bluuebunny/crossref_metadata_2025_split huggingface dataset:
GNN4DM: a graph neural network-based method to identify overlapping functional disease modules
Authors: Gézsi András , Antal Péter 
Published: September 2024

Abstract

Motivation
Identifying disease modules within molecular interaction networks is an essential exploratory step in computational biology, offering insights into disease mechanisms and potential therapeutic targets. Traditional methods often struggle with the inherent complexity and overlapping nature of biological networks, and they are limited in effectively leveraging the vast amount of available genomic data and biological knowledge. This limitation underscores the need for more effective, automated approaches to integrate these rich data sources.

Results
In this work, we propose GNN4DM, a novel graph neural network-based structured model that automates the discovery of overlapping functional disease modules. GNN4DM effectively integrates network topology with genomic data to learn the representations of the genes corresponding to functional modules and align these with known biological pathways for enhanced interpretability. Following the DREAM benchmark evaluation setting and extending with three independent data sources (GWAS Atlas, FinnGen, and DisGeNET), we show that GNN4DM performs better than several state-of-the-art methods in detecting biologically meaningful modules. Moreover, we demonstrate the method’s applicability by discovering two novel multimorbidity modules significantly enriched across a diverse range of seemingly unrelated diseases.

Availability and implementation
Source code, all training data, and all identified disease modules are freely available for download at https://github.com/gezsi/gnn4dm. GNN4DM was implemented in Python.
Multiple lines of evidence for disruption of nuclear lamina and nucleoporins in FUS amyotrophic lateral sclerosis
Authors: Okada Kensuke , Ito Daisuke , Morimoto Satoru , Kato Chris , Oguma Yuki , Warita Hitoshi , Suzuki Naoki , Aoki Masashi , Kuramoto Junko , Kobayashi Reona , Shinozaki Munehisa , Ikawa Masahito , Nakahara Jin , Takahashi Shinichi , Nishimoto Yoshinori , Shibata Shinsuke , Okano Hideyuki 
Published: September 2024

Abstract
Advanced pathological and genetic approaches have revealed that mutations in fused in sarcoma/translated in liposarcoma (FUS/TLS), which is pivotal for DNA repair, alternative splicing, translation and RNA transport, cause familial amyotrophic lateral sclerosis (ALS). The generation of suitable animal models for ALS is essential for understanding its pathogenesis and developing therapies. Therefore, we used CRISPR-Cas9 to generate FUS-ALS mutation in the non-classical nuclear localization signal (NLS), H517D (mouse position: H509D) and genome-edited mice.
Fus WT/H509D mice showed progressive motor impairment (accelerating rotarod and DigiGait system) with age, which was associated with the loss of motor neurons and disruption of the nuclear lamina and nucleoporins and DNA damage in spinal cord motor neurons. We confirmed the validity of our model by showing that nuclear lamina and nucleoporin disruption were observed in lower motor neurons differentiated from patient-derived human induced pluripotent stem cells (hiPSC-LMNs) with FUS-H517D and in the post-mortem spinal cord of patients with ALS. RNA sequence analysis revealed that most nuclear lamina and nucleoporin-linking genes were significantly decreased in FUS-H517D hiPSC-LMNs.
This evidence suggests that disruption of the nuclear lamina and nucleoporins is crucial for ALS pathomechanisms. Combined with patient-derived hiPSC-LMNs and autopsy samples, this mouse model might provide a more reliable understanding of ALS pathogenesis and might aid in the development of therapeutic strategies.
Strategic Conformity or Anti-Conformity to Avoid Punishment and Attract Reward
Authors: Dvorak Fabian , Fischbacher Urs , Schmelz Katrin 
Published: September 2024

Abstract
We provide systematic insights on strategic conformist—as well as anti-conformist—behaviour in situations where people are evaluated, i.e., where an individual has to be selected for reward (e.g., promotion) or punishment (e.g., layoffs). To affect the probability of being selected, people may attempt to fit in or stand out in order to affect the chances of being noticed or liked by the evaluator. We investigate such strategic incentives for conformity or anti-conformity experimentally in three different domains: facts, taste and creativity. To distinguish conformity and anti-conformity from independence, we introduce a new experimental design that allows us to predict participants’ independent choices based on transitivity. We find that the prospect of punishment increases conformity, while the prospect of reward reduces it. Anti-conformity emerges in the prospect of reward, but only under specific circumstances. Similarity-based selection (i.e., homophily) is much more important for the evaluators’ decisions than salience. We also employ a theoretical approach to illustrate strategic key mechanisms of our experimental setting.
Disentangling evolutionary, geometric and ecological components of the elevational gradient of diversity
Authors: Herrera-Alsina Leonel , Parvanova Rossina , Guirguis Jacinta , Bocedi Greta , Trethowan Liam , Lancaster Lesley T , Travis Justin M J 
Published: September 2024

Abstract
Despite the high importance and risk of mountain ecosystems in global biodiversity conservation, the mechanisms giving rise to and maintaining elevational biodiversity gradients are poorly understood, limiting predictions of future responses. Species richness peaks at lowlands for many taxa, which might be a consequence of mountain shape, reducing available area in highlands. For other taxa, diversity can be highest at mid elevations, suggesting the presence of mechanisms that counteract the influence of geometry. Here, we mechanistically investigate the role of mountain geometry (smaller at the peak) interaction with ecological niche width, diversification, and altitudinal dispersal to investigate the relative roles of these processes in shaping elevational biodiversity gradients. We simulated landscapes and lineages until species richness stop increasing and showed that the disproportionately large area of lowlands provides opportunity for higher species accumulation than any other elevation, even when available niche width and per-capita diversification rate are uniform across altitudes. Regardless of the underlying Elevational Diversity Gradient, altitudinal dispersal always plays a stronger role in maintaining highland than lowland diversity, due to unequal areas involved. To empirically test these predictions resulting from our model, we fit dynamic models of diversification and altitudinal dispersal to three mountainous endemic radiations whose species richness peaks in mid and high-elevation. We find that highland diversity is explained by increased diversification rates with elevation in Fijian bees, whereas niche availability is more likely to explain high altitude diversity in frailejon bushes and earless frogs, suggesting these clades are still growing. Our model and findings provide a new framework for distinguishing drivers of diversity dynamics on mountainsides and allow to detect the presence of clade-specific mechanisms underlying the geometry-diversity relationship. Understanding of these ecological and evolutionary forces can allow increased predictability of how ongoing land use and climate changes will impact future highland biodiversity.
Cross potential selection: a proposal for optimizing crossing combinations in recurrent selection using the usefulness criterion of future inbred lines
Authors: Sakurai Kengo , Hamazaki Kosuke , Inamori Minoru , Kaga Akito , Iwata Hiroyoshi 
Published: September 2024

Abstract
In plant breeding programs, rapid production of novel varieties is highly desirable. Genomic selection allows the selection of superior individuals based on genomic estimated breeding values. However, it is worth noting that superior individuals may not always be superior parents. The choice of the crossing pair significantly influences the genotypic value of the resulting progeny. This study has introduced a new crossing strategy, termed cross potential selection, designed to expedite the production of novel varieties of inbred crops. Cross potential selection integrates fast recurrent selection and usefulness criterion to generate novel varieties. It considers the segregation of each crossing pair and computes the expected genotypic values of the top-performing individuals, assuming that the progeny distribution of genotypic values follows a normal distribution. It does not consider genetic diversity and focuses only on producing a novel variety as soon as possible. We simulated a 30-year breeding program in 2 scenarios, low heritability (h2=0.3) and high heritability (h2=0.6), to compare cross potential selection with 2 other selection strategies. Cross potential selection consistently demonstrated the highest genetic gains among the 3 strategies in early cycles. In the 3rd year of the breeding program with a high heritability (h2=0.6), cross potential selection exhibited the highest genetic gains, 138 times that of 300 independent breeding simulations. Regarding long-term improvement, the other selection strategies outperformed cross potential selection. Nevertheless, compared with the other 2 strategies, cross potential selection achieved significant short-term genetic improvements. Cross potential selection is a suitable breeding strategy for the rapid production of varieties within limited time and cost.
Virus Infection Induces Immune Gene Activation with CTCF-anchored Enhancers and Chromatin Interactions in Pig Genome
Authors: Cao Jianhua , Ren Ruimin , Li Xiaolong , Zhang Xiaoqian , Sun Yan , Tian Xiaohuan , Liu Ru , Liu Xiangdong , Ruan Yijun , Li Guoliang , Zhao Shuhong 
Published: September 2024

Abstract
Chromatin organization is important for gene transcription in pig genome. However, its three-dimensional (3D) structure and dynamics are much less investigated than those in human. Here, we applied the long-read chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) method to map the whole-genome chromatin interactions mediated by CCCTC-binding factor (CTCF) and RNA polymerase II (RNAPII) in porcine macrophage cells before and after polyinosinic-polycytidylic acid [Poly(I:C)] induction. Our results reveal that Poly(I:C) induction impacts the 3D genome organization in the 3D4/21 cells at the fine-scale chromatin loop level rather than at the large-scale domain level. Furthermore, our findings underscore the pivotal role of CTCF-anchored chromatin interactions in reshaping chromatin architecture during immune responses. Knockout of the CTCF-binding locus further confirms that the CTCF-anchored enhancers are associated with the activation of immune genes via long-range interactions. Notably, the ChIA-PET data also support the spatial relationship between single nucleotide polymorphisms (SNPs) and related gene transcription in 3D genome aspect. Our findings in this study provide new clues and potential targets to explore key elements related to diseases in pigs and are also likely to shed light on elucidating chromatin organization and dynamics underlying the process of mammalian infectious diseases.
Real-world public health interventions demonstrate how research evidence informs program scale-up
Authors: Crane Melanie , Lee Karen , Wolfenden Luke , Phongsavan Philayrath , Bauman Adrian 
Published: September 2024

Abstract
Evidence-based population interventions rely on intervention testing (efficacy and effectiveness trials) to determine what works to improve public health. We investigated the characteristics of real-world public health interventions to address obesity and explored the extent to which research testing was undertaken prior to scale-up. We identified 90 population health interventions targeting physical activity, nutrition or obesity-related health behaviours and collected publicly available information on their key characteristics and outcomes. We then assessed the differences between interventions that followed a research pathway and those that did not. Two-thirds (n = 60) of the interventions were reported as having followed a research pathway. Univariate logistic regression analysis revealed that these interventions were more likely to be health education interventions [odds ratio (OR): 5.56; 95% confidence interval (CI): 1.38–22.38], developed by research institutes (OR: 12.81; 95% CI: 3.47–47.34), delivered in North America (OR: 4.13; 95% CI: 1.61–10.62), and less likely to be owned (OR: 0.35; 95% CI: 0.14–0.88) or funded by government organizations (OR: 0.37; 95% CI: 0.14–0.95). Interventions that followed a research pathway were nearly three times more likely to have a positive impact on population health (OR: 2.72; 95% CI: 1.04–7.14). Interventions that followed a research pathway to scale-up were no more likely to be sustained longer than those that did not. Differences exist across real-world interventions between those that follow a research pathway to population-scale delivery and those that do not, regarding organizational and environmental context. A key benefit of research pathway to scale-up is the impact it has on health outcomes.
Fourier Dimension Estimates for Sets of Exact Approximation Order: The Case of Small Approximation Exponents
Authors: Fraser Robert , Wheeler Reuben 
Published: September 2024

Abstract
We show for decreasing, positive approximation functions $\psi $ such that $\tau = \lim _{q \to \infty } -\frac{\log \psi (q)}{\log q} &lt; \frac{13 + \sqrt{73}}{8}$ and such that $q^{2} \psi (q) \to 0$ that the set $\operatorname{Exact}(\psi )$ of numbers approximable to the exact order $\psi $ has positive Fourier dimension. This implies that the set $\operatorname{Exact}(\psi )$ contains normal numbers.
Improved Nucleic Acid Amplification Test for the Diagnosis of Onchocerciasis and Its Use for Detection of Circulating Cell-free DNA
Authors: Bennuru Sasisekhar , Kodua Frimpong , Dahlstrom Eric , Nutman Thomas B 
Published: September 2024

Abstract

Background
The coendemicity of onchocerciasis with other filariae warrants a better diagnostic tool for elimination efforts that are highly sensitive and specific for use in surveillance and xenomonitoring.

Methods
Based on next-generation sequencing data, quantitative polymerase chain reaction (qPCR) assays were designed for 15 highly repeated targets from Onchocerca volvulus (Ov) and 11 from Onchocerca ochengi. The 2 most promising repeats Ov15R and Ov16R from Ov and OoR1 and OoR5 from O. ochengi, were selected for further testing.

Results
The analytic sensitivity of Ov15R and Ov16R was similar, with limits of detection at 1 fg and specificity approaching 100%. Using DNA obtained previously from skin snips of participants infected with Ov, Ov16R identified 17 additional samples as positive for Ov infections when compared with the gold standard O-150. Although Ov16R failed to detect circulating cell-free DNA (ccfDNA) in the plasma of individuals infected with Ov, 1-mL urine samples were variably positive for ccfDNA. Interestingly, plasma levels of ccfDNA were shown to be easily measurable as early as 12 to 24 hours following treatment. To enable processing of larger volumes of urine for better sensitivity, a chitosan-based filter technique was developed that efficiently captured ccfDNA from 1 to 15 mL of urine. Interestingly, Ov15R, Ov16R, and O-150 map to the same region(s) of the Ov genome, prompting a redesign of the standard O-150 qPCR. This resulted in a new O-150 assay that performs on par with Ov15R/Ov16R.

Conclusions
Each of these assays dramatically improve detection of Ov DNA and can easily be configured to field-friendly isothermal formats.
EDP-938 Has a High Barrier to Resistance in Healthy Adults Experimentally Infected with Respiratory Syncytial Virus
Authors: Levene Rachel Emily , DeVincenzo John , Conery Annie L , Ahmad Alaa , Or Yat Sun , Rhodin Michael H J 
Published: September 2024

Abstract

Background
EDP-938 is an oral once-daily RSV nucleoprotein (N) inhibitor with potent antiviral activity. In a human RSV challenge trial, EDP-938 significantly reduced viral load and symptom severity. During antiviral development, it is critical to understand the propensity for resistance to develop. In vitro studies of EDP-938 suggest a higher barrier to resistance as compared to RSV fusion inhibitors. We evaluated the development of viral resistance to EDP-938 in a human challenge trial.

Methods
A subset of the 124 participants with RSV infection were chosen for genetic analysis; 159 nasal wash samples from 48 participants were analyzed using next-generation sequencing of the N gene of RSV. Of the 48 participant sampled, 37 were from EDP-938–treated and 11 were placebo-treated participants, representing 45% and 26% of the participants, respectively. The effects of treatment-emergent mutations on viral load, EDP-938 efficacy, and viral fitness were evaluated.

Results
Two of the 37 EDP-938–treated participants with samples sequenced had treatment-emergent mutations: N:L139I and N:E112G. From in vitro analysis, N:L139I reduced sensitivity to EDP-938 by approximately 10-fold, while N:E112G had no effect. However, N:L139I was associated with a reduction in viral fitness, suggesting clinical resistance is associated with fitness costs. Neither of these variants were associated with reduced viral clearance.

Conclusions
In human RSV infections treated with EDP-938, emergence of RSV variants with reduced sensitivity to EDP-938 occurred in only 1 participant and was associated with reduced viral fitness. EDP-938's high barrier to resistance highlights its robust mechanism of action.

Clinical Trials Registration
NCT03691623.
Predatory protists impact plant performance by promoting plant growth-promoting rhizobacterial consortia
Authors: Guo Sai , Geisen Stefan , Mo Yani , Yan Xinyue , Huang Ruoling , Liu Hongjun , Gao Zhilei , Tao Chengyuan , Deng Xuhui , Xiong Wu , Shen Qirong , Kowalchuk George A , Li Rong 
Published: September 2024

Abstract
Plant performance is impacted by rhizosphere bacteria. These bacteria are subjected to both bottom-up control by root exudates as well as top-down control by predators, particularly protists. Protists stimulate plant growth-promoting microbes resulting in improved plant performance. However, knowledge of the mechanisms that determine the interconnections within such tripartite protist–bacteria–plant interactions remains limited. We conducted experiments examining the effects of different densities of the predatory protist Cercomonas lenta on rhizosphere bacterial communities, specifically zooming on interactions between Cercomonas lenta and key bacterial taxa, as well as interactions among key bacterial taxa. We tracked rhizosphere bacterial community composition, potential microbial interactions, and plant performance. We found that Cercomonas lenta inoculation led to an average increase in plant biomass of 92.0%. This effect was linked to an increase in plant growth-promoting rhizobacteria (Pseudomonas and Sphingomonas) and a decrease in bacteria (Chitinophaga) that negatively impact on plant growth-promoting rhizobacteria. We also found evidence for cooperative enhancements in biofilm formation within the plant growth-promoting rhizobacterial consortium. Cercomonas lenta enhanced a plant growth-promoting rhizobacterial consortium colonization by promoting its cooperative biofilm formation in the rhizosphere, leading to a 14.5% increase in phosphate solubilization that benefits plant growth. Taken together, we provide mechanistic insights into how the predatory protist Cercomonas lenta impacts plant growth, namely by stimulating plant beneficial microbes and enhancing their interactive activities such as biofilm formation. Predatory protists may therefore represent promising biological agents that can contribute to sustainable agricultural practices by promoting interactions between the plant and its microbiome.
Abiotic factors shape mosquito microbiomes that enhance host development
Authors: Kriefall Nicola G , Seabourn Priscilla S , Yoneishi Nicole M , Davis Kahiwahiwa , Nakayama Kirsten K , Weber Danya E , Hynson Nicole A , Medeiros Matthew C I 
Published: September 2024

Abstract
Metazoans rely on interactions with microorganisms through multiple life stages. For example, developmental trajectories of mosquitoes can vary depending on the microorganisms available during their aquatic larval phase. However, the role that the local environment plays in shaping such host-microbe dynamics and the consequences for the host organism remain inadequately understood. Here, we examine the influence of abiotic factors, locally available bacteria, and their interactions on the development and associated microbiota of the mosquito Aedes albopictus. Our findings reveal that leaf detritus infused into the larval habitat water, sourced from native Hawaiian tree ‘ōhi‘a lehua Metrosideros polymorpha, invasive strawberry guava Psidium cattleianum, or a pure water control, displayed a more substantial influence than either temperature variations or simulated microbial dispersal regimes on bacterial community composition in adult mosquitoes. However, specific bacteria exhibited divergent patterns within mosquitoes across detrital infusions that did not align with their abundance in the larval habitat. Specifically, we observed a higher relative abundance of a Chryseobacterium sp. strain in mosquitoes from the strawberry guava infusion than the pure water control, whereas the opposite trend was observed for a Pseudomonas sp. strain. In a follow-up experiment, we manipulated the presence of these two bacterial strains and found larval developmental success was enhanced by including the Chryseobacterium sp. strain in the strawberry guava infusion and the Pseudomonas sp. strain in the pure water control. Collectively, these data suggest that interactions between abiotic factors and microbes of the larval environment can help shape mosquito populations' success.
Spatiotemporal dynamics of giant viruses within a deep freshwater lake reveal a distinct dark-water community
Authors: Zhang Liwen , Meng Lingjie , Fang Yue , Ogata Hiroyuki , Okazaki Yusuke 
Published: September 2024

Abstract
Giant viruses (GVs) significantly regulate the ecological dynamics of diverse ecosystems. Although metagenomics has expanded our understanding of their diversity and ecological roles played in marine environments, little is known about GVs of freshwater ecosystems. Most previous studies have employed short-read sequencing and therefore resulted in fragmented genomes, hampering accurate assessment of genetic diversity. We sought to bridge this knowledge gap and overcome previous technical limitations. We subjected spatiotemporal (2 depths × 12 months) samples from Lake Biwa to metagenome–assembled genome reconstruction enhanced by long-read metagenomics. This yielded 293 GV metagenome-assembled genomes. Of these, 285 included previously unknown species in five orders of nucleocytoviruses and the first representatives of freshwater mirusviruses, which exhibited marked divergence from marine-derived lineages. The good performance of our long-read metagenomic assembly was demonstrated by the detection of 42 (14.3%) genomes composed of single contigs with completeness values &gt;90%. GVs were partitioned across water depths, with most species specific to either the sunlit epilimnion or the dark hypolimnion. Epilimnion-specific members tended to be transient and exhibit short and intense abundance peaks, in line with the fact that they regulate the surface algal blooms. During the spring bloom, mirusviruses and members of three nucleocytovirus families were among the most abundant viruses. In contrast, hypolimnion-specific ones, including a mirusvirus genome, were typically more persistent in the hypolimnion throughout the water-stratified period, suggesting that they infect hosts specific to the hypolimnion and play previously unexplored ecological roles in dark water microbial ecosystems.