bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting visual field global and local parameters from OCT measurements using explainable machine learning
Authors: Hasan Md Mahmudul , Phu Jack , Wang Henrietta , Sowmya Arcot , Meijering Erik , Kalloniatis Michael 
Published: February 2025

Abstract
Glaucoma is characterised by progressive vision loss due to retinal ganglion cell deterioration, leading to gradual visual field (VF) impairment. The standard VF test may be impractical in some cases, where optical coherence tomography (OCT) can offer predictive insights into VF for multimodal diagnoses. However, predicting VF measures from OCT data remains challenging. To address this, five regression models were developed to predict VF measures from OCT, Shapley Additive exPlanations (SHAP) analysis was performed for interpretability, and a clinical software tool called OCT to VF Predictor was developed. To evaluate the models, a total of 268 glaucomatous eyes (86 early, 72 moderate, 110 advanced) and 226 normal eyes were included. The machine learning models outperformed recent OCT-based VF prediction deep learning studies, with correlation coefficients of 0.76, 0.80 and 0.76 for mean deviation, visual field index and pattern standard deviation, respectively. Introducing the pointwise normalisation and step-size concept, a mean absolute error of 2.51 dB was obtained in pointwise sensitivity prediction, and the grayscale prediction model yielded a mean structural similarity index of 77%. The SHAP-based analysis provided critical insights into the most relevant features for glaucoma diagnosis, showing promise in assisting eye care practitioners through an explainable AI tool.
Unraveling the causal association between inflammatory bowel diseases and uveitis through mendelian randomization analysis
Authors: Zhong Min , An Hongjin , Gan Huatian 
Published: February 2025

Abstract
To investigate the causal relationship between inflammatory bowel disease (IBD) and uveitis, we conducted a two-sample bidirectional Mendelian randomization (MR) analysis utilizing summary data from genome-wide association studies (GWAS). The primary statistical analysis was performed using the inverse-variance weighted (IVW) method. False discovery rate (FDR) correction was used to control for false positives in multiple testing. In addition, sensitivity analyses were carried out using the MR Egger intercept test and Cochran’s Q test. The MR analysis revealed that genetically determined IBD (OR = 1.141, 95% CI 1.080–1.205, P = 2.21 × 10−6, PFDR = 6.90 × 10−6), ulcerative colitis (UC) (OR = 1.113, 95% CI 1.032–1.201, P = 0.006, PFDR = 0.009), and Crohn’s diseases (CD) (OR = 1.073, 95% CI 1.017–1.133, P = 0.010, PFDR = 0.011) had a causal effect on uveitis. Conversely, the reverse MR analysis did not reveal significant causal link of uveitis on IBD, including its two subtypes. Furthermore, the results of the MR-Egger and weighted median methods were consistent with the IVW method. No evidence of heterogeneity or pleiotropy was detected by sensitivity analysis. Our findings confirm that IBD and its main subtypes had a causal connection with uveitis. Further research is needed to elucidate the underlying pathophysiological mechanisms driving this association.
The transcriptomic landscape of monosomy X (45,X) during early human fetal and placental development
Authors: Suntharalingham Jenifer P. , del Valle Ignacio , Buonocore Federica , McGlacken-Byrne Sinead M. , Brooks Tony , Ogunbiyi Olumide K. , Liptrot Danielle , Dunton Nathan , Madhan Gaganjit K. , Metcalfe Kate , Nel Lydia , Marshall Abigail R. , Ishida Miho , Sebire Neil J. , Moore Gudrun E. , Crespo Berta , Solanky Nita , Conway Gerard S. , Achermann John C. 
Published: February 2025

Abstract
Monosomy X (45,X) is associated with Turner syndrome and pregnancy loss in humans, but the underlying mechanisms remain unclear. We therefore undertook an exploratory study of the transcriptomic landscape of clinically relevant human fetal 45,X tissues (including pancreas, liver, kidney, skin, placenta) with matched 46,XX and 46,XY control samples between 11 and 15 weeks post conception (n = 78). Although most pseudoautosomal region 1 (PAR1) genes are lower in monosomy X tissues, we also found reduced expression of several key genes escaping X inactivation (e.g., KDM5C and KDM6A), several ancestral X-Y gene pairs, and potentially clinically important transcripts such as genes implicated in ascending aortic aneurysm. In contrast, higher expression of an autosomal, long non-coding RNA (OVCH1-AS1) is seen in all 45,X tissues. In the placenta, lower expression of CSF2RA is demonstrated, likely contributing to immune dysregulation. Taken together, these findings provide insights into the biological consequences of a single X chromosome during early human development and potential insights in genetic mechanisms in Turner syndrome.
Holding back the damage: strong political institutions and the effect of populism on business investment
Authors: Corina Margherita , Hartwell Christopher , Carballo Alfonso 
Published: February 2025

Abstract
Populism is a political phenomenon that attempts to harness existing institutions for populist ends, often leading to negative consequences for businesses. However, can national institutions resist this pressure and mitigate the damage to firms? This paper investigates how populist electoral success influences corporate investment, unraveling the intricate connection between a country’s political institutions and the investment behavior of companies. Through the lens of political uncertainty and transaction cost economics, we theorize that countries with fortified checks and balances—facilitated by electoral systems (situated at the entrance to power), judicial independence (supervising the exercise of power), and government accountability (serving as ex-post checks)—effectively mitigate populist impulses. However, these checks and balances are also often targeted by populist leaders, as they prevent full implementation of a populist agenda. Analyzing a dataset spanning over 36,000 firms across 42 countries from 1995 to 2021, we find that existing checks and balances shield firms from populist excesses. In line with our theory, the longer a ruler is in power, the weaker these checks and balances remain. Our study highlights populism’s harm to business and the role of robust political institutions as mitigating factors.
Intravenous amino acids for renal protection in patients receiving temporary mechanical circulatory support: a secondary subgroup analysis of the PROTECTION study
Authors: Belletti Alessandro , Pisano Antonio , Scandroglio Anna Mara , Garofalo Eugenio , Calabrò Maria Grazia , Ferrod Federica , Monaco Fabrizio , Brambillasca Claudio , Baiardo Redaelli Martina , Meroi Francesco , Fominskiy Evgeny , Vignale Rosaria , Ajello Silvia , Venditto Maria , Scquizzato Tommaso , Porta Sabrina , Losiggio Rosario , Suriano Paola , Pontillo Domenico , Orso Daniele , Tomasi Enrico , Paternoster Gianluca , Lomivorotov Vladimir , Longhini Federico , Landoni Giovanni , Zangrillo Alberto , Maisano Francesco , Bellomo Rinaldo , Pieri Marina ,   PROTECTION Study Group Collaborators, D’Amico Filippo , Manazza Marco , Marmiere Marilena , Marzaroli Matteo , Monti Giacomo , Oliva Federico Mattia , Pruna Alessandro , Turi Stefano , Veneziano Marta , Vietri Simone , Zaraca Luisa , Fraja Diana Di , Verniero Luigi , Bruni Andrea , Perrelli Giulia , Prezzi Laura , Massaro Cristiano , Ferrante Palma , Arangino Cristina , Angelini Filippo , Bacchetti Giacomo , Vitielli Michelangelo , Gallicchio Francesca , Bradic Nikola , Ti Lian Kah 
Published: February 2025

Abstract

OBJECTIVES
In cardiac surgery patients, acute kidney injury (AKI) frequently occurs in the setting of haemodynamic instability and treatment with temporary mechanical circulatory support (tMCS). Recent evidence suggests amino acids (AA) infusion may reduce AKI rate. However, the effect of AA infusion in patients requiring tMCS may be less effective.

METHODS
We performed a secondary analysis of the PROTECTION multicentre randomized controlled trial including all patients treated with tMCS. Patients undergoing elective cardiac surgery with cardiopulmonary bypass were randomized to receive 2 g/kg ideal body weight/day of intravenous AA to a maximum of 100 g/day or matching placebo from operating room admission until up to 3 days, receipt of renal-replacement therapy, discharge from ICU or death. The primary outcome of the PROTECTION study was the rate of AKI, as in this secondary analysis. A total of 3511 patients were randomized in the study.

RESULTS
We studied 232 patients who received tMCS, 112 randomized to AA infusion and 120 to placebo. The median preoperative serum creatinine value was significantly higher among AA group patients (AA: 1.08, interquartile range 0.90–1.26; placebo: 0.98, interquartile range 0.85–1.15; P = 0.02). The rate of AKI, however, was lower in patients randomized to AA (44.6% vs 60.8%; relative risk 0.73; 95% confidence interval (0.57–0.94); P = 0.01; number needed to treat = 6). We found no significant differences in secondary outcomes.

CONCLUSIONS
Short-term AA infusion appears to reduce rate of AKI among patients requiring tMCS. Use of AA in this population at high-risk for renal failure appears justified.

Clinical trial registration number
ClinicalTrials.gov NCT03709264.
Scaling the fitness effects of mutations with respect to differentially adapted Arabidopsis thaliana accessions under natural conditions
Authors: Stearns Frank W , Zhou Juannan , Fenster Charles B 
Published: February 2025

Abstract
Mutations are the ultimate source of genetic variation for natural selection to act upon. A major question in evolutionary biology is the extent to which new mutations can generate genetic variation under natural conditions to permit adaptive evolution over ecological time scales. Here we collected fitness data for chemically induced (ethylmethane sulfonate, EMS) mutant lines descended from two Arabidopsis thaliana ecotypes that show differential adaptation to the local environment of our common garden plot. Using a novel nonparametric Bayesian statistical approach, we found that both ecotypes accumulated substantial proportions of beneficial mutations. The poorly adapted ecotype exhibited higher mean mutational effects and higher variance in the fitness effects of mutations compared to the well-adapted ecotype. Furthermore, we predict that it takes less than 4000 generations for the fitness space of the two ecotypes to overlap through mutation accumulation, and that a single founder, through mutation accumulation, is able to achieve the species-wide genetic variation in less than 10,000 generations. Our results provide evidence for relatively rapid local adaptation of Arabidopsis thaliana in natural conditions through new mutations, as well as the utility of a nonparametric Bayesian method for modeling the distribution of fitness effects for field-collected data.
Phytoplankton recruitment of specific microbial assemblages and phylosymbiotic patterns
Authors: Kim Joo-Hwan , Kim Jin Ho , Li Zhun , Shin Hyeon Ho , Lim Young Kyun , Baek Seung Ho , Wang Pengbin , Park Ro Young , Jin Soo Hwan , Han Myung-Soo , Park Bum Soo 
Published: February 2025

AbstractPhytoplankton and bacteria represent two major pillars of the carbon cycle in marine ecosystems. While their interactions are known to be tightly linked, the specific mechanisms underlying these interactions remain largely unexplored. Evidence of host-specific microbial assemblages could serve as a foundation for studies of detailed host-microbe interactions, yet such research remains limited in phytoplankton. Here, we not only investigate the microbial assemblages of six phytoplankton species, including multiple strains of dinoflagellates and diatoms, but also samples of phytoplankton blooms from the field. Our results reveal the presence of host-specific microbial assemblages in phytoplankton, with members of the core microbial lineages (MCGs) playing pivotal roles in shaping host-specific microbial assemblages and contributing to network structures. Deterministic processes, particularly host genotypes, were the dominant factors shaping microbial assemblages, overriding environmental influences. Consequently, microbial composition reflected the evolutionary relationships of the host species, demonstrating phylosymbiotic patterns. These findings suggest that studying MCGs will be a crucial foundation for investigating specific phytoplankton-microbe interactions and highlight the ecological and evolutionary importance of host-microbial specificity in phytoplankton.
LANTERN: Leveraging Large Language Models and Transformers for Enhanced Molecular Interactions
Authors: Nga Ha Cong , Pham Phuc , Hy Truong Son 
Published: February 2025

AbstractUnderstanding molecular interactions such as Drug-Target Interaction (DTI), Protein-Protein Interaction (PPI), and Drug-Drug Interaction (DDI) is critical for advancing drug discovery and systems biology. However, existing methods often struggle with scalability due to the vast chemical and biological space and suffer from limited accuracy when capturing intricate biochemical relationships. To address these challenges, we introduceLANTERN(Leveraging LargeLANguage Models andTransformers forEnhanced moleculaRinteractioNs), a novel deep learning framework that integrates Large Language Models (LLMs) with Transformer-based architectures to model molecular interactions more effectively. LANTERN generates high-quality, context-aware embeddings for drug and protein sequences, enabling richer feature representations and improving predictive accuracy. By leveraging a Transformer-based fusion mechanism, our framework enhances scalability by efficiently integrating diverse interaction data while maintaining computational feasibility. Experimental results demonstrate that LANTERN achieves state-of-the-art performance on multiple DTI and DDI benchmarks, significantly outperforming traditional deep learning approaches. Additionally, LANTERN exhibits competitive performance on challenging PPI tasks, underscoring its versatility across diverse molecular interaction domains. The proposed framework offers a robust and adaptable solution for modeling molecular interactions, efficiently handling a diverse range of molecular entities without the need for 3D structural data and making it a promising framework for foundation models in molecular interaction. Our findings highlight the transformative potential of combining LLM-based embeddings with Transformer architectures, setting a new standard for molecular interaction prediction. The source code and relevant documentation are available at:https://github.com/HySonLab/LANTERN.
Genetic Modifiers Influencing the Acute and Long-Term Responses to Traumatic Brain injury inDrosophila
Authors: Molina Brandon , Rojas Jesse J. , El-Mecharrafie Nadja , Ratliff Eric P. , Lipinski Marta M. , Finley Kim D. 
Published: February 2025

ABSTRACTWorldwide, traumatic brain injury (TBI) represents a major cause of mortality and long-term disability, with even mild repetitive forms of TBI (mTBI) potentially having deleterious consequences for both the acute and long-term function of the nervous system. Understanding the key cellular and molecular processes that occur following TBI exposure and potential factors that influence individual injury responses has been limited in part by the lack of comprehensivein vivoscreening technique that directly compares stress sensitive and resistant genotypes involving conserved genes and functional pathways. In this report, we use a high throughput adultDrosophilatrauma model system to compare the impact modest insulin signaling (IRS/chico) and autophagic defects (Atg8a/MAPLC3, Ref(2)P/SQSM1)have on traumatic injury outcomes. Using both severe and mild repetitive injury conditions the acute mortality indexes, longevity profiles, molecular and behavioral changes (locomotor, sleep) for individual fly genotypes were assessed. Compared to control cohorts (w1118/+), heterozygouschicomutants (chico1/+) demonstrated resistance, while aged flies (+2-weeks) or autophagy mutants (Atg8a1,Ref(2)Pc/e,Ref(2)Pe/+) showed heightened trauma sensitivity. Alterations that promote or impair autophagic function, longevity and stress responses were examined. Overall, this injury paradigm illustrates the effectiveness of using model systems to characterize conserved genetic factors that influence neuronal autophagy during complex trauma response. It also raises the potential for developing unique screens and therapies for patients that have experienced TBI.
Meta-analysis and experimental evidence reveal no impact ofNosema ceranaeinfection on honeybee carbohydrate consumption
Authors: Ostap-Chec Monika , Antoł Weronika , Bajorek Daniel , Berbeć Ewelina , Moroń Dawid , Rapacz Marcin , Miler Krzysztof 
Published: February 2025

AbstractHoneybees (Apis mellifera) are indispensable pollinators, essential for ecosystem stability and agricultural productivity. However, they face numerous challenges, including pathogens that threaten their survival and ecosystem services. Among these pathogens,Nosema ceranae, a microsporidian parasite, causes significant damage to the intestinal tract and induces energetic imbalances in an organism, posing a major threat to both individual bees and entire colonies. In response to infections, bees often engage in behavioural defenses, such as selecting foods with higher antibiotic properties. We hypothesized that bees infected withN. ceranaemight compensate behaviourally by increasing their carbohydrate consumption. To test this hypothesis, we conducted a meta-analysis of existing studies comparing sugar consumption in healthy and infected bees, complemented by an experimental study. In our experiment, we measured sugar intake and quantified trehalose levels in the hemolymph, a key indicator of energy reserves. Both the meta-analysis and experimental results consistently showed no significant differences in sugar consumption between healthy and infected bees. Similarly, trehalose levels in the hemolymph remained comparable between the two groups. Our findings suggest that the infection caused byN. ceranaedoes not elicit compensatory feeding behavior in honeybees. Moreover, the meta-analysis revealed significant gaps in current research, particularly a lack of studies focusing on forager bees, which face the highest energetic demands among colony members. Our findings call for future studies on the energetic effects of nosemosis and studies conducted under natural or semi-natural conditions.
Iron-deplete diet enhancesCaenorhabditis eleganslifespan via oxidative stress response pathways
Authors: Das Priyanka , Ravi  , Singh Jogender 
Published: February 2025

AbstractGut microbes play a crucial role in modulating host lifespan. However, the microbial factors that influence host longevity and their mechanisms of action remain poorly understood. Using the expression ofCaenorhabditis elegansFAT-7, a stearoyl-CoA 9-desaturase, as a proxy for lifespan modulation, we conduct a genome-wide bacterial mutant screen and identify 26Escherichia colimutants that enhance host lifespan. Transcriptomic and biochemical analyses reveal that these mutant diets induce oxidative stress and activate the mitochondrial unfolded protein response (UPRmt). Lifespan extension requires the oxidative stress response regulators SKN-1, SEK-1, and HLH-30. Mechanistically, these effects are linked to reduced iron availability, as iron supplementation restores FAT-7 expression, suppresses UPRmt activation, and abolishes lifespan extension. Iron chelation mimics the pro-longevity effects of the mutant diets, highlighting dietary iron as a key modulator of aging. Our findings reveal a bacterial-host metabolic axis that links iron homeostasis, oxidative stress, and longevity inC. elegans.
Integrating multi-modal transcriptomics identifies cellular subtypes with distinct roles in PDAC progression
Authors: Wu Jun , Dai Tenghui , Li Ziyue , Pan Meng , Zhang Wei , Chen Hao , Zheng Guansheng , Qiao Li , Lian Qizhou , Liu Yang , Chen Jierong 
Published: February 2025

AbstractBackgroundPancreatic ductal adenocarcinoma (PDAC) features a complex tumor microenvironment (TME) that significantly influences patient outcomes. Understanding the TME’s cellular composition and interactions is crucial for identifying therapeutic targets to improve treatment.MethodsWe performed an integrative analysis combining 88 single-cell RNA sequencing (scRNA-seq) samples with 187,520 cells, 20 Visium spatial transcriptomics (ST-seq) samples with 67,933 spots, and 1383 bulk RNA-seq samples and 2 Xenium high-resolution ST-seq samples with 307,679 cells, to delineate and characterize distinct subpopulations of fibroblasts, macrophages, T/NK cells, and B/plasma cells within the PDAC microenvironment. Correlations among major cell types across 12 PDAC datasets were assessed through gene set variation analysis (GSVA). Kaplan-Meier survival analysis was used to evaluate the prognostic significance of cell subtypes. Furthermore, multiplex immunohistochemistry (mIHC) and the Xenium platform was utilized to validate cellular interactions in human PDAC tissues at both protein and RNA levels.ResultsSix fibroblast subtypes and eight macrophage/monocyte subtypes were identified. POSTNhighfibroblasts and SPP1highmacrophages highly infiltrated tumor tissues and were associated with poor prognosis. Most immune cell subtypes mediate adverse prognoses, except for CCL4highCD8+ TEFFcells and IGHG1highplasma cells, which are linked to favorable outcomes. ST-seq revealed spatial colocalization of POSTNhighFibro and SPP1highMacro cells, as well as CCL4highCD8+ TEFFand IGHG1highplasma cells. These findings were corroborated by mIHC and validated using Xenium spatial transcriptomics with single-cell resolution, which confirmed the expression and spatial proximity of these markers at both the gene and protein levels.ConclusionThis integrative analysis of the PDAC TME underscores the prognostic importance of POSTNhighfibroblasts and SPP1highmacrophages, while also highlighting the protective roles of CCL4highCD8+ TEFFcells and IGHG1highplasma cells. These insights could improve PDAC treatment strategies.