bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose- and time-dependent effects of cobalt protoporphyrin IX on granulocyte mobilization and metabolic markers in mice
Authors: Bednarz Aleksandra , Kozuch Paweł , Kowalski Kacper , Skulimowska Izabella , Kachamakova-Trojanowska Neli , Filipek-Gorzała Jadwiga , Kwiecinska Patrycja , Gawlinska Kinga , Kubiak Andrzej , Bryniarska-Kubiak Natalia , Jozkowicz Alicja , Szade Krzysztof , Szade Agata 
Published: October 2024

AbstractRecombinant granulocyte colony-stimulating factor (G-CSF) is the most commonly used agent for treating neutropenia and mobilizing hematopoietic stem cells (HSCs) for transplantation. However, some patients do not respond effectively to existing mobilization protocols. To address this, the development of new therapeutic approaches is necessary. One potential strategy is the pharmacological induction of endogenous mobilizing factors, which can be achieved through the administration of cobalt protoporphyrin IX (CoPP). CoPP induces mobilization of HSCs and granulocytes by increasing endogenous G-CSF production, though the optimal dosing and potential side effects remain unclear.The aim of our study was to optimize the dose and timing of CoPP administration and evaluate its safety in mobilizing cells from the bone marrow to the blood. Our results show that CoPP exerts a dose-dependent mobilizing effect, with the highest G-CSF levels and number of mobilized leukocytes observed in mice treated with 10 mg/kg of CoPP. While there were no severe adverse effects, there were mild fluctuations in markers of liver and kidney function, including a slight reduction in urea nitrogen (BUN) and glucose levels during the five days of administration. Additionally, although most parameters normalized within 30 days after treatment, the decrease in BUN persisted. Mice experienced short-term weight loss following CoPP administration, but they regained their initial weight within two weeks. By day 30, leukocyte counts, hematopoietic stem and progenitor cells (HSPCs) in bone marrow, and G-CSF concentration in the blood had returned to baseline.This study demonstrates that CoPP mobilizes cells from the bone marrow to the blood in a dose-dependent manner, with mild side effects, including temporary changes in biochemical markers and a sustained reduction in BUN levels.
Rapid ecosystem change after the cod collapse in Newfoundland & Labrador
Authors: Wudrick Alannah , Regular Paul M. , Tam Jamie C. , Bélanger David , Eddy Tyler D. 
Published: October 2024

AbstractThe cod collapse of Newfoundland and Labrador in the early 1990s was predicated by collapses of the key forage fish species in the region, capelin, and the wider groundfish community. After these collapses, rapid changes in ecosystem structure and function have been observed. From the early 2000s to mid 2010s, invertebrates dominated ecosystem biomass and the snow crab fishery became important to the region. During the late 2010s, invertebrates declined as groundfish stocks increased, although not to pre collapse levels. We developed two ecosystem models representing 1) the Grand Banks and 2) the Newfoundland and Labrador Shelf ecosystem structure and function for 2018-2020. We compared these models with existing ecosystem models that represent the combined Grand Banks and Newfoundland and Labrador Shelf ecosystem for the pre collapse (1985-1987) and invertebrate dominated (2013-2015) periods. Variability in primary productivity, species biomass, and catch reveal that the two model regions are distinct in ecosystem structure and function. Primary and secondary production has increased in the most recent period, however capelin biomass – an important factor for cod recovery – has remained low. Harp seals play a strong top-down ecosystem role and may be contributing to impaired cod recovery. Since the decline in capelin abundance, Arctic cod became an important alternative prey on the Newfoundland and Labrador Shelf region compared to reliance on sand lance and squid on the Grand Banks. Capelin has not shown signs of recovery in either region. Overall, the ecosystem structure in 2018-2020 in both regions is closer to the pre-collapse state than it was in 2013-2015, and the rapid change indicates that the system is highly dynamic.
Biocultural vulnerability of traditional crops in the Indian Trans Himalaya
Authors: Jaggi Harman , Anand Akshata , Solari Katherine A. , Echeverri Alejandra , Tobge Rinchen , Tsewang Tanzin , Suryawanshi Kulbhushansingh , Tuljapurkar Shripad 
Published: October 2024

AbstractTraditional agricultural landscapes in mountain communities are critical for conserving biodiversity, biocultural diversity, and agroecological resources. Despite their significance, traditional farming systems are overlooked in modern agriculture and conservation, leading to genetic erosion and reduced cultivation of local crop landraces. Our research focuses on the fragile ecosystems of northwest Himalaya in India, and examines the ecological and genetic resilience of black pea (lesser known and understudied traditional crop) and barley (Hordeum vulgare) and compares them to the introduced cash crop of green pea (Pisum sativum L.). We conducted field experiments across elevation gradients to assess survival and reproductive traits for the three crops. We performed whole-genome sequencing to investigate the genetic diversity of black pea in relation to otherPisumspecies. Additionally, we analyzed the nutritional profile of black pea in comparison with green pea. Our findings indicate that traditional crops are better adapted to local climatic conditions in terms of their growth performance, and hold considerable genetic diversity and nutritional potential. Our results support the importance of integrating traditional knowledge with modern agroecological research and policy to promote climate-resilient, sustainable food systems. The results also argue for a reevaluation of traditional and often underutilized crops to support small-holding farmers and promote socio-ecological stability in vulnerable mountain regions.
Transposable element small and long RNAs in aging brains and implications in Huntington’s and Parkinson’s disease
Authors: Dayama Gargi , Gupta Shruti , Connizzo Brianne K. , Labadorf Adam T. , Myers Richard H. , Lau Nelson C. 
Published: October 2024

ABSTRACTTransposable Elements (TEs) are implicated in aging and neurodegenerative disorders, but the impact of brain TE RNA dynamics on these phenomena is not fully understood. Therefore, we quantified TE RNA changes in aging post-mortem human and mouse brains and in the neurodegenerative disorders Huntington’s Disease (HD) and Parkinson’s Disease (PD). We tracked TE small RNAs (smRNAs) expression landscape to assess the relationship to the active processing from TE long RNAs (lnRNAs). Human brain transcriptomes from the BrainSpan Atlas displayed a significant shift of TE smRNA patterns at age 20 years, whereas aging mouse brains lacked any such marked change, despite clear shift in aging-associated mRNA levels. Human frontal cortex displayed pronounced sense TE smRNAs during aging with a negative relationship between the TE smRNAs and lnRNAs indicative of age associated regulatory effects. Our analysis revealed TE smRNAs dysregulation in HD, while PD showed a stronger impact on TE lnRNAs, potentially correlating with the early average age of death for HD relative to PD. Furthermore, TE-silencing factor TRIM28 was down-regulated only in aging human brains, possibly explaining the lack of substantial TE RNA changes in aging mouse brains. Our study suggests brain TE RNAs may serve as novel biomarkers of human brain aging and neurodegenerative disorders.
A DJ123 allele at the heading date quantitative trait locusqHd7.1promotes early heading without yield penalties under natural short-day and low fertility conditions in Madagascar
Authors: Kondo Katsuhiko , Hori Kiyosumi , Rakotondramanana Mbolatantely , Ranaivo Harisoa Nicole , Ueda Yoshiaki , Wissuwa Matthias 
Published: October 2024

AbstractQTL analysis of heading date (Hd) was performed using a recombinant inbred line population derived from a cross between rice cultivars ʻIR64’ and ʻDJ123’. Phenotypic data was obtained from sites in Japan and Madagascar differing in photoperiod and soil fertility. The Japan site had long-days (LD) and high fertility, while the Madagascar site had short-days (SD) and low fertility conditions. Under LD in Japan, we discovered two Hd QTL on chromosome 7,qHd7.1andqHd7.2, whereas only one of these (qHd7.1) was detected under SD conditions in Madagascar. RILs carrying DJ123 alleles at both QTLs headed 9.5 days earlier in Japan (LD) compared to IR64 alleles, whereas the effect of DJ123 alleles atqHd7.1under SD conditions of Madagascar was 4 days and a combined effect ofqHd7.1andqHd7.2did not exist. In Madagascar, early heading did not carry a yield penalty, whereas it caused reduced grain yield in Japan. These results suggest that RILs harboring the DJ123 allele ofqHd7.1have high yield potential and good adaptation to low fertility conditions in Madagascar and that this can be achieved in a shortened cultivation period, improving resilience to effects of climate change for African rice farmers.
Root Remodeling Mechanisms and Salt Tolerance Trade-Offs: The Roles of HKT1, TMAC2, and TIP2;2 in Arabidopsis
Authors: Alshareef N. O. , Melino V. J. , Saber N. , De Rosa A. , Rey E. , Wang J.Y. , Al Babili S. , Byrt C. , Tester M.A. , Julkowska M. M. 
Published: October 2024

AbstractPlant responses to salt stress involve complex processes integrating short- and long-term adaptations, including changes in ion transport, systemic signaling, root architecture, and biomass distribution. A key adaptive mechanism involves the regulation of sodium (Na+) and potassium (K+) ion transport via Class 1 HKT1 transporters, which reduce Na+accumulation in shoots, thereby enhancing salinity tolerance but at the expense of lateral root development. In this study, we identified differential roles of TMAC2 in modulating ABA accumulation and lateral root development under salt stress in two distinct Arabidopsis genotypes, Col-0 and C24. Overexpression of TMAC2 in the Col-0 background increased ABA accumulation, resulting in reduced lateral root development, suggesting a positive feedback loop involving HKT1, TMAC2, and ABA signaling. In contrast, TMAC2 overexpression in C24 reduced ABA accumulation in lines overexpressing HKT1, indicating genotype-specific differences in the TMAC2-HKT1 interaction. Additionally, we observed that the co-expression of TMAC2 and HKT1 in Col-0 induced ABI4 and ABI5 transcription factors, which are known to mediate salt sensitivity. These findings reveal a regulatory network where TMAC2 and HKT1 modulate salt stress responses through genotype-dependent feedback mechanisms. Our results highlight the complexity of root remodeling under salt stress and the crucial role of genetic background in shaping these adaptive responses.
Metastable phase-separated droplet generation and long-time DNA enrichment by laser-induced Soret effect
Authors: Kobayashi Mika , Minagawa Yoshihiro , Noji Hiroyuki 
Published: October 2024

AbstractSpatiotemporally controlled laser-induced phase separation (LIPS) offers unique research avenues and has a potential for biological and biomedical applications. However, LIPS conditions often have drawbacks for practical use, which limit their applications. For instance, LIPS droplets are tentative and diminish after the laser is terminated. Here, we developed a novel LIPS method using laser-induced Soret effect with a simple setup to solve these problems. We generate liquid-liquid phase-separated (LLPS) droplets using LIPS in an aqueous two-phase system (ATPS) of dextran (DEX) and polyethylene glycol (PEG). When DEX-rich droplets were generated in the DEX/PEG mix on the phase boundary, the droplets showed unprecedently high longevity; the DEX droplets were retained over 48 h. This counterintuitive behavior suggests that the droplet is in an unknown metastable state. By exploiting the capability of DEX-rich droplets to enrich nucleic acid polymers, we achieved stable DNA enrichment in LIPS DEX droplets with a high enrichment factor of 1400 ± 400. Further, we patterned DNA-carrying DEX-rich droplets into a designed structure to demonstrate the stability and spatiotemporal controllability of DEX-rich droplet formation. This is the first report for LIPS droplet generation in a DEX/PEG system with flexible conditions for the usage of LIPS droplets, opening new avenues for biological and medical applications of LIPS.
TheMedicago truncatulaLYR4 intracellular domain serves as a scaffold in immunity signaling independent of its phosphorylation activity
Authors: Simonsen Bine , Rübsam Henriette , Kolte Marie Vogel , Larsen Maria Meisner , Krönauer Christina , Gysel Kira , Laursen Mette , Feng Feng , Kaya Gülendam , Oldroyd Giles E. D. , Stougaard Jens , Fort Sébastien , Radutoiu Simona , Andersen Kasper Røjkjær 
Published: October 2024

AbstractPlants perceive and respond to chitin derived from fungal cell walls through lysine motif (LysM) receptor kinases. In the model legumeMedicago truncatula, CERK1 and LYR4 represent the LysM receptor pair important for chitin-triggered immunity signaling. Here, we show that both the active kinase receptor CERK1 and the pseudokinase receptor LYR4 contribute to immunity signaling, leading to the production of reactive oxygen species (ROS). We determine the crystal structure of the LYR4 core intracellular domain with a bound nucleotide analog in the active site. Biochemical characterization shows that LYR4 binds ATP and has both autophosphorylation as well as transphosphorylation activity towards CERK1. However,in plantaexperiments demonstrate that the phosphorylation ability is not necessary for the function of LYR4 in chitin-triggered ROS production, but that the presence of its intracellular domain is indispensable. Together, we show that in chitin-triggered immunity the intracellular domain of LYR4 serves as a signaling scaffold independent of its catalytic activity.
Regulating ferredoxin electron transfer using nanobody and antigen interactions
Authors: Truong Albert , Silberg Jonathan J. 
Published: October 2024

AbstractFission and fusion can be used to generate new regulatory functions in proteins. This approach has been used to create ferredoxins (Fd) whose cellular electron transfer is dependent upon small molecule binding. To investigate whether Fd fragments can be used to monitor macromolecular binding reactions, we investigated the effects of fusing fragments ofMastigocladus laminosusFd to nanobodies and their protein antigens. When Fd fragments arising from fission were fused to green fluorescent protein (GFP) and three different anti-GFP nanobodies, split proteins were identified that supported Fd-mediated electron transfer from Fd-NADP reductase (FNR) to sulfite reductase (SIR) inEscherichia coli. However, the order of nanobody and antigen fusion to the Fd fragments affected cellular electron transfer. Insertion of these anti-GFP nanobodies within Fd had differing effects on electron transfer. One domain-insertion variant was unable to support cellular electron transfer unless it was coexpressed with GFP, while others supported electron transfer in the absence of GFP. These findings show how Fds can be engineered so that their electron transfer is regulated by macromolecules, and they reveal the importance of exploring different nanobody homologs and fusion strategies when engineering biomolecular switches.
AI-readiness for Biomedical Data: Bridge2AI Recommendations
Authors: Clark Timothy , Caufield Harry , Parker Jillian A. , Al Manir Sadnan , Amorim Edilberto , Eddy James , Gim Nayoon , Gow Brian , Goar Wesley , Haendel Melissa , Hansen Jan N. , Harris Nomi , Hermjakob Henning , Joachimiak Marcin , Jordan Gianna , Lee In-Hee , K. McWeeney Shannon , Nebeker Camille , Nikolov Milen , Shaffer Jamie , Sheffield Nathan , Sheynkman Gloria , Stevenson James , Chen Jake Y. , Mungall Chris , Wagner Alex , Kong Sek Won , Ghosh Satrajit S. , Patel Bhavesh , Williams Andrew , Munoz-Torres Monica C. 
Published: October 2024

AbstractBiomedical research and clinical practice are in the midst of a transition toward significantly increased use of artificial intelligence (AI) and machine learning (ML) methods. These advances promise to enable qualitatively deeper insight into complex challenges formerly beyond the reach of analytic methods and human intuition while placing increased demands on ethical and explainable artificial intelligence (XAI), given the opaque nature of many deep learning methods.The U.S. National Institutes of Health (NIH) has initiated a significant research and development program, Bridge2AI, aimed at producing new “flagship” datasets designed to support AI/ML analysis of complex biomedical challenges, elucidate best practices, develop tools and standards in AI/ML data science, and disseminate these datasets, tools, and methods broadly to the biomedical community.An essential set of concepts to be developed and disseminated in this program along with the data and tools produced are criteria for AI-readiness of data, including critical considerations for XAI and ethical, legal, and social implications (ELSI) of AI technologies. NIH Bridge to Artificial Intelligence (Bridge2AI) Standards Working Group members prepared this article to present methods for assessing the AI-readiness of biomedical data and the data standards perspectives and criteria we have developed throughout this program. While the field is rapidly evolving, these criteria are foundational for scientific rigor and the ethical design and application of biomedical AI methods.
A methodological framework for deriving the German food-based dietary guidelines 2024: food groups, nutrient goals, and objective functions
Authors: Schäfer Anne Carolin , Boeing Heiner , Gazan Rozenn , Conrad Johanna , Gedrich Kurt , Breidenassel Christina , Hauner Hans , Kroke Anja , Linseisen Jakob , Lorkowski Stefan , Nöthlings Ute , Richter Margrit , Schwingshackl Lukas , Vieux Florent , Watzl Bernhard 
Published: October 2024

AbstractBackgroundFor a growing number of food-based dietary guidelines (FBDGs), diet optimization is the tool of choice to account for the complex demands of healthy and sustainable diets. However, decisions about such optimization models’ parameters are rarely reported nor systematically studied.ObjectivesThe objectives were to develop a framework for (i) the formulation of decision variables based on a hierarchical food classification system; (ii) the mathematical form of the objective function; and (iii) approaches to incorporate nutrient goals.MethodsTo answer objective (i), food groups from FoodEx2 levels 3-7 were applied as decision variables in a model using acceptability constraints (5thand 95thpercentile for food intakes of German adults (n=10,419)) and minimizing the deviation from the average observed dietary intakes. Building upon, to answer objectives (ii) and (iii), twelve models were run using decision variables from FoodEx2 level 3 (n=255), applying either a linear or squared and a relative or absolute way to deviate from observed dietary intakes, and three different lists of nutrient goals (allNUT-DRV, incorporating all nutrient goals; modNUT-DRV excluding nutrients with limited data quality; modNUT-AR using average requirements where applicable instead of recommended intakes).ResultsFoodEx2 food groups proved suitable as diet optimization decision variables. Regarding deviation, the largest differences were between the four different objective function types, e.g. in the linear-relative modNUT-DRV model, 46 food groups of the observed diet were changed to reach the model’s goal, in linear-absolute 78 food groups, squared-relative 167, and squared-absolute 248. The nutrient goals were fulfilled in all models, but the number of binding nutrient constraints was highest in the linear-relative models (e.g. allNUT-DRV: 11 vs. 7 in linear-absolute).ConclusionConsidering the various possibilities to operationalize dietary aspects in an optimization model, this study offers valuable contributions to a framework for developing FBDGs via diet optimization.
Identifying and Characterizing Bias at Scale in Clinical Notes Using Large Language Models
Authors: Apakama Donald U. , Nguyen Kim-Anh-Nhi , Hyppolite Daphnee , Soffer Shelly , Mudrik Aya , Ling Emilia , Moses Akini , Temnycky Ivanka , Glasser Allison , Anderson Rebecca , Parchure Prathamesh , Woullard Evajoyce , Edalati Masoud , Chan Lili , Kronk Clair , Freeman Robert , Kia Arash , Timsina Prem , Levin Matthew A. , Khera Rohan , Kovatch Patricia , Charney Alexander W. , Carr Brendan G. , Richardson Lynne D. , Horowitz Carol R. , Klang Eyal , Nadkarni Girish N. 
Published: October 2024

ABSTRACTImportanceDiscriminatory language in clinical documentation impacts patient care and reinforces systemic biases. Scalable tools to detect and mitigate this are needed.ObjectiveDetermine utility of a frontier large language model (GPT-4) in identifying and categorizing biased language and evaluate its suggestions for debiasing.DesignCross-sectional study analyzing emergency department (ED) notes from the Mount Sinai Health System (MSHS) and discharge notes from MIMIC-IV.SettingMSHS, a large urban healthcare system, and MIMIC-IV, a public dataset.ParticipantsWe randomly selected 50,000 ED medical and nursing notes from 230,967 MSHS 2023 adult ED visiting patients, and 500 randomly selected discharge notes from 145,915 patients in MIMIC-IV database. One note was selected for each unique patient.Main Outcomes and MeasuresPrimary measure was accuracy of detection and categorization (discrediting, stigmatizing/labeling, judgmental, and stereotyping) of bias compared to human review. Secondary measures were proportion of patients with any bias, differences in the prevalence of bias across demographic and socioeconomic subgroups, and provider ratings of effectiveness of GPT-4’s debiasing language.ResultsBias was detected in 6.5% of MSHS and 7.4% of MIMIC-IV notes. Compared to manual review, GPT-4 had sensitivity of 95%, specificity of 86%, positive predictive value of 84% and negative predictive value of 96% for bias detection. Stigmatizing/labeling (3.4%), judgmental (3.2%), and discrediting (4.0%) biases were most prevalent. There was higher bias in Black patients (8.3%), transgender individuals (15.7% for trans-female, 16.7% for trans-male), and undomiciled individuals (27%). Patients with non-commercial insurance, particularly Medicaid, also had higher bias (8.9%). Higher bias was also seen in health-related characteristics like frequent healthcare utilization (21% for >100 visits) and substance use disorders (32.2%). Physician-authored notes showed higher bias than nursing notes (9.4% vs. 4.2%, p < 0.001). GPT-4’s suggested revisions were rated highly effective by physicians, with an average improvement score of 9.6/10 in reducing bias.Conclusions and RelevanceA frontier LLM effectively identified biased language, without further training, showing utility as a scalable fairness tool. High bias prevalence linked to certain patient characteristics underscores the need for targeted interventions. Integrating AI to facilitate unbiased documentation could significantly impact clinical practice and health outcomes.