bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are new pediatric trauma centers located close to the high-risk populations? A geolocation study
Authors: Williams Keyonna M. , Scholtz Nicole O. , Plagens Connor , Tubbs Darrell , Ehrlich Peter F. 
Published: October 2024

BACKGROUNDHigher rates of injury occur in children who live in low socioeconomic areas. Since 2010, the number of verified Level I and Level II pediatric trauma centers (PTCs) has doubled. The purpose of this study is to look at the location of new verified PTC in relation to children living in high-risk areas.METHODSHistorical and recent data about verified Level I and Level II PTCs were obtained from the American College of Surgeons (ACS), the American Trauma Society, and State Data where available. Census data were obtained from the US Census Bureau's American Community Survey for 2010 and 2020 for children younger than 18 years. The pediatric population was stratified by (1) poverty threshold and (2) living within 30 miles of PTC. The census data and trauma center locations were geocoded using the ArcGIS Pro program. Data analysis was performed at the census tract level.RESULTSA total of 55 Level I or Level II ACS-verified PTCs were in the United States in 2010 and 116 in 2020. In 2010, there were 14.5 million children (19.6%) below the poverty threshold and 12.9 million (17.8%) in 2020. In 2010, 23 states did not have an ACS-verified PTC either in the state or in a neighboring state within 30 miles. By 2020, only nine states did not have an ACS-verified PTC or a center in a neighboring state within 30 miles. When state level data were included, this dropped to four. The 19 states who had new verified PTCs covered between 14% and 21% of children below the poverty level. The percentage of children below the poverty threshold and less than 30-mile access to a Level I or Level II PTC in 2010 was 74.56% compared with children above poverty and less than 30-mile access, which was 70.34% (p< 0.0001). In 2020, children below poverty without 30-mile access had been reduced to 52% and 45.54% for children above poverty level (p< 0.0001). Thus, there was a greater increase in 30-mile access for children above the poverty level than for those below the poverty level (24.8% vs. 22.6%,p< 0.001).CONCLUSIONOn a national level, despite doubling the number of PTC, it has not improved 30-mile access for high-risk children. Alternatively, 19 states now have better access.LEVEL OF EVIDENCEPrognostic and Epidemiological; Level IV.
Nanocluster-Mediated Signaling Crosstalk between FcγR and TLR4 in Macrophage Inflammatory Responses
Authors: Lee Seonik , Yu Yan 
Published: October 2024

AbstractReceptor crosstalk, the interaction between different receptors to modulate signaling, is crucial for fine-tuning the inflammatory responses of innate immune cells. Although the synergistic crosstalk between Toll-like receptor (TLR)4 and Fc gamma receptor (FcγR) is well documented, the detailed mechanism underlying this synergy remains unclear. In this study, we addressed this knowledge gap by imaging the molecular organization of TLR4 and FcγR on the macrophage cell surface and correlating it with their synergistic co-activation using ligands functionalized on lipid bilayers. We confirmed that co-activation of TLR4 and FcγR enhances whole-cell pro-inflammatory responses and tyrosine phosphorylation at the receptor level. Super-resolution microscopy revealed that TLR4 and FcγR each form discrete nanoclusters after ligand stimulation, and their synergistic co-activation significantly increases both the size and spatial overlap of these nanoclusters, leading to amplified immune signaling. Contrary to previous assumptions that TLR4 and FcγR form heterodimers during their crosstalk, our results emphasize the critical role of receptor nanocluster interactions in modulating innate immune responses. Additionally, these findings align with similar receptor interaction mechanisms that we previously reported in other receptor pairs, such as Dectin-1/TLR2 and FcγR/TLR2, suggesting that nanocluster interactions may represent a predominant mechanism governing crosstalk between TLRs and ITAM-containing receptors.
Effect of the Environmental Mechanical Heterogeneity on T Cell Function
Authors: Pandit Jatin Jawhir , Yassin Abed Al-Kader , Martin Carlos Ureña , Le Saux Guillaume , Porgador Angel , Schvartzman Mark 
Published: October 2024

AbstractT cells, key players in the immune system, recognize antigens via T-cell receptors (TCRs) and require additional costimulatory and cytokine signals for full activation. Beyond biochemical signals, T cells also respond to mechanical cues such as tissue stiffness. Traditionalex-vivomechanostimulating platforms, however, present a uniform mechanical environment, unlike the heterogeneous conditions T cells encounterin-vivo. This work introduces a novel mechanically heterogeneous environment, with alternating soft and stiff microdomains, to mimic the complex mechanical signals T cells face. Results show that T cells exposed to this heterogeneous environment do not average the mechanical signals but instead respond similarly to those on a homogeneously soft surface, leading to lower activation compared to those on a stiff surface. Interestingly, long-term exposure to these patterns enhances the proliferation of central memory and effector T cell phenotypes, similar to stiff environments. These findings reveal the non-linear nature of T cell mechanosensing and suggest that mechanical heterogeneity plays a critical role in modulating T cell responses, providing new insights into T cell activation and potential implications for immunotherapies.
FragLlama: Next-fragment prediction for molecular design
Authors: Shen Jian , Zhou Shengmin , Che Xing 
Published: October 2024

AbstractThe emergence of ChatGPT has drawn significant attention to Large Language Models (LLMs) due to their impressive performance. While LLMs primarily focus on next token/word prediction, we apply this principle to molecular design by reframing the task as predicting the next token/fragment. We present FragLlama, a large language model trained for molecular design, featuring custom tokens that represent molecular fragments and functional groups. The model is for generating molecules given one or two fragments, for application scenarios like general hit-to-lead and lead optimization stage drug design, PROTAC linker design; mapping to commonly used drug design strategies like fragment growing and scaffold hopping. In the pre-training stage, we adapted the Llama 3 architecture to create FragLlama, training it to learn conditional probabilities of these fragment-level tokens. The subsequent alignment stage employed fine-tuning to guide the model towards generating molecules with desired properties. The effectiveness of FragLlama is demonstrated through its applications in designing molecular glue libraries, PROTAC linkers and EGFR binders. FragLlama demonstrates proficiency in reproducing expert-level designs while also exploring novel and promising chemical spaces, highlighting its potential to augment the capabilities of medicinal chemists in drug design.
Global patterns, drivers and impacts of metabolic traits across amniotes
Authors: Yang Qi , Wang Ziyi , Fan Liqing , Wang Dehua , Lei Fumin , Xiong Ying 
Published: October 2024

AbstractMetabolism and climate are thought to influence species richness and diversification, yet few studies have examined whether global patterns of metabolic traits are linked to climate and diversification rate. Here we investigate the drivers of global metabolic rates and their impacts on biodiversity across 2,633 amniote vertebrates. We found consistent distribution patterns of metabolic rates in terrestrial amniotes and marine birds, with metabolic rates increasing with distance from the equator across latitudes. Temperature is a primary climatic variable affecting metabolic rates in birds and mammals, whereas precipitation dominates in terrestrial reptiles. Furthermore, elevated metabolic rates promote diversification rates and reduce extinction risks in birds and terrestrial mammals. Conversely, high metabolic rates decrease diversification rates and increase extinction risks in reptiles. Our results show that global patterns of metabolic rates are driven by various climate variables and may shape diversification and extinction patterns among amniotes in the context of climate change.
Tissue-Targeted Prime/Pull/Keep Therapeutic Herpes Simplex Virus Vaccine Protect Against Recurrent Ocular Herpes Diseases in HLA-A*0201 Transgenic Rabbits
Authors: Chentoufi Aziz A , Prakash Swayam , Vahed Hawa , Quadiri Afshana , BenMohamed Lbachir 
Published: October 2024

ABSTRACTHerpes Simplex Virus type 1 (HSV-1) continues to be one of the most prevalent viral infections globally, with approximately 3.72 billion individuals affected worldwide. A clinical herpes vaccine is still lacking. In the present study, a novel prime/pull/keep vaccine was tested in Human Leukocyte Antigen transgenic rabbit model of ocular herpes (HLA-A*0201 Tg rabbit). Ten asymptomatic (ASYMP) CD8+ T cell peptide epitopes and 3 CD4+ T-cell epitopes were selected from the HSV-1 glycoproteins D and B (gD and gB), viral tegument proteins (VP11/12 and VP13/14) and the DNA replication binding helicase (UL9), all preferentially recognized by CD8+and CD4+T-cells from “naturally protected” HSV-1-seropositive healthy ASYMP individuals (who never had recurrent corneal herpetic disease). HLA Tg rabbits were ocularly infected with HSV-1 then during latency at day 30 post-infection, the rabbits were ocularly vaccinated with a recombinant neurotropic AAV8 vector (107GC/ eye) encoding for the 10 CD8+ T cell peptide and 4 CD4+ T cells peptide (prime), T cell-attracting CXCL-11 (Pull) and T-cell keeping IL-2/IL-15 cytokines (keep). The rabbits were followed up for eye disease and viral loads in tears for 28 days. The frequency, function and protective efficacy of HSV-specific CD8+T cells induced by the prime/pull/keep vaccine were assessed in the trigeminal ganglia (TG), cornea, Spleen, and peripheral blood. Compared to the mock group (unvaccinated), the peptides/CXCL11/IL-2/IL-15 vaccine generated frequent resident CD8+T cells that infiltrated the TG. CD8+T cells mobilization and retention into TG of prime/pull/keep vaccinated rabbits was associated with a significant reduction in corneal herpes infection and disease after an ocular HSV-1 challenge (McKrae). These findings draw attention to the novel prime/pull/keep therapeutic vaccine strategy to mobilize and retain anti-viral T cells into tissues protecting them against herpetic infection and disease.IMPORTANCEThere is an urgent need for a vaccine against widespread human herpes simplex virus infections. The present study demonstrates that immunization of humanized HLA-A*0201 transgenic rabbits with CD8+ and CD4+ T-cell epitope peptides (prime)/ CXCL11 (pull)/ IL-2/IL-15 (Keep) AAV8-based vaccine triggered mobilization ad retention of HSV-1-specific CD8+T cells locally in the cornea and TG, the sites of acute and latent herpes infections. Mobilization and retention of antiviral CD8+T cells into cornea and TG of HSV-1 infected rabbits that received the prime/pull/keep vaccine was associated with protection against ocular herpes infection and disease. These results highlight the importance of the prime/pull/keep vaccine strategy to bolster the number and function of protective CD8+T cells within infected tissues.
Population genomics for coral reef restoration - a case study of staghorn corals in Micronesia
Authors: Rios Dareon , Torrado Hector , Lemer Sarah , Drury Crawford , Burdick David , Raymundo Laurie , Combosch David J. 
Published: October 2024

AbstractStaghornAcroporacorals are ecological keystone species in shallow lagoons and back reef habitats throughout the tropics. Their widespread decline coupled with their amenability for asexual propagation propelled them to the forefront of global coral restoration efforts - albeit frequently without much scientific input. To guide these efforts and as a blueprint for similar projects, we conducted a comprehensive population genomic study ofAcropora cf. pulchra, a major restoration target species in the Indo-Pacific. Our results revealed thatA.cf.pulchrapopulations in the Mariana Islands are characterized by large clonal clusters and extremely low levels of genetic diversity. Differentiation among populations followed a significant isolation-by-distance pattern and delineated two distinct metapopulations on Guam. Our investigation identified critical population genetic parameters, necessitating targeted management strategies, and provides actionable guidelines for effective conservation efforts. For management and conservation, two populations emerged as pivotal connectivity hubs with elevated genetic diversity. For restoration, we show thatA. cf.pulchrapopulations demonstrated a suitability for extensive asexual propagation and provide guidelines how to best apply that. To preserve and augment genetic diversity, strategies to mitigate inbreeding are crucial until sexual reproduction can be fully integrated into restoration protocols. Critical sites for restoration include local connectivity hubs, fringing lagoons that connect metapopulations, and back reefs around a particularly isolated population. These findings offer crucial insights into the genetic landscape of a keystone coral species and provide actionable recommendations for coral conservation and restoration. By advocating for the preservation of population connectivity and the promotion of genotypic, genetic, and symbiont diversity in coral restoration, our study serves as a blueprint for leveraging population genomic studies to enhance the efficacy and resilience of restoration projects on remote islands.
Deep Learning-Based Inference of Uterine Contractions from Maternal ECG
Authors: Tanaka Shunsuke , Ito Keisuke , Takano Kyohei , Takasaki Yohsuke 
Published: October 2024

AbstractBackgroundPreterm birth and stillbirth have multifaceted causes, many of which remain unknown. Factors such as maternal age, sexually transmitted infections, and genetic abnormalities are notably implicated. Globally, there has been minimal improvement in preterm birth rates, leading to substantial economic losses and underscoring the need for innovative approaches.ObjectiveThis study aims to analyze and detect uterine contractions by applying deep learning techniques to physiological data derived from maternal electrocardiograms (ECGs). Leveraging ECGs, which are easily obtainable from wearable devices, allows for effective and convenient monitoring of uterine contractions outside clinical settings. Since uterine contractions are a critical indicator for assessing the risk of preterm birth, our algorithm has the potential to facilitate early identification of high-risk individuals, thereby contributing to timely interventions and improved maternal-fetal outcomes.MethodsParticipants meeting all inclusion criteria and none of the exclusion criteria were recruited from patients admitted to or attending outpatient services at Saintpaulia Misao Ladies Hospital in Gifu, Japan, between December 6, 2023, and July 31, 2024. Our deep learning model was developed using maternal ECG data, uterine contraction waveforms obtained from cardiotocograms (CTGs). The collected data were divided into training and evaluation datasets. The AI-generated uterine contraction waveforms from the developed model were compared with ground truth labels obtained from the fetal monitoring devices. This study was reviewed and approved by the Ethics Committee of the Graduate School of Medicine at Gifu University and was conducted as a collaborative research effort with nonat Inc. (the lead research institution) and Saintpaulia Misao Ladies Hospital (joint research institution).ResultsFinally, 73 participants took part in this study, and 57 datasets were used for algorithm development and evaluation. Multiple measurements were taken on the same subjects on different days only with their consent. Our analysis demonstrated a strong correlation between the uterine contraction waveforms estimated by the developed model and the ground truth waveforms from CTGs, achieving an average correlation across all evaluation data (Pearson correlation coefficient = 0.53).ConclusionThis is the world’s first trial to detect uterine contractions from maternal ECGs using deep learning algorithms. In this study, we successfully developed a deep learning algorithm capable of accurately inferring uterine contraction waveforms from maternal ECGs. Given that ECGs can be easily obtained using wearable devices, this approach may provide healthcare professionals with objective and precise information on uterine contractions—a crucial indicator of preterm labor—even in resource-limited settings outside hospital environments.
Contextual enhancement on binge-like overconsumption of palatable sugar in mice
Authors: Matsui Hiroshi , Yasoshima Yasunobu 
Published: October 2024

AbstractBinge eating disorder is an eating disorder characterized by the excessive intake of food within a short period, often beyond physiological needs. Studies using animal models have shown that binge eating animals consume food in quantities that surpass physiological necessity, and that the neural mechanisms underlying this behavior overlap with those involved in habit formation. Habitual behaviors are thought to be automatic responses acquired through extended behavioral training and are dependent on the context in which they were learned. Therefore, this study hypothesized that binge eating has a context-dependent component. We investigated whether the excessive palatable sugar intake observed in an animal model of binge eating is triggered by an associated context as a learned behavior. To test this, mice were trained to develop binge-like sugar consumption in a specific context. During the test phase, we reduced the animals’ hedonic needs for sugar solution by providing a two-hour satiety period. Sugar solution was then presented in both the training context and a novel context. The results showed that in the training context, the mice continued to consume sugar solution at levels similar to those observed at the onset of the satiation. In contrast, this context-induced sugar consumption was not observed in the novel context. These findings suggest that, like habitual behaviors, binge eating is induced under in the context-dependent manner and insensitive to the consequence of the behavior.
Sustained attention processes in very preterm adolescents and their relationship to socio-emotional competence
Authors: Fernandez NB. , Siffredi V. , Awada J. , Miehlbradt J. , Borradori-Tolsa C. , Liverani MC. , Ha-Vinh Leuchter R. 
Published: October 2024

AbstractVery preterm (VPT) adolescents are at high risk of impaired sustained attention processes, as well as behavioral and socio-emotional problems. Previous studies have highlighted altered attentional patterns of brain activation in this population, but results are inconsistent. The current study aims to explore brain activity related to sustained attention in VPT and full-term adolescents aged 11-18, as well as its associations with attentional capacities and socio-emotional competences. Event-related functional MRI (fMRI) was used to assess sustained attention performance and associated brain activations by comparing VPT (n = 34) and their age-matched full-term (FT, n = 28) peers from a previously validated continuous performance task with gradual onset (gradCPT) paradigm, using two different modality versions (i.e., face and scene). In both groups, linear regression analyses were performed to examine associations between attentional and socio-emotional difficulties and brain activations related to sustained attention. Results show preserved sustained attention processes in VPT adolescents, indicated by comparable behavioral attentional performance and cerebral patterns of activations in both groups across the two modalities of the gradCPT. In addition, VPT adolescents showed over-recruitments in posterior occipital areas compared to FT adolescents. Moreover, higher socio-emotional difficulties (i.e., higher anxiety and social difficulties) in VPT were linked to altered activations specifically in the right middle frontal gyrus, occipito-temporal gyri and bilateral cerebellum, but exclusively observed during the face modality of the gradCPT. Overall, these results suggest that despite preserved sustained attention competences, VPT adolescents present a less mature sustained attention cerebral network, particularly during a task with a social context.
PRESSED FLOWERworks downstream ofASYMMETRIC LEAVES 2to affect sepal flatness inArabidopsis
Authors: Liu Ruoyu , Wang Zeming , He Xi , Zhou Heng , Xu Yiru , Hong Lilan 
Published: October 2024

ABSTRACTThe development of flattened organs such as leaves and sepals is essential for proper plant function. While much research has focused on leaf flatness, little is known about how sepals achieve flat organ morphology. Previous study has shown that in Arabidopsis anASYMMETRIC LEAVES 2(AS2) gene mutationas2-7Dcauses ectopicAS2expression on the abaxial sepal epidermis, which leads to growth discoordination between the two sides of sepals, resulting in outgrowth formation on abaxial sepal epidermis and sepal flatness disruption. Here we report that thePRESSED FLOWER(PRS) works downstream ofAS2in affecting sepal flatness. Genetic analysis showed thatPRSmutations suppressed the outgrowth formation on the abaxial sepal epidermis inas2-7Dmutant. Through tracking thePRSexpression dynamics at a cellular resolution throughout the early developmental stages in WT andas2-7Dsepals, we found that on the abaxial epidermis ofas2-7Dsepals, ectopicAS2expression up-regulatedPRSexpression, leading to the epidermal outgrowth initiation. AS2 affected PRS activity on multiple levels: AS2 activatedPRSexpression through direct binding toPRSpromoter region; AS2 also physically interacted with PRS. Our study highlights the complex interplay between AS2 and PRS in modulating sepal flatness.
Tunicate-specific protein Epi-1 is essential for conferring hydrophilicity to the larval tunic in the ascidianCiona
Authors: Kuroiwa Kazu , Mita-Yoshida Kaoru , Hamada Mayuko , Hozumi Akiko , Nishino Atsuo S. , Sasakura Yasunori 
Published: October 2024

AbstractAnimals must avoid adhesion to objects in the environment to maintain their mobility and independence. The marine invertebrate chordate ascidians are characterized by an acellular matrix tunic enveloping their entire body for protection and swimming. The tunic of ascidian larvae consists of a surface cuticle layer and inner matrix layer. Hydrophilic substances coat the cuticle; this modification is thought to be for preventing adhesion. However, the molecule responsible for regulating this modification has not been clarified. We here found that the tunicate-specific protein Epi-1 is responsible for preventing adhesiveness of the tunic in the ascidianCiona intestinalisType A.Cionamutants with homozygous knockouts ofEpi-1exhibited adhesion to plastic plates and to other individuals. The cuticle of theEpi-1mutants was fragile, and it lost the glycosaminoglycans supplied by test cells, the accessory cells that normally attach to the tunic surface. Although it has an apparent signal peptide for membrane trafficking, we showed that the Epi-1 protein is localized to the cytosol of the epidermal cells. Our study demonstrated that the emergence of the tunicate-specific protein Epi-1 accelerated the immediate ancestor of tunicates to evolve a tunic by providing a way to avoid the adhesiveness of this structure.HighlightsThe ascidianCionatunic has a glycosaminoglycan (GAG)-coated hydrophilic cuticle.Epi-1 is a protein expressed in the epidermis of tunicates during embryogenesis.Epi-1 Cionamutants have GAG-free, hydrophobic and therefore sticky cuticles.Epi-1 acquisition may have prevented adhesion of tunicates to environmental objects.