bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wastewater-integrated pathogen surveillance dashboards enable real-time, transparent, and interpretable public health risk assessment and dissemination
Authors: Msomi Nosihle S. , Levy Joshua I. , Matteson Nathaniel L. , Ndlovu Nkosenhle , Ntuli Phindile , Baer Adam , Mabasa Victor , Gwala Sipho , Singh Natasha , Subramoney Kathleen , Phalane Emmanuel , Macheke Mokgaetji , Motloung Mantshali , Mangena Thabo , Monametsi Lethabo , Rabotapi Lebohang , Maposa Sibonginkosi , Birmingham Amanda , Zeller Mark , Karthikeyan Smruthi , Harris Simon , Knight Rob , Laurent Louise C. , Andersen Kristian G. , McCarthy Kerrigan , Yousif Mukhlid 
Published: January 2025

ABSTRACTTimely pathogen surveillance and reporting is essential for effective public health guidance. Web dashboards have become a key tool for communicating public health information to stakeholders, health care workers, and the broader community. Over the SARS-CoV-2 pandemic, wastewater surveillance has increasingly been incorporated into public health workflows for outbreak monitoring and response, enabling community-representative and low-cost monitoring to supplement clinical surveillance. However, the methods used for visualization and dissemination of clinical and wastewater surveillance data differ across programs and best practices are yet to be defined. In this work, we demonstrate data workflows and dashboards used to perform wastewater-based public health surveillance in tandem with clinical data across local and national scales, leveraging custom-built, reproducible, and open-source software. Using a centralized data aggregation and analysis hub approach, we establish multiple data pipelines for data storage, wrangling, and standardized analyses, and deploy custom-built web dashboards that allow for immediate public release. We find that our approach is effective across scales, computing architectures, and dissemination strategies, and provides an adaptable model to incorporate additional pathogens and epidemiological data.
Physical confinement regulates transition in nematode motility
Authors: Dey Saheli , Sreepadmanabh M , Kundu Sayan , Arun Ashitha B , Koushika Sandhya P , Thutupalli Shashi , Hewitt Duncan , Bhattacharjee Tapomoy 
Published: January 2025

AbstractHow do worms navigate their complex natural surroundings? Undulatory microswimmers such as nematodes typically inhabit environments such as soil, vegetable matter, and host tissues. While the natural habitats of nematodes are often three-dimensional granular niches with spatiotemporally varying visco-elasto-plastic material properties that impose physical constraints on their motion, current knowledge about nematode motility patterns broadly comes from investigating model organisms such asCaenorhabditis eleganseither inside liquid cultures or the surface of soft agar pads. How nematodes move through 3D granular niches across different degrees of physical confinement remains poorly understood due to a lack of optically transparent 3D granular matrices. We bridge this gap by engineering an optically transparent granular matrix to directly visualise and quantitatively analyse nematode motion. Importantly, nematodes can freely move through this matrix by generating a minimal yield stress; once the nematode moves away, the matrix self-heals to ensure the material properties remain invariant. Using these platforms, we observe that the propulsive speed of nematodes shows a non-monotonic relation with the yield stress of their microenvironment. This non-monotonicity emerges as nematodes optimize for efficient navigation at higher yield stress, wherein, their forward propulsive speed matches the wave speed along their body. This regulation of locomotory behaviour is purely dictated by the physical interaction of the nematode with its environment without involving soft-touch sensory neurons. Remarkably, predictions from a slender body theory of undulatory motion exactly capture the scaling behaviour for both efficiency and mode of motion as obtained from the experimental data. Finally, in a phase space described by non-dimensional propulsive efficiency and a non-dimensional time scale of motility, we capture a gait transition from poorly efficient thrashing under low confinement to more efficient crawling under high confinement. Thus, our work establishes a new regulatory paradigm describing how distinct modes of undulatory motion emerge under different degrees of physical confinement.
A cyanobacterial screening platform for Rubisco mutant variants
Authors: Hoffmann Ute A. , Schuppe Anna Z. , Knave Axel , Sporre Emil , Brismar Hjalmar , Englund Elias , Syrén Per-Olof , Hudson Elton P. 
Published: January 2025

AbstractRubisco is the main entry point of inorganic carbon into the biosphere and a central player in the global carbon system. Its relatively low catalytic constant as well as its tendency to also accept O2as a substrate have made it a common target of enzyme engineering. We have developed an enzyme engineering and screening platform for Rubisco using the model cyanobacteriumSynechocystissp. PCC 6803. Starting with the Form II Rubisco fromGallionella,we first show that the enzyme can replace the native Form I Rubisco inSynechocystisand that growth rates become sensitive to CO2and O2levels. We address the challenge of designing a zero-shot input library, without prior experimental knowledge, by coupling the phylogenetically-guided model EVmutation with “in silicoevolution”. Starting with this targeted mutagenesis library, we used competitive growth coupled to deep sequencing to compare the properties of Rubisco protein variants under different cultivation conditions. We identified an amino acid exchange which increased the thermostability ofGallionellaRubisco and conveyed resilience to detrimental exchanges. The establishment of this platform is a first step towards high-throughput screening of Rubisco variants inSynechocystisand creating optimized enzyme variants to accelerate the Calvin-Benson-Bassham cycle in cyanobacteria and possibly chloroplasts.
Adaptive Plasticity Tumor Cells Modulate MAPK-Targeting Therapy Response in Colorectal Cancer
Authors: Villarreal Oscar E. , Xu Yixin , Tran Ha , Machado Annette , Prescod Dionne , Anderson Amanda , Minelli Rosalba , Peoples Mike , Martinez Alejandro Hernandez , Lee Hey Min , Wong Chi Wut , Fowlkes Natalie , Kanikarla Preeti , Sorokin Alexey , Alshenaifi Jumanah , Coker Olu , Lin Kangyu , Bristow Chris , Viale Andrea , Shen John Paul , Parseghian Christine , Marszalek Joseph R. , Corcoran Ryan , Kopetz Scott 
Published: January 2025

AbstractMAPK pathway inhibitors (MAPKi) are increasingly used in the treatment of advanced colorectal cancer, but often produce short-lived responses in patients. Although acquired resistance byde novomutations in tumors have been found to reduce response in some patients, additional mechanisms underlying the limited response durability of MAPK targeting therapy remain unknown. Here, we denote new contributory tumor biology and provide insight on the impact of tumor plasticity on therapy response. Analysis of MAPKi treated patients revealed activation of stemness programs and increased ASCL2 expression, which are associated with poor outcomes. Greater ASCL2 with MAPKi treatment was also seen in patient-derived CRC models, independent of driver mutations. We find ASCL2 denotes a distinct cell population, arising from phenotypic plasticity, with a proliferative, stem-like phenotype, and decreased sensitivity to MAPKi therapy, which were named adaptive plasticity tumor (APT) cells. MAPK pathway suppression induces the APT phenotype in cells, resulting in APT cell enrichment in tumors and limiting therapy response in preclinical and clinical data. APT cell depletion improved MAPKi treatment efficacy and extended MAPKi response durability in mice. These findings uncover a cellular program that mitigates the impact of MAPKi therapies and highlights the importance of addressing tumor plasticity to improve clinical outcomes.
Optimized protocols for commonly-used murine models of heart failure with preserved ejection fraction
Authors: McIntosh Bailey , Elbassioni Ali Mohamed , Raheem Anmar , McDonald Eilidh , Nicklin Stuart A. , Koay Yen Chin , Cameron Ewan R. , Loughrey Christopher M. , O’Sullivan John F. 
Published: January 2025

AbstractBackgroundHFpEF is a leading cause of death worldwide and clinically relevant preclinical models are required to identify new therapeutic targets. The most clinically representative murine models of heart failure with preserved ejection fraction (HFpEF) in common use include a “2-hit” model combining metabolic stress with hypertension (high-fat diet [HFD] + N(gamma)-nitro-L-arginine methyl ester [L-NAME]) and a “3-hit” model that includes age as an additional “hit” (age + HFD + deoxycorticosterone pivalate [DOCP]). However, both models have reproducibility challenges, and sub-strain and sex dependency. Here we optimize both preclinical models to overcome these challenges.MethodsIn this study we optimized both models: (1) The 2-hit model was optimised to reproduce HFpEF (defined as the induction and maintenance of obesity, hypertension, diastolic dysfunction, left ventricular hypertrophy, lung congestion, and exercise intolerance) in both C57BL/6N and 6J mice using increasing L-NAME doses (0.5 g/L to 1.75 g/L) and protocol lengths (7 weeks to 13 weeks); and (2) The 3-hit model used 12-week-old C57BL/6N and 6J mice and two aging protocols were compared: HFD for 7 months, or healthy chow for 5 months then high fat diet for 7 months. After HFD, mice received an intraperitoneal injection of DOCP to induce hypertensionviasodium retention. To enhance and prolong the effect of DOCP, mice received 1% NaCl drinking water at the time of injection until sacrifice, henceforth called “4-hit”. To ensure the phenotype was maintained, a second bolus of DOCP was administered 8 weeks after the first.ResultsFor the 2-hit protocol, HFpEF was successfully induced in C57BL/6J mice when exposed to a 13-week L-NAME protocol with gradually increasing dosage from 1.0 g/L to 1.75 g/L. C57BL/6N mice showed the desired parameters after 7-weeks of 0.5 g/L L-NAME, which were not augmented by increased dosage or time administered. For the 4-hit mice, after addition of 1% NaCl drinking water following DOCP administration, a clear HFpEF phenotype was observed in C57BL/6N and 6J mice in both male and females, and maintained for up to 12 weeks.ConclusionsOur modifications ensure the 2-hit model is equally effective in both commonly used J and N substrains of C57BL/6 mice. Our 4-hit model overcomes the challenges of the 3-hit model, enhances reproducibility and robustness, which we demonstrate across sexes and substrains. Both of these new protocols will enhance clinically relevant mechanistic studies on HFpEF.
Winter rye root growth and plasticity in response to nitrogen and phosphorus omission under field conditions
Authors: Nyameasem John Kormla , Seidel Sabine J. , Hadir Sofia , Lopez Gina , Bauke Sara L. , Hernandez-Ochoa Ixchel M. 
Published: January 2025

AbstractNitrogen (N) and phosphorus (P) deficiencies can significantly reduce crop yield. Despite their importance, the impacts of N and P deficiencies under field conditions on cereal roots, particularly winter rye, remain poorly understood. This study investigates the effects of N and P deficiencies on winter rye growth and root architecture under field conditions. A sampling campaign was conducted during the 2022 season at the long-term fertilizer experiment Dikopshof, Germany. Four fertilizer treatments were chosen: (1) fully fertilized with manure (NPKCa+m+s), (2) fully fertilized without manure (NPKCa), (3) N omitted (_PKCa), and (4) P omitted (N_KCa). Shoot biomass was assessed at five growth stages, alongside with topsoil root biomass, number of nodal roots and tillers, and root angle. The results showed that shoot and root biomass were highest in the NPKCa+m+s treatment and lowest under N omission. Although the treatment ranking of root traits varied between dates, a trend for an enhanced number of roots in the N and P omission treatments was observed around flowering. P omission fostered an increased number of tillers and N omission caused steeper root angles compared to other treatments. These findings demonstrate the strong impact of the environment and development stage on root phenotypic plasticity.
Transcriptome mining reveals diversity and evolution of iflaviruses in Lepidoptera
Authors: van Valkengoed Devin , Bryon Astrid , Ros Vera I.D. , Kupczok Anne 
Published: January 2025

AbstractInsects are associated with a wide variety of diverse RNA viruses, including iflaviruses, a group of positive stranded RNA viruses that mainly infect arthropods. Whereas some iflaviruses cause severe diseases in insects, numerous iflaviruses that were detected in healthy populations of butterflies and moths (order: Lepidoptera) do not show apparent symptoms. Compared to other hosts, only few iflavirus genomes for lepidopteran hosts could be found in publicly available databases and we know little about the occurence of iflaviruses in natural and laboratory lepidopteran populations. To expand the known diversity of iflaviruses in Lepidoptera, we developed a pipeline that automatically reconstructs complete virus genomes from public transcriptome data, yielding 1,548 complete virus genomes from 55 different lepidopteran species. To include incompletely assembled genomes, we developed a reference-based patching approach, resulting in 240 patched genomes. By including publicly available genomes, we inferred a phylogeny consisting of 139 non-redundant iflavirus genomes. Of these, 65 represent novel complete genomes, of which 39 might even belong to novel virus species. Our analysis expanded virus host range, where highly similar viruses were found in the transcriptomes of different lepidopteran species, genera or even families. Additionally, we find two groups of lepidopteran species depending on the diversity of viruses that infect them: some species were only infected by closely related viruses, whereas other species are infected by highly diverse viruses from different regions of the phylogeny. Finally, we show that the evolution of one virus species,Iflavirus betaspexiguae, is impacted by recombination within the species, which is also supported by the co-occurrence of multiple strains within data sets. Our analysis demonstrates how data mining of publicly available sequencing data can be used at a large scale to reconstruct intra-family viral diversity which serves as a basis to study virus host range and evolution. Our results contain numerous novel viruses and novel virus-host associations, including viruses for relevant insect pests, highlighting the impact of iflaviruses in insect ecology and as potential biological control agents in the future.
Exploring the role of transposable elements to sex gap in longevity in Drosophila species
Authors: Merenciano Miriam , Janillon Sonia , Mermet-Bouvier Camille , Burlet Nelly , Rodriguez-Rada Valentina , Ronget Victor , Gibert Patricia , Gaillard Jean-Michel , Lemaitre Jean-François , Marais Gabriel AB , Boulesteix Matthieu , Fablet Marie , Vieira Cristina 
Published: January 2025

SUMMARYIn Drosophila, like in many other animal species, females tend to live longer than males, a phenomenon known as sex gap in longevity (SGL). One of the possible causes underlying this phenomenon could be related to the high content of transposable elements (TE) in the Y chromosome (toxic Y hypothesis). TE activity is normally repressed by epigenetic mechanisms, but this regulation weakens with age. Since the Y chromosome is rich in TEs, age-related TE activity should be more pronounced in old males than in old females, likely affecting longevity patterns. In this work, we studied the natural variation in SGL in wild-type populations of three different Drosophila species that vary in their TE content:Drosophila melanogaster,Drosophila simulans, andDrosophila suzukii. Transcriptomic data revealed increased copy-specific TE expression inD. melanogasterandD. suzukiiolder flies. Moreover, we observed a higher number of upregulated TEs in old males compared to old females across all the three species tested. Additionally, we detected an increase in TE-chimeric transcript generation in some aged samples, particularly inD. suzukiimales. Finally, the replacement of the Y chromosome between strains with different SGL led to a progressive reduction in male lifespan and increased TE transcriptional release over generations, suggesting a Y chromosome important role in male longevity. Our work contributes to a better understanding of the genomic differences that lead to variation in longevity patterns between sexes in several species, and emphasizes the importance of studying the role of TEs in male longevity.
17β-Estradiol Counteracts Pathological Microtubule Remodeling To Enhance Cardiac Function
Authors: Moon Ryan , Vogel Neal T. , Mendelson Jenna B. , Hartweck Lynn M. , Carney John P. , Kim Minwoo , Gardner Melissa K. , Prisco Sasha , Prins Kurt W. 
Published: January 2025

AbstractThe female-predominate sex hormone 17β-estradiol exerts cardioprotective effects via multiple mechanisms. Available data demonstrate 17β-estradiol modulates microtubule dynamicsin vitro, but its effects on pathogenic microtubule remodeling in pressure-overloaded cardiomyocytes are unexplored. Here, we show 17β-estradiol directly blunts microtubule polymerizationin vitro, counteracts endothelin-mediated microtubule remodeling in iPSC-cardiomyocytes, and mitigates microtubule stabilization in pulmonary artery banded right ventricular cardiomyocytes. 17β-estradiol treatment blunts cardiomyocyte and nuclear hypertrophy, restores t-tubule architecture, and prevents mislocalization of connexin-43 in RV cardiomyocytes of pulmonary artery banded rats. These cellular phenotypes are paired with significant improvements in RV function. Thus, we propose 17β-estradiol exerts cardioprotective effects via direct modulation of microtubules in addition to its well ascribed signaling functions.
ChemBERTaDDI: Transforming Drug-Drug Interaction Prediction with Transformers and Clinical Insights
Authors: Gromova Anastasiya A. , Maida Anthony S. 
Published: January 2025

AbstractThe problem of polypharmacy arises when two or more drugs taken in combination cause adverse side effects, even when the use of the drugs individually causes no harm. Drug-drug interactions (DDIs) are a major cause of these reactions, contributing to increased morbidity and mortality. As the potential for harmful DDI grows exponentially, the prediction of drug-drug interactions is increasingly critical for patient safety and effective healthcare management. In this paper, we develop theChemBERTaDDIframework, which effectively combines clinical domain data, represented by the mono side-effect features with the enriched chemical molecular representations derived fromChemBERTa-77M-MLM, a transformer-based language model. Experiments performed on a benchmark data set show superior performance compared with five state-of-the-art methods: Decagon, DeepWalk, DEDICOM, NNPS, and RESCAL. The evaluation demonstrates thatChemBERTaDDIachieves an F1 score of 0.94 and an AUROC of 0.97 outperforming the baseline architectures and generalizing to new introduced drug compounds.
A strong relationship between environmental DNA metabarcoding and rank-based abundance of fish
Authors: Littlefair Joanne E , Hayhurst Lauren D , Yates Matthew C , Rennie Michael D , Cristescu Melania E 
Published: January 2025

AbstractIncreasingly, molecular methods of species monitoring are integrated into freshwater biodiversity surveys and fisheries management. Inferring organism abundance or biomass from sequence counts derived from metabarcoding data has been an exciting but contentious concept in the biomonitoring community for some time. Although demonstrating a strong correlation with abundance has proven difficult, many researchers have assumed that quantitative metabarcoding data can at least provide broad-scale ranking of abundance. However, robust field validations of this widely-held assumption remain scarce.Here, we analyse metabarcoding read counts of fish eDNA data derived from 20 lakes and use betabinomial mixed effects models to compare this to rank abundance generated from long-term fish survey data. Rank abundance data for 18 species was generated within-species across-sites, meaning that ranks compare the abundance of the same species in different lakes. We also investigated a possible allometric effect on eDNA production by analysing a subset of data for effects of fish body mass on the amount of eDNA sequences.We found a good relationship between species-specific eDNA sequences and within-species rank abundance categories for fishes, with rare fish producing 3% of sequences in a library, moderately abundant producing 7% and abundant fish producing 29%, according to model predictions.We found a small negative effect of body mass on the amount of eDNA sequences, where the proportion of reads recovered significantly decreased with increased mean body mass of the population.Synthesis and applications:The benefit of this approach is the potential for rapid assessment of rank abundance for multiple species, including smaller species which are often missed by conventional methods such as gillnetting, with relatively low amounts of additional effort. This approach will assist practitioners taking a species-based approach to freshwater habitat management in lakes worldwide.
VPS13Dmutations affect mitochondrial homeostasis and locomotion inCaenorhabditis elegans
Authors: Yin Xiaomeng , Wang Ruoxi , Thackeray Andrea , Baehrecke Eric H. , Alkema Mark J. 
Published: January 2025

AbstractMitochondria control cellular metabolism, serve as hubs for signaling and organelle communication, and are important for the health and survival of cells.VPS13Dencodes a cytoplasmic lipid transfer protein that regulates mitochondrial morphology, mitochondria and endoplasmic reticulum (ER) contact, quality control of mitochondria.VPS13Dmutations have been reported in patients displaying ataxic and spastic gait disorders with variable age of onset. Here we used CRISPR/Cas9 gene editing to createVPS13Drelated-spinocerebellar ataxia-4 (SCAR4) missense mutations and C-terminal deletion inVPS13D’s orthologuevps-13DinC. elegans. Consistent with SCAR4 patient movement disorders and mitochondrial dysfunction,vps-13Dmutant worms exhibit locomotion defects and abnormal mitochondrial morphology. Importantly, animals with avps-13Ddeletion or a N3017I missense mutation exhibited an increase in mitochondrial unfolded protein response (UPRmt). The cellular and behavioral changes caused byVPS13Dmutations inC. elegansadvance the development of animal models that are needed to study SCAR4 pathogenesis.