bluuebunny/crossref_metadata_2025_split huggingface dataset:
BirdNET is as good as experts for acoustic bird monitoring in a European city
Authors: Fairbairn Andrew J. , Burmeister Josija-Simeon , Weisser Wolfgang W. , Meyer Sebastian T. 
Published: September 2024

AbstractBirdNET has become a leading AI for recognising bird species in audio recordings. However, the effect of parameter settings on the algorithm’s performance is not well understood, leaving questions about its applicability in ecological research. We compared the species identification of BirdNET against expert identification using an acoustic dataset consisting of 930 minutes of recordings collected in Munich, Germany. The performance of BirdNET was evaluated using three performance metrics: precision, recall, and F1-score. The metrics were calculated using 24 combinations of the parameters week, sensitivity, and overlap at four temporal aggregations, to also test the effects of recording length. We found that BirdNET closely matched expert identification, particularly when given more data (higher temporal aggregation) and when including the parameters week of the year, a suitable sensitivity, and an overlap of one to two seconds. Thus, our study shows that BirdNET can provide species lists and richness comparable to that of expert ornithologists in acoustic surveys in urban environments. We provide a set of recommendations and parameter settings for BirdNET.
Differences in growth features between species are driving cereal-legume intercrop yield: a statistical learning approach based on aggregated dataset
Authors: Mahmoud Rémi , Gaudio Noémie , Gendre Xavier , Hilgert Nadine , Casadebaig Pierre 
Published: September 2024

AbstractIncreasing crop diversification is crucial for developing more sustainable agricultural systems, and cereal-legume intercropping is a promising strategy. This study investigates the factors influencing the yield of cereal-legume intercrops using data from six field experiments in southwestern France, where durum wheat was intercropped with either faba bean or pea. We assessed how differences in plant traits between the associated species (e.g., height or biomass growth rates) are related to the intercrop productivity. Additionally, we developed a novel modeling approach, combining machine learning and mixed-effects models, to identify the key traits driving intercrop performance based on variable importance.Our results show that interspecific differences in plant traits, particularly in biomass accumu-lation rate, maximum leaf area index, and elongation rate, were the most important factors explaining intercrop yield. These traits and their differences mainly suggest that compet-itive processes shape the outcome of a mixture and highlight the importance of dynamic measurements in agronomic experiments. The relationship between species yield and trait differences was symmetric for both intercropped species. Furthermore, these relationships were scale-dependent, with trends observed at the aggregate level not always consistent at the level of individual experiments.Our study highlights the importance of considering trade-offs when designing intercropping systems for practical applications and demonstrates the value of combining machine learning with ecological knowledge to gain insights into complex agricultural systems from aggregated datasets.HighlightsJoint analysis of experimental datasets provided new insights into crop mixtures func-tioning.Differences in growth traits between species in the mixture predicted their perfor-mance.The strength of the correlation between performance and trait distance was similar for both species.Farmers and researchers need to consider trade-offs when designing intercropping sys-tems.
Single-cell Landscape of Immune Cells in Blood and Skin in Psoriasis
Authors: Deng Jingwen , Nordkamp Michel Olde , Ye Shuyan , Yu Jingjie , Balak Deepak , Yu Wanlin , Radstake Timothy , Borghans José A. M. , Lu Chuanjian , Pandit Aridaman , Gerritsen Bram 
Published: September 2024

AbstractBackgroundPsoriasis is a systemic inflammatory disease for which there is currently no cure, in part due to an incomplete understanding of its pathophysiology.MethodsTo better understand the immune response in psoriasis, we performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) and on lesional and non-lesional skin samples from a cohort of 11 psoriasis patients and 8 healthy controls. Additionally, we conducted flow cytometry on PBMCs from a separate cohort of 13 psoriasis patients and 11 ankylosing spondylitis.FindingsOur study revealed altered immune signatures of specific myeloid and lymphocyte subsets in blood and skin, both in terms of cell numbers and gene expression. Specifically, we discovered elevated proportions of circulating CD14++monocytes, increased expression of major histocompatibility complex (MHC) class II molecule by circulating CD16+monocytes, as well as increased expression of genes related to skin homing and to pro-inflammatory responses in psoriasis by circulating plasmacytoid dendritic cells (pDCs). Circulating CD8+T effector memory cells in psoriasis patients exhibited reduced abundance but increased skin-homing potential. In psoriatic lesions, we observed a hyperinflammatory myeloid-cell state and enrichment of IL17-producing cells with a tissue-resident memory T-cell signature.InterpretationThe changes in immune cell numbers and gene expression indicate a significant alteration in the immune landscape of psoriasis patients. This suggests that the immune system in psoriasis is reprogrammed, affecting both innate and adaptive branches. These findings provide new insights into the aberrant immune-cell signatures in the circulation and skin lesions in psoriasis, and thereby help to understand its pathophysiology.FundingThis study was financially supported by the National Natural Science Foundation of China (U23A6012), Science and Technology Planning Project of Guangzhou (2024A03J0055, 202206080005), Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-C-202204).
Evaluation of genomic and phenomic prediction for application in apple breeding
Authors: Jung Michaela , Hodel Marius , Knauf Andrea , Kupper Daniela , Neuditschko Markus , Bühlmann-Schütz Simone , Studer Bruno , Patocchi Andrea , Broggini Giovanni AL 
Published: September 2024

AbstractApple breeding schemes can be improved by using genomic prediction models to forecast the performance of breeding material. These models’ predictive ability depends on factors like trait genetic architecture, training set size, relatedness of the selected material to the training set, and the validation method used. Alternative genotyping methods such as RADseq and complementary data from near-infrared spectroscopy could help improve the cost-effectiveness of genomic selection. However, the impact of these factors and alternative approaches on predictive ability beyond experimental populations still need to be investigated. In this study, we evaluated 137 prediction scenarios varying the described factors and alternative approaches, offering recommendations for implementing genomic selection in apple breeding. Our results show that extending the training set with germplasm related to the predicted breeding material can improve average predictive ability across eleven studied traits by up to 0.08. The study emphasizes the usefulness of leave-one-family-out validation, reflecting the application of genomic selection to a new family, although it reduced average predictive ability across traits by up to 0.24 compared to cross-validation. Similar average predictive abilities across traits indicate that imputed RADseq data could be a suitable genotyping alternative to SNP array datasets. The best-performing scenario using near-infrared spectroscopy data for phenomic prediction showed a 0.35 decrease in average predictive ability across traits compared to conventional genomic prediction, suggesting that the tested phenomic selection approach is impractical. These findings offer valuable guidance for applying genomic selection in apple breeding, ultimately leading to the development of breeding material with improved quality.
Tenascin-C in the early lung cancer tumor microenvironment promotes progression through integrin αvβ1 and FAK
Authors: Samson Shiela C. , Rojas Anthony , Zitnay Rebecca G. , Carney Keith R. , Hettinga Wakeiyo , Schaelling Mary C. , Sicard Delphine , Zhang Wei , Gilbert-Ross Melissa , Dy Grace K. , Cavnar Michael J. , Furqan Muhammad , Browning Robert F. , Naqash Abdul R. , Schneider Bryan P. , Tarhini Ahmad , Tschumperlin Daniel J. , Venosa Alessandro , Marcus Adam I. , Emerson Lyska L. , Spike Benjamin T. , Knudsen Beatrice S. , Mendoza Michelle C. 
Published: September 2024

AbstractPre-cancerous lung lesions are commonly initiated by activating mutations in the RAS pathway, but do not transition to lung adenocarcinomas (LUAD) without additional oncogenic signals. Here, we show that expression of the extracellular matrix protein Tenascin-C (TNC) is increased in and promotes the earliest stages of LUAD development in oncogenic KRAS-driven lung cancer mouse models and in human LUAD. TNC is initially expressed by fibroblasts and its expression extends to tumor cells as the tumor becomes invasive. Genetic deletion of TNC in the mouse models reduces early tumor burden and high-grade pathology and diminishes tumor cell proliferation, invasion, and focal adhesion kinase (FAK) activity. TNC stimulates cultured LUAD tumor cell proliferation and migration through engagement of αv-containing integrins and subsequent FAK activation. Intringuingly, lung injury causes sustained TNC accumulation in mouse lungs, suggesting injury can induce additional TNC signaling for early tumor cell transition to invasive LUAD. Biospecimens from patients with stage I/II LUAD show TNC in regions of FAK activation and an association of TNC with tumor recurrence after primary tumor resection. These results suggest that exogenous insults that elevate TNC in the lung parenchyma interact with tumor-initiating mutations to drive early LUAD progression and local recurrence.
Advancing Clinical Response Against Glioblastoma: Evaluating SHP1705 CRY2 Activator Efficacy in Preclinical Models and Safety in Phase I Trials
Authors: Chan Priscilla , Nagai Yoshiko , Wu Qiulian , Hovsepyan Anahit , Mkhitaryan Seda , Wang Jiarui , Karapetyan Gevorg , Kamenecka Theodore , Solt Laura A. , Cope Jamie , Moats Rex A. , Hirota Tsuyoshi , Rich Jeremy N. , Kay Steve A. 
Published: September 2024

ABSTRACTBackgroundIt has been reported that circadian clock components, Brain and Muscle ARNT-Like 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK), are uniquely essential for glioblastoma (GBM) stem cell (GSC) biology and survival. Consequently, we developed a novel Cryptochrome (CRY) activator SHP1705, which inhibits BMAL1-CLOCK transcriptional activity.MethodsWe analyzed buffy coats isolated from Phase 1 clinical trial subjects’ blood to assess any changes to circadian, housekeeping, and blood transcriptome-based biomarkers following SHP1705 treatment. We utilized GlioVis to determine which circadian genes are differentially expressed in non-tumor versus GBM tissues. We employedin vitroandin vivomethods to test the efficacy of SHP1705 against patient-derived GSCs and xenografts in comparison to earlier CRY activator scaffolds. Additionally, we applied a novel-REV-ERB agonist SR29065, which inhibitsBMAL1transcription, to determine whether targeting both negative limbs of the circadian transcription-translation feedback loop (TTFL) would yield synergistic effects against various GBM cells.ResultsSHP1705 is safe and well-tolerated in Phase I clinical trials. SHP1705 has increased selectivity for the CRY2 isoform and potency against GSC viability compared to previously published CRY activators. SHP1705 prolonged survival in mice bearing GBM tumors established with GSCs. When combined with the novel REV-ERB agonist SR29065, SHP1705 displayed synergy against multiple GSC lines and differentiated GSCs (DGCs).ConclusionsThese demonstrate the efficacy of SHP1705 against GSCs, which pose for GBM patient outcomes. They highlight the potential of novel circadian clock compounds in targeting GBM as single agents or in combination with each other or current standard-of-care.KEY POINTSSHP1705 is a novel CRY2 activator that has shown success in Phase 1 safety trialsSHP1705 has a significantly improved efficacy against GSCs and GBM PDX tumorsNovel REV-ERB agonist SR29065 and SHP1705 display synergistic effects against GSCsIMPORTANCE OF THE STUDYCRY2is decreased in GBM tissues compared toCRY1suggesting that promoting CRY2 activity will be an efficacious GBM treatment paradigm. SHP1705, a CRY2 activator that has shown success in Phase 1 safety trials, has significantly improved preclinical efficacy. Novel REV-ERB agonist SR29065 displays synergistic effects against diverse GBM cells.
Myofiber-specific FoxP1 knockout protects against pancreatic cancer-induced muscle wasting in male but not female mice
Authors: Schonk Martin M , Ducharme Jeremy B , Neyroud Daria , Nosacka Rachel L , Tucker Haley O , Judge Sarah M , Judge Andrew R 
Published: September 2024

ABSTRACTCancer cachexia affects up to 80% of cancer patients and results in reduced quality of life and survival. We previously demonstrated that the transcriptional repressor Forkhead box P1 (FoxP1) is upregulated in skeletal muscle of cachectic mice and people with cancer, and when overexpressed in skeletal muscle is sufficient to induce pathological features characteristic of cachexia. However, the role of myofiber-derived FoxP1 in both normal muscle physiology and cancer-induced muscle wasting remains largely unexplored. To address this gap, we generated a conditional mouse line with myofiber-specific ablation of FoxP1 (FoxP1SkmKO) and found that in cancer-free mice, deletion of FoxP1 in skeletal myofibers resulted in increased myofiber size in both males and females, with a significant increase in muscle mass in males. In response to murine KPC pancreatic tumor burden, we found that myofiber-derived FoxP1 is required for cancer-induced muscle wasting and diaphragm muscle weakness in male mice. In summary, our findings identify myofiber-specific FoxP1 as a negative regulator of skeletal muscle with sex-specific differences in the context of cancer.NEW & NOTEWORTHYHere we identify myofiber-derived FoxP1 as a negative regulator of skeletal muscle with sex-specific effects in cancer. Under cancer-free conditions, FoxP1 knockout increased myofiber size in male and female mice. However, in response to pancreatic cancer, FoxP1 was required for muscle wasting and weakness in males but not females. This highlights the need to consider sexual dimorphism in cancer-induced muscle pathologies and provides evidence suggesting that targeting FoxP1 could help mitigate these effects in males.
Room-Temperature Aerosol Dehydration of Green Fluorescent Protein
Authors: Pan Zehao , Wang Junshi , Stone Howard A. , Mezhericher Maksim 
Published: September 2024

ABSTRACTRapid Room-Temperature Aerosol Dehydration (RTAD) is a novel, scalable drying technology for powderization and thermal stabilization of pharmaceutical drug products. Compared to conventional spray drying, RTAD utilizes sub-20µm droplets that evaporate rapidly at room temperature, thereby reducing drying-induced stresses for thermally sensitive biologics. In this study, we employed Green Fluorescent Protein (GFP) as a model biological molecule to optimize the RTAD system design and process parameters. We investigated the effects of droplet size, multiphase flow patterns in the drying chamber, and usage of polysorbate 20 as a model surfactant on GFP fluorescence after drying and powder reconstitution. The experiments demonstrated that the presence of polysorbate 20 in the formulation significantly influenced GFP fluorescence intensity, especially for smaller droplets. The numerical studies using Computational Fluid Dynamics simulations revealed that the intensity of GFP fluorescence in the produced dry powders was dependent on the patterns of multiphase flow in the drying chamber. Non-axisymmetric flows and closed circulating streamlines near the drying gas inlet negatively impacted the GFP fluorescence intensity. Through iterative optimization of chamber design, process parameters, and feedstock formulation, we achieved the recovery (compared to the initial samples) of GFP fluorescence intensity exceeding 96% in the obtained dry powders. This work establishes GFP as a sensitive model biologic and its fluorescence intensity as a powerful tool for rapidly assessing bioactivity following dehydration. The insights gained from this study have broad implications for the design and scale-up of room-temperature drying technologies, which can potentially transform the production of dry powder biopharmaceuticals.
Integration of metabolomic and transcriptomic analyses reveals novel regulatory functions of the ChREBP transcription factor in energy metabolism
Authors: An Jie , Astapova Inna , Zhang Guofang , Cangelosi Andrew L. , Ilkayeva Olga , Marchuk Hannah , Muehlbauer Michael J. , George Tabitha , Brozinick Joseph , Herman Mark A. , Newgard Christopher B. 
Published: September 2024

AbstractCarbohydrate Response Element-Binding Protein (ChREBP) is a transcription factor that activates key genes involved in glucose, fructose, and lipid metabolism in response to carbohydrate feeding, but its other potential roles in metabolic homeostasis have not been as well studied. We used liver-selective GalNAc-siRNA technology to suppress expression of ChREBP in rats fed a high fat/high sucrose diet and characterized hepatic and systemic responses by integrating transcriptomic and metabolomic analyses. GalNAc-siChREBP-treated rats had lower levels of multiple short-chain acyl CoA metabolites compared to rats treated with GalNAc-siCtrl containing a non-targeting siRNA sequence. These changes were related to a sharp decrease in free CoA levels in GalNAc-siChREBP treated-rats, accompanied by lower expression of transcripts encoding enzymes and transporters involved in CoA biosynthesis. These activities of ChREBP likely contribute to its complex effects on hepatic lipid and energy metabolism. While core enzymes of fatty acid (FA) oxidation are induced by ChREBP knockdown, accumulation of liver acylcarnitines and circulating ketones indicate diversion of acetyl CoA to ketone production rather than complete oxidation in the TCA cycle. Despite strong suppression of pyruvate kinase and activation of pyruvate dehydrogenase, pyruvate levels were maintained, likely via increased expression of pyruvate transporters, and decreased expression of lactate dehydrogenase and alanine transaminase. GalNAc-siChREBP treatment increased hepatic citrate and isocitrate levels while decreasing levels of distal TCA cycle intermediates. The drop in free CoA levels, needed for the 2-ketoglutarate dehydrogenase reaction, as well as a decrease in transcripts encoding the anaplerotic enzymes pyruvate carboxylase, glutamate dehydrogenase, and aspartate transaminase likely contributed to these effects. GalNAc-siChREBP treatment caused striking increases in PRPP and ZMP/AICAR levels, and decreases in GMP, IMP, AMP, NaNM, NAD(P), and NAD(P)H levels, accompanied by reduced expression of enzymes that catalyze late steps in purine and NAD synthesis. ChREBP suppression also increased expression of a set of plasma membrane amino acid transporters, possibly as an attempt to replenish TCA cycle intermediates. In sum, combining transcriptomic and metabolomic analyses has revealed regulatory functions of ChREBP that go well beyond its canonical roles in control of carbohydrate and lipid metabolism to now include mitochondrial metabolism and cellular energy balance.
Microbial strategies of environmental adaptation revealed by trait-environmental relationships
Authors: Ren Minglei , Hu Ang , Zhao Zhonghua , Yao Xiaolong , Kimirei Ismael Aaron , Zhang Lu , Wang Jianjun 
Published: September 2024

AbstractMicrobial trait variation along environment gradients is crucial to understanding their ecological adaptation mechanisms. With the increasing availability of microbial genomes, making full use of the genome-based traits to decipher their adaptation strategies becomes promising and urgent. Here, we examined microbial communities in water and sediments of 20 East African lakes with pH values ranging from 7.2 to 10.1 through taxonomic-profiling and genome-centric metagenomics. We identified functional traits important for microbial adaptation to the stresses of alkalinity and salinity based on the significant trait-environment relationships (TERs), including those involved in cytoplasmic pH homeostasis, compatible solute accumulation, cell envelope modification and energy requisition. By integrating these significant-TER traits, we further developed an environmental adaptation index to quantify the species-level adaptive capacity for environmental stresses, such as high pH environments. The adaptation index of pH showed consistently significant positive relationships with species pH optima across regional and global genomic datasets from freshwater, marine and soda lake ecosystems. The generality of the index for quantifying environmental adaptation was demonstrated by showing significant relationships with the species niche optima for the gradients of soil temperature and seawater salinity. These results highlight the importance of trait-environment relationships in facilitating the inference of microbial genomic-based adaptation mechanisms, and expand our understanding of ecological adaptative strategies along environmental gradients.
Distinct duration and diet dependent lipid profiles and renal complications in GCK-MODY
Authors: Huang Yadi , Fan Yuxin , Liu Yang , Liu Xuan , Li Wei , Yang Ying , Zhang Ziyue , Ma Shifeng , Ji Shuhui , Chen Shanshan , Shu Hua , Feng Wenli , Wang Kunling , He Qing , Qi Wenjun , Fan Yu , Li Xin , Liu Ming 
Published: September 2024

AbstractHeterozygous inactivating mutations in the glucokinase (GCK) gene cause one of the most common types of maturity-onset diabetes of the young type 2 (MODY2), also named GCK-MODY. Studies suggest that, unlike other types of diabetes, patients with GCK-MODY do not have increased risk of diabetic complications and therefore do not typically require antihyperglycemic therapy. However, long-term outcomes of GCK-MODY on lipid profiles and chronic complications under different dietary scenarios remain unclear. Herein, using a knock-in mouse model expressing a novel MODY causing mutation GCK-Q26L (GCKMut), we examined age- and diet-related lipid profiles and diabetic complications. We found that, although GCKMutmice exhibited mild elevated blood glucose, the lipid profiles, body fat composition, and diabetic kidney disease (DKD) were initially improved in high-fat-diet (HFD) fed mice at the age of 28 weeks, supporting potential beneficial effects of GCKMuton lipid metabolism and kidney health. Unexpectedly however, those protective effects diminished by 40 weeks, and became more severe dyslipidemia and kidney injury associated with renal fibrosis and inflammation at 60-week-old mice fed with normal diet (ND) or HFD. Those findings revealed distinct duration- and diet-dependent effects of inactivating GCK mutation on lipid profiles and DKD, highlighting previously unrealized long-term chronic complications in GCK-MODY.