bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systems vaccinology identifies clinical and immunological correlates of SARS-CoV-2 vaccine response in solid-organ transplant recipients
Authors: Gemander Nicolas , Neumann Julika , Veiga Rafael , Etienne Isabelle , Prezzemolo Teresa , Kemlin Delphine , Pannus Pieter , Depickère Stéphanie , Olislagers Véronique , Vu Duc Inès , Waegemans Alexandra , Gerbaux Margaux , Bücken Leoni , Dahma Hafid , Martin Charlotte , Dauby Nicolas , Goossens Maria E , Desombere Isabelle , Roca Carlos P , Willemsen Mathijs , Goriely Stanislas , Le Moine Alain , Marchant Arnaud , Liston Adrian , Humblet-Baron Stephanie 
Published: April 2024

AbstractSolid organ transplant (SOT) recipients are at enhanced risk of adverse outcomes following infectious challenges due to immunosuppressive treatment and additional comorbidities. Unfortunately, SOT recipients are also poor responders to the key medical intervention to preventing infection: vaccines. Here we performed a systems vaccinology study on a cohort of 59 kidney transplant recipients and 31 lung transplant recipients who received the mRNA Pfizer-BioNTech COVID-19 vaccine. Analyzing the immunological status of the patients prior to vaccination, we were able to identify multiple immunological associates of relatively improved vaccine responses following two or three doses of mRNA-based SARS-CoV-2 vaccine. These immunological associates predicted, with 95.0% and 93.3% accuracy, vaccine response after the second and third dose, respectively. Comparison of the immunological associates with vaccine response in SOT recipients revealed two distinct immune configurations: a non-classical configuration, distinct from the immune state of healthy subjects, associated with responses to two doses of mRNA vaccine and that could be mediated partly by the presence of double negative B cell subsets which are more prominently represented in responsive SOT recipients, and a “normalized” configuration, closer to the immune state of healthy subjects, associated with potent antibody responses to three doses of mRNA vaccine. These results suggest that immunosuppression in SOT recipients can result in distinct immune states associated with different trade-offs in vaccine responsiveness. Immune phenotyping of SOT recipients for immune constellation may be an effective approach for identifying patients most at risk of poor vaccine responses and susceptibility to vaccine-preventable diseases.One-sentence summarySOT recipients showed distinct immune states at baseline associated with different profiles of vaccine-associated immune response.
How subject-specific biomechanics influences tendon strains in Achilles tendinopathy patients: A finite element study
Authors: Funaro Alessia , Shim Vickie , Mylle Ine , Vanwanseele Benedicte 
Published: April 2024

AbstractThe treatment of Achilles tendinopathy is challenging, as 40% of patients do not respond to the existing rehabilitation protocols. These rehabilitation protocols do not consider the individual differences in the Achilles tendon (AT) characteristics, which are crucial in creating the optimal strain environment that promotes healing. While previous research suggests an optimal strain for AT regeneration (6% tendon strains), it is still unclear if the current rehabilitation protocols meet this condition. Consequently, this study aimed to investigate the influence of a selection of rehabilitation exercises on strains in patients with Achilles tendinopathy using subject-specific finite element (FE) models of the free AT. Secondly, the study aimed to explain the influence of muscle forces and material properties on the AT strains. The 21 FE models of the AT included the following subject-specific features: geometry estimated from 3D freehand ultrasound images, Elastic modulus estimated from the experimental stress-strain curve, and muscle forces estimated using a combination of 3D motion capture and musculoskeletal modelling. These models were used to determine tendon strain magnitudes and distribution patterns in the mid-portion of the AT. The generalized ranking suggested a progression of exercises to gradually increase the strains in the mid-portion of the AT, starting from the concentric and eccentric exercises and going to more functional exercises, which impose a higher load on the AT: bilateral heel rise (0.031 ± 0.010), bilateral heel drop (0.034 ± 0.009), unilateral heel drop (0.066 ± 0.023), walking (0.069 ± 0.020), unilateral heel drop with flexed knee (0.078 ± 0.023), and bilateral hopping (0.115 ± 0.033). Unilateral heel drop and walking exercises were not significantly different and they both fell within the optimal strain range. However, when examining individual strains, it became evident that there was diversity in exercise rankings among participants, as well as exercises falling within the optimal strain range. Furthermore, the strains were influenced more by the subject-specific muscle forces compared to the material properties. Our study demonstrated the importance of tailored rehabilitation protocols that consider not only individual subject-specific morphological and material characteristics but especially subject-specific muscle forces. These findings make a significant contribution to shape future rehabilitation protocols with a foundation in biomechanics.
Quality of care when using a digital clinical decision support algorithm to manage sick children at primary care health facilities in Tanzania: a cross-sectional cluster randomized controlled trial (DYNAMIC study)
Authors: Tan Rainer , Kavishe Godfrey , Kulinkina Alexandra V , Renggli Sabine , Luwanda Lameck B , Mangu Chacha , Ashery Geofrey , Jorram Margaret , Mtebene Ibrahim Evans , Agrea Peter , Mhagama Humphrey , Keitel Kristina , Le Pogam Marie-Annick , Ntinginya Nyanda , Masanja Honorati , D’Acremont Valérie 
Published: April 2024

AbstractDigital clinical decision support tools have contributed to improved quality of care at primary care level health facilities. However, data from real-world randomized trials are lacking.We conducted a cluster randomized, open-label trial in Tanzania evaluating the use of a digital clinical decision support algorithm (CDSA), enhanced by point-of-care tests, training and mentorship, compared with usual care, among sick children 2 to 59 months old presenting to primary care facilities for an acute illness in Tanzania (ClinicalTrials.govNCT05144763). The primary outcome was the mean proportion of 14 major Integrated Management of Childhood Illness (IMCI) symptoms and signs assessed by clinicians. Secondary outcomes included antibiotic prescription, counselling provided, and the appropriateness of antimalarial and antibiotic prescriptions.A total of 450 consultations were observed in 9 intervention and 9 control health facilities. The mean proportion of major symptoms and signs assessed in intervention health facilities was 46.4% (range 7.7% to 91.7%) compared to 26.3% (range 0% to 66.7%) in control health facilities, an adjusted difference of 15.1% (95% confidence interval [CI] 4.8% to 25.4%). Only weight, height, and pallor were assessed more often when using the digital CDSA than in controls. Observed antibiotic prescription was 37.3% in intervention facilities, and 76.4% in control facilities (adjusted risk ratio 0.5; 95% CI 0.4 to 0.7; p<0.001). Appropriate antibiotic prescription was 81.9% in intervention facilities and 51.4% in control facilities (adjusted risk ratio 1.5; 95% CI 1.2 to 1.8; p=0.003).The implementation of a digital CDSA improved only slightly the mean proportion of IMCI symptoms and signs assessed in consultations with sick children, and most symptoms and signs were assessed infrequently. Nonetheless, antibiotics were prescribed less often, and more appropriately Innovative approaches to overcome barriers related to clinicians’ motivation and work environment are needed.
Simulating human-in-the-loop optimization of exoskeleton assistance to compare optimization algorithm performance
Authors: Kutulakos Zoe , Slade Patrick 
Published: April 2024

AbstractAssistive robotic devices like exoskeletons offer the promise of improving mobility for millions of people. However, developing devices that improve an objective mobility metric is challenging. Human-in-the-loop optimization is a systematic approach for personalizing robotic assistance to maximize a mobility metric that has improved device performance for different metrics and applications. Successfully performing human-in-the-loop optimization requires the experimenter to make many decisions, like selecting the appropriate optimization algorithm, hyperparameters, and convergence criteria. Typically, selecting these experimental settings involves pilot experimentation. We propose an approach that uses a probabilistic surrogate model, mapping assistance parameters to corresponding experimental evaluations of the objective mobility metric, to simulate human-in-the-loop optimization and inform these decisions. In this paper, we form a surrogate model of the metabolic landscape of walking with exoskeleton assistance using an existing experimental dataset. We simulate human-in-the-loop optimization by using a synthetic metabolic landscape model to evaluate the metabolic cost of walking with different assistance parameters, instead of performing an experimental measurement. We perform three simulated scenarios optimizing assistance for an expert subject, a novice subject adapting to the device, and an expert subject with up to 20 assistance parameters. The code and analyses from this work are open-source to promote use by other researchers. Simulation enables direct comparison of optimization settings to inform experimental human-in-the-loop optimization and potentially reduce the resources and time required to develop effective assistive devices.
Blocking MIF secretion enhances CAR T-cell efficacy against neuroblastoma
Authors: Strijker Josephine G. M. , Pascual-Pasto Guillem , Kalmeijer Yannine J. , Kalaitsidou Elisavet , Zhao Chunlong , McIntyre Brendan , Matlaga Stephanie , Visser Lindy L. , Barisa Marta , Himsworth Courtney , Shah Rivani , Muller Henrike , Schild Linda G. , Hains Peter G. , Zhong Qing , Reddel Roger , Robinson Phillip J. , Catena Xavier , Soengas María S. , Margaritis Thanasis , Dekker Frank J. , Anderson John , Molenaar Jan J. , Bosse Kristopher R. , Wu Wei , Wienke Judith 
Published: April 2024

AbstractWhile chimeric antigen receptor (CAR) T-cell therapies are showing highly promising first results in neuroblastoma, immunosuppressive tumor microenvironments (TME) limit T cell persistence and durable clinical efficacy. To improve CAR T-cell efficacy further, we applied a multi-omics approach including single-cell RNA sequencing and proteomics, which identified 13 targetable immunosuppressive factors in neuroblastoma. Of these, macrophage migration inhibitory factor (MIF) and midkine (MDK) were validated across multiple published RNA datasets. Moreover, they were secreted in high abundance by neuroblastoma tumoroids. Functional validation experiments revealed MIF as a potent inhibitor of CAR T-cells,in vitroandin vivo.Degradation of MIF by PROTAC technology significantly enhanced CAR T-cell activation targeting GPC2 and B7-H3, providing a potential intervention against MIF. By defining the immunosuppressive effects of neuroblastoma’s TME on CAR T-cell efficacy, particularly the pivotal role of MIF, we provide a therapeutic strategy for improving adoptive cell therapies for this pediatric malignancy.
The pathway to resolve dimeric forms distinguishes plasmids from megaplasmids in Enterobacteriaceae
Authors: Fournes Florian , Campos Manuel , Cury Jean , Schiavon Caroline , Pagès Carine , Touchon Marie , Rocha Eduardo PC , Rousseau Philippe , Cornet François 
Published: April 2024

AbstractBacterial genomes contain a plethora of secondary replicons of divergent size. Circular replicons must carry a system for resolving dimeric forms, resulting from recombination between sister copies. These systems use site-specific recombinases. Among these, the XerCD recombinase resolves dimers of chromosomes and certain plasmids using different controls. We have analyzed the dimer resolution functions in enterobacterial secondary replicons and show that, in addition to the main chromosomes, XerCD is preferentially used by small plasmids and by the largest secondary replicons, megaplasmids and secondary chromosomes. Indeed, all replicons longer than 250 kb host an active XerCD recombination site. These sites, in contrast to those of small plasmids, use the same control as chromosomes, coupled to cell division by the FtsK protein. We conclude that a chromosome-like mode of dimer resolution is mandatory for the faithful inheritance of large plasmids and chromids, its acquisition being a prerequisite for the genesis of secondary chromosomes from plasmids.
Temporal Dynamics of Neocortical Development in Organotypic Mouse Cultures: A Comprehensive Analysis
Authors: Bak Aniella , Schmied Katharina , Jakob Morten , Bedogni Francesco , Squire Olivia , Gittel Birgit , Jesinghausen Maik , Schünemann Kerstin , Weber Yvonne , Kampa Björn , van Loo Karen M. J. , Koch Henner 
Published: April 2024

AbstractMurine organotypic brain slice cultures have been widely used in neuroscientific research and are offering the opportunity to study neuronal function under normal and disease conditions. Despite the brought application, the mechanisms governing the maturation of immature cortical circuitsin vitroare not well understood. In this study, we present a detailed investigation into the development of the neocortexin vitro. Utilizing a holistic approach, we studied organotypic whole-hemisphere brain slice cultures from postnatal mice and tracked the development of the somatosensory area over a five-week period. Our analysis revealed the maturation of passive and active intrinsic properties of pyramidal cells together with their morphology, closely resemblingin vivodevelopment. Detailed Multi-electrode array (MEA) electrophysiological assessments and RNA expression profiling demonstrated stable network properties by two weeks in culture, followed by the transition of spontaneous activity towards more complex patterns including high-frequency oscillations. However, weeks 4 and 5 exhibited increased variability and initial signs of neuronal loss, highlighting the importance of considering developmental stages in experimental design. This comprehensive characterization is vital for understanding the temporal dynamics of the neocortical developmentin vitro, with implications for neuroscientific research methodologies, particularly in the investigation of diseases such as epilepsy and other neurodevelopmental disorders.
A newly-identified IncY plasmid from multi-drug resistantEscherichia coliisolated from dairy cattle feces in Poland
Authors: Zalewska Magdalena , Błażejewska Aleksandra , Gawor Jan , Adamska Dorota , Goryca Krzysztof , Szeląg Michał , Kalinowski Patryk , Popowska Magdalena 
Published: April 2024

AbstractComprehensive whole-genome sequencing was performed on two multi-drug resistantEscherichia colistrains isolated from cattle manure from a typical dairy farm in Poland in 2020. The identified strains are resistant to beta-lactams, aminoglycosides, tetracyclines, trimethoprim/sulfamethoxazole, and fluoroquinolones. The complete sequences of the harbored plasmids revealed antibiotic-resistance genes (ARGs) located within many mobile genetic elements (e.g., insertional sequences or transposons), and genes facilitating conjugal transfer or promoting horizontal gene transfer. These plasmids are hitherto undescribed. Similar plasmids have been identified, but not in Poland. The identified plasmids carried resistance genes, including the tetracycline resistance genetet(A), aph family aminoglycoside resistance genesaph(3”)-lbandaph(6)-ld, β-lactam resistance genesblaTEM-1, blaCTX-M-15, sulfonamide resistance genesul2, fluoroquinolone resistance geneqnrS1, and the trimethoprim resistance genedfrA14. The characterized resistance plasmids were categorized into the IncY incompatibility group, indicating a high possibility for dissemination among theEnterobacteriaceae. While similar plasmids (99% identity) have been found in environmental and clinical samples, none have been identified in farm animals. This findings are significant within the One Health framework, as they underline the potential for antimicrobial-resistantE. colifrom livestock and food sources to be transmitted to humans and vice versa. It highlights the need for careful monitoring and strategies to limit the spread of antibiotic resistance in the One Health approach.
Land use effects on soil microbiome composition and traits with consequences for its ecosystem carbon use efficiency
Authors: Cole Lisa , Goodall Tim , Jehmlich Nico , Griffiths Robert I. , Gleixner Gerd , Gubry-Rangin Cecile , Malik Ashish A. 
Published: April 2024

AbstractThe soil microbiome determines the fate of belowground inputs of plant fixed carbon. The shifts in soil properties caused by changes in land use leads to modifications in microbiome structure and function, resulting in either loss or gain of soil organic carbon (SOC). Soil pH is the primary factor regulating microbiome characteristics leading to distinct pathways of microbial carbon cycling, but the underlying mechanisms remain understudied. Here, the taxa-trait relationships behind the variable fate of SOC were investigated across two temperate paired land use intensity contrasts with differing soil pH using metaproteomics, metabarcoding and a13C labelled litter decomposition experiment.13C incorporation into microbial biomass increased with land use intensification in low pH soils but decreased in high pH soils, impacting ecosystem carbon use efficiency (CUE) in opposing directions. Reduction in biosynthesis traits across land use intensity contrasts was due to increased abundance of proteins linked to resource acquisition and stress tolerance. These community-level trait trade-offs were underpinned by land use intensification-induced changes in dominant taxa with distinct traits. These trait changes alter the balance of decomposition and stabilisation of carbon in soil through divergent pH-controlled pathways. In low pH soils, land use intensification alleviates microbial abiotic stress resulting in increased CUE but promotes decomposition and SOC loss. In contrast, in high pH soils, land use intensification increases microbial physiological constraints and decreases CUE, leading to reduced necromass build-up and SOC stabilisation. We demonstrate how microbial CUE can be decoupled from SOC highlighting the need for its careful consideration in predicting or managing SOC storage for soil health and climate change mitigation.
Cockroach social network position does not influence exploration tendency
Authors: Louca Vasilis , Savorelli Smilla , Vuorio Nea , Fisher David N. 
Published: April 2024

AbstractIn group-living organisms, we might expect relationships between social position and exploration, such as if certain patterns of social associations encourage exploration or if certain personality types both link different groups and are more likely to explore their environment. However, directly testing these ideas is challenging as exploration can be hard to track in the field and is a difficult trait to measure in the laboratory. Furthermore, invertebrate exploration is less commonly quantified as their small size makes them hard to track. Here we quantified social networks in multiple groups of the gregarious cockroachBlaptica dubiain the laboratory and related three measures of social network position (representing overall sociability, connectedness in local cliques, and connectedness to the wider network) to measures of exploration either assayed alone or as part of a group. We found none of the social network measures related to either of the measures of exploration, which were themselves not correlated. We also found that sociability and connectedness to the wider network were positively correlated, suggesting a single axis of variation in centrality within a group. We found no effects of mass or sex, but there were differences between the two blocks our experiments were performed in, suggesting some effect of observer variability. Overall, our results suggest that exploration is not linked to social behaviour in this species, that cockroaches differ in the social behaviour along a syndrome integrating sociability and the tendency to move between groups, and that study replication should be encouraged so we can be confident identified trends are robust.
The IncC and IncX1 resistance plasmids present in multi-drug resistantEscherichia colistrains isolated from poultry manure in Poland
Authors: Zalewska Magdalena , Błażejewska Aleksandra , Gawor Jan , Adamska Dorota , Goryca Krzysztof , Szeląg Michał , Kalinowski Patryk , Popowska Magdalena 
Published: April 2024

AbstractThe study describes the whole-genome sequencing of two antibiotic-resistant representativeEscherichia colistrains, isolated from poultry manure in 2020. The samples were obtained from a commercial chicken meat production facility in Poland. The antibiotic resistance profile was characterized by co-resistance to β-lactam antibiotics, aminoglycosides, and fluoroquinolones. The three identified resistance plasmids (R-plasmids), pECmdr13.2, pECmdr13.3 and pECmdr14.1, harbored various genes conferring resistance to tetracyclines (tetR[A]) for, aminoglycoside (aph, aacandaadfamilies), β-lactam (blaCMY-2,blaTEM-176), sulfonamide (sul1, sul2), fluoroquinolone (qnrS1), and phenicol (floR). These plasmids, which have not been previously reported in Poland, were found to carry IS26 insertion elements, the intI1-integrase gene, as well as conjugal transfer genes, facilitating horizontal gene transfer. Plasmids pECmdr13.2 and pECmdr14.1 also possessed a mercury resistance gene operon related to transposon Tn1696; this promotes plasmid persistence even without antibiotic selection pressure due to co-selection mechanisms such as co-resistance. The chicken manure-derived plasmids belonged to the IncX1 (narrow host range) and IncC (broad host range) incompatibility groups. Similar plasmids have been identified in various environments, clinical isolates, and farm animals, including cattle, swine, and poultry. This study holds significant importance for the One Health approach, as it highlights the potential for antimicrobial-resistant bacteria from livestock and food sources, particularlyE. coli, to transfer through the food chain to humans and vice versa. This underscores the need for vigilant monitoring of R-plasmids prevalence in the human, animal and natural environments, and to implement strategies to mitigate the spread of antibiotic resistance.