bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Quantification of Extracellular Trap Cell Death-Derived Products as Diagnostic Biomarkers for Otitis Media With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Eosinophilic Otitis Media
Authors: Morita Shinya , Nakamaru Yuji , Fukuda Atsushi , Fujiwara Keishi , Suzuki Masanobu , Hoshino Kimiko , Honma Aya , Homma Akihiro 
Published: November 2021

Objective:
This study aimed to quantify the cell-free deoxyribonucleic acid (DNA), citrullinated-histone H3 (cit-H3)-DNA complex, and myeloperoxidase (MPO)-DNA complex as extracellular trap cell death (ETosis)-derived products in the middle ear fluid, and to identify diagnostic biomarkers for the discrimination of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) from eosinophilic otitis media (EOM).

Study Design:
Prospective study.

Setting:
Tertiary referral center.

Patients:
OMAAV patients were eligible for inclusion in this analysis. Patients with EOM were examined as controls.

Intervention:
All samples were obtained from the middle ear fluid in patients with OMAAV or EOM. The fluid samples were aspirated from the middle ear through the anterior-inferior portion of the tympanic membrane using a 1-ml tuberculin syringe with a 24- or 26-gauge needle under a microscope.

Main Outcome Measures:
The levels of cell-free DNA, cit-H3-DNA complex and MPO-DNA complex in the fluid samples were quantified using an enzyme-linked immunosorbent assay.

Results:
Patients with OMAAV showed significantly higher levels of MPO-DNA complex compared to patients with EOM, regardless of the serum ANCA status at the time of sampling (p < 0.001 and p < 0.001, respectively). Meanwhile, there were no significant differences in the values of cell-free DNA or cit-H3-DNA complex between the OMAAV and EOM patients.

Conclusion:
The findings of this study suggest that the detection and quantification of MPO-DNA complex in the otitis media fluid can be utilized to discriminate OMAAV, especially in cases of eosinophilic granulomatosis with polyangiitis, from EOM regardless of the serum ANCA status. It should be noted that it is possible for cell-free DNA and cit-H3-DNA complex in fluid samples to be derived from dead cells other than neutrophils that undergo ETosis.
Prebending of Prefabricated Orbital Implants: Towards Improved Orbital Angle Symmetry Post Craniofacial Trauma Surgery
Authors: Zhang Trisha , Young Stephanie , Lang Stephanie S. , Sundar Gangadhara 
Published: November 2021

Purpose:
Reconstructive surgery after craniofacial trauma aim to restore orbital anatomy for function and aesthetic reasons. The purpose of this study is to improve postoperative orbital symmetry with the use of prebent prefabricated titanium implants.

Methods:
In this retrospective study, patients with combined unilateral medial wall and floor fractures who underwent orbital reconstruction surgery were selected. The angle of inferomedial orbital strut (AIOS) was measured at 3 standard locations on preoperative facial computed tomography guided scans of the nonfractured orbit in the coronal view and used as a guide to bend the prefabricated titanium implants intraoperatively. The corresponding values were measured on the postoperative computed tomography and compared for symmetry.

Results:
Out of 83 patients recruited for the study, 54 were in the prebent group while 29 were in the control group. All other demographics were similar among the 2 groups. Anterior AIOS has a difference of 4.9° between 2 orbits in the prebent group whereas a difference of 15.5° was noted in the nonprebent group. For middle AIOS, a difference of 4.7° was noted in the prebent group whereas nonprebent group had a difference of 14.1°. For posterior AIOS, the prebent group had a difference of 3.8° versus 14.1° in the nonprebent group. The difference in AIOS at all 3 points between the prebent and nonprebent group were significant.

Conclusions:
Anatomical prefabricated titanium plates are versatile implants that facilitate orbital reconstruction. Prebending of these implants according to the fellow orbit can achieve better surgical outcomes in a cost-effective manner.
Dairy products as sources of methanogens for humans
Authors: Guindo Cheick Oumar , Drancourt Michel , Grine Ghiles 
Published: November 2021

ABSTRACTMethanogens are detected in human gut from the first moments of life and there is a diversification of methanogens during infancy. However, the sources of acquisition of methanogens are not well elucidated. We therefore investigated 56 dairy products as potential sources of methanogens by applying molecular biology. In the presence of negative controls, we obtained an overall prevalence of methanogens in 85.7% (48/56) of samples by real-time PCR. Further PCR-sequencing identified 73.2% (41/56) of Methanobrevibacter smithii. We also found for the first time in dairy products 1.8% (1/56) of Methanobrevibacter oralis, 7.1% (4/56) of Methanobrevibacter millerae, 1.8% (1/56) of Methanobrevibacter ruminantium, 1.8% (1/56) of Methanocorpusculum sp. We observed a significant presence (p-value=0.001) of methanogens in fermented dairy products compared to unfermented dairy products. This study gives credit to the fact that dairy products could be considered as a source of methanogens for humans, especially for children.
Population Imaging of Central Sensitization
Authors: Warwick Charles , Salsovic Joseph , Hachisuka Junichi , Smith Kelly M. , Chen Haichao , Ibinson James , Koerber H. Richard , Ross Sarah E. 
Published: November 2021

AbstractCapsaicin applied locally to the skin causes central sensitization that results in allodynia, a state in which pain is elicited by innocuous stimuli. Here, we used two-photon calcium imaging of neurons in the dorsal spinal cord to visualize central sensitization across excitatory interneurons and spinal projection neurons. To distinguish among excitatory neuron subtypes, we developed CICADA, a cell profiling approach that leverages the expression of distinct Gq-coupled receptors. We then identified capsaicin-responsive and capsaicin-sensitized neuronal populations. Capsaicin-sensitized neurons showed emergent responses to low threshold input and increased receptive field sizes consistent with the psychophysical phenomenon that allodynia is observed across an extended secondary zone. Finally, we identified spinal projection neurons that showed a shift in tuning toward low threshold input. These experiments provide a population-level view of central sensitization and a framework with which to model somatosensory integration in the dorsal horn.HighlightWarwick et al. use two-photon calcium imaging coupled with pharmacological profiling to identify neuronal populations in the spinal dorsal horn that mediate capsaicin-induced central sensitization.
Computational Compensatory Mutation Discovery Approach: Predicting a PARP1 Variant Rescue Mutation
Authors: Ravishankar Krithika , Jiang Xianli , Leddin Emmett M. , Morcos Faruck , Cisneros G. Andrés 
Published: November 2021

AbstractThe prediction of protein mutations that affect function may be exploited for multiple uses. In the context of disease variants, the prediction of compensatory mutations that reestablish functional phenotypes could aid in the development of genetic therapies. In this work, we present an integrated approach that combines coevolutionary analysis and molecular dynamics (MD) simulations to discover functional compensatory mutations. This approach is employed to investigate possible rescue mutations of a poly(ADP-ribose) polymerase 1 (PARP1) variant, PARP1 V762A, associated with lung cancer and follicular lymphoma. MD simulations show PARP1 V762A exhibits noticeable changes in structural and dynamical behavior compared with wild type PARP1. Our integrated approach predicts A755E as a possible compensatory mutation based on coevolutionary information, and molecular simulations indicate that the PARP1 A755E/V762A double mutant exhibits similar structural and dynamical behavior to WT PARP1. Our methodology can be broadly applied to a large number of systems where single nucleotide polymorphisms (SNPs) have been identified as connected to disease and can shed light on the biophysical effects of such changes as well as provide a way to discover potential mutants that could restore wild type-like functionality. This can in turn be further utilized in the design of molecular therapeutics that aim to mimic such compensatory effect.Significance StatementDiscovering protein mutations with desired phenotypes can be challenging due to its combinatorial nature. Herein we employ a methodology combining gene SNP association to disease, direct coupling analysis and molecular dynamics simulations to systematically predict rescue mutations. Our workflow identifies A755E as a potential rescue for the PARP1 V762A mutation, which has been associated with cancer. This methodology is general and can be applied broadly.
Evolution of immune genes in island birds: reduction in population sizes can explain island syndrome
Authors: Barthe Mathilde , Doutrelant Claire , Covas Rita , Melo Martim , Illera Juan Carlos , Tilak Marie-Ka , Colombier Constance , Leroy Thibault , Loiseau Claire , Nabholz Benoit 
Published: November 2021

AbstractShared ecological conditions encountered by species that colonize islands often lead to the evolution of convergent phenotypes, commonly referred to as “island syndrome”. Reduced immune functions have been previously proposed to be part of this syndrome, as a consequence of the reduced diversity of pathogens on island ecosystems. According to this hypothesis, immune genes are expected to exhibit genomic signatures of relaxed selection pressure in island species. In this study, we used comparative genomic methods to study immune genes in island species (N = 20) and their mainland relatives (N = 14). We gathered public data as well as generated new data on innate (TLR: Toll-Like Receptors, BD: Beta Defensins) and acquired immune genes (MHC: Major Histocompatibility Complex classes I and II), but also on hundreds of genes with various immune functions. As a control, we used a set of 97 genes, not known to be involved in immune functions based on the literature, to account for the increased drift effects of the lower effective population sizes in island species. We used synonymous and non-synonymous variants to estimate the selection pressure acting on immune genes. We found that BDs and TLRs have higher ratios of non-synonymous over synonymous polymorphisms (Pn/Ps) than randomly selected control genes, suggesting that they evolve under a different selection regime. However, simulations show that this is unlikely to be explained by ongoing positive selection or balancing selection. For the MHC genes, which evolve under balancing selection, we used simulations to estimate the impact of population size variation. We found a significant effect of drift on immune genes of island species leading to a reduction in genetic diversity and efficacy of selection. However, the intensity of relaxed selection was not significantly different from control genes, except for MHC class II genes. These genes exhibit a significantly higher level of non-synonymous loss of polymorphism than expected assuming only drift and evolution under frequency dependent selection, possibly due to a reduction of extracellular parasite communities on islands. Overall, our results showed that demographic effects lead to a decrease in the immune functions of island species, but the relaxed selection that is expected to be caused by a reduced parasite pressure may only occur in some categories of immune genes.
Artificial Intelligence Guided Conformational Mining of Intrinsically Disordered Proteins
Authors: Gupta Aayush , Dey Souvik , Zhou Huan-Xiang 
Published: November 2021

AbstractArtificial intelligence recently achieved the breakthrough of predicting the three-dimensional structures of proteins. The next frontier is presented by intrinsically disordered proteins (IDPs), which, representing 30% to 50% of proteomes, readily access vast conformational space. Molecular dynamics (MD) simulations are promising in sampling IDP conformations, but only at extremely high computational cost. Here, we developed generative autoencoders that learn from short MD simulations and generate full conformational ensembles. An encoder represents IDP conformations as vectors in a reduced-dimensional latent space. The mean vector and covariance matrix of the training dataset are calculated to define a multivariate Gaussian distribution, from which vectors are sampled and fed to a decoder to generate new conformations. The ensembles of generated conformations cover those sampled by long MD simulations and are validated by small-angle X-ray scattering profile and NMR chemical shifts. This work illustrates the vast potential of artificial intelligence in conformational mining of IDPs.
Mitotic Outcomes in Fibrous Environments
Authors: Jana Aniket , Zhang Haonan , Wang Ji , Kapania Rakesh , Gov Nir , DeLuca Jennifer , Nain Amrinder S. 
Published: November 2021

AbstractDuring mitosis, cells round up and generate outward forces to create space and orient the mitotic spindles. Here, using suspended ECM-mimicking nanofiber networks, we recapitulate in vivo adhesion organization and confinement to interrogate mitotic outcomes for various interphase cell shapes. Elongated cells attached to single fibers through two focal adhesion clusters (FACs) at their extremities result in perfect spherical mitotic cell bodies that undergo large 3D displacement while being held by retraction fibers. Increasing the number of parallel fibers increases cellular extremity FACs and retraction fiber-driven stability, leading to reduced 3D cell-body movement, metaphase plate rotations, and significantly faster division times. Interestingly, interphase kite shapes on a crosshatch pattern of four fibers undergo mitosis resembling single-fiber outcomes due to rounded bodies being primarily held in position by retraction fibers from two perpendicular suspended fibers. We develop a cortex-astral microtubule analytical friction and force model to capture retraction-fiber-driven stability of the metaphase plate rotations. We report that reduced orientational stability results in increased monopolar mitotic defects. In the case of cells attached to two parallel fibers, rounded mitotic cells can get confined between the suspended fibers, allowing estimation of the mitotic forces through measurement of the outward deflection of the fibers. Interestingly, confinement causes rotated mitotic spindles similar to those reported in dense tissues. Overall, we establish dynamics of mitosis in fibrous environments governed by fiber arrangement and architecture-driven differences in interphase cell shapes, adhesion geometries, and varying levels of mechanical confinement.
A portable and high-integrated 3D microfluidic chip for bacterial quantification and antibiotic susceptibility testing
Authors: Wu Wenshuai , Cai Gaozhe , Liu Yang 
Published: November 2021

ABSTRACTOn-site single-cell antibiotic susceptibility testing (sc-AST) provides unprecedented technical potential to improve the treatment of bacterial infections and study heterogeneous resistance to antibiotics. Herein, we developed a portable and high-integrated 3D polydimethylsiloxane (PDMS) chip to perform fast and on-site bacteria quantification and sc-AST. The 3D arrangement of the chambers significantly improved the integration of reaction units (∼10000/cm2) and widened the dynamic range to 5 orders of magnitude. A capillary valve-based flow distributor was adopted for flow equidistribution in 64 parallel channels and uniform sample loading in as short as 2 s. The degassed PDMS enabled this device to independently dispense the sample into 3D chamber array with almost 100% efficiency. The quantification of Escherichia coli (E. coli) strains with various activity was accomplished in 0.5-2 h, shortened by 20 h in comparison to the traditional plate counting. The functionality of our platform was demonstrated with several effective antibiotics by determining minimum inhibitory concentrations at single-cell level. Furthermore, we utilized the lyophilization of test reagents and needle-mediated reagents rehydration to realize one-step on-site sc-AST. The results indicate that the proposed sc-AST platform is portable, highly sensitive, fast, accurate and user-friendly, thus it has the potential to facilitate precise therapy in time and monitor the treatment. Meanwhile, it could serve as an approach for investigating the mechanisms of heteroresistance at single-cell resolution.
Long-lasting and responsive DNA/enzyme-based programs in serum-supplemented extracellular media
Authors: Galas Jean-Christophe , Estevez-Torres André , Van Der Hofstadt Marc 
Published: November 2021

AbstractDNA molecular programs are emerging as promising pharmaceutical approaches due to their versatility for biomolecular sensing and actuation. However, the implementation of DNA programs has been mainly limited to serum-deprived in vitro assays due to the fast deterioration of the DNA reaction networks by the nucleases present in the serum. Here, we show that DNA/enzyme programs are functional in serum for 24h but are latter disrupted by nucleases that give rise to parasitic amplification. To overcome this, we implement 3-letter code networks that suppress autocatalytic parasites while still conserving the functionality of DNA/enzyme programs for at least 3 days in the presence of 10% serum. In addition, we define a new buffer that further increases the biocompatibility and conserves responsiveness to changes in molecular composition across time. Finally, we demonstrate how serum-supplemented extracellular DNA molecular programs remain responsive to molecular inputs in the presence of living cells, having responses 6-fold faster than cellular division rate and are sustainable for at least 3 cellular divisions. This demonstrates the possibility of implementing in situ biomolecular characterization tools for serum-demanding in vitro models. We foresee that the coupling of chemical reactivity to our DNA programs by aptamers or oligonucleotide conjugations will allow the implementation of extracellular synthetic biology tools, which will offer new biomolecular pharmaceutical approaches and the emergence of complex and autonomous in vitro models.
TheBacillusphage SPβ and its relatives: A temperate phage model system reveals new strains, species, prophage integration loci, conserved proteins and lysogeny management components
Authors: Kohm Katharina , Floccari Valentina A. , Lutz Veronika T. , Nordmann Birthe , Mittelstädt Carolin , Poehlein Anja , Dragoš Anna , Commichau Fabian M. , Hertel Robert 
Published: November 2021

AbstractTheBacillusphage SPβ has been known for about 50 years, but only a few strains are avalible. We isolated four new wild type strains of theSPbetaspecies. Phage vB_BsuS-Goe14 introduces its prophage into thespoVKlocus, previously not observed to be used by SPβ-like phages. We could also reveal the SPβ-like phage genome replication strategy, the genome packaging mode, and the phage genome opening point. We extracted 55 SPβ-like prophages from publicBacillusgenomes, thereby discovering three more integration loci and one additional type of integrase. The identified prophages resembled four new species clusters and three species orphans in the genusSpbetavirus. The determined core proteome of all SPβ-like prophages consists of 38 proteins. The integration cassette proved to be not conserved even though present in all strains. It consists of distinct integrases. Analysis of SPβ transcriptomes revealed three conserved genes,yopQ,yopR, andyokI, to be transcribed from a dormant prophage. WhileyopQandyokIcould be deleted from the prophage without activating the prophage, damaging ofyopRled to a clear-plaque phenotype. Under the applied laboratory conditions, theyokImutant showed an elevated virion release implying the YokI protein being a component of the arbitrium system.
The factors influencing the innovative performance of leaders in nurses’ professional: a developing country perspective
Authors: Abed Shaymaa Najm , Abdulmuhsin Amir A. , Alkhwaldi Abeer F. 
Published: November 2021

Purpose
The health-care services in Iraq currently face many challenges. The most noted is the lack of effective nursing leaders to meet the growing needs of the health-care services. Effective nursing leadership is critical to the health-care system, affecting work performance, quality of care and staff satisfaction. The literature suggests that nursing leaders in Iraq are not adequately trained to provide leadership to improve the nursing profession and have limited involvement in decision-making. The purpose of this study is to explore the views of nurses on what they believe constitutes effective leadership in Iraq.

Design/methodology/approach
A qualitative methods approach is used involving 20 semi-structured interviews of senior nurses. The sample of nurses came from two large general hospitals in Iraq. The qualitative data was thematically analyzed and interpreted.

Findings
The study results indicated that there were factors that influence the performance of nurse leader, namely, excessive workload, personal relationship with nursing staff, professional recognition of nursing and selection criteria of leaders. Test results show that there were significant differences in views of the nurses toward nurse leaders’ performance. This research concludes that the nurse leader performance in developing countries is affected by excessive workload, personal relationship with nursing staff, professional recognition of nursing and selection criteria of leaders.

Originality/value
The relevance of the study stems from the scarcity of research on the leader performance in developing countries, while studies on the factors influencing the innovative performance of leaders in nurses’ professional are significantly limited. This study is one of the earliest studies that investigate these factors influencing the nurse leader’s performance.
Funding issues and development of digital libraries in Nigeria
Authors: Abdussalam Titilola Aminat Bayero , Adewara Janet Oluseyi , Abdulraheem Jamiu Wankasi , Oyedokun Tunde Toyese , Balogun Tawakalitu Raufu 
Published: November 2021

Purpose
Funding issues is observed to be the major stumbling block for the development of digital libraries in Nigeria. Hence, this paper aims to explore issues in obtaining and allocating funds for digital library development.

Design/methodology/approach
The review is an explorative report of the state of affairs of digital library development in Nigeria with the associated fundraising issues.

Findings
Digital library initiatives are coincidental development with transformational change in the technology-driven world of global information distribution. The desire of the information users to have better-unrestricted access to information becomes the hallmark of digital content development and web-based information services. The goal of making information accessible globally to large and diverse information users was achievable with the development of a digital library that provides enhanced information services, improves access and usability of digital information resources.

Originality/value
The library of the future has already materialized in form of digital library services, but the cost of developing a digital library is not foreseeable cheap, and if Nigerian libraries are to achieve digital library service goal, alternative sources of finance need to be sought after through fundraising scheme from friends of the library, rental services, consultation fees and collaboration effort on library consortia as well as advocacy for open access initiatives.