bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term multi-meta-omics resolves the ecophysiological controls of seasonal N2O emissions
Authors: Roothans Nina , Pabst Martin , Menno van Diemen , Mexicano Claudia Herrera , Zandvoort Marcel , Abeel Thomas , Mark van Loosdrecht , Laureni Michele 
Published: April 2024

AbstractThe potent greenhouse gas nitrous oxide (N2O) originates primarily from natural and engineered microbiomes. Emission seasonality is widely reported while the underlying metabolic controls remain largely unresolved, hindering effective mitigation. We use biological wastewater treatment as tractable model ecosystem over nearly two years. Long-term metagenomic-resolved metaproteomics is combined withex situkinetic and full-scale operational characterization. By leveraging the evidence independently obtained at multiple ecophysiological levels, from individual genetic potential to actual metabolism and emergent community phenotype, the cascade of environmental and operational triggers driving N2O emissions is resolved. We explain the dynamics in nitrite accumulation with the kinetic unbalance between ammonia and nitrite oxidisers, and identify nitrifier denitrification as the prime N2O-producing pathway. The dissolved O2emerged as the key actionable parameter for emission control. This work exemplifies the yet-to-be-realized potential of multi-meta-omics approaches for the mechanistic understanding and ecological engineering of microbiomes, ultimately advancing sustainable biotechnological developments.
De novo design of protein minibinder agonists of TLR3
Authors: Adams Chloe S. , Kim Hyojin , Burtner Abigail E. , Lee Dong Sun , Dobbins Craig , Criswell Cameron , Coventry Brian , Kim Ho Min , King Neil P. 
Published: April 2024

AbstractToll-like Receptor 3 (TLR3) is a pattern recognition receptor that initiates antiviral immune responses upon binding double-stranded RNA (dsRNA). Several nucleic acid-based TLR3 agonists have been explored clinically as vaccine adjuvants in cancer and infectious disease, but present substantial manufacturing and formulation challenges. Here, we use computational protein design to create novel miniproteins that bind to human TLR3 with nanomolar affinities. Cryo-EM structures of two minibinders in complex with TLR3 reveal that they bind the target as designed, although one partially unfolds due to steric competition with a nearby N-linked glycan. Multimeric forms of both minibinders induce NF-κB signaling in TLR3-expressing cell lines, demonstrating that they may have therapeutically relevant biological activity. Our work provides a foundation for the development of specific, stable, and easy-to-formulate protein-based agonists of TLRs and other pattern recognition receptors.
Quantifying Leaf Symptoms of Sorghum Charcoal Rot in Images of Field-Grown Plants Using Deep Neural Networks
Authors: Gonzalez Emmanuel , Zarei Ariyan , Calleja Sebastian , Christenson Clay , Rozzi Bruno , Demieville Jeffrey , Hu Jiahuai , Eveland Andrea L. , Dilkes Brian , Barnard Kobus , Lyons Eric , Pauli Duke 
Published: April 2024

ABSTRACTCharcoal rot of sorghum (CRS) is a significant disease affecting sorghum crops, with limited genetic resistance available. The causative agent,Macrophomina phaseolina(Tassi) Goid, is a highly destructive fungal pathogen that targets over 500 plant species globally, including essential staple crops. Utilizing field image data for precise detection and quantification of CRS could greatly assist in the prompt identification and management of affected fields and thereby reduce yield losses. The objective of this work was to implement various machine learning algorithms to evaluate their ability to accurately detect and quantify CRS in red-green-blue (RGB) images of sorghum plants exhibiting symptoms of infection. EfficientNet-B3 and a fully convolutional network (FCN) emerged as the top-performing models for image classification and segmentation tasks, respectively. Among the classification models evaluated, EfficientNet-B3 demonstrated superior performance, achieving an accuracy of 86.97%, a recall rate of 0.71, and an F1 score of 0.73. Of the segmentation models tested, FCN proved to be the most effective, exhibiting a validation accuracy of 97.76%, a recall rate of 0.68, and an F1 score of 0.66. As the size of the image patches increased, both models’ validation scores increased linearly, and their processing time decreased exponentially. The models, in addition to being immediately useful for breeders and growers of sorghum, advance the domain of automated plant phenotyping and may serve as a base for drone-based or other automated field phenotyping efforts. Additionally, the models presented herein can be accessed through a web-based application where users can easily analyze their own images.Core ideasAutomated phenotyping tools are required for the efficient detection and quantification of charcoal rot of sorghum.Classification and segmentation models can distinguish between concurrent plant stresses with similar symptoms.Larger image patch sizes generally improve model performance and reduce processing time.
Are text-message based programs targeting adolescents and their parents an acceptable approach to preventing adolescent e-cigarette use?
Authors: Barnes Courtney , Janssen Lisa , Mantach Stephanie , McCrabb Sam , Turon Heidi , Groombridge Daniel , Bartlem Kate , Bialek Caitlin , Couper Lucy , Wolfenden Luke 
Published: April 2024

ABSTRACTAdolescent e-cigarette use (also known as vaping), globally and within Australia, has steadily increased in recent years, with e-cigarettes now the most heavily used nicotine-containing products amongst adolescents. In response to the rise in prevalence, governments have introduced legislation to curb the supply of e-cigarettes to adolescents. To supplement these legislation measures, leading (inter)national public health agencies have called for the development of education and communication programs aimed at reducing adolescent e-cigarette uptake. Text-message programs for adolescents represent a potentially potent approach to achieve this. In this study, we assessed the acceptability of text-messages sent to adolescents and their parents to target factors associated with e-cigarette use. Text-messages were found to be acceptable to both adolescents and their parents however the effectiveness of the program on adolescent e-cigarette use still needs to be established prior to broader scale-up and investment.
Translation, cultural adaption, and validation of the PHQ-9 and GAD-7 in Kinyarwanda for primary care in the United States
Authors: Müller Frank , Hansen Alexis , Kube Megan , Arnetz Judith E. , Alshaarawy Omayma , Achtyes Eric D. , Holman Harland T. 
Published: April 2024

AbstractBackgroundDepression and anxiety are significant health burdens that greatly impact the quality of life of refugees and migrants. In this study, we have translated and culturally adapted the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Screener (GAD-7) into Kinyarwanda and performed a validation study in a United States (US) primary care setting.MethodsA committee of experts translated and culturally adapted the PHQ-9 and GAD-7, incorporating feedback from cognitive interviews with bilingual participants. The translated instruments were then tested in a cross-sectional validation study. Analyses include internal consistency, discriminative validity, principal component analyses, and confirmatory factor analyses.ResultsAnalyses of 119 responses indicated overall good internal consistency with Cronbach’s α of 0.85 (PHQ-9) and 0.92 (GAD-7). Both scales showed acceptable factor loadings between 0.44 and 0.90 in the principal component analyses and showed strong correlations with health-related quality of life and depression/anxiety symptoms measured with visual analog scales. Significantly higher scores for PHQ-9 and GAD-7 were shown among participants with known psychiatric conditions.DiscussionPHQ-9 and GAD-7 demonstrated commendable applicability for Kinyarwanda-speaking patients in primary healthcare settings in the US. Culturally adapted translations of these tools may aid in mitigating health disparities among refugee and migrant populations. Future research should further validate these tools against gold-standard diagnostics in larger, geographically diverse samples.
Computational flow cytometry immunophenotyping at diagnosis is unable to predict relapse in childhood B-cell Acute Lymphoblastic Leukemia
Authors: Martínez-Rubio Álvaro , Chulián Salvador , Niño-López Ana , Picón-González Rocío , Rodríguez Gutiérrez Juan F. , Gálvez de la Villa Eva , Caballero Velázquez Teresa , Molinos Quintana Águeda , Robleda Ana Castillo , Ramírez Orellana Manuel , Martínez Sánchez María Victoria , Minguela Puras Alfredo , Fuster Soler José Luis , Blázquez Goñi Cristina , Pérez-García Víctor M. , Rosa María 
Published: April 2024

AbstractB-cell Acute Lymphoblastic Leukemia is the most prevalent form of childhood cancer, with approximately 15% of patients undergoing relapse after initial treatment. Further advancements depend on novel therapies and more precise risk stratification criteria. In the context of computational flow cytometry and machine learning, this paper aims to explore the potential prognostic value of flow cytometry data at diagnosis, a relatively unexplored direction for relapse prediction in this disease. To this end, we collected a dataset of 252 patients from three hospitals and implemented a comprehensive pipeline for multicenter data integration, feature extraction, and patient classification, comparing the results with existing algorithms from the literature. The analysis revealed no significant differences in immunophenotypic patterns between relapse and non-relapse patients and suggests the need for alternative approaches to handle flow cytometry data in relapse prediction.
The Probability of Reducing Hospitalization Rates for Bronchiolitis: A Bayesian Analysis
Authors: Dong Larry , Klassen Terry P. , Johnson David W. , Correll Rhonda , Gouin Serge , Bhatt Maala , Patel Hema , Joubert Gary , Black Karen J. L. , Turner Troy W. S. , Whitehouse Sandra R. , Plint Amy C. , Heath Anna 
Published: April 2024

Structured AbstractBackgroundBronchiolitis exerts a high burden on children, their families and the healthcare system. The Canadian Bronchiolitis Epinephrine Steroid Trial (CanBEST) assessed whether administering epinephrine alone, dexamethasone alone, or in combination (EpiDex) could reduce bronchiolitis-related hospitalizations among children less than 12 months of age compared to placebo. CanBEST demonstrated a statistically significant reduction in 7-day hospitalization risk with EpiDex in an unadjusted analysis but not after adjustment.ObjectiveTo explore the probability that EpiDex results in a reduction in hospitalizations using Bayesian methods.Study DesignUsing prior distributions that represent varying levels of preexisting enthusiasm or skepticism and information about the treatment effectbeforedata were collected, the Bayesian distribution of the relative risk of hospitalization compared to placebo was determined. The probability that the treatment effect is less 1, 0.9, 0.8 and 0.6, indicating increasing reductions in hospitalization risk, are computed alongside 95% credible intervals.ResultsCombining a minimally informative prior distribution with the data from CanBEST provides comparable results to the original analysis. Unless strongly skeptical views about the effectiveness of EpiDex were considered, the 95% credible interval for the treatment effect lies below 1, indicating a reduction in hospitalizations. There is a 90% probability that EpiDex results in a clinically meaningful reduction in hospitalization of 10% even when incorporating skeptical views, with a 67% probability when considering strongly skeptical views.ConclusionA Bayesian analysis demonstrates a high chance that EpiDex reduces hospitalization rates for bronchiolitis, although strongly skeptical individuals may require additional evidence to change practice.
Concurrent validity and discriminative ability of force plate measures of balance during the sub-acute stage of stroke recovery
Authors: Aryan Raabeae , Patterson Kara K. , Inness Elizabeth L. , Mochizuki George , Mansfield Avril 
Published: April 2024

ABSTRACTBackgroundMany objective measures of balance control, including force plate measures of standing balance, lack sufficient validation for use in the stroke population.Research questionsDo force plate measures of quiet standing balance during the sub-acute stage of stroke recovery have concurrent validity (i.e., correlate with functional balance measures) and discriminative ability (i.e., differentiate fallers from non-fallers and/or those with low-moderate versus high risk of falling)?MethodsParticipants completed one trial of quiet standing with eyes open, lasting for 30 seconds. Mean speeds of centre of pressure along the anterior-posterior and medial-lateral axes, weight-bearing asymmetry, and symmetry index were calculated. Concurrent validity of these measures were established against the Berg Balance Scale; their abilities in differentiating fallers from non-fallers, and individuals with low-moderate versus high risk of falling were evaluated using the area under the receiver operating curve (AUC).ResultsAmong the measures studied, mean speed of centre of pressure along the anterior-posterior axis demonstrated the strongest correlation with the Berg Balance Scale (ρ=-0.430, p-value=0.01). Weight-bearing asymmetry showed the highest ability in differentiating fallers from non-fallers (AUC= 0.69), as well as individuals with low-moderate versus high risk of falling (AUC= 0.66).SignificanceOur findings suggest that speed of centre of pressure along the anterior-posterior axis, and weight-bearing asymmetry are valid for use in the sub-acute stage of stroke recovery. These validated measures can better inform rehabilitation practice about the ability of upright standing balance following a stroke.
Pharmacodynamic effects of semorinemab on plasma and CSF biomarkers of Alzheimer’s disease pathophysiology
Authors: Schauer Stephen , Toth Balazs , Lee Julie , Honigberg Lee A. , Ramakrishnan Vidya , Jiang Jenny , Kollmorgen Gwendlyn , Bayfield Anna , Wild Norbert , Hoffman Jennifer , Ceniceros Ryan , Dolton Michael , Bohorquez Sandra Sanabria , Hoogenraad Casper C. , Wildsmith Kristin R. , Teng Edmond , Monteiro Cecilia , Anania Veronica , Yeh Felix L. 
Published: April 2024

ABSTRACTINTRODUCTIONSemorinemab, an anti-tau monoclonal antibody, was evaluated in two Phase II trials as a disease-modifying treatment for Alzheimer’s disease (AD). Plasma and cerebrospinal fluid (CSF) samples were collected from trial participants to evaluate the pharmacodynamic effects of semorinemab and elucidate its mechanism of action.METHODSQualified immunoassays were used to measure plasma and CSF biomarkers of tau, amyloidosis, glial activity, neuroinflammation, synaptic function, and neurodegeneration from participants enrolled in the Tauriel (NCT03289143) and Lauriet (NCT03828747) Phase II trials in prodromal-to-mild (P2M) and mild-to-moderate (M2M) AD.RESULTSSignificant increases in plasma phosphorylated Tau 181 (pTau181) and CSF Chitinase-3-like protein 1 (YKL-40) followed administration of semorinemab in both studies. In the Lauriet study, plasma glial fibrillary protein (GFAP) levels rose progressively over the study period in the placebo group, but remained stable over time with the administration of semorinemab. In contrast, this was not observed in the Tauriel study. Semorinemab had no consistent impact on other biomarkers of AD pathophysiology that were evaluated.DISCUSSIONSemorinemab engages and stabilizes plasma pTau181 in a manner consistent with previously reported data [1,2], and levels do not decrease after prolonged drug exposure. Increases to CSF YKL-40 suggest that semorinemab may stimulate microglia activation, while stabilization of plasma GFAP levels in Lauriet participants indicate that semorinemab may moderate reactive gliosis in M2M AD.
Identifying and quantifying the contribution of maize plant traits to nitrogen uptake and use through plant modelling
Authors: Lu Jie , Stomph Tjeerd Jan , Mi Guohua , Yuan Lixing , Evers Jochem 
Published: April 2024

AbstractBreeding for high nitrogen use efficient crops can contribute to maintaining or even increasing yield with less nitrogen. Nitrogen use is co-determined by N uptake and physiological use efficiency (PE, biomass per unit of N taken up), to which soil processes as well as plant architectural, physiological and developmental traits contribute. The relative contribution of these crop traits to N use is not well known but relevant to identify breeding targets in important crop species like maize. To quantify the contribution of component plant traits to maize N uptake and use, we used a functional-structural plant model. We evaluated the effect of varying both shoot and root traits on crop N uptake across a range of nitrogen levels. Root architectural traits were found to play a more important role in root N uptake than physiological traits. Phyllochron determined the structure of the shoot through changes in source: sink ratio over time which, in interaction with light and temperature, resulted in a significant effect on PE and N uptake. Photosynthesis traits were more relevant to biomass accumulation rather than yield, especially under high nitrogen conditions. The traits identified in this study are potential targets in maize breeding for improved crop N uptake and use.HighlightOur research provides insight into the relevance of a range of traits for maize N uptake and N use, and identifies several potential target traits based on underlying mechanisms to assist maize breeding.
Seed tuber microbiome is a predictor of next-season potato vigor
Authors: Song Yang , Atza Elisa , Sanchez Gil Juan J. , Akkermans Doretta , de Jonge Ronnie , de Rooij Peter G.H. , Kakembo David , Bakker Peter A.H.M. , Pieterse Corné M.J. , Budko Neil V. , Berendsen Roeland L. 
Published: April 2024

SummaryPotato vigor, an important agronomic trait, is heavily influenced by the field of seed tuber production. Soil microbiota vary significantly between fields, impacting plant health and crop yield. Our study demonstrates that seed potato vigor can be predicted based on microbiota associated with seed tuber eyes, the dormant buds that grow out in the next season. By combining time-resolved drone-imaging of potato crop development with microbiome sequencing of seed tuber eyes from 6 varieties produced in 240 fields, we established correlations between microbiome fingerprints and potato vigor parameters. Employing Random Forest algorithms, we developed a predictive “Potato-Microbiome Informed” model, revealing variety-specific relationships between seed tuber microbiome composition and next season’s potato vigor in trial fields. The model accurately predicted vigor of seed tubers to which the model was naïve and pinpointed key microbial indicators of potato vigor. By connecting variety-specific microbiome fingerprints to crop performance in the field, we pave the way for microbiome-informed breeding strategies.
Genetic variants associated with longevity in long-living Indians
Authors: Pemmasani Sandhya Kiran , Shakthiraju R G , Suraj V , Bhattacharya Raunaq , Patel Chetan , Gupta Anil Kumar , Acharya Anuradha 
Published: April 2024

ABSTRACTGenetic factors play a significant role in determining an individual’s longevity. The present study was aimed at identifying the genetic variants associated with longevity in Indian population. Long living individuals (LLIs), aged 85+, were compared with younger controls, aged 18-49 years, using data from GenomegaDB, a genetic database of Indians living in India. An in-house developed custom chip, having variants associated with various cancers, cardiovascular, neurological, gastro-intestinal, metabolic and auto-immune disorders, was used to generate genotype data. Logistic regression analysis with top five genetic principal components as covariates resulted in 11 variants to be significantly associated with longevity at a p-value threshold of 5×10−4. Alleles associated with slower heart rate (rs365990, MYH6), lower risk of osteoporosis and short body height (rs2982570, ESR1), decreased risk of schizophrenia (rs1339227, RIMS1-KCNQ5) and decreased risk of anxiety and neuroticism (rs391957, HSPA5) were found to have higher frequency in LLIs. Alleles associated with increased risk of atrial fibrillation (rs3903239, GORAB-PRRX1) and biliary disorders (rs2002042, ABCC2) were found have lower frequency. The G allele of rs2802292 from FOXO3A gene, associated with longevity in Japanese, German and French centenarians, was also found to be significant in this population (P=0.027). Pathway enrichment analysis revealed that the genes involved in oxidative stress, apoptosis, DNA damage repair, glucose metabolism and energy metabolism were significantly involved in increasing the longevity. Results of our study demonstrate the genetic basis of healthy aging and longevity in the population.
Phase structure of extra-dimensional gauge theories with fermions
Authors: Pastor-Gutiérrez Álvaro , Yamada Masatoshi 
Published: April 2024

We study the phase structure of five-dimensional Yang-Mills theories coupled to Dirac fermions. In order to tackle their nonperturbative character, we derive the flow equations for the gauge coupling and the effective potential for the Aharonov-Bohm phases employing the functional renormalization group. We analyze the infrared and ultraviolet fixed-point solutions in the flow of the gauge coupling as a function of the compactification radius of the fifth dimension. We discuss various types of trajectories which smoothly connect both dimensional limits. Last, we investigate the phase diagram and vacuum structure of the gauge potential for different fermion content.

Published by the American Physical Society
2024