bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular vesicles, RNA sequencing, and bioinformatic analyses: Challenges, solutions, and recommendations
Authors: Miceli Rebecca T. , Chen Tzu‐Yi , Nose Yohei , Tichkule Swapnil , Brown Briana , Fullard John F. , Saulsbury Marilyn D. , Heyliger Simon O. , Gnjatic Sacha , Kyprianou Natasha , Cordon‐Cardo Carlos , Sahoo Susmita , Taioli Emanuela , Roussos Panos , Stolovitzky Gustavo , Gonzalez‐Kozlova Edgar , Dogra Navneet 
Published: December 2024

AbstractExtracellular vesicles (EVs) are heterogeneous entities secreted by cells into their microenvironment and systemic circulation. Circulating EVs carry functional small RNAs and other molecular footprints from their cell of origin, and thus have evident applications in liquid biopsy, therapeutics, and intercellular communication. Yet, the complete transcriptomic landscape of EVs is poorly characterized due to critical limitations including variable protocols used for EV‐RNA extraction, quality control, cDNA library preparation, sequencing technologies, and bioinformatic analyses. Consequently, there is a gap in knowledge and the need for a standardized approach in delineating EV‐RNAs. Here, we address these gaps by describing the following points by (1) focusing on the large canopy of the EVs and particles (EVPs), which includes, but not limited to – exosomes and other large and small EVs, lipoproteins, exomeres/supermeres, mitochondrial‐derived vesicles, RNA binding proteins, and cell‐free DNA/RNA/proteins; (2) examining the potential functional roles and biogenesis of EVPs; (3) discussing various transcriptomic methods and technologies used in uncovering the cargoes of EVPs; (4) presenting a comprehensive list of RNA subtypes reported in EVPs; (5) describing different EV‐RNA databases and resources specific to EV‐RNA species; (6) reviewing established bioinformatics pipelines and novel strategies for reproducible EV transcriptomics analyses; (7) emphasizing the significant need for a gold standard approach in identifying EV‐RNAs across studies; (8) and finally, we highlight current challenges, discuss possible solutions, and present recommendations for robust and reproducible analyses of EVP‐associated small RNAs. Overall, we seek to provide clarity on the transcriptomics landscape, sequencing technologies, and bioinformatic analyses of EVP‐RNAs. Detailed portrayal of the current state of EVP transcriptomics will lead to a better understanding of how the RNA cargo of EVPs can be used in modern and targeted diagnostics and therapeutics. For the inclusion of different particles discussed in this article, we use the terms large/small EVs, non‐vesicular extracellular particles (NVEPs), EPs and EVPs as defined in MISEV guidelines by the International Society of Extracellular Vesicles (ISEV).
Spatiotemporal controls on organic matter sourcing to minerogenic salt marshes
Authors: Peck Erin K. , Goñi Miguel , Wheatcroft Robert A. 
Published: December 2024

AbstractSalt marshes are important carbon sinks; however, identification of the drivers of carbon burial rates is challenging because estuaries sit at terrestrial and marine interfaces. Here, we address the questions: what are the sources of organic matter sequestered in minerogenic salt marshes, and how do sources change through time? We characterized down‐core sediment biogeochemistry (C : N, δ13C, δ15N) for the last century in seven Oregon USA high marshes and used a mixing model to elucidate differences in organic matter sources across estuaries and through time. Autochthonous biomass production consistently accounted for only half of overall organic matter accumulation, and the remainder was allochthonous, originating from a combination of estuarine and terrestrial sources. Salt marshes with high sediment loads buried more terrestrial organic matter, whereas those with low loads and substantial subtidal habitat buried more estuarine‐derived organic matter. When assessed through depth/time, stable isotope trends indicated that decomposition is not the primary control. Instead, organic matter became increasingly more terrestrial in recent decades, especially in salt marshes with low fluvial loads. We hypothesize that salt marshes with lower loads took longer to regain lost elevation following coseismic subsidence of the 1700 ce Cascadia earthquake. This result magnifies the role of river floods in sediment and carbon accumulation on the marsh surface. Ultimately, the highest carbon burial rates coincided with highest fractions of terrestrially sourced organic matter, though spatiotemporal complexities obscured any potentially significant trends. While the term “blue” typically excludes terrestrial carbon, minerogenic salt marshes still perform the important ecosystem function of burying organic matter.
Exploiting Response Surface Methodology to Engineer the Mechanical Properties of Alginate‐based Hydrogels
Authors: Bucciarelli Alessio , Zhao Chen , Bai Xue , Kay Rebekah , Latif Ayşe , Williams Kaye J. , Tirella Annalisa 
Published: December 2024

AbstractEngineering human tissue microenvironments that recapitulate the composition and biomechanics of extracellular matrix (ECM) in vitro is challenging. New mechanically tunable alginate‐based hydrogels are presented, enabling to precise model multiple ECM features in the context of breast cancer. Combining alginate, oxidized alginate (OA), and gelatin with different crosslinking strategies a library of mechanically controlled hydrogels supporting human cell growth (MDA‐MB‐231) is obtained. The compressive moduli and stability of alginate‐based hydrogels are characterized and modeled using a response surface methodology (RSM); this enables to selection of precision‐hydrogels decoupling their biochemical composition with mechanical properties (1–30 kPa). Specific alginate‐based hydrogels are selected as enhanced technologies to model breast‐specific microenvironments in vitro to study the impact of biomechanical and biochemical properties on cell behavior. Doxorubicin is selected as a model drug and as first‐line treatment for breast cancer to investigate the correlation between drug efficacy and breast tumor ECM stiffness. Results demonstrate that doxorubicin is less effective (EC50 0.495 µm vs EC50 0.189 µm) in cells cultured in softer hydrogels (6.9 kPa) than in stiffer (21.0 kPa). In the context of breast cancer, engineered hydrogels prove valuable technologies to model tissue‐specific ECM in vitro for biological studies, advancing understanding of therapeutic response and resistance.
Optimising Musculoskeletal Patient Flow Through Digital Triage and Supported Self‐Management: A Service Evaluation Set Within Community Musculoskeletal Care
Authors: Burgess R. , Tucker K. , Smithson R. , Dimbleby P. , Casey C. 
Published: December 2024

ABSTRACTIntroductionMusculoskeletal (MSK) conditions are one of the leading causes of years of living with disability in the UK, resulting in pressure on the health system and the UK economy. In response to the increasing levels of patients accessing NHS care with MSK conditions across Sandwell and West Birmingham (SWB), a digital triage and self‐management tool was implemented in 2023.AimsTo optimise safety, efficiency, and choice within the community MSK service from the first contact through to specialist MSK care through digital triage and supported self‐management.MethodsSWB's community MSK service implemented two digital tools in January 2023. Objectives included 1. Increase safety, through providing 24/7 access to rapid digital MSK triage; 2. Optimise workforce by releasing clinicians back to face‐to‐face care, increasing clinical capacity, 3. Increase patient choice by offering digitally supported self‐management to appropriate low risk patients.Results4804 patients self‐referred to the MSK service through the digital triage tool within the first 12 months. 378 of these patients were offered, accepted, and accessed self‐management support using the digital self‐management app. These innovations led to the release of 1240 clinical hours for face‐to‐face care, an average 8‐week reduction in waiting times and high patient satisfaction (80% good/very good).ConclusionEvaluation over the first 12 month showed that the digital innovations were safe, led to enhanced access to and choice of care pathways, optimised use of clinical staff, and received positive patient feedback. Research is needed in this newly emerging area of practice to support further adoption across the healthcare system.
Methodology of cfHPV‐DNA Detection in Head and Neck Cancer: A Systematic Review and Meta‐analysis
Authors: Thomas Jerin , Mazzara Eden , Guller Meytal , Landsberger Hannah , Tham Tristan , Cooper Dylan , Pereira Lucio , Kamdar Dev , Frank Douglas , Miles Brett , Mandal Rajarsi 
Published: December 2024

AbstractObjectiveWe aim to compare the diagnostic accuracy of the different methodologies used in the detection of cell‐free human papillomavirus (HPV) DNA in HPV‐associated head and neck squamous cell carcinoma detection using bivariate analysis methods.Data SourcesPubmed, Embase, and Scopus were queried using a broad search strategy to search for relevant studies.Review MethodsTest characteristics were extracted from 33 studies following literature screening, and underwent analyses utilizing a bivariate approach. Summary statistics were identified for each type of methodology, and forest plots and summary receiver operating characteristic curves were constructed. Bias was estimated using Deek's Funnel Plot and the QUADAS‐2 tool.ResultsIn terms of diagnostic accuracy, digital droplet polymerase chain reaction (ddPCR) based testing exhibited the highest diagnostics odds ratio at 138 (59.5, 318), followed closely by next‐generation sequencing (NGS) at 120 (39.7, 362), then by polymerase chain reaction (PCR) at 31.4 (14.4, 68.6), and quantitative PCR at 8.74 (4.63, 16.5).ConclusionNGS and ddPCR are comparable in overall diagnostic accuracy, bringing into question their relative roles in diagnosis and screening. Cost‐effective ddPCR assays may serve as useful diagnostic and screening tests in the clinic with their low false positive rates and high sensitivity. However, NGS assays also offer high sensitivity and companion metrics, suggesting they may have a more precise role in disease monitoring. Importantly, assay development and benchmarking need further standardization to improve comparison between assays. Finally, saliva‐based testing needs to be further investigated using NGS and ddPCR to further understand its limitations in disease detection and monitoring.
Assessing pest control treatments from phenology models and field data
Authors: Rincon Diego F. , Gutierrez‐Illan Javier , Crowder David W. 
Published: December 2024

AbstractBACKGROUNDEfficacy of insecticides is often determined from apparent yield loses due to a target pest. However, pests can affect yields even when controls work as expected. Further, most pest populations are monitored through adult counts without procedures to assess dynamics of immature stages. Here, we propose a framework to assess the efficacy of control treatments from adult counts in non‐experimental setups based on the shifts in temporal patterns of adult emergence caused during the residual period of treatments applied to kill immatures. We use phenology models scaled to field counts to track the stage structure of pest populations across a season and produce reference population trajectories with and without the treatment. Field‐collected trajectories are then classified as with or without an effective control through a time‐sequential probability ratio test. The method was evaluated using pheromone trap captures of codling moth, Cydia pomonella, and four of the most widely implemented treatment programs in apple and pear orchards.RESULTSSimulations revealed that when field‐collected trajectories are classified as treated with a control, there is 70% chance that the treatment program is > 50% effective, or that the program is < 66% effective when field‐collected trajectories are classified as untreated, provided the trajectories are made of ≥ 15 pheromone traps.CONCLUSIONThis framework is a powerful, evidence‐based tool to optimize the selection of inputs and application protocols for pest control and could be applied to virtually any pest that can be sampled regularly and whose phenology can be modeled as a function of degree‐days. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
A Combination of Few Physicochemical and Fungal Parameters Can Explain the Soil‐Dependent Variation in Wheat Biomass After Inoculation With Cladosporium tenuissimum
Authors: von Saldern Lena , Thurre Loïc , Jan Waelchli , Kobler Judith , Krenz Juliane , Schlaeppi Klaus 
Published: December 2024

ABSTRACTIntroductionIntensive agriculture causes substantial negative impacts on agroecosystems. One approach to reduce impacts while maintaining productivity is the inoculation with beneficial microbes. Inoculants can positively affect crop growth for instance through enhancing nutrient uptake or pathogen protection. However, the efficacy of inoculants is inconsistent across different agricultural soils. In this study, we investigated to which degree the varying growth responses to an inoculant can be modelled from soil parameters.Materials and MethodsAs inoculant, we worked with the commercially available fungus Cladosporium tenuissimum and tested its effectivity on wheat plants. Variation between soils was specifically tested, while keeping other factors constant in pot experiments under controlled conditions. We assessed 25 field soils for their influence on wheat biomass response to inoculation (BRI). For each soil, we measured physicochemical parameters and characterised the soil fungal community composition. We then performed variable selection and exhaustive model screenings to find the best model explaining variations in BRI.ResultsA combined model incorporating physicochemical and fungal soil parameters outperformed models using only one of the two types of data. The best model was based on six predictors and explained 80% of the observed variability in BRI. Predictive parameters included water holding capacity and organic carbon levels as well as soil fungi of the taxa Alternaria, Cladosporium (another species than the inoculant), Acrostalagmus and Fusicolla. Organic carbon and Alternaria negatively affected the effectivity of the inoculant while the other parameters were positive predictors for inoculation success.ConclusionWe showed that six soil parameters were sufficient to explain most of the variation of wheat responses to inoculation with C. tenuissimum. This result serves as proof‐of‐concept that the effectivity of inoculants can be modelled from soil parameters. It is now necessary to take this approach to practice and evaluate predictions for inoculant efficacy under field conditions.
Innovative Use of Hermetia illucens Frass Extract as Priming to Promote Tomato and Wheat Growth and Protection
Authors: Coviello Leonardo , Nuzzaci Maria , Falabella Patrizia , Scieuzo Carmen , Salvia Rosanna , Ronga Domenico , Vitti Antonella 
Published: December 2024

ABSTRACTFrass deriving from Hermetia illucens was explored as a new sustainable tool to induce biostimulation and/or antifungal activity in Solanum lycopersicum L. var Cerasiforme and Triticum durum Desf. var Simeto against the soil‐borne pathogens Fusarium spp. Phytotoxicity and in vitro antagonism assessments (mycelial growth inhibition of about 40%) allowed to define the optimal dilution of 10% of pasteurised‐frass extract (pFE) to employ for seed priming. Germination tests on water agar demonstrated the priming effectiveness for wheat, but not for tomato, as the analysed parameters were not positively affected. The pFE was used also in combination with the known biocontrol agent Trichoderma harzianum T22 (T22), demonstrating that they could work together to obtain a good growth promotion and protective effect in wheat. Indeed, the priming with pFE significantly reduced the disease incidence of almost 60% or 80%, compared to the infected control, if used alone or combined with T22, respectively. The ability of frass extract to control F. sporotrichioides in wheat was attributed to both enzymatic and non‐enzymatic responses, due to observed differences in total phenolic content (TPC) and superoxide dismutase activity (SOD) in seedlings derived from treated seeds, compared to untreated control. Our findings highlight the great potential of H. illucens frass as a sustainable, green, and circular economy‐based tool in agricultural systems.
Design, Synthesis, Molecular Docking and Hypoglycemic Activity of Novel Coumarin Analogues
Authors: Verma Anchal , Thakur Alok Singh , Dewangan Smriti 
Published: December 2024

AbstractDiabetes and its associated conditions are significant causes of morbidity and mortality. Despite the abundance of available medications for diabetes treatment, their limitations have spurred ongoing research in this field. Consequently, there is a need to discover a potential therapeutic molecule for managing diabetes and its complications. In current research work a series of novel coumarin analogs (5a–5e) were designed, synthesized, characterized through FTIR, 1H NMR, 13C NMR, and mass spectroscopy and evaluated for antidiabetic property. Molecular docking study was performed to link its binding affinity toward AMPK. DPPH scavenging assay was performed for in vitro antioxidant activity, for reference standard ascorbic acid was taken. In vivo hypoglycemic activity was performed on streptozotocin and nicotinic acid induced diabetic rats. All synthesized molecule showed good docking, score among them compound 5b has lowest docking score −11.25 kcal/mol. Molecule 5b and 5c showed greater antioxidant potential with good IC50 value, i.e., 20.4 g/mL and 21.6 g/mL. In vivo antidiabetic study showed good control on blood glucose level, cholesterol, triglyceride, Hb1AC as well as SGOT and SGPT level on animals fed 5b when compared to metformin. This result showed that test molecule 5b has potential to lower the blood glucose level without causing any toxicity.
Theoretical Investigation of Physicochemical Properties, Bioactivity, and Toxicity of Common Anxiety Medications
Authors: Banerjee Soumadip , Ghosh Pritha , Rathi Rama , Ghosh Avik , Roy Ria Sinha , Das Abhijit K. 
Published: December 2024

AbstractPhysicochemical properties, bioactivity scores, toxicity, chemical reactivity descriptor (GCRD), polarizability, and UV–vis spectroscopy of 10 common medicines used for the treatment of anxiety have been investigated to understand their activity and adverse effect in the human body. GCRD, polarizability, and UV–vis data of the drug molecules have been analyzed at the density functional M06‐2X/cc‐pVTZ level. Molinspiration, Osiris Property Explorer, and the SwissTargetPrediction tools have been used to study the molecular and physicochemical properties, drug likeness/bioactivity scores, and toxicity of the drug molecules. The calculated results show that all drug molecules have good bioavailability and are orally active, which corroborate with the clinical data. Most of the theoretical results are first reported, and the predicted results agree well with the clinical data and published reports wherever available. The calculated GCRD parameters confirm that chlordiazepoxide (D3) is the most reactive drug molecule. Drug likeness and drug score indicate that alprazolam (D1), chlordiazepoxide (D3), paroxetine (D7), and selegiline (D9) are safe medicines for humans. The predicted toxicities also substantiate the clinical data. The BOILED‐Egg plot illustrates that as alprazolam (D1) and paroxetine (D7) are the substrates of the P‐glycoprotein (PGP+), they are actively pumped up from the brain or to the gastrointestinal lumen.
Influence of Particle Size of Lignite‐Based Hard Carbon on Sodium Storage Performance
Authors: Yang Zhitao , Wei Yukuan , Liu Gang , Zhang Leilei , Huang Tengfei , Xue Haohao , Zhang Yuhang , Lin Zishun 
Published: December 2024

AbstractThe particle size of hard carbon used as an anode material for sodium‐ion batteries (SIBs) directly affects critical physical properties, including specific surface area and conductivity of the electrode, thereby influencing the electrode's sodium storage performance. However, related research is limited. In this work, lignite‐derived hard carbons with various particle sizes were investigated as anode materials for SIBs. The electrochemical performance and Na+ diffusion capability were evaluated. The results show that smaller particle sizes in hard carbon anodes lead to reduced mesopore volumes, specific surface areas, and coating densities, which effectively improve cycle stability, initial coulombic efficiency (ICE), and rate capability of the electrode. Specifically, hard carbon anodes within a 1–15 µm particle size distribution exhibited a reversible capacity of 251 mAh g−1 and an ICE of 73.67% at a current density of 25 mA g−1. Even after 100 cycles at 0.2 C, these anodes maintained a reversible capacity of 238 mAh g−1, achieving a capacity retention rate of 99.85%.
When corporate silence is costly: Negative consumer responses to corporate silence on social issues
Authors: Qin Marco Shaojun , Luo Xueming , Schifeling Todd , Wang Yang 
Published: December 2024

AbstractResearch SummaryThe growth of corporate activism on contentious social issues creates a puzzle as to why companies would risk engaging on divisive topics. Indeed, a mixed body of evidence identifies that such activism often reduces stakeholder support. We shed light on this puzzle by reversing attention to the costs of not engaging in corporate activism. Grounded in the cognitive model of stakeholder behavior, we theorize whether and when consumers will negatively respond to corporate silence on a social issue based on the visibility of silence. Our theory also suggests that peer activism and market niche are pivotal contingencies that exacerbate or mitigate such negative responses. Using a rigorous within‐company cross‐platform difference‐in‐differences econometric model, we find support for our theory and uncover substantial costs of corporate inaction.Managerial SummaryWe study stakeholder responses to corporate silence on social issues, using the empirical context of fashion firms and the Blackout Tuesday event in support of the Black Lives Matter movement, which occurred on Instagram but not Twitter. We find that there are sizeable risks to staying silent on a highly salient social issue. For firms that do not participate in the event, follower growth slows 33% and likes on their posts drop 12% in the following month on Instagram as compared to Twitter. In addition to issue salience, managers should closely attend to peer activism, which exacerbates these negative reactions. They should also consider their market niche, as a narrow niche offers protection while firms with a wider market experience larger declines in stakeholder support.