bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal Control Prevents Itself from Eradicating Stochastic Disease Epidemics
Authors: Russell Rachel , Cunniffe Nik J. 
Published: April 2024

AbstractThe resources available for managing disease epidemics – whether in animals, plants or humans – are limited by a range of practical and financial constraints. This motivates study of where these resources should be allocated to maximise their impact. Optimal control has been widely explored for optimising management of epidemics. The most common approach assumes a deterministic, continuous model based on differential equations to approximate the epidemic dynamics. However, real systems are stochastic and so a range of outcomes are possible for any given epidemic situation and choice of control. The deterministic models are also known to be poor approximations in cases where the number of infected hosts is low – either globally or within a subset of the population – and these cases are highly relevant in the context of control. Hence, this work explores the effectiveness of disease management strategies derived using optimal control theory when applied to a more realistic, stochastic form of disease model. We demonstrate that solutions to the deterministic optimal control are not optimal in cases where the disease is eradicated or close to eradication. The range of potential outcomes in the stochastic models means that optimising the deterministic case will not reliably eradicate disease, even when it is possible. For effective eradication, the rate of control must be higher than optimal control as applied to the deterministic model would predict. Using Model Predictive Control, in which the optimisation is performed repeatedly as the system evolves to correct for deviations from the optimal control predictions, improves performance but does not fix the underlying issue and the level of control calculated at each repeated optimisation is still insufficient. To demonstrate this, we present several very simple heuristics to identify which sites to control which can outperform the strategies calculated by MPC when the control budget is sufficient for eradication to be possible. Our illustration uses examples based on stochastic simulation of the spatial spread of plant disease but similar issues would be expected in any deterministic model where infection is driven close to zero or targeted to remain below some critical value.
Assessing the probability and time of weed control failure due to herbicide resistance evolution
Authors: Lauenroth Dana , Gokhale Chaitanya S. 
Published: April 2024

AbstractThe recurrent exposure to herbicides in agricultural landscapes forces weeds to adapt in a race against extinction. What role newly arising mutations and pre-existing variation play in this evolution of herbicide resistance is critical for developing management strategies. Here, we present a model of rapid adaptation in response to strong selection, capturing complex life cycles of sexual and asexual reproduction and dormancy in a perennial weed. Using a multitype Galton-Watson process, we derive the probability of herbicide resistance evolution and the waiting time distribution until resistant plants appear in the field. We analyse the effect of seed bank dynamics and details of the reproductive system in defining the probability and timing of resistance adaptation inSorghum halepense. Further, we investigate key factors determining the primary source of adaptive variation. We find that even small fitness costs associated with resistance reduce adaptation from standing genetic variation. For herbicide resistance inherited in a (incompletely) dominant fashion, self-pollination also diminishes standing variation for herbicide resistance by increasing the homozygosity. Our study highlights the importance of seed banks for weeds’ adaptive potential, preserving genetic information of forgone selection and prolonging the period in which the population can adapt.
Steep logarithmic increase of genetic variation in naturalArabidopsis thalianaaccessions across geographic scales
Authors: Hesen Vera , Boele Yvet , Holmer Rens , Boesten René , Wijfjes Raúl , Aarts Mark G. M. , van der Putten Wim H. , Scheres Ben , Willemsen Viola 
Published: April 2024

AbstractArabidopsis thaliana’slarge native range across Eurasia and display of considerable genetic variation is key to its increasing use in eco-evolutionary studies. The structure and amount of this genetic variation has been studied on various geographic scales. On a continental scale, the genetic variation was postulated to follow an ‘isolation by distance’ model, implying less genetic variation at smaller geographic distances. However, recent studies showed that the genetic variation is already high on small geographic scales, yet direct comparisons of the genetic variation across different geographic scales are rare. Here, we present a new local diversity panel covering 19 km2with accessions of the Veluwe, the Netherlands. We compared the genetic variation of this local diversity panel to a national and a continentalA. thalianadiversity panel. Direct comparison of these three geographic scales showed that local accessions harbour already 41.8% of the genetic variation found on a continental scale despite the substantial difference in geographic surface area covered. Moreover, a rapidly ascending logarithmic relationship between genetic and geographic distances was observed at continental, national and local scale and thus irrespective of the geographic scale considered. The high level of local genetic variation reported here poses new questions on which evolutionary forces are driving and maintaining this, and how much this constrains experimental design when using localA. thalianapopulations in future eco-evolutionary studies.
Unveiling inverted D genes and D-D fusions in human antibody repertoires unlocks novel antibody diversity
Authors: Ponraj Prabakaran , Gupta Abhinav , Rao Sambasiva P , Rajpal Deepak , Wendt Maria , Qiu Yu , Chowdhury Partha S. 
Published: April 2024

AbstractAntibodies, fundamental to immune defense, derive their diversity primarily from the intricate rearrangement of variable (V), diversity (D), and joining (J) gene segments. Traditionally, D genes in the forward (5’-3’) direction contribute to this diversity by rearranging with V and J segments. However, the existence and significance of inverted D genes (InvDs), which are D genes oriented in the inverted (3’-5’) direction, were previously obscured by limitations in data and detection methods. Here, we carried out a comprehensive analysis of a large-scale public next-generation sequencing (NGS) dataset encompassing antibody repertoires from 13 healthy donors using a novel immunoinformatics workflow. Our analysis, for the first time, uncovers the existence of all 25 unique InvDs across all three reading frames within human antibody repertoires, including both naïve and memory B cells. This finding challenges previous assumptions, revealing the extensive presence of InvDs and identifying a broad spectrum of D-D fusions, especially those involving InvDs. Notably, InvDs enrich for unique amino acids such as histidine, proline, and lysine, not commonly found in forward D genes, and exhibit reduced use of certain negatively charged and bulky amino acids, including aspartate, tryptophan, and methionine. The unique amino acid profile of InvDs discloses new diversity and functionality in the human antibody repertoire, evidenced by over two dozen documented antibodies featuring InvDs, targeting a wide array of antigens. By opening exciting avenues for immunogenetics research, including new chromatin compaction models, innovative antibody libraries, and advancements in antibody engineering, these findings hold promise for the development of novel therapeutics and vaccines.
Flipping the Script:WolbachiaFavoring Males in a NeotropicalDrosophila
Authors: Moreira Marina Magalhães , Dias Luísa de Paula Bouzada , Guzman Yoan Camilo , Sena Letícia , de Almeida João Paulo Pereira , Yotoko Karla 
Published: April 2024

AbstractAs skilful strategists, intracellular endosymbionts, particularlyWolbachia, have evolved the ability to induce phenotypes that frequently enhance the fitness of female hosts, often at the cost of male fitness, to ensure the transmission to subsequent host generations. Natural selection plays a pivotal role in this interaction, potentially amplifying, diminishing, or eradicating endosymbionts based on their impact on host fitness. This study investigated the relationship between theWolbachiastrainwStv Vi andDrosophila sturtevanti, the most abundant Neotropical drosophilid. We combined field sampling and controlled crosses ofWolbachia-infected and antibiotic-treated individuals to assess the endosymbiont’s host effects. We found that contrary to initial expectations,Wolbachiareduced female fecundity while boosting male fertility, yielding a similar number of offspring in both infected and treated pairs. However, infected females produced fewer larvae when crossed with treated males. A key observation was protogyny in treated but not infected individuals, suggestingWolbachia’sinfluence on host ontogeny, potentially increasing mating among infected siblings and restoring infected females’ fitness. From these results, we concluded that this whole strategy balanced the fitness of infected and non-infected pairs. In fact, repeated sampling, at the same site, revealed fluctuations in Wolbachia prevalence and high, but not perfect, vertical transmission. Our results indicate that the strategies for persistence in a particular host extend far beyond favoring females. They also imply that environmental factors may favor one group over another in varying circumstances, potentially explaining the observed fluctuations in infection and variable prevalence ofWolbachiainD. sturtevantipopulations.
Impacts of Deforestation and Land Use/Land Cover Change on Carbon Stock and Dynamics in the Jomoro District, Ghana
Authors: Grieco Elisa , Vangi Elia , Chiti Tommaso , Collalti Alessio 
Published: April 2024

AbstractTropical deforestation in the African continent plays a key role in the global carbon cycle and bears significant implications in terms of climate change and sustainable development. Especially in Sub-Saharan Africa, where more than two-thirds of the population rely on forest and woodland resources for their livelihoods, deforestation and land use changes for crop production lead to a substantial loss of ecosystem-level carbon stock. Unfortunately, the impacts of deforestation and land use change can be more critical than in any other region, but these are poorly quantified. We analyse changes in the main carbon pools (above- and below-ground, soil and litter, respectively) after deforestation and land use/land cover change, for the Jomoro District (Ghana), by assessing the initial reference level of carbon stock for primary forest and the subsequent stock changes and dynamics as a consequence of conversion to the secondary forest and to six different tree plantations (rubber, coconut, cocoa, oil palm, and mixed plantations). Results indicate overall a statistically significant carbon loss across all the land uses/covers and for all the carbon pools compared to the primary forest with the total carbon stock loss ranging between 85% and 35% but with no statistically significant differences observed in the comparison between primary forest and mixed plantations and secondary forest. Results also suggest that above-ground carbon and soil organic carbon are the primary pools contributing to the total carbon stocks but with opposite trends of carbon loss and accumulation. Strategies for sustainable development, policies to reduce emissions from deforestation and forest degradation, carbon stock enhancement (REDD+), and planning for sustainable land use management should carefully consider the type of conversion and carbon stock dynamics behind land use change for a win-win strategy while preserving carbon stocks potential in tropical ecosystems.
To be or not to be - Decoding the Trabecular Meshwork Cell Identity
Authors: Tian Alice , Baidouri Hasna , Kim Sangbae , Li Jin , Cheng Xuesen , Li Yumei , Chen Rui , Raghunathan VijayKrishna 
Published: April 2024

ABSTRACTThe trabecular meshwork within the conventional outflow apparatus is critical in maintaining intraocular pressure homeostasis.In vitrostudies employing primary cell cultures of the human trabecular meshwork (hTM) have conventionally served as surrogates for investigating the pathobiology of TM dysfunction. Despite its abundant use, translation of outcomes fromin vitrostudies toex vivoand/orin vivostudies remains a challenge. Given the cell heterogeneity, performing single-cell RNA sequencing comparing primary hTM cell cultures to hTM tissue may provide important insights on cellular identity and translatability, as such an approach has not been reported before. In this study, we assembled a total of 14 primary hTMin vitrosamples across passages 1-4, including 4 samples from individuals diagnosed with glaucoma. This dataset offers a comprehensive transcriptomic resource of primary hTMin vitroscRNA-seq data to study global changes in gene expression in comparison to cells in tissuein situ. We have performed extensive preprocessing and quality control, allowing the research community to access and utilize this public resource.
A comparative analysis of Parkinson’s disease and inflammatory bowel disease gut microbiomes highlights shared depletions in key butyrate-producing bacteria
Authors: Krueger Maeve E. , Boles Jake Sondag , Simon Zachary D. , Alvarez Stephan D. , McFarland Nikolaus R. , Okun Michael S. , Zimmermann Ellen M. , Forsmark Christopher E. , Tansey Malú Gámez 
Published: April 2024

AbstractEpidemiological studies reveal that a diagnosis of inflammatory bowel disease (IBD) is associated with an increased risk of developing Parkinson’s disease (PD). The presence of gut dysbiosis has been documented in both PD and IBD patients, however it is currently unknown how alterations in the gut microbiome may contribute to the epidemiological link between both diseases. To identify shared and distinct features of the PD and IBD microbiome, we performed the first joint analysis of 54 PD, 26 IBD, and 16 healthy control gut metagenomes recruited from clinics at the University of Florida, and directly compared the gut microbiomes from PD and IBD persons. Larger, publicly available PD and IBD metagenomic datasets were also analyzed to validate and extend our findings. Depletions in short-chain fatty acid (SCFA) producing bacteria, includingRoseburia intestinalis, Faecalibacterium prausnitzii, Anaerostipes hadrus,andEubacterium rectale, as well as depletions in SCFA synthesis pathways, were demonstrated across PD and IBD datasets. We posit that direct comparison of PD and IBD gut microbiomes will be important in identifying features within the IBD gut which may be associated with PD. The data revealed a consistent depletion in SCFA-producing bacteria across both PD and IBD, suggesting that loss of these microbes may influence the pathophysiology of both disease states.
EYE-Llama, an in-domain large language model for ophthalmology
Authors: Haghighi Tania , Gholami Sina , Sokol Jared Todd , Kishnani Enaika , Ahsaniyan Adnan , Rahmanian Holakou , Hedayati Fares , Leng Theodore , Alam Minhaj Nur 
Published: April 2024

AbstractBackgroundTraining Large Language Models (LLMs) with in-domain data can significantly enhance their performance, leading to more accurate and reliable question-answering (QA) systems essential for supporting clinical decision-making and educating patients.MethodsThis study introduces LLMs trained on in-domain, well-curated ophthalmic datasets. We also present an open-source substantial ophthalmic language dataset for model training. Our LLMs (EYE-Llama), first pre-trained on an ophthalmology-specific dataset, including paper abstracts, textbooks, EyeWiki, and Wikipedia articles. Subsequently, the models underwent fine-tuning using a diverse range of QA datasets. The LLMs at each stage were then compared to baseline Llama 2, ChatDoctor, and ChatGPT (GPT3.5) models, using four distinct test sets, and evaluated quantitatively (Accuracy, F1 score, and BERTScore) and qualitatively by two ophthalmologists.ResultsUpon evaluating the models using the American Academy of Ophthalmology (AAO) test set and BERTScore as the metric, our models surpassed both Llama 2 and ChatDoctor in terms of F1 score and performed equally to ChatGPT, which was trained with 175 billion parameters (EYE-Llama: 0.57, Llama 2: 0.56, ChatDoctor: 0.56, and ChatGPT: 0.57). When evaluated on the MedMCQA test set, the fine-tuned models demonstrated a higher accuracy compared to the Llama 2 and ChatDoctor models (EYE-Llama: 0.39, Llama 2: 0.33, ChatDoctor: 0.29). However, ChatGPT outperformed EYE-Llama with an accuracy of 0.55. When tested with the PubmedQA set, the fine-tuned model showed improvement in accuracy over both the Llama 2, ChatGPT, and ChatDoctor models (EYE-Llama: 0.96, Llama 2: 0.90, ChatGPT: 0.93, ChatDoctor: 0.92).ConclusionThe study shows that pre-training and fine-tuning LLMs like EYE-Llama enhances their performance in specific medical domains. Our EYE-Llama models surpass baseline Llama 2 in all evaluations, highlighting the effectiveness of specialized LLMs in medical QA systems. (Funded by NEI R15EY035804 (MNA) and UNC Charlotte Faculty Research Grant (MNA).)
Stress granule induction in rat retinas damaged by constant LED light
Authors: Benedetto María M. , Malcolm Melisa , Bruera Manuel G. , Penazzi Laura G. , Guido Mario E. , Contín María A. , Garbarino-Pico Eduardo 
Published: April 2024

ABSTRACTObjectivesStress granules (SGs) are cytoplasmic biocondensates formed in response to various cellular stressors, contributing to cell survival. While implicated in diverse pathologies, their role in retinal degeneration (RD) remain unclear. We aimed to investigate SG formation in the retina and its induction by excessive LED light in a RD model.MethodsRat retinas were immunohistochemically analyzed for SG markers G3BP1 and eIF3, and SGs were also visualized by RNA FISH. Additionally, SGs were induced in primary retinal cell and eyeball cultures using sodium arsenite. Light exposure experiments utilized LED lamps with a color temperature of 5,500 K and 200 lux intensity for short-term or 2-8-day exposures.ResultsSGs were predominantly detected in retinal ganglion cells (RGCs) and inner nuclear layer (INL) cells, confirmed by sodium arsenite induction. SG abundance was higher in animals exposed to light for 2-8 days compared to light/dark cycle controls. RGCs consistently exhibited more SGs than INL cells, and INL cells more than outer nuclear layer cells (Scheirer-Ray-Hare test: H 13.2, p = 0.0103 for light condition, and H 278.2, p < 0.00001 for retinal layer). These observations were consistent across four independent experiments, each with three animals per light condition.ConclusionsThis study identifies SGs in the mammalian retina for the first time, with increased prevalence following excessive LED light exposure. RGCs and INL cells showed heightened SG formation, suggesting a potential protective mechanism against photodamage. Further investigations are warranted to elucidate SGs’ role in shielding against light stress and their implications in retinopathies.
Aperiodic pupil fluctuations at rest predict orienting of visual attention
Authors: Wang Rongwei , Jia Jianrong 
Published: April 2024

AbstractThe aperiodic exponent features signals in various neuroimaging modalities and has been linked to the excitation/inhibition balance of the neural system. Leveraging the rich temporal dynamics of resting-state pupil fluctuations, the present study investigated the association between the aperiodic exponent of pupil fluctuations and the neural excitation/inhibition balance in attentional processing. In separate phases, we recorded participants’ pupil size during resting state and assessed their attentional orienting using the Posner cueing tasks with different cue validities (i.e., 100% and 50%). We found significant correlations between the aperiodic exponent of resting pupil fluctuations and both the microsaccadic and behavioral cueing effects. Critically, this relationship was particularly evident in the 50% cue-validity condition rather than in the 100% cue-validity condition. The microsaccadic responses mediated the association between the aperiodic exponent and the behavioral response. Further analysis showed that the aperiodic exponent of pupil fluctuations predicted the self-rated hyperactivity/impulsivity trait across individuals, suggesting its potential as a marker of attentional deficits. These findings highlight the rich information contained in pupil fluctuations and provide a novel approach to assessing the neural excitation/inhibition balance in attentional processing.
Dementia Risk Scores,APOE,and risk of Alzheimer disease: one size does not fit all
Authors: Andrews Shea J. , Boeriu Ana I. , Belloy Michael E. , Renton Alan E. , Fulton-Howard Brian , Brenowitz Willa D. , Yaffe Kristine ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2024

AbstractIntroductionEvaluating the generalizability of dementia risk scores, primarily developed in non-Latinx White (NLW) participants, and interactions with genetic risk factors in diverse populations is crucial for addressing health disparities.MethodsWe analyzed the association of the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) and modified CAIDE (mCAIDE) scores with dementia risk using logistic regression models stratified by race/ethnicity in NACC and ADNI, and assessed their interaction withAPOE.ResultsHigher CAIDE scores were associated with an increased risk of dementia in Asian, Latinx, and NLW participants but not in Black participants. In contrast, higher mCAIDE scores were also associated with an increased risk of dementia in Black participants. Unfavorable mCAIDE risk profiles exacerbated theAPOE*ε4 risk effect and attenuated theAPOE*ε2 protective effect.DiscussionOur findings underscore the importance of evaluating the validity of dementia risk scores in diverse populations for their use in personalized medicine approaches to promote brain health.