bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning genotype–phenotype associations from gaps in multi-species sequence alignments
Authors: Islam Uwaise Ibna , Campelo dos Santos Andre Luiz , Kanjilal Ria , Assis Raquel 
Published: February 2025

Abstract
Understanding the genetic basis of phenotypic variation is fundamental to biology. Here we introduce GAP, a novel machine learning framework for predicting binary phenotypes from gaps in multi-species sequence alignments. GAP employs a neural network to predict the presence or absence of phenotypes solely from alignment gaps, contrasting with existing tools that require additional and often inaccessible input data. GAP can be applied to three distinct problems: predicting phenotypes in species from known associated genomic regions, pinpointing positions within such regions that are important for predicting phenotypes, and extracting sets of candidate regions associated with phenotypes. We showcase the utility of GAP by exploiting the well-known association between the L-gulonolactone oxidase (Gulo) gene and vitamin C synthesis, demonstrating its perfect prediction accuracy in 34 vertebrates. This exceptional performance also applies more generally, with GAP achieving high accuracy and power on a large simulated dataset. Moreover, predictions of vitamin C synthesis in species with unknown status mirror their phylogenetic relationships, and positions with high predictive importance are consistent with those identified by previous studies. Last, a genome-wide application of GAP identifies many additional genes that may be associated with vitamin C synthesis, and analysis of these candidates uncovers functional enrichment for immunity, a widely recognized role of vitamin C. Hence, GAP represents a simple yet useful tool for predicting genotype–phenotype associations and addressing diverse evolutionary questions from data available in a broad range of study systems.
Deciphering optimal molecular determinants of non-hemolytic, cell-penetrating antimicrobial peptides through bioinformatics and Random Forest
Authors: Kumar Ashok , Chadha Sonia , Sharma Mradul , Kumar Mukesh 
Published: February 2025

Abstract
Antimicrobial peptides (AMPs) are promising molecules for combating resistant pathogens, offering several advantages like broad-spectrum effectiveness and multi-targeted action. While most AMPs exhibit membranolytic activity similar to hemolytic peptides (HPs), some act by entering cells like cell-penetrating peptides (CPPs). The toxicity of AMPs towards the host is the major hurdle in their development and application. Given the peptides’ function and toxicity largely depend on their molecular properties, identifying and fine-tuning these factors is imperative for developing effective and safe AMPs. To address these knowledge gaps, we present a study that employs a holistic strategy by investigating the molecular descriptors of AMPs, CPPs, HPs, and non-functional equivalents. The prediction of functional properties categorized datasets of 3697 experimentally validated peptides into six groups and three clusters. Predictive and statistical analyses of physicochemical and structural parameters revealed that AMPs have a mean hydrophobic moment of 1.2, a net charge of 4.5, and a lower isoelectric point of 10.9, with balanced hydrophobicity. For cluster AC-nHPs containing peptides with antimicrobial, cell-penetrating, and non-hemolytic properties, disordered conformation and aggregation propensities, followed by amphiphilicity index, isoelectric point, and net charge were identified as the most critical properties. In addition, this work also explains why most AMPs and HPs are membrane-disruptive, while CPPs are non-membranolytic. In conclusion, the study identifies optimal molecular descriptors and offers valuable insights for designing effective, non-toxic AMPs for therapeutic use.
American politics, international relations, and educational movements after 1945
Authors: Sawyer Elizabeth 
Published: February 2025

Abstract
International Relations (IR) theory’s own explanations about its relationship with Thucydides are inconsistent, and the role of Thucydides in IR theory, as that of the discipline’s ‘founding father’, is an American trope in particular. Important IR theorists in the 1940s and early 1950s, such as Carr, Morgenthau, Wight, and Waltz, are assumed by critics today to have been heavily influenced by Thucydides, although early editions of their works show a notable absence of references to the classical author. The inclusion of references in later editions happened not because of research into Thucydides or particular interest in him from IR theorists, but because of the growing traction of the Great Books educational movement and its nationalist rhetoric, the end of the Second World War, and the start of the Cold War.
Age-Related Integrative Transcriptomic Profiling of Human Granulosa Cells Reveals mRNA-microRNA Regulatory Network Associated with Key Ovulation Dynamics
Authors: Rogers Heather M , Gad Ahmed , Cork Gentry K , Menjivar Nico G , Schoolcraft William B , Tesfaye Dawit , Yuan Ye 
Published: February 2025

Abstract
Advanced maternal age (AMA) patients experience decreased success from assisted reproductive technologies (ART), attributed to the quantity and quality of oocytes, which is significantly influenced by the intrafollicular granulosa cells (GCs). In this study, we compared the mRNA and microRNA (miRNA) transcriptomes between young (&lt; 32 y.o.) and AMA (&gt; 38 y.o.) patients’ GCs to identify potential ovarian aging-related molecular signatures. We identified 293 and 21 differentially expressed genes (DEGs) and miRNAs (DE miRNAs), respectively, between young and aged GCs. Highly expressed mitochondrial-encoded genes, MT-ND3, MT-ND6, and MT-CYB, were downregulated in aged GCs, indicating potential mitochondrial insufficiency. Additionally, pathway analysis indicates DEGs are involved in inflammation, cytokine signaling, extracellular matrix (ECM) remodeling, and angiogenesis. Key DEGs related to these processes include CXCL8, IL1B, NLRP3, SIGIRR, ANGPT2, ADAM8, and ADAMTS14. Additionally, target gene prediction and pathway analysis of DE miRNAs indicates their potential post-transcriptional regulation of genes associated with cell signaling, mitochondrial function, oxidative stress, apoptosis, and senescence pathways in addition to cytokine signaling, angiogenesis, and ECM remodeling. To investigate regulatory mechanisms further, we looked at the DEGs’ convergence with the DE miRNAs predicted target genes and we identified miR-483-3p, miR-1268a, miR-4497, miR-7704, miR-135a-5p, miR-1261, and miR-4791 as potential crucial regulators of genes involved in pathways associated with inflammation, ECM, and angiogenesis. This data suggests that aged GCs have an impaired ability to elicit the same pro-inflammatory response combined with dysregulation of angiogenesis and ECM remodeling compared to young GCs, and miRNA may play a role in regulating key ovulatory processes. While this study identifies potential regulatory relationships between DE miRNAs and DEGs, experimental validation is necessary to confirm the relationships and biological relevance.
Stroke risk in ADPKD patients treated by dialysis: a retrospective study
Authors: Cerasuolo Damiano , Tejeda-Reyes Darbelis , Couchoud Cécile , Guerrot Dominique , Touré-Diabira Fatouma , Vacher-Coponat Henri , Lobbedez Thierry , Morello Rémy , Béchade Clémence , Guittet Lydia 
Published: February 2025

Abstract

Background and hypothesis
The risk of ischaemic or haemorrhagic strokes in patients living with end-stage renal disease (ESRD) and receiving replacement therapy is more than double that of non-dialysed individuals. Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder associated with renal and non-renal manifestations, including intracerebral aneurysms (ICA). The role of underlying nephropathy in determining the onset of the stroke is unclear.

Methods
All patients who started dialysis between January 1st, 2015, and December 31st, 2019, were included in the analysis. Data were retrieved from the REIN registry and the French national Health Data System (SNDS). Cases of stroke were extracted from the SNDS, by using ICD-10 codes. The first stroke observed during the follow-up, irrespective of its nature, was considered as the event of the main analysis, based on semi-parametric survival model.

Results
40 980 patients on dialysis were included. Overall, 1 549 patients experienced stroke during the follow-up. The first stroke was ischaemic in 1 148 (74.1%), and haemorrhagic in the remaining 281 patients. The cumulative incidence of stroke on dialysis was 1.58 per 100 person-years (95%CI = 1.51; 1.70). Among 2 182 ADPKD patients, only 44 (2%) experienced stroke. ADPKD was not significantly associated with an increased risk of all type of stroke, after considering major risk factors.

Conclusions
We found no increase in the risk of stroke in ADPKD patients under dialysis. We believe that the findings of our study support a similar screening strategy in ADPKD patients on dialysis compared to patients not on dialysis.
Endothelial c-REL orchestrates atherosclerosis at regions of disturbed flow through crosstalk with TXNIP-p38 and non-canonical NF-κB pathways
Authors: Tardajos Ayllon Blanca , Bowden Neil , Souilhol Celine , Darwish Hazem , Tian Siyu , Duckworth Carrie , Pritchard D Mark , Xu Suowen , Sayers Jon , Francis Sheila , Serbanovic-Canic Jovana , Oakley Fiona , Evans Paul C 
Published: February 2025

Abstract

Aims
Atherosclerosis initiation at sites of disturbed blood flow involves heightened inflammation coupled to excessive endothelial cell (EC) proliferation. Here, we unveil the pivotal role of c-REL, a member of the NF-κB transcription factor family, in orchestrating these processes by driving dual pathological inflammatory and cell cycle pathways.

Methods and results
Analysis of cultured EC and murine models revealed enrichment and activation of c-REL at atherosusceptible sites experiencing disturbed flow. Transcriptome analysis, extensively validated in vitro and in vivo, demonstrates that endothelial c-REL drives inflammation via a TXNIP-p38 MAP kinase signalling pathway and enhances proliferation through a non-canonical NFKB2-p21 pathway. Consistent with its pivotal role in EC pathology, genetic deletion of c-Rel in EC significantly reduces plaque burden in hypercholesterolemic mice.

Conclusions
These findings underscore the fundamental role of c-REL in endothelial responses to disturbed flow and highlight therapeutic targeting of endothelial c-REL as a potential strategy for atherosclerosis treatment.
Rapid onset of myocardial calcification following septic shock due to influenza superinfection: a case report
Authors: Gobé Thibaut , Werquin Adrien , Polge Nicolas , Cholley Bernard 
Published: February 2025

Abstract

Background
Myocardial calcification is an unusual complication of septic cardiomyopathy. Dystrophic calcification may occur after damage to myocardial tissue, but its occurrence is rare.

Case summary
A 42-year-old pregnant woman with no past medical history was admitted in intensive care for respiratory distress caused by bacterial superinfection of influenza. Subepicardial calcification of the left ventricle appeared on a computed tomography at Day 8. Calcification worsened quickly, but we observed a paradoxical improvement in left ventricle function, as assessed by left ventricular ejection fraction and global longitudinal strain using echocardiography with speckle tracking.

Discussion
The pathophysiology of myocardial calcification is not fully understood, but prolonged haemodynamic failure, profound acidosis, high vasopressor doses, and acute respiratory distress syndrome were previously associated with septic-related myocardial calcification.
Enclosure Riots on the Commons: Memory and Conflict at Lytham Priory, 1200–1540
Authors: Brown A T 
Published: February 2025

Abstract
Enclosure riots in England have been understood through their importance to early modern social history, representing a conflict over rights and access to resources. Driven by Tudor demographic growth, these disputes demarcate changing social relations in the sixteenth century. Yet, as this article shows, enclosure riots could reflect a much longer heritage of disputation, including centuries-old boundary disputes. An enclosure riot involving the monks of Lytham Priory and neighbouring tenants in the 1530s had its origins over three centuries before, in the original grant of land to the monks, and raised its head in every century until the suppression of the priory. Through these conflicts, we can understand the construction and inculcation of popular and institutional memory across this period, as both their neighbouring tenants and the monks of Lytham sought to justify their occupation of the commons. Above all, this case-study highlights the importance of the interpretative framework that we use as historians: if read forwards, the conflict of the 1530s takes on all the features of the archetypal early modern enclosure riot, presaging the struggle for the commons of the sixteenth and seventeenth centuries; but if read backwards, it becomes the culmination of centuries of medieval boundary disputes before the eventual suppression of the priory. This article demonstrates both the artificial nature of temporal boundaries in the study of history and how the access rights of tenants could align with the jurisdictional claims of lords against an outside seigneurial authority, producing conflict but not necessarily class conflict.
Isolate-specific rat brain transcriptional responses to rat lungworm (Angiostrongylus cantonensis)
Authors: Rivory Phoebe , Lee Rogan , Šlapeta Jan 
Published: February 2025

Abstract
The rat lungworm (Angiostrongylus cantonensis) is an invasive parasite of rats that in accidental hosts, such as dogs and humans, causes eosinophilic meningitis. In Australia, only two distinct rat lungworm cox1 haplotypes have been detected in clinically affected dogs, with haplotype Ac13 implicated in most cases. Using locally sourced isolates, we inquired whether the brain migrating larvae elicit different host response in its natural host. We examined brain transcriptome, faecal shedding rates and adult worm of A. cantonensis isolates representing two distinct cox1 haplotypes, SYD.1 and Ac13 (represented by isolate SYD.2), in experimentally infected Wistar rats. For SYD.1-infected rats, only one differentially expressed gene (DEG) was upregulated in the compared to controls. In contrast, the transcriptome of SYD.2-infected rats included 100 DEGs, with enrichment of functional terms related to immune response, neuroactivity, and signalling. Faecal shedding did not differ between SYD.1- and SYD.2-infected rats, but adult worm burdens were higher in the SYD.1 group. The increased immune response in SYD.2-infected rats provides evidence that there is strain specific virulence that is pronounced in its natural host. This study provides initial parasite-specific evidence why clinically affected dogs are more frequently presented with A. cantonensis haplotype Ac13.
Evolving Spectrum of Pneumocystis Host Specificity, Genetic Diversity, and Evolution
Authors: Ma Liang , Weissenbacher-Lang Christiane , Latinne Alice , Babb-Biernacki Spenser , Blasi Barbara , Cissé Ousmane H , Kovacs Joseph A 
Published: February 2025

Abstract
Following over a century's worth of research, our understanding of Pneumocystis has significantly expanded in various facets, spanning from its fundamental biology to its impacts on animal and human health. Its significance in public health has been underscored by its inclusion in the 2022 WHO fungal priority pathogens list. We present this review to summarize pivotal advancements in Pneumocystis epidemiology in relation to its host specificity and evolution. Following a concise discussion of Pneumocystis species classification and divergence at the species and strain levels, we devoted the main focus to the following aspects: the epidemiological characteristics of Pneumocystis across nearly 300 mammal species, the increasing recognition of coinfection involving multiple Pneumocystis species in the same host species, the diminishing host specificity of Pneumocystis among closely related host species, and the intriguingly discordant evolution of certain Pneumocystis species with their host species. A comprehensive understanding of host specificity, genetic diversity and evolution of Pneumocystis can provide important insights into pathogenic mechanisms and transmission modes. This, in turn, holds the potential to facilitate the development of innovative strategies for the prevention and control of Pneumocystis infection.
Amino acid properties, substitution rates, and the nearly neutral theory
Authors: James Jennifer E , Lascoux Martin 
Published: February 2025

Abstract
Do the properties of amino acids affect their rates of substitution? The neutral theory predicts that greater selective constraint leads to slower rates of evolution; similarly, we expect amino acids that are more different from each other to have lower rates of exchange because such changes are most likely to affect protein structure and function. Here we test these predictions, using substitution rates estimated from empirical amino acid exchangeability matrices. To measure degree of amino acid difference, we focussed on two physicochemical properties, hydrophobicity and molecular weight, uncorrelated metrics that are known to have important implications for protein structure and function. We find that for both hydrophobicity and molecular weight, amino acid pairs with large differences had lower rates of substitution. We also found that amino acids that differed in both properties had the lowest rates of substitution, suggesting that both physicochemical properties are under selective constraint. Mutation properties, such as the number of mutations or the number of transitions as opposed to transversions separating amino acid pairs, were also important predictors of substitution rates. The relationship between amino acid substitution rates and differences in their physiochemical properties holds across several taxonomically restricted datasets. This finding suggests that purifying selection affects amino acid substitution rates in a similar manner across taxonomic groups with different effective population sizes.
Returning individualized wearable sensor results to older adult research participants: A pilot study
Authors: Bachman Shelby L , Leonard-Corzo Krista S , Blankenship Jennifer M , Busa Michael A , Serviente Corinna , Limoges Matthew W , Marcotte Robert T , Clay Ieuan , Lyden Kate 
Published: February 2025

Abstract

Background
Wearable sensors that monitor physical behaviors are increasingly adopted in clinical research. Older adult research participants have expressed interest in tracking and receiving feedback on their physical behaviors. Simultaneously, researchers and clinical trial sponsors are interested in returning results to participants, but the question of how to return individual study results derived from research-grade wearable sensors remains unanswered. In this study, we (1) assessed the feasibility of returning individual physical behavior results to older adult research participants and (2) obtained participant feedback on the returned results.

Methods
Older adult participants (N=20; ages 67-96) underwent 14 days of remote monitoring with two wearable sensors. We then used a semi-automated process to generate a 1-page report summarizing each participant’s physical behaviors across the 14 days. This report was delivered to each participant via email, and they were asked to evaluate the report.

Results
Participants found the reports easy to understand, health-relevant, interesting, and visually pleasing. They had valuable suggestions to improve data interpretability and raised concerns such as comparisons with measures derived from their consumer-grade sensors.

Conclusions
We have demonstrated the feasibility of returning individual physical behavior results from research-grade devices to older research participants, and our results indicate that this practice is well-received. Further research to develop more efficient and scalable systems to return results to participants, and to understand the preferences of participants in larger, more representative samples, is warranted.
Modeling induced seismicity in Groningen based on subcritical stressed faults
Authors: Hainzl Sebastian , Dahm Torsten , Zöller Gert 
Published: February 2025

Summary
Probabilistic forecasts of earthquakes caused by anthropogenic changes in subsurface stresses require seismicity models that link rupture nucleation to stress states in geological faults. The recently introduced time-dependent stress response (TDSR) model is based on an exponential dependence of the time-to-failure on stress and is a generalization of the well-known rate-and-state (RS) seismicity model. Unlike RS, TDSR can directly incorporate estimates of the initial stress distribution on affected faults in the seismogenic zone. For the case of the Groningen gas field in the Netherlands, we utilize detailed field and borehole studies to estimate the initial stress distribution and rock properties of the reservoir faults. Using these initial conditions, we show that TDSR outperforms the Coulomb failure model, which assumes instantaneous failure, as well as the RS model, which relies on simplified pre-stress assumptions. Furthermore, an instantaneous Coulomb failure model cannot explain the effect of seasonal gas production in Groningen on the timing of induced earthquakes, in contrast to the TDSR model, which shows a good agreement between prediction and observation. Pseudo-prospective tests show that the seismic response to the reduced production since 2014 could have been predicted as early as 2010 if the production scenario had been known.
Identifying the intersegmental line using a concave portion during upper lobe apical segmentectomies
Authors: Kato Hirohisa , Abiko Masami , Sato Kaito 
Published: February 2025

Abstract

OBJECTIVES
The hilum approach of intersegmental division along the intersegmental vein is difficult in the case with central vein type during upper lobe apical segmentectomy. We aimed to explore the possibilities of the simple intersegmental division used the concave portion of the apical pleura with computed tomography images.

METHODS
We evaluated computed tomography images of patients who underwent anatomical lung resection between June 2020 and April 2024. The upper pulmonary vein branching pattern was categorised into apical, apico-central, and central vein types. We evaluated whether the peripheral points of intersegmental veins (left V1 + 2a or right V1b) could be identified on which portions (anterior-convex, concave, and apical-convex) within the apical pleura in each branching pattern, using three-dimensional computed tomography images.

RESULTS
The peripheral points of the intersegmental veins of 175 subjected patients were concentrated in the anterior-convex, concave, and apical-convex portions. In the left lung, the peripheral points were significantly concentrated in the concave (n = 106, 60.9%) and the anterior-convex portion of the right lung (n = 115, 67.2%). By contrast, the peripheral points were significantly identified in the concave portion of the central vein type (n = 9, 100%) in the left lung for each branching pattern of the upper pulmonary vein. There was no similar tendency in the right lung.

CONCLUSIONS
Peripheral intersegmental points obtained from the intersegmental veins were concentrated in the three portions constituting the concave portion of the apical pleura and especially in the concave portion of the left lung, suggesting that they can serve as convenient intersegmental line markers during upper segmentectomy.