bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased bacterial taxonomic and functional diversity is associated with impaired rotavirus vaccine immunogenicity in infants from India and Malawi
Authors: Cunningham-Oakes Edward , Bronowski Christina , Chinyama End , Jere Khuzwayo C. , Sindhu Kulandaipalayam Natarajan C. , Kang Gagandeep , Iturriza-Gómara Miren , Darby Alistair C. , Parker Edward P. K. 
Published: March 2023

ABSTRACTThe immunogenicity and effectiveness of oral rotavirus vaccines (ORVs) against severe rotavirus-associated gastroenteritis is impaired in low- and middle-income countries (LMICs) where the burden of disease is highest. Determining risk factors for impaired ORV response may help identify strategies to enhance vaccine effectiveness. In this study, we use metagenomic sequencing to provide a high-resolution taxonomic analysis of stool samples collected at 6 weeks of age (coinciding with the first ORV dose) during a prospective study of ORV immunogenicity in India and Malawi. We then analyse the functional capacity of the developing microbiome in these cohorts. Microbiome composition differed significantly between countries, although functional capacity was more similar than taxonomic composition. Our results confirm previously reported findings that the developing microbiome is more diverse in taxonomic composition in ORV non-seroconverters compared with seroconverters, and we additionally demonstrate a similar pattern in functional capacity. Although taxonomic or functional feature abundances are poor predictors of ORV response, we show that skews in the direction of associations within these microbiome data can be used to identify consistent markers of ORV response across LMIC infant cohorts. We also highlight the systemic under-representation of reference genes from LMICs that limit functional annotation in our study (7% and 13% annotation at pathway and enzyme commission level, respectively). Overall, higher microbiome diversity in early life may act as marker for impaired ORV response in India and Malawi, whilst a holistic perspective of functional capacity may be hidden in the “dark matter” of the microbiome.
A prescriptive optimization approach to identification of minimal barriers for surgical patients
Authors: Khaniyev Taghi , Copenhaver Martin S. , Safavi Kyan C. , Zenteno Langle Ana Cecilia , Starobinski Keren S. , Daily Bethany , Dunn Peter , Levi Retsef 
Published: March 2023

Problem definitionEnsuring timely patient discharges is central to managing a hospital’s patient flow; however, discharges are dependent on the coordination of multiple care teams and thus are highly decentralized in nature. Therefore, central capacity teams often lack transparency into how to prioritize scarce resources (e.g., imaging, post-hospital facility placement) for patients who need them for timely discharge. Our goal is to identify a small subset of such barriers for hospitalized surgical patients by balancing two aims: a high likelihood that the patient will be discharged from the hospital in the next 24 hours if these barriers are resolved; and a high likelihood that these barriers will indeed be resolved.Methodology/resultsWe leverage a machine learning model that predicts the likelihood of a patient’s discharge in the next 24 hours and train another set of machine learning models that predict, for each open barrier of a patient, the likelihood that the barrier will be resolved prior to discharge. We then combine these predictive models with a mixed-integer prescriptive optimization model to identify a subset of issues called minimal barriers. We empirically demonstrate the efficacy of the proposed formulation and solution methodology in identifying a small number of minimal barriers using real data from a large academic medical center. We also study the influence of variability in discharge prediction estimates on the prescribed barriers; we introduce a robust optimization variant which incorporates this directly, and we demonstrate that this is capable of overcoming several shortcomings of the nominal approach.Managerial implicationsThe modeling framework we propose can significantly enhance the ability of capacity management teams to identify significant barriers to care progression and understand which barriers are most important to address (based on their relationship with patient discharge) while taking into account the heterogeneity of barriers and their resolution.
Methamphetamine (MA) use, MA dependence, and MA-induced psychosis are associated with increasing aberrations in the compensatory immunoregulatory system and interleukin-1α and CCL5 levels
Authors: Kalayasiri Rasmon , Dadwat Kanokwan , Thika Supaksorn , Sirivichayakul Sunee , Maes Michael 
Published: March 2023

AbstractComprehensive immunological profiles have not been studied in relation to methamphetamine (MA) use, MA dependency, or MA-induced psychosis (MAP). Using the BioPlex Pro Human Cytokine 48-Plex panel, this study measured M1 macrophage, T helper (Th)-1, Th-2, growth factor, and chemokine profiles, as well as the immune inflammatory response system (IRS) and compensatory immunoregulatory system (CIRS) in peripheral blood samples from patients with MA use (n=51), MA dependence (n=47), and MAP (n=43) in comparison with healthy controls (n=43). We discovered that persistent MA use had a robust dose-dependent suppressive impact on all immunological profiles, suggesting extensive immunosuppression. The most reliable biomarker profile of MA use is the combination of substantial CIRS suppression and a rise in selected pro-inflammatory cytokines, namely CCL27 (CTACK), CCL11 (eotaxin), and interleukin (IL)-1α. In addition, MA dependency is related with a more severe immunosuppression, as demonstrated by lower stem cell factor and higher IL-10 levels. MAP is related with a significant decrease in all immunological profiles, particularly CIRS, and an increase in CCL5 (RANTES), IL-1α, and IL-12p70 signaling. In conclusion, long-term MA use and dependency severely undermine immune homeostasis. This results in widespread immunosuppression, which may increase the likelihood of infectious and immune illness or exacerbate disorders such as hepatitis and AIDS. Elevated levels of CCL5, CCL11, CCL27, IL-1α, and/or IL-12p70 may be associated with severe peripheral (atherosclerosis, cutaneous inflammation, immune aberrations, hypospermatogenesis) and central (neuroinflammation, neurotoxic, neurodegenerative, depression, anxiety and psychosis) side effects. Our message: “cease using MA, or better yet, never begin using MA”.
Interpretable spatial cell learning enhances the characterization of patient tissue microenvironments with highly multiplexed imaging data
Authors: Lu Peng , Oetjen Karolyn A. , Oh Stephen T. , Thorek Daniel L.J. 
Published: March 2023

AbstractMultiplexed imaging technologies enable highly resolved spatial characterization of cellular environments. However, exploiting these rich spatial cell datasets for biological insight is a considerable analytical challenge. In particular, effective approaches to define disease-specific microenvironments on the basis of clinical outcomes is a complex problem with immediate pathological value. Here we present InterSTELLAR, a geometric deep learning framework for multiplexed imaging data, to directly link tissue subtypes with corresponding cell communities that have clinical relevance. Using a publicly available breast cancer imaging mass cytometry dataset, InterSTELLAR allows simultaneous tissue type prediction and interested community detection, with improved performance over conventional methods. Downstream analyses demonstrate InterSTELLAR is able to capture specific pathological features from different clinical cancer subtypes. The method is able to reveal potential relationships between these regions and patient prognosis. InterSTELLAR represents an application of geometric deep learning with direct benefits for extracting enhanced microenvironment characterization for multiplexed imaging of patient samples.
Predictive outcome models in ischemic stroke: Comparison of Latin American Stroke Registry and RESILIENT against models
Authors: Torrealba-Acosta Gabriel , Barboza-Elizondo Miguel , Arauz Antonio , Amaya Pablo F , Ameriso Sebastian F , Cano Vanessa , Flores-Flores Alan , Lavados Pablo M , Pujol-Lereis Virginia A , Serrano Fabiola , Martins Sheila , Nogueira Raul Gomes , Kent Thomas A , Mandava Pitchaiah 
Published: March 2023

AbstractIntroductionDespite the significant stroke burden in the region, the RESILIENT trial remains the only randomized controlled trial (RCT) for stroke treatment in Latin America. Imbalances in baseline factors typically hamper comparisons between stroke populations. The Latin American Stroke Registry (LASE) is a registry of patients receiving tPA and thrombectomy from 17 centers across 9 countries. We compared the outcomes of LASE and RESILIENT at each cohort’s baseline characteristics against models derived from other RCTs.MethodsA systematic search identified RCTs that provided median NIHSS, mean age, percentage of patients receiving tPA, time-to-randomization, 90-day mRS0-2, and mortality. Akaike Information Criterion (AIC) was used to select the best model amongst 31 combinations of 5 variables. 90-day outcomes of LASE and RESILIENT were compared at their baseline values against the selected model.Results35 RCTs encompassing 8376 subjects were identified. Models based on baseline NIHSS and the percentage of intravenous thrombolysis (IVT) were considered the most optimum in terms of AIC. The LASE registry included 950 patients receiving IVT alone, 127 that received IVT and mechanical thrombectomy (MT), and 101 receiving only MT. LASE & RESILIENT outcomes were plotted onto the models at their baseline values. LASE IVT alone group outcomes were in line with the RCT-informed model. LASE MT alone and MT + IVT, and the RESILIENT MT arm (68.5% IVT) demonstrated superior efficacy compared to no-MT. The RESILIENT control arm (71.8% tPA) had higher-than-expected mortality, while mortality of all other arms was within the predicted range.ConclusionFunctional outcomes and mortality of patients from the LASE and RESILIENT trial receiving MT and MT+IVT compared favorably to the 90-day functional and mortality outcomes predicted in a model derived from no-MT data from other stroke RCTs, indicating Latin American MT systems of care are comparable to those of more resourceful regions. Higher mortality from IVT in the RESILIENT trial requires further investigation.
The genomics and evolution of inter-sexual mimicry and female-limited polymorphisms in damselflies
Authors: Willink B. , Tunström K. , Nilén S. , Chikhi R. , Lemane T. , Takahashi M. , Takahashi Y. , Svensson E. I. , Wheat C. W. 
Published: March 2023

AbstractSex-limited morphs can provide profound insights into the evolution and genomic architecture of complex phenotypes. Inter-sexual mimicry is one particular type of sex-limited polymorphism in which a novel morph resembles the opposite sex. While inter-sexual mimics are known in both sexes and a diverse range of animals, their evolutionary origin is poorly understood. Here, we investigated the genomic basis of female-limited morphs and male mimicry in the Common Bluetail damselfly. Differential gene expression between morphs has been documented in damselflies, but no causal locus has been previously identified. We found that male-mimicry originated in an ancestrally sexually-dimorphic lineage in association with multiple structural changes, probably driven by transposable element activity. These changes resulted in ∼900 kb of novel genomic content that is partly shared by male mimics in a close relative, indicating that male mimicry is a trans-species polymorphism. More recently, a third morph originated following the translocation of part of the male-mimicry sequence into a genomic position ∼3.5 mb apart. We provide evidence of balancing selection maintaining male-mimicry, in line with previous field population studies. Our results underscore how structural variants affecting a handful of potentially regulatory genes and morph-specific genes, can give rise to novel and complex phenotypic polymorphisms.
Intraspecific chemical variation ofTanacetum vulgareaffects plant growth and reproductive traits in field plant communities
Authors: Ojeda-Prieto Lina , Medina-van Berkum Pamela , Unsicker Sybille B. , Heinen Robin , Weisser Wolfgang W. 
Published: March 2023

AbstractIntraspecific plant chemodiversity plays a fundamental role in interactions between plants and their interaction partners. However, how chemodiversity at the stand level (plant communities that vary in the number and type of plant chemotypes that grow in them, i.e., chemotype richness) affects ecosystem functioning is not fully understood.We describe a biodiversity experiment using six chemotypes of common tansy (Tanacetum vulgareL., Asteraceae) to manipulate intraspecific plant chemodiversity at the plot level. We tested the effects of chemotype identity and plot-level chemotype richness (1-6) on plant growth and reproductive traits at plant and plot levels.We found that chemotypes differed in growth and reproductive traits and that traits were affected by the plot-level chemotype richness. Although morphological differences became less pronounced over time, reproductive phenology patterns persisted. It suggests that chemotypes initially adopted different growth strategies, which may facilitate their establishment in nature.Although chemotype richness did not lead to overyielding effects, plot-level trait means were affected by the presence or absence of certain chemotypes in a plot, and the direction of the effect depended on the chemotype.We analyzed plot-level headspace emissions and found that blends released from plant communities were neither richer nor more diverse with increasing plot-level chemotype richness. However, we found that plots became more dissimilar in their headspace terpenoids as they were more dissimilar in their leaf-terpenoid profiles.This long-term field experiment will allow further investigation into plant-insect interactions and insect community assembly in response to intraspecific chemodiversity.
A three filament mechanistic model of musculotendon force and impedance
Authors: Millard Matthew , Franklin David W. , Herzog Walter 
Published: March 2023

AbstractThe force developed by actively lengthened muscle depends on different structures across different scales of lengthening. For small perturbations, the active response of muscle is well captured by a linear-time-invariant (LTI) system: a stiff spring in parallel with a light damper. The force response of muscle to longer stretches is better represented by a compliant spring that can fix its end when activated. Experimental work has shown that the stiffness and damping (impedance) of muscle in response to small perturbations is of fundamental importance to motor learning and mechanical stability, while the huge forces developed during long active stretches are critical for simulating and predicting injury. Outside of motor learning and injury, muscle is actively lengthened as a part of nearly all terrestrial locomotion. Despite the functional importance of impedance and active lengthening, no single muscle model has all of these mechanical properties. In this work, we present the viscoelastic-crossbridge active-titin (VEXAT) model that can replicate the response of muscle to length changes great and small. To evaluate the VEXAT model, we compare its response to biological muscle by simulating experiments that measure the impedance of muscle, and the forces developed during long active stretches. In addition, we have also compared the responses of the VEXAT model to a popular Hill-type muscle model. The VEXAT model more accurately captures the impedance of biological muscle and its responses to long active stretches than a Hill-type model and can still reproduce the force-velocity and force-length relations of muscle. While the comparison between the VEXAT model and biological muscle is favorable, there are some phenomena that can be improved: the low frequency phase response of the model, and a mechanism to support passive force enhancement.
Altered muscle niche contributes to myogenic deficit in the D2-mdxmodel of severe DMD
Authors: Mázala Davi A. G. , Hindupur Ravi , Moon Young Jae , Shaikh Fatima , Gamu Iteoluwakishi H. , Alladi Dhruv , Panci Georgiana , Weiss-Gayet Michèle , Chazaud Bénédicte , Partridge Terence A. , Novak James S. , Jaiswal Jyoti K. 
Published: March 2023

AbstractLack of dystrophin is the genetic basis for the Duchenne muscular dystrophy (DMD). However, disease severity varies between patients, based on specific genetic modifiers. D2-mdxis a model for severe DMD that exhibits exacerbated muscle degeneration and failure to regenerate even in the juvenile stage of the disease. We show that poor regeneration of juvenile D2-mdxmuscles is associated with enhanced inflammatory response to muscle damage that fails to resolve efficiently and supports excessive accumulation of fibroadipogenic progenitors (FAPs). Unexpectedly, the extent of damage and degeneration of juvenile D2-mdxmuscle is reduced in adults and is associated with the restoration of the inflammatory and FAP responses to muscle injury. These improvements enhance myogenesis in the adult D2-mdxmuscle, reaching levels comparable to the milder (B10-mdx) mouse model of DMD.Ex vivoco-culture of healthy satellite cells (SCs) with the juvenile D2-mdxFAPs reduced their fusion efficacy andin vivoglucocorticoid treatment of juvenile D2 mouse improved muscle regeneration. Our findings indicate that aberrant stromal cell response contributes to poor myogenesis and greater muscle degeneration in dystrophic juvenile D2-mdxmuscles and reversal of this reduces pathology in adult D2-mdxmouse muscle, identifying these as therapeutic targets to treat dystrophic DMD muscles.
Structural characterization of a novel luciferase-like-monooxygenase fromPseudomonas meliae– an in-silico approach
Authors: Rayhan Mohammad , Siddiquee Mohd. Faijanur-Rob , Shahriar Asif , Ahmed Hossain , Mahmud Aar Rafi , Alam Muhammad Shaiful , Uddin Muhammad Ramiz , Acharjee Mrityunjoy , Shimu Mst. Sharmin Sultana , Shamsir Mohd. Shahir , Emran Talha Bin 
Published: March 2023

AbstractBackgroundLuciferase is a well-known oxidative enzyme that produces bioluminescence. ThePseudomonas meliaeis a plant pathogen that causes wood rot on nectarine and peach and possesses a luciferase-like monooxygenase. After activation, it produces bioluminescence, and the pathogen’s bioluminescence is a visual indicator of diseased plants.MethodsThe present study aims to model and characterize the luciferase-like monooxygenase protein inP. meliaefor its similarity to well-established luciferase. In this study, the luciferase-like monooxygenase fromP. meliaeinfects chinaberry plants has been modeled first and then studied by comparing it with existing known luciferase. Also, the similarities between uncharacterized luciferase fromP. meliaeand template fromGeobacillus thermodenitrificanswere analyzed to find the novelty ofP. meliae.ResultsThe results suggest that the absence of bioluminescence inP. meliaecould be due to the evolutionary mutation in positions 138 and 311. The active site remains identical except for two amino acids;P. meliaeTyr138 instead of His138 and Leu311 instead of His311. Therefore, theP. meliaewill have a potential future application, and mutation of the residues 138 and 311 can be restored luciferase light-emitting ability.ConclusionsThis study will help further improve, activate, and repurpose the luciferase fromP. meliaeas a reporter for gene expression.
The impact of FASTQ and alignment read order on structural variation calling from long-read sequencing data
Authors: Lesack Kyle , Wasmuth James D. 
Published: March 2023

AbstractBackgroundStructural variation (SV) calling from DNA sequencing data has been challenging due to several factors, such as the ambiguity of short-read alignments, multiple complex SVs in the same genomic region, and the lack of “truth” datasets for benchmarking. Additionally, caller choice, parameter settings, and alignment method are known to affect SV calling. However, the impact of FASTQ read order on SV calling has not been explored for long-read data.ResultsIn this study, we used PacBio DNA sequencing data from 15Caenorhabditis elegansisolates to evaluate the dependence of different SV callers on FASTQ read order. Comparisons of variant call format (VCF) files generated from the original and permutated FASTQ files demonstrated that the order of input data had a large impact on SV prediction, particularly for pbsv. The overall differences were lowest for Sniffles, regardless of the aligner used. The type of variant most affected by read order varied by caller. For pbsv, most differences occurred for deletions and duplications, while for Sniffles, permutating the read order had a stronger impact on insertions. For SVIM, inversions and deletions accounted for most differences.ConclusionThe results of this study highlight the dependence of SV calling on the order of reads encoded in FASTQ files, which has not been recognized in long-read approaches. These findings have implications for the replication of SV studies and the development of consistent SV calling protocols. Our study suggests that researchers should pay attention to the order of reads when analyzing long-read sequencing data for SV calling.
Comparative Analysis of Tylosema esculentum Mitochondrial DNA Revealed Two Distinct Genome Structures
Authors: Li Jin , Cullis Christopher 
Published: March 2023

AbstractTylosema esculentum(marama bean), an underutilized legume with edible and nutritious seeds, has the potential to improve local food security in southern Africa. This study investigated the diversity of marama mitogenomes by mapping sequencing data from 84 individuals to the previously published reference mitogenome. Two distinct germplasms were found, and a new mitogenome structure containing three circular molecules and one long linear chromosome was identified, with a unique 2,108 bp fragment and primers were designed on that for marama mitogenome typing. This structural variation increases copy number of certain genes, includingnad9,rrnsandrrn5. The two mitogenomes also differed at 230 loci, with only one nonsynonymous substitution inmatR. The evolutionary analysis suggested that the divergence of marama mitogenomes may be related to soil moisture level. Heteroplasmy in the marama mitogenome was concentrated at specific loci, including 127,684 bp to 127,686 bp on chromosome LS1 (OK638188), and may be crucial in the evolution. Additionally, the mitogenomes of marama contained a cpDNA insertion of over 9 kb with numerous polymorphisms, resulting in the loss of function of the genes on that segment. This comprehensive analysis of marama mitogenome diversity may provide valuable insight for future improvement of the bean.HighlightThe analysis of 84 marama mitogenomes revealed two germplasms and the structural variation affects certain gene copy numbers. Soil moisture levels may have played important roles in the mitogenome divergence.