performs better in the basins of northern China than in those of southern China, particularly for the small spike flood event class in the Songliao and Yellow River Basins, with hit rates of 80.0% ± 3.2% and 78.8% ± 3.2%, respectively. Our results indicate that the new approach will help improve the prediction performance of flood events and their corresponding classes, and provide deep insights into the comprehensive dynamic patterns of flood events for early warning and control management.
Quantifying the Impact of Internal Variability on the CESM2 Control Algorithm for Stratospheric Aerosol Injection
Authors: Connolly Charlotte , Prewett Emily , Barnes Elizabeth A. , Hurrell James W. 
Published: June 2024

AbstractEarth system models are powerful tools to simulate the climate response to hypothetical climate intervention strategies, such as stratospheric aerosol injection (SAI). Recent simulations of SAI implement a tool from control theory, called a controller, to determine the quantity of aerosol to inject into the stratosphere to reach or maintain specified global temperature targets, such as limiting global warming to 1.5°C above pre‐industrial temperatures. This work explores how internal (unforced) climate variability can impact controller‐determined injection amounts using the Assessing Responses and Impacts of Solar climate intervention on the Earth system with Stratospheric Aerosol Injection (ARISE‐SAI) simulations. Since the ARISE‐SAI controller determines injection amounts by comparing global annual‐mean surface temperature to predetermined temperature targets, internal variability that impacts temperature can impact the total injection amount as well. Using an offline version of the ARISE‐SAI controller and data from Earth system model simulations, we quantify how internal climate variability and volcanic eruptions impact injection amounts. While idealized, this approach allows for the investigation of a large variety of climate states without additional simulations and can be used to attribute controller sensitivities to specific modes of internal variability.
The Global Biogeochemical Cycle of the Rare Earth Elements
Authors: Hatje V. , Schijf J. , Johannesson K. H. , Andrade R. , Caetano M. , Brito P. , Haley B. A. , Lagarde M. , Jeandel C. 
Published: June 2024

AbstractTo improve our understanding and guide future studies and applications, we review the biogeochemistry of the rare earth elements (REE). The REEs, which form a chemically uniform group due to their nearly identical physicochemical properties, include the lanthanide series elements plus scandium (Sc) and yttrium (Y). These elements, in conjunction with the neodymium isotopes, are powerful tools for understanding key oceanic, terrestrial, biological and even anthropogenic processes. Furthermore, their unique properties render them essential for various technological processes and products. Here, we delve into the characteristics of REE biogeochemistry and discuss normalization procedures and REE anomalies. We also examine the aqueous speciation of REEs, contributing to a better understanding of their behavior in aquatic settings, including the role of neodymium isotopes. We then focus on their environmental distribution, fractionation, and controlling processes in different environmental systems across the land‐ocean continuum. In addition, we analyze sinks, sources, and the mobility of REEs, providing insights into their behavior in these environments. We further investigate the sources of anthropogenic REEs and their bioavailability, bioaccumulation, and transfer along food webs. We also explore the potential effects of climate change on the cycling, mobility and bioavailability of REEs, underlining the importance of current research in this evolving field. In summary, we provide a comprehensive review of REE behavior in the environment, from their properties and roles to their distribution and anthropogenic impacts, offering valuable insights and pinpointing key knowledge gaps.
Tectonically Controlled Establishment of Modern‐Like Precipitation Patterns in East and Central Asia During the Early Late Miocene
Authors: Zhang Tao , Han Wenxia , Tian Qian , Zhang Jian , Kemp David B. , Wang Zhixiang , Yan Xinting , Mai Li , Fang Xiaomin , Ogg James 
Published: June 2024

AbstractDeciphering how modern precipitation patterns became established in monsoon‐dominated East Asia and the arid interior Asia is crucial for predicting future precipitation trends under accelerated global warming and increased climate extremes. However, this effort is hindered by a scarcity of quantitative paleo‐precipitation data in this region. Here we reconstruct the pattern of Middle to Late Miocene paleo‐precipitation across an east‐to‐west transect from the summer monsoon‐dominated East Asian region through the transition zone and into interior Asia. Our work is based on a newly established precipitation calculation equation and quantitative pollen‐based precipitation conversion. Analysis indicates a common trend of precipitation across the studied region prior to ca, 11 Ma, followed by a clear divergence of precipitation variations between East and interior Asia since at least 11–9 Ma. This divergence is characterized by increasing precipitation in East Asia, but a coeval decrease in rainfall in the transition zone and interior Asia. The timing of this precipitation divergence was contemporaneous with intense tectonic activity in the northern Tibetan Plateau, which differentially affected the efficacy of water vapor transport into East and interior Asia. Modeling work using different topographic settings corroborates this tectonic influence. Our study demonstrates the early establishment of modern‐like precipitation patterns in East‐interior Asia at least in the early Late Miocene.
EMM EMUS Observations of FUV Aurora on Mars: Dependence on Magnetic Topology, Local Time, and Season
Authors: Chirakkil Krishnaprasad , Lillis Robert J. , Deighan Justin , Chaffin Michael S. , Jain Sonal K. , Brain David A. , Fillingim Matthew O. , Susarla Raghuram , Holsclaw Greg , Fang Xiaohua , Schneider Nick M. , AlMazmi Hoor , AlMatroushi Hessa , Gacesa Marko , El‐Kork Nayla , Thiemann Ed , Halekas Jasper S. 
Published: June 2024

AbstractWe present a comprehensive study of the nightside aurora phenomenon on Mars, utilizing observations from EMUS onboard Emirates Mars Mission. The oxygen emission at 130.4 nm is by far the brightest FUV auroral emission line observed at Mars. Our statistical analysis reveals geographic, solar zenith angle, local time, and seasonal dependencies of auroral occurrence. Higher occurrence of aurora is observed in regions of open magnetic topology, where crustal magnetic fields are either very weak or both strong and vertical. Aurora occurs more frequently closer to the terminator and is more likely on the dusk side than on the dawn side of the night hemisphere. A pronounced auroral feature appears close to midnight local times in the southern hemisphere, consistent with the spot of energetic electron fluxes previously identified in the Mars Global Surveyor data. This auroral spot is more frequent after midnight than before. Additionally, some regions on Mars are “aurora voids” where essentially no aurora occurs. Aurora exhibits a seasonal dependence, with a major enhancement near perihelion. Non–crustal field aurora additionally shows a secondary enhancement near Ls 30°. This seasonal variability is a combination of the variability in ionospheric photoelectrons and thermospheric atomic oxygen abundance. Auroral occurrence also shows an increase with the rise of Solar Cycle 25. The brightest auroral pixels are observed during space weather events such as Coronal Mass Ejections and Stream Interaction Regions. These observations not only shed light on where and when Martian aurora occurs, but also add to our understanding of Mars' magnetic environment and its interaction with the heliosphere.
Bringing Statistics to Storylines: Rare Event Sampling for Sudden, Transient Extreme Events
Authors: Finkel Justin , O’Gorman Paul A. 
Published: June 2024

AbstractA leading goal for climate science and weather risk management is to accurately model both the physics and statistics of extreme events. These two goals are fundamentally at odds: the higher a computational model's resolution, the more expensive are the ensembles needed to capture accurate statistics in the tail of the distribution. Here, we focus on events that are localized in space and time, such as heavy precipitation events, which can start suddenly and decay rapidly. We advance a method for sampling such events more efficiently than straightforward climate model simulation. Our method combines elements of two existing approaches: adaptive multilevel splitting (AMS), a rare event algorithm that generates rigorous statistics but fails to enhance the sampling of sudden, transient extremes; and “ensemble boosting,” which generates physically plausible storylines of these events but not their statistics. We modify AMS by splitting trajectories well in advance of the event's onset, following the approach of ensemble boosting. Early splitting requires a rejection step that reduces efficiency, but it is critical for amplifying and diversifying simulated events in tests with the Lorenz‐96 model, for which we demonstrate improved sampling of extreme local energy fluctuations by approximately a factor of 10 relative to direct sampling. Our method is related to previous algorithms, including subset simulation and anticipated AMS, but is distinctly tailored to handle bursting events caused by chaotic traveling waves. Our work makes progress toward the goal of efficiently sampling such transient local extremes in atmospheric models.
The contract between NHS dentistry and communities and how this varies by neighbourhood types
Authors: Clark Stephen 
Published: June 2024

AbstractIntroduction There is a growing concern that the NHS's ability to deliver dental care is not keeping pace with population growth. Also, existing capacity may not be evenly distributed, potentially creating dental deserts in some neighbourhoods.Aims This study aims to explore recent trends in NHS general practice dental capacity in England and analyse if these trends vary depending on neighbourhood context.Design This research employs a descriptive analysis of time trends.Materials and methods The study uses data on NHS-contracted capacity in England, measured in units of dental activity (UDAs). These UDAs are geo-located to neighbourhood types using practice postcodes. Changes in the populations of these neighbourhoods provide context for the capacity trends.Results Some trends remain stable over time, albeit at insufficient levels. Rural areas continue to have the lowest capacity for NHS dental treatments. Additionally, areas with previously generous provision are experiencing significant percentage decreases in capacity.Discussion To prevent the formation of dental deserts, two critical issues require attention: firstly, the accessibility of NHS treatment and how it varies across urban/suburban and rural neighbourhoods; secondly, balancing supply and demand by matching the supply of dental care with the demand, conditioned by socio-economic and socio-demographic factors within different neighbourhoods.
RANKL/RANK signaling recruits Tregs via the CCL20–CCR6 pathway and promotes stemness and metastasis in colorectal cancer
Authors: Ouyang Jing , Hu Shuang , Zhu Qingqing , Li Chenxin , Kang Tingting , Xie Wenlin , Wang Yun , Li Yan , Lu Yingsi , Qi Junhua , Xia Ming , Chen Jinrun , Yang Yingqian , Sun Yazhou , Gao Tianshun , Ye Liping , Liang Qian , Pan Yihang , Zhu Chengming 
Published: June 2024

AbstractTNF receptor superfamily member 11a (TNFRSF11a, RANK) and its ligand TNF superfamily member 11 (TNFRSF11, RANKL) are overexpressed in many malignancies. However, the clinical importance of RANKL/RANK in colorectal cancer (CRC) is mainly unknown. We examined CRC samples and found that RANKL/RANK was elevated in CRC tissues compared with nearby normal tissues. A higher RANKL/RANK expression was associated with a worse survival rate. Furthermore, RANKL was mostly produced by regulatory T cells (Tregs), which were able to promote CRC advancement. Overexpression of RANK or addition of RANKL significantly increased the stemness and migration of CRC cells. Furthermore, RANKL/RANK signaling stimulated C-C motif chemokine ligand 20 (CCL20) production by CRC cells, leading to Treg recruitment and boosting tumor stemness and malignant progression. This recruitment process was accomplished by CCL20–CCR6 interaction, demonstrating a connection between CRC cells and immune cells. These findings suggest an important role of RANKL/RANK in CRC progression, offering a potential target for CRC prevention and therapy.
ALKBH4 impedes 5-FU Sensitivity through suppressing GSDME induced pyroptosis in gastric cancer
Authors: Jiang Xin , Zhu Zhiman , Ding Lina , Du Wenqi , Pei Dongsheng 
Published: June 2024

Abstract5-Fluorouracil (5-FU) is the primary treatment option for advanced gastric cancer. However, the current challenge lies in the absence of validated biomarkers to accurately predict the efficacy and sensitivity of 5-FU in individual patients. It has been confirmed that 5-FU can regulate tumor progression by promoting gasdermin E (GSDME, encoded by DFNA5) cleavage to induce pyroptosis. Lysine demethylase ALKBH4 has been shown to be upregulated in a variety of tumors to promote tumor progression. However, its role in gastric cancer is not clear. In this study, we observed a significant upregulation of ALKBH4 expression in gastric cancer tissues compared to adjacent normal tissues, indicating its potential as a predictor for the poor prognosis of gastric cancer patients. On the contrary, GSDME exhibits low expression levels in gastric cancer and demonstrates a negative correlation with poor prognosis among patients diagnosed with gastric cancer. In addition, we also found that high expression of ALKBH4 can inhibit pyroptosis and promote the proliferation of gastric cancer cells. Mechanistically, ALKBH4 inhibits GSDME activation at the transcriptional level by inhibiting H3K4me3 histone modification in the GSDME promoter region, thereby reducing the sensitivity of gastric cancer cells to 5-FU treatment. These findings provide further insight into the regulatory mechanisms of ALKBH4 in the progression of gastric cancer and underscore its potential as a prognostic marker for predicting the sensitivity of gastric cancer cells to 5-FU treatment.
Orb2 enables rare-codon-enriched mRNA expression during Drosophila neuron differentiation
Authors: Stewart Rebeccah K. , Nguyen Patrick , Laederach Alain , Volkan Pelin C. , Sawyer Jessica K. , Fox Donald T. 
Published: June 2024

AbstractRegulation of codon optimality is an increasingly appreciated layer of cell- and tissue-specific protein expression control. Here, we use codon-modified reporters to show that differentiation of Drosophila neural stem cells into neurons enables protein expression from rare-codon-enriched genes. From a candidate screen, we identify the cytoplasmic polyadenylation element binding (CPEB) protein Orb2 as a positive regulator of rare-codon-dependent mRNA stability in neurons. Using RNA sequencing, we reveal that Orb2-upregulated mRNAs in the brain with abundant Orb2 binding sites have a rare-codon bias. From these Orb2-regulated mRNAs, we demonstrate that rare-codon enrichment is important for mRNA stability and social behavior function of the metabotropic glutamate receptor (mGluR). Our findings reveal a molecular mechanism by which neural stem cell differentiation shifts genetic code regulation to enable critical mRNA stability and protein expression.
Simultaneous enhancement of multiple functional properties using evolution-informed protein design
Authors: Fram Benjamin , Su Yang , Truebridge Ian , Riesselman Adam J. , Ingraham John B. , Passera Alessandro , Napier Eve , Thadani Nicole N. , Lim Samuel , Roberts Kristen , Kaur Gurleen , Stiffler Michael A. , Marks Debora S. , Bahl Christopher D. , Khan Amir R. , Sander Chris , Gauthier Nicholas P. 
Published: June 2024

AbstractA major challenge in protein design is to augment existing functional proteins with multiple property enhancements. Altering several properties likely necessitates numerous primary sequence changes, and novel methods are needed to accurately predict combinations of mutations that maintain or enhance function. Models of sequence co-variation (e.g., EVcouplings), which leverage extensive information about various protein properties and activities from homologous protein sequences, have proven effective for many applications including structure determination and mutation effect prediction. We apply EVcouplings to computationally design variants of the model protein TEM-1 β-lactamase. Nearly all the 14 experimentally characterized designs were functional, including one with 84 mutations from the nearest natural homolog. The designs also had large increases in thermostability, increased activity on multiple substrates, and nearly identical structure to the wild type enzyme. This study highlights the efficacy of evolutionary models in guiding large sequence alterations to generate functional diversity for protein design applications.
In vivo CRISPR screens reveal SCAF1 and USP15 as drivers of pancreatic cancer
Authors: Martinez Sebastien , Wu Shifei , Geuenich Michael , Malik Ahmad , Weber Ramona , Woo Tristan , Zhang Amy , Jang Gun Ho , Dervovic Dzana , Al-Zahrani Khalid N. , Tsai Ricky , Fodil Nassima , Gros Philippe , Gallinger Steven , Neely G. Gregory , Notta Faiyaz , Sendoel Ataman , Campbell Kieran , Elling Ulrich , Schramek Daniel 
Published: June 2024

AbstractFunctionally characterizing the genetic alterations that drive pancreatic cancer is a prerequisite for precision medicine. Here, we perform somatic CRISPR/Cas9 mutagenesis screens to assess the transforming potential of 125 recurrently mutated pancreatic cancer genes, which revealed USP15 and SCAF1 as pancreatic tumor suppressors. Mechanistically, we find that USP15 functions in a haploinsufficient manner and that loss of USP15 or SCAF1 leads to reduced inflammatory TNFα, TGF-β and IL6 responses and increased sensitivity to PARP inhibition and Gemcitabine. Furthermore, we find that loss of SCAF1 leads to the formation of a truncated, inactive USP15 isoform at the expense of full-length USP15, functionally coupling SCAF1 and USP15. Notably, USP15 and SCAF1 alterations are observed in 31% of pancreatic cancer patients. Our results highlight the utility of in vivo CRISPR screens to integrate human cancer genomics and mouse modeling for the discovery of cancer driver genes with potential prognostic and therapeutic implications.
Increasing control over biomineralization in conodont evolution
Authors: Shirley Bryan , Leonhard Isabella , Murdock Duncan J. E. , Repetski John , Świś Przemysław , Bestmann Michel , Trimby Pat , Ohl Markus , Plümper Oliver , King Helen E. , Jarochowska Emilia 
Published: June 2024

AbstractVertebrates use the phosphate mineral apatite in their skeletons, which allowed them to develop tissues such as enamel, characterized by an outstanding combination of hardness and elasticity. It has been hypothesized that the evolution of the earliest vertebrate skeletal tissues, found in the teeth of the extinct group of conodonts, was driven by adaptation to dental function. We test this hypothesis quantitatively and demonstrate that the crystallographic order increased throughout the early evolution of conodont teeth in parallel with morphological adaptation to food processing. With the c-axes of apatite crystals oriented perpendicular to the functional feeding surfaces, the strongest resistance to uniaxial compressional stress is conferred along the long axes of denticles. Our results support increasing control over biomineralization in the first skeletonized vertebrates and allow us to test models of functional morphology and material properties across conodont dental diversity.