bluuebunny/crossref_metadata_2025_split huggingface dataset:
GPT-4 Improves Readability of Institutional Heart Failure Patient Education Materials: An Observational Study
Authors: King Ryan C. , Samaan Jamil S. , Haquang Joseph , Bharani Vishnu , Margolis Samuel , Srinivasan Nitin , Peng Yuxin , Yeo Yee Hui , Ghashghaei Roxana 
Published: November 2024

AbstractIntroductionHeart failure management involves comprehensive lifestyle modifications such as daily weights, fluid and sodium restriction, and blood pressure monitoring placing additional responsibility on patients and caregivers with successful adherence often requiring extensive counseling and understandable patient education materials (PEMs). Prior research has shown PEMs related to cardiovascular disease often exceed the American Medical Association’s 5th-6thgrade recommended reading level. The large language model (LLM) Chat Generative Pre-trained Transformer (ChatGPT) may be a useful tool for improving PEM readability.Materials and MethodsA total of 143 heart failure PEMs were collected from the websites of the top 10 institutions listed on the 2022-2023 US News & World Report for “Best Hospitals for Cardiology, Heart & Vascular Surgery”. PEMs were individually entered into GPT-4 (Version updated 20 July 2023) preceded by the prompt “please explain the following in simpler terms”. The readability of the institutional PEM and ChatGPT revised PEM were both assessed usingTextstatlibrary in Python and theTextstat readabilitypackage in R software. The accuracy and comprehensiveness of revised GPT-4 PEMs were assessed by a board-certified cardiologist.ResultsThe Flesch-Kincaid grade reading level ranged from 8th grade to college freshman with a median of 10th grade vs 6thto 8thgrade with a median of 7thgrade for institutional PEMs and GPT-4 PEMs (p< 0.001), respectively. There were 13/143 (9.1%) institutional PEMs below the 6thgrade reading level which improved to 33/143 (23.1%) after revision by GPT-4 (p<0.001). No GPT-4 revised PEMs were graded as less accurate or less comprehensive compared to institutional PEMs. A total of 33/143 (23.1%) GPT-4 PEMs were graded as more comprehensive.ConclusionsGPT-4 significantly improved the readability of institutional heart failure PEMs. The model may be a promising adjunct resource in addition to care provided by a licensed healthcare professional for patients living with heart failure. Further rigorous testing and validation is needed to investigate its safety, efficacy and impact on patient health literacy.
Hydrocarbon effects on cell survival and antioxidant system of breast tumorigenic and non-tumorigenic cells
Authors: Mardirosian Mariana , Lasagna Marianela , Núñez Mariel , Galarza Tamara , Espert Nuria , Venturino Andrés , Cocca Claudia 
Published: November 2024

ABSTRACTOver the last decades, environmental pollution with polycyclic aromatic hydrocarbons (PAH) has risen due to human development and industrial activities. The consequences of potential contamination with oil or any of its components must be evaluated. Here, we faced the effects on cell growth and detoxification that might arise from the exposure to hydrocarbons sourced from contaminated waters. MCF-7 and MDA-MB-231 human breast cancer cells and/or MCF-10A epithelial non-tumorigenic cells were exposed to water-accommodated oil fraction (WAF) or anthracene as a PAH currently found in the environment to evaluate clonogenicity, viability, GST and CAT activities. WAF decreased MDA-MB-231 cells clonogenicity and MDA-MB-231 and MCF-7 cells viability. Anthracene significantly reduced non-tumorigenic cells’ viability and clonogenicity, without affecting the survival of tumorigenic cells. Both tumorigenic cells responded mainly by activating the antioxidant system through the increment of CAT when exposed to low concentrations of WAF. In both cell lines, WAF also increased GST. Anthracene exposure significantly decreased CAT activity of the three cell lines evaluated. GST activity decreased 38% after 28 µM anthracene exposure in MDA-MB-231 cells (p<0.05) and 15, 17 and 21% after 7 (p<0.05), 14 and 28 µM (p<0.01) in MCF-10A cells, while in MCF-7 cells 28 µM anthracene increased GST activity by 75% (p<0.001). We conclude that the sensitivity of cells to the different contaminants evaluated is affected by the degree of cellular tumorigenicity and exposure to WAF or anthracene may exacerbate malignant conditions. The integration of multiple parameters, analyzed through multivariate methods, offers a comprehensive evaluation of toxicant effects.HIGHLIGHTSWAF and anthracene affect tumorigenic mammary cells viability and clonogenicityNon tumorigenic mammary cells show more sensitivity to anthracene exposureWAF activates antioxidant and detoxicant system in tumorigenic mammary cellsAnthracene decreased CAT activity of tumorigenic and non-tumorigenic mammary cellsAnthracene affected GST activity of tumorigenic and non-tumorigenic mammary cells
Physical vitrification and nanowarming at human organ scale to enable cryopreservation
Authors: Gangwar Lakshya , Han Zonghu , Scheithauer Cameron , Namsrai Bat-Erdene , Kantesaria Saurin , Goldstein Rob , Etheridge Michael L. , Finger Erik B. , Bischof John C. 
Published: November 2024

AbstractOrgan banking by vitrification could revolutionize transplant medicine. However, vitrification and rewarming have never been demonstrated at the human organ scale. Using modeling and experimentation, we tested the ability to vitrify and rewarm 0.5 – 3 L volumes of three common cryoprotective agent (CPA) solutions: M22, VS55, and 40% EG+0.6M Sucrose. We first demonstrated our ability to avoid ice formation by convectively cooling faster than the critical cooling rates of these CPAs while also maintaining adequate uniformity to avoid cracking. Vitrification success was then verified by visual, thermometry, and x-ray μCT inspection. M22 and EG+sucrose were successfully vitrified in 0.5 L bags, but only M22 was vitrified at 3 L. VS55 did not vitrify at any tested volumes. As additional proof of principle, we successfully vitrified a porcine liver (∼1L) after perfusion loading with 40% EG+0.6M Sucrose. Uniform volumetric rewarming was then achieved in up to 2 L volumes (M22 with ∼5 mgFe/mL iron-oxide nanoparticles) using nanowarming, reaching a rate of ∼88 °C/min with a newly developed 120 kW radiofrequency (RF) coil operating at 35kA/m and 360kHz. This work demonstrates that human organ scale vitrification and rewarming is physically achievable, thereby contributing to technology that enables human organ banking.
Distilling Structural Representations into Protein Sequence Models
Authors: Ouyang-Zhang Jeffrey , Gong Chengyue , Zhao Yue , Krähenbühl Philipp , Klivans Adam R. , Diaz Daniel J. 
Published: November 2024

AbstractProtein language models, like the popular ESM2, are widely used tools for extracting evolution-based protein representations and have achieved significant success on downstream biological tasks. Representations based on sequence and structure models, however, show significant performance differences depending on the downstream task. A major open problem is to obtain representations that best capture both the evolutionary and structural properties of proteins in general. Here we introduceImplicitStructureModel(ISM), a sequence-only input model with structurally-enriched representations that outperforms state-of-the-art sequence models on several well-studied benchmarks including mutation stability assessment and structure prediction. Our key innovations are a microenvironment-based autoencoder for generating structure tokens and a self-supervised training objective that distills these tokens into ESM2’s pre-trained model. We have madeISM’s structure-enriched weights easily available: integrating ISM into any application using ESM2 requires changing only a single line of code. Our code is available athttps://github.com/jozhang97/ISM.
Video tracking of single cells to identify clustering behaviour
Authors: Korsnes Mónica Suárez , Ramberg Håkon André , Taskén Kristin Austlid , Korsnes Reinert 
Published: November 2024

AbstractCancer cell clustering is a critical factor in metastasis, with cells often believed to migrate in groups as they establish themselves in new environments. This study presents preliminary findings from anin vitroexperiment, suggesting that co-culturing cells provides an effective method for observing this phenomenon, even though the cells are grown as monolayers. We introduce a novel single-cell tracking approach based on graph theory to identify clusters in PC3 cells cultivated in both monoculture and co-culture with PC12 cells, using 66-hour time-lapse recordings. The initial step consists of defining ‘linked’ pairs of PC3 cells, laying the foundation for the application of graph theory. We propose two alternative definitions for cell pairings. The first method,Method 1, defines cells as ‘linked’ at a given timetif they are close together within a defined time period before and aftert. A second potential alternative method,Method 2, pairs cells if there is an overlap between the convex hulls of their respective tracks during this time period. Pairing cells enables the application of graph theory for subsequent analysis. This framework represents a cell as a vertex (node) and a relation between two cells as an edge. An interconnected set of high-degree nodes (nodes with many connections or edges) forms a subgraph, or backbone, that defines a patch (cluster) of cells. All nodes connected to this backbone are part of the subgraph. The backbone of high-degree nodes functions as a partition (or cut) of the initial graph. Two consecutive clusters in the video are considered to share the same identity if the following cluster contains at leastp= 75 % of the cells from the preceding cluster, and the mean positions of their cells are within △r= 75 µm. PC3 cells grown in co-culture appear to form persistent clusters exceeding 10 cells after 40 to 50 h incubation following seeding. In contrast, PC3 cells cultured alone (mono-culture) did not exhibit this behaviour. This approach is experimental and requires further validation with a broader dataset.
Small proteins from prokaryotes in marine water column at full ocean depth
Authors: Li Qing-Mei , He Li-Sheng , Wang Yong 
Published: November 2024

ABSTRACTSmall proteins (SPs,≤50 amino acids) are usually ignored by automated bioinformatic algorithms and difficult to be detected by traditional protein purification. In this study, 193,281 prokaryotic SP clusters were generated using 433,311 small open reading frames (sORFs) predicted in assemblies of 71 full-ocean-depth marine water metagenomes from the western pacific. Further filtration with at least 5 copies per million reads resulted in 75,581 prevalent SP clusters, among which 4,307 clusters have coding capacity as predicted by RNAcode. For these RNAcode-filtered SP (RfSP) clusters hosted largely by Proteobacteria, Thaumarchaeota and Marinimicrobia, 29.16% of them show homology () in all prokaryotic genomes. About 2% of the RfSP clusters were estimated as potential antimicrobial peptides and were distributed across all depth zones. Transcription of 7.96% of the RfSP clusters was verified in 12 deep-sea metatranscriptomes, and translation of 34 prevalent SP clusters was detected in 14 metaproteomes. The transcribed RfSP clusters are involved in processes such as DNA stability under stress condition, betaine transport and cell division regulation for a rapid response to varying deep-sea environments. This study uncovers a vast reservoir of SPs with pivotal functions in potential antibiotic activities, hyperoxide detoxification and pressure resistance for fitness of marine prokaryotes in deep ocean.
Inferring the demographic history of aye-ayes (Daubentonia madagascariensis) from high-quality, whole-genome, population-level data
Authors: Terbot John W. , Soni Vivak , Versoza Cyril J. , Pfeifer Susanne P. , Jensen Jeffrey D. 
Published: November 2024

ABSTRACTThe nocturnal aye-aye,Daubentonia madagascariensis, is one of the most elusive lemurs on the island of Madagascar. The timing of its activity and arboreal lifestyle has generally made it difficult to obtain accurate assessments of population size using traditional census methods. Therefore, alternative estimates provided by population genetic inference are essential for yielding much needed information for conservation measures and for enabling ecological and evolutionary studies of this species. Here, we utilize genomic data from 17 unrelated individuals — including 5 newly sequenced, high-coverage genomes — to estimate this history. Essential to this estimation are recently published annotations of the aye-aye genome which allow for variation at putatively neutral genomic regions to be included in the estimation procedures, and regions subject to selective constraints, or in linkage to such sites, to be excluded owing to the biasing effects of selection on demographic inference. By comparing a variety of demographic estimation tools to develop a well-supported model of population history, we find strong support for the species to consist of two demes, separating northern Madagascar from the rest of the island. Additionally, we find that the aye-aye has experienced two severe reductions in population size. The first occurred rapidly, approximately 3,000 to 5,000 years ago, and likely corresponded with the arrival of humans to Madagascar. The second occurred over the past few decades and is likely related to substantial habitat loss, suggesting that the species is still undergoing population decline and remains at great risk for extinction.
A pedigree-based map of crossovers and non-crossovers in aye-ayes (Daubentonia madagascariensis)
Authors: Versoza Cyril J. , Lloret-Villas Audald , Jensen Jeffrey D. , Pfeifer Susanne P. 
Published: November 2024

ABSTRACTGaining a better understanding of rates and patterns of meiotic recombination is crucial for improving evolutionary genomic modelling, with applications ranging from demographic to selective inference. Although previous research has provided important insights into the landscape of crossovers in humans and other haplorrhines, our understanding of both the considerably more common outcome of recombination (i.e., non-crossovers) as well as the landscapes in more distantly-related primates (i.e., strepsirrhines) remains limited owing to difficulties associated with both the identification of non-crossover tracts as well as species sampling. Thus, in order to elucidate recombination patterns in this under-studied branch of the primate clade, we here characterize crossover and non-crossover landscapes in aye-ayes utilizing whole-genome sequencing data from six three-generation pedigrees as well as three two-generation multi-sibling families, and in so doing provide novel insights into this important evolutionary process shaping genomic diversity in one of the world’s most critically endangered primate species.
Rapid Caspian sea level decline requires dynamic spatio-temporal conservation planning to keep biodiversity protection measures relevant
Authors: Court Rebecca , Lattuada Matteo , Shumeyko Nataliya , Baimukanov Mirgaliy , Eybatov Tariel , Kaidarova Altynay , Mamedov Elchin V. , Rustamov Eldar , Tasmagambetova Aselle , Prange Matthias , Wilke Thomas , Hassall Christopher , Goodman Simon J. 
Published: November 2024

AbstractThe Caspian Sea is the world’s largest landlocked waterbody, providing habitat for hundreds of endemic and migratory species, along with ecosystem services that sustain millions of people. Global warming is projected to drive declines in water levels of up to 21 m by 2100. Using geospatial analyses, we assessed the impact of sea level decline on habitats, protected areas, and human infrastructure. We show that a water level decline of just 5–10 m will critically disrupt key ecosystems, reduce existing marine protected area coverage by up to 94%, and render billions of dollars of civil and industrial infrastructure obsolete. Urgent action is needed to replace traditional static conservation planning with a pre-emptive, dynamic approach that allows protected areas to track shifting ecosystems. This will be essential to help the Caspian Sea’s endemic biodiversity adapt to these changes, and avoid conflicts with mitigation efforts directed at protecting human activity.Russian abstractАбстрактКаспийское море – крупнейший в мире внутренний водоем, обеспечивающий среду обитания для сотен эндемичных и мигрирующих видов, а также экосистемные услуги, обеспечивающие жизнедеятельность миллионов людей. Согласно прогнозам, глобальное потепление приведет к снижению уровня воды до 21 м к 2100 году. С помощью геопространственного анализа проведена оценка влияния снижения уровня моря на места обитания, охраняемые территории и объекты инфраструктуры. Мы показываем, что снижение уровня воды всего на 5–10 м приведет к критическим нарушениям в ключевых экосистемах, сократит охват существующих морских охраняемых районов до 94% и приведет к выводу из эксплуатации гражданской и промышленной инфраструктуры стоимостью в миллиарды долларов. Необходимы безотлагательные меры по замене традиционного статичного планирования природоохранной деятельности упреждающим, динамичным подходом, который позволит корректировать границы охраняемых районов вслед за смещением экосистем. Это необходимо для адаптации эндемичного биоразнообразия Каспийского моря к изменениям, а также для того, чтобы усилия по его сохранению не вступали в конфликт с мерами по защите деятельности человека.
Maternal inheritance of primary sex ratios in the dark-winged fungus gnatLycoriella ingenua
Authors: Shlyakonova Maria , Monteith Katy M. , Ross Laura , Baird Robert B. 
Published: November 2024

AbstractSex determination mechanisms in insects are extraordinarily diverse, although most species have zygotic genotypic sex determination where sex is established by sex chromosomes upon fertilisation. Dark-winged fungus gnats (Diptera: Sciaridae) are a large and speciose family of flies where sex determination is a result of an unusual interplay of zygotic, maternal, and environmental factors. This causes some species to produce clutches of offspring that deviate considerably from the standard 1:1 Fisherian sex ratio. An early study suggested that these primary sex ratios may be heritable from mother to daughter, but this observation has not been corroborated and the genetic basis for this trait remains unknown. Other studies have found that in some species, there is an additional temperature effect on the primary sex ratio, but again the mechanism is unknown. Here, we perform sibling crosses and temperature-shift experiments in a recently isolated line of the speciesLycoriella ingenuaand find evidence for highly variable and heritable primary sex ratios, but no significant environmental effect. We discuss the consequences of our findings for understanding the mechanisms that produce these unusual sex ratios, and the evolution of sex determination more broadly in this clade.
CelLink: integrating single-cell multi-omics data with weak feature linkage and imbalanced cell populations
Authors: Luo Xin , Huang Yuanhao , Tao Yicheng , Feng Fan , Hopkirk Alexander , Bate Thomas S.R. , Saunders Diane C. , Orchard Peter , Robertson Catherine , Shrestha Shristi , Cartailler Jean-Philippe , Parker Stephen C. J. , Brissova Marcela , Liu Jie 
Published: November 2024

AbstractSingle-cell multi-omics technologies capture complementary molecular layers, enabling a comprehensive view of cellular states and functions. However, integrating these data types poses significant challenges when their features are weakly linked and cell population sizes are imbalanced. Currently, no method efficiently addresses these two issues simultaneously. Therefore, we developed CelLink, a novel single-cell multi-omics data integration method designed to overcome these challenges. CelLink normalizes and smooths feature profiles to align scales across datasets and integrates them through a multi-phase pipeline that iteratively employs the optimal transport algorithm. It dynamically refines cell-cell correspondences, identifying and excluding cells that cannot be reliably matched, thus avoiding performance degradation caused by erroneous imputations. This approach effectively adapts to weak feature linkage and imbalanced cell populations between datasets. Benchmarking CelLink on scRNA-seq and spatial proteomics datasets, as well as paired CITE-seq data, demonstrates its superior performance across various evaluation metrics, including data mixing, cell manifold structure preservation, and feature imputation accuracy. Compared to state-of-the-art methods, CelLink significantly outperforms others in imbalanced cell populations while consistently achieving better performance for balanced datasets. Moreover, CelLink uniquely enables cell subtype annotation, correction of mislabelled cells, and spatial transcriptomic analyses by imputing transcriptomic profiles for spatial proteomics data. CelLink sets a new milestone for multi-omics data integration. Its great ability to impute large-scale paired single-cell multi-omics profiles positions it as a pivotal tool for building single-cell multi-modal foundation models and advancing spatial cellular biology.
Leveraging genetic ancestry continuum information to interpolate PRS for admixed populations
Authors: Ruan Yunfeng , Bhukar Rohan , Patel Aniruddh , Koyama Satoshi , Hull Leland , Truong Buu , Hornsby Whitney , Zhang Haoyu , Chatterjee Nilanjan , Natarajan Pradeep 
Published: November 2024

AbstractThe relatively low representation of admixed populations in both discovery and fine-tuning individual-level datasets limits polygenic risk score (PRS) development and equitable clinical translation for admixed populations. Under the assumption that the most informative PRS weight for a homogeneous sample varies linearly in an ancestry continuum space, we introduce a GeneticDistance-assisted PRSCombination Pipeline forDiverse GeneticAncestries(DiscoDivas) to interpolate a harmonized PRS for diverse, especially admixed, ancestries, leveraging multiple PRS weights fine-tuned within single-ancestry samples and genetic distance. DiscoDivas treats ancestry as a continuous variable and does not require shifting between different models when calculating PRS for different ancestries. We generated PRS with DiscoDivas and the current conventional method, i.e. fine-tuning multiple GWAS PRS using the matched or similar ancestry samples. DiscoDivas generated a harmonized PRS of the accuracy comparable to or higher than the conventional approach, with the greatest advantage exhibited in admixed individuals.