bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic modeling reveals synergistic growth benefits of engineering maize symbiosis with rhizobia and arbuscular mycorrhizal fungi
Authors: Kaste Joshua A.M. , Ji Rourou , Sydow Patrick , Sawers Ruairidh J. H. , Matthews Megan L. 
Published: February 2025

AbstractEngineering N2-fixing rhizobia symbiosis in cereals and enhancing association with arbuscular mycorrhizal fungi (AMF) are two strategies being pursued to improve agricultural sustainability. However, the metabolic fluxes and consequent costs and benefits of these strategies in a cereal crop have not been examined. We developed a metabolic model describing how the relative growth rate ofZea maysis impacted by hypothetical association with the rhizobiumBradyrhizobium diazoefficiensand the AMFRhizophagus irregularis. We found that the lower N content of cereal crops makes the relative growth rate cost associated with acquiring nitrogen from N2-fixing rhizobia smaller than in legumes. Our model also predicts positive synergies between rhizobia and AMF under nutrient-limited conditions but negative synergies under nutrient, particularly phosphorus, replete conditions. These findings indicate that these bioengineering strategies could improve cereal crop yields and may achieve greater gains in tandem, but soil nutrient status of target sites should be considered.Significance StatementFertilizer application is responsible for substantial environmental impacts and represents a significant cost to farmers, both barriers to sustainable agricultural development. Engineering cereal crops to associate with N2-fixing rhizobia and enhancing existing associations between crops and arbuscular mycorrhizal fungi (AMF) are two strategies that could address these challenges. However, quantitative predictions of their potential effectiveness have not been determined. We use metabolic modeling to demonstrate that engineering maize to associate with N2-fixing rhizobia could be a highly metabolic and cost-effective strategy for sustainably supplying nitrogen to cereal crops. We also develop and experimentally validate a model of plant-AMF carbon and nutrient exchanges and demonstrate that AMF and rhizobia symbioses can act synergistically under nitrogen– and phosphorus-deprivation to improve crop growth.
Lower Bounds on the Sample Complexity of Species Tree Estimation when Substitution Rates Vary Across Loci
Authors: Hill Max , Roch Sebastien 
Published: February 2025

AbstractIn this paper we analyze the effect of substitution rate heterogenity on the sample complexity of species tree estimation. We consider a model based on the multi-species coalescent (MSC), with the addition that gene trees exhibit random i.i.d. rates of substitution. Our first result is a lower bound on the number of loci needed to distinguish 2-leaf trees (i.e., pairwise distances) with high probability, when substitution rates satisfy a growth condition. In particular, we show that to distinguish two distances differing by lengthfwith high probability, one requiresO(f−2) loci, a significantly higher bound than the constant rate case. The second main result is a lower bound on the amount of data needed to reconstruct a 3-leaf species tree with high probability, when mutation rates are gamma distributed. In this case as well, we show that the number of gene trees must grow asO(f−2).
Investigation of immune response to Mesenchymal Stromal Cell-derived Extracellular Vesicles in the cancer setting
Authors: Gilligan Katie E , Treacy Oliver , ’Neill Clodagh P O , McCarthy Elan C , McDermott Emma , Mammen Elma , Dockery Peter , Ryan Aideen E , Dwyer Róisín M 
Published: February 2025

AbstractMesenchymal Stromal Cell derived extracellular vesicles (MSC-EVs) may retain the cancer targeting and immune privilege of MSCs. The immense potential MSC-EVs hold as tumour-targeted therapeutics warrants an understanding of potential adverse events to support clinical translation. This study aimed to determine whether MSC-EVs would elicit an immune response following administration in tumour-bearing immunocompetent animals. Secreted EVs were isolated from both human and murine bone marrow derived MSCs and characterized. hMSC-EVs or mMSC-EVs were administered intravenously into 4T1 breast tumour-bearing Balb/c mice or healthy controls. Tumour tissue, draining lymph nodes and spleens were harvested, dissociated into a single cell suspension and flow cytometry performed targeting T cells, myeloid derived suppressor cells (MDSCs), macrophages, dendritic cells and natural killer (NK) cells. The 4T1 model immune profile was first determined by comparing the spleen of tumour-bearing animals to healthy controls. T cells were increased in tumour-bearing animals (CD4+/CD25+ p=0.041; CD8+/CD25+ p=0.02). A significant elevation of GR-1+ MDSCs (p=0.002), CD11b+ macrophages (p=0.023) and CD11c+ dendritic cells (p=0.001) was also observed. In contrast, CD27+ NK cells were significantly decreased compared to the spleen of healthy animals (p=0.006). Collectively this data validated the immune profile and supported the determination of any changes in response to hMSC-EVs or mMSC-EVs administration. No significant activation of CD4+ (p=0.20) or CD8+ (p=0.57) T cells were seen in tumour tissue in both groups. The percentage of GR-1+ MDSCs (28% vs 27%, p=0.92), CD11b+, CD11c+ and CD27+ cells were similar regardless of EV origin. No significant changes in T cells, MDSCs, macrophages, dendritic or NK cells were observed in the lymph node or spleen of animals that received hMSC-EV versus mMSC-EVs. In conclusion, human MSC-EVs elicited no discernible immune response in mice, supporting the hypothesis that MSC-EVs retain the immune privilege of the secretory cell. This reinforces the therapeutic potential of MSC-EVs.
Overcoming Immune Checkpoint Inhibitor Resistance via Potent and Selective Dual αvβ6/8 Inhibitors Based on Engineered Lasso Peptides
Authors: Lechner Anna , Jordan Peter A. , da Cruz Gabriella Costa Machado , Lamson Jacob , Gordon Jessica , Okada Bethany K. , Anderson Kelsey , Chaudhari Rajan , Rosario Christopher J. , Mikesell Jasmine , McPhee Scott A. , Burk Mark J. 
Published: February 2025

AbstractIntegrins αvβ6 and αvβ8 in the tumor microenvironment (TME) have been shown to activate immunosuppressive TGF-β, which serves as an important mechanism for immune checkpoint inhibitor resistance in a range of tumors. In this study, we demonstrate the utility of lasso peptides as versatile scaffolds for designing new therapeutics. A series of highly potent and selective dual αvβ6/8 inhibitors were engineered through a combination of epitope scanning, computational design, and directed evolution. Several analogs, such as lassotides36and47, were fully characterized and physicochemical, in vitro pharmacological, and in vivo data are reported. Lassotide47, a half-life extended derivative of36, was shown to strongly sensitize anti-mPD-1-resistant tumors in mice when dosed in combination with the checkpoint inhibitor. The47/anti-mPD-1 combination was shown to halt tumor growth and regress tumors in mouse models of triple negative breast and ovarian cancers. Dual inhibition of αvβ6/8 integrins expressed in the TME thus represents a promising tumor-specific strategy to overcome TGF-β-driven resistance and enhance the anti-tumor efficacy of immune checkpoint inhibitors.
Divergent ecological selection causes partial reproductive isolation and vast genomic instability in yeast
Authors: Bendixsen Devin P. , Gilchrist Ciaran , Haberkorn Chloé , Persson Karl , Geijer Cecilia , Warringer Jonas , Stelkens Rike 
Published: February 2025

AbstractPopulations evolving independently in divergent environments accumulate genetic differences and potentially evolve reproductive isolation as a by-product of divergence. The speed and mechanisms underlying this process are difficult to investigate because we rarely get the opportunity to witness them in natural settings, and histories of selection and gene flow between populations are often unknown. Here, we experimentally evolved yeast for 1000 generations of evolution in both divergent and parallel environments. At regular time points during experimental evolution, we made crosses between parallel- and divergent-evolving populations to measure postzygotic reproductive isolation (gamete viability). We used whole genome population sequencing to determine the mutational load, the number and types of structural variation, and other genomic features of the parent, F1, and F2 intraspecific hybrids. We found evidence for large scale phenotypic and genome-wide differentiation in response to divergent laboratory selection. Divergent-selected populations produced hybrids with reduced gamete viability - a classic signature of postzygotic reproductive isolation in the form of hybrid breakdown. Parallel-selected populations on the other hand remained reproductively compatible. We found that F2 hybrid genomes contained vast genomic instability, i.e., new structural variants (especially insertions, deletions, and interchromosomal translocations) that were not observed in parent and F1 genomes, which is likely a result of chromosome missegregation and recombination errors in hybrid meiosis. Our results provide phenotypic and genomic evidence that partial reproductive isolation evolved due to adaptation to divergent environments, consistent with predictions of ecological speciation theory.
The interplay of sexual selection and hybridization can drive sexual radiation
Authors: Kagawa Kotaro 
Published: February 2025

AbstractSexual selection is considered a major driver of species diversification, but little is known about whether and how sexual selection may contribute to the incipient stages of speciation and sexual radiation. Based on evolutionary simulations, here I propose that an interplay of sexual selection and hybridization can drive the rapid formation of multiple species with diverse exaggerated sexual displays within a lineage. Existing theories suggest that sexual selection can cause evolutionary dynamics with multiple stable equilibria, with which multiple species with distinct sexual displays and mate preferences can persist stably. However, the stability of each equilibrium hinders the formation of new species from an existing species that is already occupying one of the stable equilibria. In such situations, hybridization between phenotypically similar but genetically distinct lineages can catalyze speciation. Hybridization can generate genetic variation by recombining alleles from different lineages. I provide evolutionary simulations demonstrating that hybridization that gives rise to genetic variation in mate preference can modify the sexual selection regime to open up opportunities for the evolution of sexually selected displays toward previously unoccupied stable equilibria. Hybridization thus can trigger evolutionary shifts between alternative evolutionary equilibria that sexual selection generates, driving the incipient formation of sexual radiation.
Estimation of total mediation effect for a binary trait in a case-control study for high-dimensional omics mediators
Authors: Kang Zhiyu , Chen Li , Wei Peng , Xu Zhichao , Li Chunlin , Yang Tianzhong 
Published: February 2025

AbstractMediation analysis helps uncover how exposures impact outcomes through intermediate variables. Traditional mean-based total mediation effect measures can suffer from the cancellation of opposite component-wise effects and existing methods often lack the power to capture weak effects in high-dimensional mediators. Additionally, most existing work has focused on continuous outcomes, with limited attention to binary outcomes, particularly in case-control studies. To fill in this gap, we propose anR2total mediation effect measure under the liability framework, providing a causal interpretation and applicable to various high-dimensional mediation models. We develop a cross-fitted, modified Haseman-Elston regression-based estimation procedure tailored for case-control studies, which can also be applied to cohort studies with reduced efficiency. Our estimator remains consistent with non-mediators and weak effect sizes in extensive simulations. Theoretical justification on consistency is provided under mild conditions. In the Women’s Health Initiative of 2150 individuals, we found that 89% (CI: 73% 91%) of the variation in the underlying liability for coronary heart disease associated with BMI can be explained by metabolomics.
Exploring the implemented guidelines for dyslipidemia treatment and care among nurses and physicians in Jordanian hospitals
Authors: bani Salameh Rana K. , Al-Smadi Ahmed M. , Gammoh Omar , Shajrawi Abedalmajeed M. , Ashour Ala , Alrfooh Omar , Fitzsimons Donna , Hatahet Taher , Binsaleh Ammena Yahia , Shilbayeh Sireen Abdul Rahim 
Published: February 2025

AbstractBackgroundDyslipidemia is a major risk factor for ischemic heart disease in the world. The last updated ACC/AHA and ESC/EAS guidelines for dyslipidemia management aimed to control blood cholesterol and reduce cardiovascular risk. In Jordan, no national guidelines have been published to date, so these guidelines are commonly used. There are a few studies exploring the implementation of these guidelines in Jordan.purposeTo explore the implementation of updated ACC/AHA and ESC/EAS guidelines for the treatment and care of dyslipidemia among nurses and physicians in Jordan.MethodSemi-structured interviews (three focus group) with open-ended questions was conducted to gain deeper understanding of implemented practice and guidelines among nurses and physicians.ResultsFocus group interviews revealed that health care professionals try to implement specific guidelines and reach for optimal goals, but many barriers prevent them from reaching therapeutic goals, like workload, limited resources, and a lack of support from health institutions. They reported many suggestions that may enhance their ability to implement dyslipidemia management guidelines and wanted to improve specific guidelines in Jordan for dyslipidemia management.ConclusionsResults indicated limited implementation of any dyslipidemia management guidelines among Jordanian nurses and physicians in their clinical practices.
Improving Post Kidney Transplant Related Outcomes through Video Based Educational Platforms
Authors: Byrns Jennifer , Bodner Jason , Watson Michael , Conca Tresa , Roberts John 
Published: February 2025

ABSTRACTPURPOSEKidney transplant recipients’ medical knowledge and comprehension of transplant care are critical to successful long-term outcomes. While transplant centers focus on pre-transplant patient education, post-transplant education receives less emphasis. At Duke University Hospital, an online digital library of short patient-centric videos was created to provide transplant education. The purpose of this study was to evaluate the impact of these videos on improving patient outcomes and patient perceived ability to effectively manage their own care.METHODSThis was a prospective, single center study, evaluating the impact of education via patient-centric videos on medical knowledge, medication adherence, hospital readmissions, and patient satisfaction. Patients were randomized to receive education via online videos versus standard of care (in person and written education). Ten videos were created to cover the entire transplant process. A survey was conducted to assess outcomes. Descriptive statistics were used to compare groups with absolute numbers (%) and means (SD).RESULTSThere were a total of 83 patients enrolled. Response rates to the surveys was 61.4%. Patients who completed the survey were evaluated. Twenty seven patients were included in the video group and there were 24 control patients. The video group expressed extreme satisfaction with the videos. All patients reported that they would recommend the videos to other patients, and 84% stated that they would return to watch the videos to gain additional transplant knowledge. Patients in the video group reported confidence in their ability and the medical team’s ability to manage their health. The assessment of transplant knowledge was similar between groups, but limited by video completion rates and timing of survey completion. Readmission rates were no different.CONCLUSIONSTransplant education provided via video based format helped to improve patients’ confidence in their ability to maintain their own self-care. The videos were well received and helped give patients a method to learn about transplant. These videos are now used institution wide to help improve patient outcomes
Characterization of the Cellular Immune Response to Group B Streptococcal Vaginal Colonization
Authors: Spencer Brady L. , Nguyen Dustin T. , Marroquin Stephanie M. , Gapin Laurent , O’Brien Rebecca L. , Doran Kelly S. 
Published: February 2025

AbstractIntroductionGroup BStreptococcus(GBS) asymptomatic colonizes the female genital tract (FGT) but can contribute to adverse pregnancy outcomes including pre-term birth, chorioamnionitis, and neonatal infection. We previously observed that GBS elicits FGT cytokine responses, including IL-17, during murine vaginal colonization; yet the anti-GBS cellular immune response during colonization remained unknown. We hypothesized that GBS may induce cellular immunity, resulting in FGT clearance.MethodsHerein, we utilize depleting antibodies and knockout mice and performed flow cytometry to investigate cellular immunes responses during GBS colonization.ResultsWe found that neutrophils (effectors of the IL-17 response) are important for GBS mucosal control as neutrophil depletion promoted increased GBS burdens in FGT tissues. Flow cytometric analysis of immune populations in the vagina, cervix, and uterus revealed, however, that GBS colonization did not induce a marked increase in FGT CD45+ immune cells. We also found that that Vγ6+ γδ T cells comprise a primary source of FGT IL-17. Finally, using knockout mice, we observed that IL-17-producing γδ T cells are important for the control of GBS in the FGT during murine colonization.ConclusionsTaken together, this work characterizes FGT cellular immunity and suggests that GBS colonization does not elicit a significant immune response, which may be a bacterial directed adaptive outcome. However, certain FGT immune cells, such as neutrophils and ɣδ T cells, contribute to host defense and control of GBS colonization.
Somatostatin Receptor 2 Overexpression in Hepatocellular Carcinoma: Implications for Cancer Biology and Theranostic Applications
Authors: Momeny Majid , Vargas Servando Hernandez , AghaAmiri Solmaz , Adams Jack T. , Bateman Tyler M. , Ghosh Sukhen C. , Acidi Belkacem , Khalaj Vahid , Kaseb Ahmed O. , Cao Hop S. Tran , Azhdarinia Ali 
Published: February 2025

Abstract(1)BackgroundSomatostatin receptor 2 (SSTR2) is overexpressed in various tumors, including hepatocellular carcinoma (HCC), yet its role in tumorigenesis remains unclear. This study examines the roles of SSTR2 in the molecular pathology of HCC and explores its potential as a target for SSTR2-directed radiopharmaceuticals in this malignancy.(2)MethodsSSTR2 expression was analyzed across 22 malignancies using TNMplot and specifically in HCC through The Human Protein Atlas. Transcriptomic data, protein expression, and copy number alterations in HCC patients with varying SSTR2 levels were compared using The Cancer Genome Atlas (TCGA). Gene Ontology (GO) enrichment analysis was performed using SRplot, while survival analysis was conducted with GEO datasets.(3)ResultsMost HCC patients exhibit moderate levels of SSTR2 expression. Elevated SSTR2 expression is associated with worse overall and disease-specific survival, as well as the activation of pathways involved in tumor growth and metastasis. Furthermore, SSTR2 expression is linked to key oncogenes and receptor tyrosine kinases.(4)ConclusionsSSTR2 in HCC signifies an oncogenic network and represents a promising therapeutic target to inhibit tumor invasion and serve as a theranostic biomarker. HCC patients with elevated SSTR2 expression could benefit from SSTR2-targeted theranostics, enabling enhanced tumor detection and more effective therapy.
How Does Sampling Affect the AI Prediction Accuracy of Peptides’ Physicochemical Properties?
Authors: Yan Meiru , Abuduhebaier Ankeer , Zhou Haojin , Wang Jiaqi 
Published: February 2025

AbstractAccurate AI prediction of peptide physicochemical properties is essential for advancing peptide-based biomedicine, biotechnology, and bioengineering. However, the performance of predictive AI models is significantly affected by the representativeness of the training data, which depends on the sample size and sampling methods employed. This study addresses the challenge of determining the optimal sample size and sampling methods to enhance the predictive accuracy and generalization capacity of AI models for estimating the aggregation propensity, hydrophilicity, and isoelectric point of tetrapeptides. Four sampling methods were evaluated: Latin Hypercube Sampling (LHS), Uniform Design Sampling (UDS), Simple Random Sampling (SRS), and Probability-Proportional-to-Size Sampling (PPS), across sample sizes ranging from 100 to 20,000. A sample size of approximately 12,000 (7.5% of the total tetrapeptide dataset) marks a key threshold for stable and consistent model performance. This study provides valuable insights into the interplay between sample size, sampling strategies, and model performance, offering a foundational framework for optimizing data collection and AI model training for the prediction of peptides’ physicochemical properties, especially for prediction in the complete sequence space of longer peptides with more than four amino acids.
Genetic evidence for a fall spawning group of Gulf sturgeon (Acipenser oxyrinchus desotoi) in the Apalachicola River, Florida
Authors: Zona Jacob O. , Kreiser Brian R. , Kaeser Adam J. , Fox Adam G. , D’Ercole Mark J. 
Published: February 2025

AbstractThe Gulf sturgeon (Acipenser oxyrinchus desotoi) is a large, long-lived, anadromous fish inhabiting the northern Gulf of Mexico. This charismatic fish was hunted to near extinction in the early 1900’s and in 1991 was listed as threatened under the Endangered Species Act. Recovery continues to be challenged by threats such as habitat destruction, fisheries bycatch, and climate change. There are seven known natal rivers, historically thought to each contain a single, spring-spawning group. In recent years, multiple rivers (Suwannee, Choctawhatchee) have been shown to contain a second, fall-spawning group. This study utilizes genetic techniques to investigate the proposed existence of a fall-spawning group in the Apalachicola River, Florida. This river once supported one of the largest Gulf sturgeon populations, but post-exploitation faces a difficult path to recovery. The Jim Woodruff Lock and Dam blocks access to the majority of historic habitat in the system, with the only known remaining spawning grounds located immediately downriver. Tissue samples from juvenile Gulf sturgeon were collected between 2013 and 2022 and used to assess genetic population structure within the Apalachicola River. Analyses suggested two distinct genetic groups (FST= 0.085). Based on dates of capture, length frequency distributions, and genetic assignment of spawning adults, these were identified as spring- and fall-spawning groups. Approximately 90% of juveniles collected were assigned to the spring, but only slight differences in genetic diversity were detected between groups. The temperature window for spawning was found to be three weeks shorter on average in the fall than the spring, highlighting the need for additional research into differing environmental or anthropogenic influences on these populations. The discovery of a fall-spawning group of Gulf sturgeon in the Apalachicola River improves our understanding of the representation, redundancy, and resiliency of the species and provides critical information for improved management of this river system.