bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing frequency of booster vaccination to prevent severe COVID-19 by risk group in the United States
Authors: Park Hailey J. , Gonsalves Gregg S. , Tan Sophia T. , Kelly J. Daniel , Rutherford George W. , Wachter Robert M. , Schechter Robert , Paltiel A. David , Lo Nathan C. 
Published: July 2023

AbstractThere is a public health need to understand how different frequencies of COVID-19 booster vaccines may mitigate the risk of severe COVID-19, while accounting for waning of protection and differential risk by age and immune status. By analyzing United States COVID-19 surveillance and seroprevalence data in a microsimulation model, here we show that more frequent COVID-19 booster vaccination (every 6-12 months) in older age groups and the immunocompromised population would effectively reduce the burden of severe COVID-19, while frequent boosters in the younger population may only provide modest benefit against severe disease. In persons 75+ years, the model estimated that annual boosters would reduce absolute annual risk of severe COVID-19 by 199 (uncertainty interval: 188-229) cases per 100,000 persons, compared to a one-time booster dose. In contrast, for persons 18-49 years, the model estimated that annual boosters would reduce this risk by 14 (11-19) cases per 100,000 persons. Those with prior infection had lower benefit of more frequent boosting, and immunocompromised persons had larger benefit. Scenarios with emerging variants with immune evasion increased the benefit of more frequent variant-targeted boosters. This study underscores the benefit of considering key risk factors to inform frequency of COVID-19 booster vaccines in public health guidance and ensuring at least annual boosters in high-risk populations.
Pre-stroke loop diuretics and anemia in elderly patients were associated with severe renal dysfunction at the onset of acute stroke
Authors: Mori Takahisa , Yano Tetsundo , Yoshioka Kazuhiro , Miyazaki Yuichi 
Published: July 2023

AbstractIntroductionSevere renal dysfunction (SRD) is a common complication of chronic kidney disease (CKD) that is a risk factor for heart disease and acute stroke (AS).Furthermore, SRD can limit the treatment options for AS patients and influence their prognosis. Thus, preventing CKD progression to SRD and identifying the factors contributing to SRD at AS onset is crucial. However, the frequency of SRD in AS patients and the associated factors are poorly understood in different genders. In this study, we aimed to investigate the frequency of SRD in AS patients and analyze the associated factors by sex.MethodsOur cross-sectional study included patients who met the following criteria: 1) admission within 24 hours of AS onset between 2013 and 2019 and 2) availability of pre-stroke medication information. We used the Cockcroft-Gault equation for calculating creatinine clearance (Ccr) and defined SRD as Ccr <30 ml/min. Then, we performed a multivariable logistic regression analysis to identify independent factors associated with SRD on admission separately for males and females.ResultsOut of 4294 patients with AS, 3472 were included for analysis. Of these, 1905 (54.9%) were male, with a median age of 75 and 81 years for males and females, respectively. The prevalence of SRD was 9.7% in males and 18.7% in females. For males, factors associated with SRD were loop diuretics, aspirin, L-type calcium channel blockers, alpha-beta blockers, and anemia. For females, factors associated with SRD were loop diuretics, mineralocorticoid receptor antagonists, and anemia.ConclusionsLoop diuretic use and anemia before AS onset were associated with SRD in both males and females. To prevent SRD, individualized drug and anemia management are essential. Further prospective studies are warranted to confirm our findings and to elucidate the causal mechanism of SRD in patients with AS.
Granular retrosplenial cortex layer 2/3 generates high-frequency oscillations coupled with hippocampal theta and gamma in online states or sharp-wave ripples in offline states
Authors: Arndt Kaiser C. , Gilbert Earl T. , Klaver Lianne M. F. , Kim Jongwoon , Buhler Chelsea M. , Basso Julia C. , McKenzie Sam , English Daniel Fine 
Published: July 2023

AbstractNeuronal oscillations support information transfer by temporally aligning the activity of anatomically distributed ‘writer’ and ‘reader’ cell assemblies. High-frequency oscillations (HFOs) such as hippocampal CA1 sharp-wave ripples (SWRs; 100-250 Hz) are sufficiently fast to initiate synaptic plasticity between assemblies and are required for memory consolidation. HFOs are observed in parietal and midline cortices including granular retrosplenial cortex (gRSC). In ‘offline’ brain states (e.g. quiet wakefulness) gRSC HFOs co-occur with CA1 SWRs, while in ‘online’ states (e.g. ambulation) HFOs persist with the emergence of theta oscillations. The mechanisms of gRSC HFO oscillations, specifically whether the gRSC can intrinsically generate HFOs, and which layers support HFOs across states, remain unclear. We addressed these issues in behaving mice using optogenetic excitation in individual layers of the gRSC and high density silicon-probe recordings across gRSC layers and hippocampus CA1. Optogenetically induced HFOs (iHFOs) could be elicited by depolarizing excitatory neurons with 100 ms half-sine wave pulses in layer 2/3 (L2/3) or layer 5 (L5) though L5 iHFOs were of lower power than in L2/3. Critically, spontaneous HFOs were only observed in L2/3 and never in L5. Intra-laminar monosynaptic connectivity between excitatory and inhibitory neurons was similar across layers, suggesting other factors restrict HFOs to L2/3. To compare HFOs in online versus offline states we analyzed, separately, HFOs that did or did not co-occur with CA1 SWRs. Using current-source density analysis we found uniform synaptic inputs to L2/3 during all gRSC HFOs, suggesting layer-specific inputs may dictate the localization of HFOs to L2/3. HFOs occurring without SWRs were aligned with the descending phase of both gRSC and CA1 theta oscillations and were coherent with CA1 high frequency gamma oscillations (50-80 Hz). These results demonstrate that gRSC can internally generate HFOs without rhythmic inputs and that HFOs occur exclusively in L2/3, coupled to distinct hippocampal oscillations in online versus offline states.
High throughput functional profiling of genes at intraocular pressure loci reveals distinct networks for glaucoma
Authors: Greatbatch Connor J , Lu Qinyi , Hung Sandy , Wing Kristof , Liang Helena , Han Xikun , Zhou Tiger , Siggs Owen M , Mackey David A , Cook Anthony L , Senabouth Anne , Liu Guei-Sheung , Craig Jamie E , MacGregor Stuart , Powell Joseph E , Hewitt Alex W 
Published: July 2023

ABSTRACTINTRODUCTIONPrimary open angle glaucoma (POAG) is a leading cause of blindness globally. Characterised by progressive retinal ganglion cell degeneration, the precise pathogenesis remains unknown. Genome-wide association studies (GWAS) have uncovered many genetic variants associated with elevated intraocular pressure (IOP), one of the key risk factors for POAG. This study sought to investigate the morphological and transcriptional consequences of perturbation of key genes at IOP loci in trabecular meshwork cell (TMC); the cellular regulators of IOP. We aimed to identify genetic and morphological variation that can be attributed to TMC dysfunction and raised IOP in POAG.METHODS62 genes across 55 loci were knocked-out in a primary human TMC line. Each knockout group, including five non-targeting control groups, underwent single-cell RNA-sequencing (scRNA-seq) for differentially-expressed gene (DEG) analysis. Multiplexed fluorescent staining of key organelles, was coupled with high-throughput microscopy for single-cell morphological analysis using CellProfiler image analysis.RESULTSAcross many of the individual gene knockouts scRNA-seq highlighted genes relating to matrix metalloproteinases and interferon-induced proteins. Our work has prioritised genes at four loci of interest to identify gene knockouts that may contribute to the pathogenesis of POAG, includingANGPTL2, LMX1B, CAV1,andKREMEN1. Three genetic networks of gene knockouts with similar transcriptomic profiles were identified (ABO/CAV1/MYOC,ANGPT2/PKHD1/TNS1/TXNRD2, andCAPZA1/KALRN/LMO7/PLEKHA7/GNB1L/TEX41), suggesting a synergistic function in trabecular meshwork cell physiology.TEKknockout caused significant upregulation of nuclear granularity on morphological analysis, whilst knockout ofTRIOBP, TMCO1andPLEKHA7increased granularity and intensity of actin and the cell-membrane.CONCLUSIONHigh throughput analysis of cellular structure and function through multiplex fluorescent single-cell analysis and scRNA-seq assays enabled the direct study of genetic perturbations at the single-cell resolution. This work provides a framework for investigating the role of genes in the pathogenesis of glaucoma and heterogenous diseases with a strong genetic basis.
kGWASflow: a modular, flexible, and reproducible Snakemake workflow for k-mers-based GWAS
Authors: Corut Adnan Kivanc , Wallace Jason G. 
Published: July 2023

AbstractGenome-wide association studies (GWAS) have been widely used to identify genetic variation associated with complex traits. Despite its success and popularity, the traditional GWAS approach comes with a variety of limitations. For this reason, newer methods for GWAS have been developed, including the use of pan-genomes instead of a reference genome and the utilization of markers beyond single-nucleotide polymorphisms, such as structural variations and k-mers. The k-mers based GWAS approach has especially gained attention from researchers in recent years. However, these new methodologies can be complicated and challenging to implement. Here we present kGWASflow, a modular, user-friendly, and scalable workflow to perform GWAS using k-mers. We adopted an existing kmersGWAS method into an easier and more accessible workflow using management tools like Snakemake and Conda and eliminated the challenges caused by missing dependencies and version conflicts. kGWASflow increases the reproducibility of the kmersGWAS method by automating each step with Snakemake and using containerization tools like Docker. The workflow encompasses supplemental components such as quality control, read-trimming procedures, and generating summary statistics. kGWASflow also offers post-GWAS analysis options to identify the genomic location and context of trait-associated k-mers. kGWASflow can be applied to any organism and requires minimal programming skills. kGWASflow is freely available on GitHub (https://github.com/akcorut/kGWASflow) and Bioconda (https://anaconda.org/bioconda/kgwasflow).
miR-324 mediates bone homeostasis through the regulation of osteoblast and osteoclast differentiation and activity
Authors: Hayman Dan J. , Lin Hua , Prior Amanda , Charlesworth Gemma , Johnson de Sousa Brito Francesca M. , Hao Yao , Patel Krutik , Soul Jamie , Clark Ian M. , Piróg Katarzyna A. , Barter Matt J. , Van ’T Hof Rob , Young David A. 
Published: July 2023

AbstractmicroRNAs (miRNAs) are non-coding RNAs which modulate the expression of other RNA molecules. One miRNA can target many transcripts, allowing each miRNA to play key roles in many biological pathways. miR-324 is a miRNA previously implicated in bone and cartilage maintenance, defects of which result in common age-related diseases, such as osteoporosis or osteoarthritis (OA).In global miR-324-null mice cartilage damage was increased in both surgically and ageing-induced OA, despite minimal changes to the cartilage transcriptome, with few predicted miR-324 targets dysregulated. However, micro-computed tomography and histology demonstrated that global miR- 324-null the mice had an increase in bone mineral density, trabecular thickness and cortical thickness, with many parameters increasing with age. The bone marrow of miR-324-null mice also had reduced lipid content while andin vivoTRAP staining revealed a decrease in osteoclasts, with histomorphometry demonstrating an increased rate of bone formation in miR-324-null mice.Ex vivoassays revealed that the high bone mass phenotype of the miR-324-null mice resulted from increased osteoblast activity and decreased osteoclastogenesis. RNA-seq and qRT-PCR followed by miR-324 target prediction and validation in osteoblasts, osteoclasts and bone marrow macrophages identified the osteoclast fusion regulatorPin1as a miR-324 target in the osteoclast lineage and the master osteogenic regulatorRunx2as a target of miR-324-5p in osteoblasts, thein vitrooverexpression of which recapitulated the increased osteogenesis and decreased adipogenesis phenotype observedin vivo.These data point to important roles of miR-324 in skeletal biology with altered bone homeostasis in miR-324-null mice potentially causal for the increased cartilage damage observed during OA and ageing. Elucidation of pathways regulated by miR-324 offer promise for the treatment of bone diseases such as osteoporosis.
The protein interactome of the citrus Huanglongbing pathogenCandidatusLiberibacter asiaticus
Authors: Carter Erica W. , Peraza Orlene Guerra , Wang Nian 
Published: July 2023

AbstractCandidatusLiberibacter asiaticus (CLas) is the causal agent of the devastating citrus Huanglongbing (HLB) disease. Our understanding of the pathogenicity mechanism and biology of CLas remain limited because CLas has not been cultured in artificial media. CLas encodes 1136 proteins of which 415 have unknown functions. Since genetic studies of CLas genes with unknown functions are impossible, we utilized genome-wide protein-protein interactions (PPIs) yeast-two-hybrid (Y2H) assays to help solve the mystery. PPIs are fundamental to all cellular processes and machinery and instrumental in investigating uncharacterized proteins and inferring biological pathways. In total, 916 bait and 936 prey proteins were included in the three-phase screening, which identified 4245 interactions. The false positive rate of the Y2H assay was estimated to be 3.1%. Pull-down assays confirmed the robustness of our Y2H. The average interactions per node for CLas Y2H interactome were approximately 15.6, significantly higher than free-living bacteria, indicating genome reduction has led to a multi-function of proteins. PPIs provide clues for functions of 371 uncharacterized proteins of CLas. Forty HUB node proteins were identified which might play critical roles in CLas, including a quinone oxidoreductase and LysR that are known to protect bacteria against oxidative stress. This explains why CLas survives well in the phloem even though it triggers immune-mediated disease, systemic and chronic production of reactive oxygen species, and phloem cell death. This PPI database facilitates the investigation of CLas cellular biochemistry and physiology, functions of uncharacterized proteins, and pathogenicity mechanisms of the pathogen.
C-terminal truncation of CXCL10 attenuates inflammatory activity but retains angiostatic properties
Authors: Dillemans Luna , Yu Karen , De Zutter Alexandra , Noppen Sam , Gouwy Mieke , Berghmans Nele , De Bondt Mirre , Vanbrabant Lotte , Brusselmans Stef , Martens Erik , Schols Dominique , Marques Pedro Elias , Struyf Sofie , Proost Paul 
Published: July 2023

ABSTRACTInterferon-γ-inducible protein of 10 kDa (IP-10/CXCL10) is a dual-function CXC chemokine that coordinates chemotaxis of activated T cells and natural killer (NK) cells via interaction with its G protein-coupled receptor (GPCR), CXC chemokine receptor 3 (CXCR3). As a consequence of natural posttranslational modifications, human CXCL10 exhibits a high degree of structural and functional heterogeneity. However, the biological effect of natural posttranslational processing of CXCL10 at the carboxy (C)-terminus has remained partially elusive. The truncated CXCL10 proteoform CXCL10(1-73), lacking the four endmost C-terminal amino acids, was previously identified in human cell culture supernatant. To further explore the functioning of CXCL10(1-73), we optimized its production in this study through Fmoc-based solid phase peptide synthesis (SPPS) and propose an SPPS strategy to efficiently generate human CXCL10 proteoforms. Compared to intact CXCL10(1-77), CXCL10(1-73)had diminished affinity for glycosaminoglycans including heparin, heparan sulfate and chondroitin sulfate A. Moreover, CXCL10(1-73)exhibited an attenuated capacity to induce CXCR3A-mediated signaling, as evidenced in calcium mobilization assays and through quantification of phosphorylated extracellular signal-regulated kinase-1/2 (ERK1/2) and protein kinase B/Akt. Furthermore, CXCL10(1-73)incited reduced primary human T lymphocyte chemotaxisin vitroand evoked less peritoneal ingress of CXCR3+T lymphocytes in mice receiving intraperitoneal chemokine injections. In contrast, loss of the four endmost C-terminal residues did not affect the inhibitory properties of CXCL10 on spontaneous and/or FGF-2-induced migration, proliferation, wound healing, phosphorylation of ERK1/2, and sprouting of human microvascular endothelial cells. Thus, C-terminally truncated CXCL10 has attenuated inflammatory properties, but preserved anti-angiogenic capacity.GRAPHICAL ABSTRACT
The effects of protein supplementation, fumagillin treatment, and colony management on the productivity and long-term survival of honey bee (Apis mellifera) colonies in Canada
Authors: Peirson Michael , Ibrahim Abdullah , Ovinge Lynae P. , Hoover Shelley E. , Guarna M. Marta , Melathopoulos Andony , Pernal Stephen F. 
Published: July 2023

AbstractIn this study, we intensively measured the longitudinal productivity and survival of 362 commercially managed honey bee colonies in Canada, over a two-year period. A full factorial experimental design was used, whereby two treatments were repeated across apiaries situated in three distinct geographic regions: Northern Alberta, Southern Alberta and Prince Edward Island, each having unique bee management strategies. In the protein supplemented treatment, colonies were continuously provided a commercial protein supplement containing 25% w/w pollen, in addition to any feed normally provided by beekeepers in that region. In the fumagillin treatment, colonies were treated with the label dose of Fumagilin-B®each year during the fall. Our study shows that that neither treatment provided consistent benefits across all sites and dates. Fumagillin was associated with a large increase in honey production only at the Northern Alberta site, while protein supplementation produced an early season increase in brood production only at the Southern Alberta site. The protein supplement provided no long-lasting benefit at any site and was also associated with an increased risk of death and decreased colony size later in the study. Differences in colony survival and productivity among regions, and among colonies within beekeeping operations, were far larger than the effects of either treatment, suggesting that returns from extra feed supplements and fumagillin were highly contextually dependent. We conclude that use of fumagillin is safe and sometimes beneficial, but that beekeepers should only consider excess protein supplementation when natural forage is limiting.
An ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoV
Authors: Guo Hailong , Cho Bomsoo , Hinton Paul R , He Sijia , Yu Yongjun , Ramesh Ashwin Kumar , Sivaccumar Jwala Priyadarsini , Ku Zhiqiang , Campo Kristen , Holland Sarah , Sachdeva Sameer , Mensch Christopher , Dawod Mohamed , Whitaker Annalis , Eisenhauer Philip , Falcone Allison , Honce Rebekah , Botten Jason W. , Carroll Stephen F , Keyt Bruce A , Womack Andrew W , Strohl William R , Xu Kai , Zhang Ningyan , An Zhiqiang , Ha Sha , Shiver John W , Fu Tong-Ming 
Published: July 2023

AbstractThe capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, are now appreciated as a constant pandemic threat. We present here a new antiviral approach featuring inhalation delivery of a recombinant viral trap composed of ten copies of angiotensin-converting enzyme 2 (ACE2) fused to the IgM Fc. This ACE2 decamer viral trap is designed to inhibit SARS-CoV-2 entry function, regardless of viral RBD sequence variations as shown by its high neutralization potency against all known SARS-CoV-2 variants, including Omicron BQ.1, BQ.1.1, XBB.1 and XBB.1.5. In addition, it demonstrates potency against SARS-CoV-1, human NL63, as well as bat and pangolin CoVs. The multivalent trap is effective in both prophylactic and therapeutic settings since a single intranasal dosing confers protection in human ACE2 transgenic mice against viral challenges. Lastly, this molecule is stable at ambient temperature for more than twelve weeks and can sustain physical stress from aerosolization. These results demonstrate the potential of a decameric ACE2 viral trap as an inhalation solution for ACE2-dependent coronaviruses of current and future pandemic concerns.
Physics-informed deep generative learning for quantitative assessment of the retina
Authors: Brown Emmeline , Guy Andrew , Holroyd Natalie , Sweeney Paul , Gourmet Lucie , Coleman Hannah , Walsh Claire , Markaki Athina , Shipley Rebecca , Rajendram Ranjan , Walker-Samuel Simon 
Published: July 2023

AbstractDisruption of retinal vasculature is linked to various diseases, including diabetic retinopathy and macular degeneration, leading to vision loss. We present here a novel algorithmic approach that generates highly realistic digital models of human retinal blood vessels based on established biophysical principles, including fully-connected arterial and venous trees with a single inlet and outlet. This approach, using physics-informed generative adversarial networks (PI-GAN), enables the segmentation and reconstruction of blood vessel networks that requires no human input and out-performs human labelling. Our findings highlight the potential of PI-GAN for accurate retinal vasculature characterization, with implications for improving early disease detection, monitoring disease progression, and improving patient care.
Use of nanomaterials-modified carbon microfibre electrode material for superior electrochemical performance in lake sediment inoculated microbial fuel cells
Authors: Somasiri Maheshi , Amandani Tanusha , Basnayaka Charitha , Ahsan Ahmed , Dilangani Gayani P , Herath Ajith C. , Bandara Sampath , Nazeer Zumaira , Thilini Nirath , Kyazze Godfrey , Fernando Eustace Y. 
Published: July 2023

ABSTRACTHigh cathodic overpotential of the oxygen reduction reaction (ORR) in MFC carbon-based cathodes is one of the key barriers to the widespread adoption of the technology. Current Pt-based ORR catalysts are expensive. The use of novel and inexpensive catalysts as replacements for platinum is therefore desirable. In this study, nanomaterials were directly chemically synthesized on carbon microfiber electrodes to improve the performance of lake sediment inoculated MFCs. Nanomaterial of MnO2, MnO2/polyaniline (PANI), ZnO/NiO and ZnO/NiO/PANI attachments were directly chemically synthesized on the carbon material and used as cathode electrodes. The maximum power densities recorded for the different treatments were; MnO278.5 mW/m2, MnO2/PANI (Polyaniline) 141.6 mW/m2, ZnO/NiO 67.6 mW/m2, and ZnO/NiO/PANI 129.4 mW/m2. The current and poswer densities were more than six-fold higher in ZnO/NiO/PANI and MnO2/PANI nanoparticle modified cathodes compared to the control MFCs with no catalyst. Cyclic voltammetry (CV) and FTIR data and SEM images suggest that the nanoparticle attached carbon material is morphologically, chemically and electrochemically different from the controls with no nanomaterial attachment. The outcome of this study demonstrates that nanomaterials-incorporated carbon microfiber cathodes bring about significant enhancements to power densities and may potentially have applications in cost-effective MFCs.