bluuebunny/crossref_metadata_2025_split huggingface dataset:
β-lactam non-susceptible Group A Streptococcus isolated from clinical samples in Guyana
Authors: Kalladeen Melissa , Cheddie Paul , Akpaka Patrick Eberechi 
Published: December 2023

Introduction: Streptococcus pyogenes (or Group A streptococci [GAS]), is the causative agent of pharyngitis and various other syndromes involving cellulitis, streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis.

Methods: In this study, we sought to use Sanger sequencing to identify mutations in PBP genes of Streptococcus pyogenes isolated from hospitalised patients that could confer reduced PBP affinity for penicillin and/or cephalosporin antibiotics. All isolates were screened for susceptibility to penicillin, amoxicillin, and cefazolin using E-test strips.

Results: While there no documented cases of reduced susceptibility to penicillin or amoxicillin. There were 13 isolates were cefazolin non-susceptible. Examination of pbp1a by Sanger sequencing revealed several isolates with single amino acid substitutions, which could potentially reduce the affinity of PBP 1A for cefazolin and possibly other first generation cephalosporins.

Conclusion: Penicillin and penicillin-derived antibiotics remain effective treatment options for GAS infections, but active surveillance is needed to monitor for changes to susceptibility patterns against these and other antibiotics and understand the genetic mechanisms contributing to them.
Planting diversity begets multifaceted tree diversity in oil palm landscapes
Authors: Paterno Gustavo Brant , Brambach Fabian , Guerrero-Ramírez Nathaly , Zemp Delphine Clara , Cantillo Aiza Fernanda , Camarretta Nicolò , Moura Carina C. M. , Gailing Oliver , Ballauff Johannes , Polle Andrea , Schlund Michael , Erasmi Stefan , Iddris Najeeb Al-Amin , Khokthong Watit , Sundawati Leti , Irawan Bambang , Hölscher Dirk , Kreft Holger 
Published: December 2023

AbstractOptimizing restoration outcomes is crucial for enhancing multifaceted diversity, resilience, and ecosystem functioning in monoculture-dominated landscapes globally. Here, we experimentally tested the performance of passive and active restoration strategies to recover taxonomic, phylogenetic, and functional diversity by establishing 52 tree islands in an oil palm landscape. Tree diversity via natural regeneration was shaped by local rather than landscape properties, with the diversity of planted tree species and tree island size driving higher multifaceted diversity. We show that large tree islands with higher initial planted diversity catalyze the recovery of multifaceted diversity at both the local and landscape level, including forest-associated species. Our results demonstrate that planted diversity begets regenerating diversity, overcoming major limitations of natural regeneration in highly modified landscapes. By elucidating the contribution of experimental, local, and landscape drivers to natural regeneration, these findings provide practical insights to make oil palm landscapes more biodiversity-friendly by enhancing functional and phylogenetic diversity within plantations.
Opportunities to improve goat production and food security in Botswana through forage nutrition and the use of supplemental feeds
Authors: Cooke Andrew S. , Machekano Honest , Ventura-Cordero Javier , Louro-Lopez Aranzazu , Joseph Virgil , Gwiriri Lovemore C. , Takahashi Taro , Morgan Eric R. , Lee Michael R. F. , Nyamukondiwa Casper 
Published: December 2023

AbstractGoats fulfil a central role in food security across Africa with over half of households owning or rearing goats in rural areas. However, goat performance is poor and mortality high. This study assessed the nutritional quality of commonly used feeds and proposes feed-baskets to enhance goat nutrition and health. Feeds were collected from 11 areas within the Central District of Botswana, and macronutrient analyses were conducted, including crude protein, fibre fractions, ash, and metabolizable energy (ME). Forage nutrition was compared across seasons and soil types. Additionally, seasonal supplementation trials were conducted to evaluate consumption rates of various supplements, including crop residues, pellets, Lablab purpureus, and Dichrostachys cinerea. Each supplement was provided ad libitum for a 24-hour period, and consumption rates determined. Findings revealed significant differences in nutrition among various feed sources, across seasons, and in relation to soil types (p < 0.001). Consumption rates of supplements were higher during the dry season, possibly due to reduced forage availability. Supplement consumption rates varied across supplements, with crop residues accounting for approximately 1% of dry matter intake, compared to up to 45% for pellets, 13% for L. purpureus, and 15% for D. cinerea. While wet season feed baskets exhibited higher ME values compared to dry-season feed-baskets, the relative impact of supplementation was more pronounced during the dry season. These results highlight the potential for optimizing goat diets through improved grazing and browsing management, especially during the reduced nutritional availability in the dry season.
A Benchmark of state-of-the-art Deconvolution Methods in Spatial Transcriptomics: Insights from Cardiovascular Disease and Chronic Kidney Disease
Authors: Slabowska Alban Obel , Pyke Charles , Hvid Henning , Jessen Leon Eyrich , Baumgart Simon , Das Vivek 
Published: December 2023

AbstractA major challenge in sequencing based spatial transcriptomics (ST) is resolution limitations. Tissue sections are divided into hundreds-to thousands of spots, where each spot invariably contains a mixture of cell types. Methods have been developed to deconvolute the mixed transcriptional signal into its constituents. While ST is becoming essential for drug discovery especially in Cardiometabolic diseases, to date no deconvolution benchmark has been performed on these types of tissues and diseases. However, the three methods Cell2location, RCTD and spatialDWLS have previously been shown to perform well in brain tissue and simulated data. Here, we compare these methods to assess best performance when using human data from Cardiovascular Disease (CVD) data and Chronic Kidney Disease (CKD) from patients at different pathological states, evaluated using expert annotation.In this benchmark, we found that all three methods performed comparably well in deconvoluting verifiable cell types including smooth muscle cells and macrophages in vascular samples and podocytes in kidney samples. RCTD shows the best performance accuracy scores in CVD samples while Cell2location on average achieved the highest performance across test experiments. While all three methods had similar accuracies Cell2location need less reference data to converge at the expense of higher computational intensity. Finally, we also report that RCTD has the fastest computational time and the simplest workflow requiring fewer computational dependencies. In conclusion, we find that each method has particular advantages, and the optimal choice depends on the use case.
Macrophage transplantation rescues RNASET2-deficient leukodystrophy by replacing deficient microglia in a zebrafish model
Authors: Rutherford Holly A , Candeias Diogo , Duncan Christopher JA , Renshaw Stephen A , Hamilton Noémie 
Published: December 2023

AbstractRNaseT2-deficient leukodystrophy is a rare infantile white matter disorder mimicking a viral infection and resulting in severe psychomotor impairments. Despite its severity, there remain no treatments for this disorder, with little understanding of cellular mechanisms of pathogenesis. Recent research using thernaset2mutant zebrafish model has suggested that microglia – brain-resident phagocytes – may be the drivers of neuroinflammation in this disorder, due to their failure to digest apoptotic debris during early development. As such, the current study aimed to develop a strategy for microglial replacement and test the effects of this intervention onrnaset2mutant zebrafish pathology. We developed a strategy for microglial replacement through transplantation of adult whole kidney marrow-derived macrophages into embryonic hosts. Using live imaging, we revealed that transplant-derived macrophages can engraft within host brains and express microglia-specific markers, suggesting adoption of a microglial phenotype. Tissue clearing strategies revealed the persistence of transplanted cells in host brains beyond embryonic stages We demonstrated that transplanted cells clear apoptotic cells within the brain, as well as rescuing overactivation of the antiviral response otherwise seen in mutant larvae. RNA sequencing at the point of peak transplant-derived cell engraftment confirms that transplantation can reduce the brain-wide immune response, and particularly the antiviral response, inrnaset2-deficient brains. Crucially, this reduction in neuroinflammation resulted in behavioural rescue - restoringrnaset2mutant motor activity to wild type levels in embryonic and juvenile stages. Together, these findings demonstrate the role of microglia as the cellular drivers of neuropathology inrnaset2mutants, and that macrophage transplantation is a viable strategy for microglial replacement in the zebrafish. Therefore, microglia-targeted interventions may have therapeutic benefits in RNaseT2-deficient leukodystrophy.
Orientia tsutsugamushiAnk5 directs ubiquitination and proteasomal degradation of NLRC5 to inhibit major histocompatibility complex class I expression
Authors: Adcox Haley E. , Hunt Jason R. , Rodino Kyle G. , Ottens Andrew K. , Carlyon Jason A. 
Published: December 2023

ABSTRACTHow intracellular bacteria subvert the major histocompatibility complex (MHC) class I pathway is poorly understood. Here, we show that the obligate intracellular bacteriumOrientia tsutsugamushiuses its effector protein, Ank5, to orchestrate proteasomal degradation of the MHC class I gene transactivator, NLRC5. Ank5 uses a tyrosine in its fourth ankyrin repeat to bind the NLRC5 N-terminus while its F-box directs host SCF complex ubiquitination of K1194 in the leucine-rich repeat region that dictates NLRC5 susceptibility toOrientia- and Ank5-mediated degradation. The ability ofO. tsutsugamushistrains to degrade NLRC5 correlates withank5genomic carriage. Ectopically expressed Ank5 that can bind but not degrade NLRC5 protects the transactivator duringOrientiainfection. Thus, Ank5 is an immunoevasin that uses its bipartite architecture to rid host cells of NLRC5 and MHC class I molecules. This study offers insight into how intracellular pathogens can impair MHC class I expression to benefit their survival.
Dysregulated Repeat Element Viral-like Immune Response in Hepatocellular Carcinoma
Authors: Coley Avril K. , Lu Chenyue , Pankaj Amaya , Emmett Matthew J. , Lang Evan R. , Song Yuhui , Xu Katherine H. , Xu Nova , Patel Bidish K. , Chougule Abhijit , Nieman Linda T. , Aryee Martin J. , Ferrone Cristina R. , Deshpande Vikram , Franses Joseph W. , Ting David T. 
Published: December 2023

ABSTRACTPurposeDysregulation of viral-like repeat RNAs are a common feature across many malignancies that are linked with immunological response, but the characterization of these in hepatocellular carcinoma (HCC) is understudied. In this study, we performed RNAin situhybridization (RNA-ISH) of different repeat RNAs, immunohistochemistry (IHC) for immune cell subpopulations, and spatial transcriptomics to understand the relationship of HCC repeat expression, immune response, and clinical outcomes.Experimental DesignRNA-ISH for LINE1, HERV-K, HERV-H, and HSATII repeats and IHC for T-cell, Treg, B-cell, macrophage, and immune checkpoint markers were performed on 43 resected HCC specimens. Spatial transcriptomics on tumor and vessel regions of interest was performed on 28 specimens from the same cohort.ResultsHigh HERV-K and high LINE1 expression were both associated with worse overall survival. There was a positive correlation between LINE1 expression and FOXP3 T-regulatory cells (r = 0.51 p < 0.001) as well as expression of the TIM3 immune checkpoint (r = 0.34, p = 0.03). Spatial transcriptomic profiling of HERV-K high and LINE-1 high tumors identified elevated expression of multiple genes previously associated with epithelial mesenchymal transition, cellular proliferation, and worse overall prognosis in HCC including SSX1, MAGEC2, and SPINK1.ConclusionRepeat RNAs may serve as useful prognostic biomarkers in HCC and may also serve as novel therapeutic targets. Additional study is needed to understand the mechanisms by which repeat RNAs impact HCC tumorigenesis.
Developing Cardiac Digital Twins at Scale: Insights from Personalised Myocardial Conduction Velocity
Authors: Qian Shuang , Ugurlu Devran , Fairweather Elliot , Strocchi Marina , Toso Laura Dal , Deng Yu , Plank Gernot , Vigmond Edward , Razavi Reza , Young Alistair , Lamata Pablo , Bishop Martin , Niederer Steven 
Published: December 2023

AbstractLarge-cohort studies using cardiovascular imaging and diagnostic datasets have assessed cardiac anatomy, function, and outcomes, but typically do not reveal underlying biological mechanisms. Cardiac digital twins (CDTs) provide personalized physics- and physiology-constrainedin-silicorepresentations, enabling inference of multi-scale properties tied to these mechanisms.We constructed 3464 anatomically-accurate CDTs using cardiac magnetic resonance images from UK biobank and personalised their myocardial conduction velocities (CVs) from electrocardiograms (ECG), through an automated framework.We found well-known sex-specific differences in QRS duration were fully explained by myocardial anatomy, as CV remained consistent across sexes. Conversely, significant associations of CV with ageing and increased BMI suggest myocardial tissue remodelling. Novel associations were observed with left ventricular ejection fraction and mental-health phenotypes, through a phenome-wide association study, and CV was also linked with adverse clinical outcomes.Our study highlights the utility of population-based CDTs in assessing intersubject variability and uncovering strong links with mental health.
Healthcare-associated Urinary tract infection and its determinants among Adult Patients Admitted to Intensive Care Units of Addis Ababa Public Governmental Hospitals, Ethiopia; 2020
Authors: Genaneh Wondimagegn , Nega Tigist , Argeta Hindu , Gashaw Silenat , Shimeles Eyouel 
Published: December 2023

ABSTRACTBack groundUrinary tract infections are common bacterial infections that affect almost 150 million people internationally each year. A catheter-associated urinary tract infection arises when germs enter the urinary tract via a urinary catheter, leading to infection and have been linked with increased mortality, morbidity, healthcare costs in intensive care units. It is one of the highest prevalent health care-related infections, accounting for nearly 30% of intensive care unit (ICU) reports because of its association to urinary catheterization, but has great preventive potential.MethodInstitutional based cross-sectional study design applied to determine the prevalence and associated factors of Health care-associated urinary tract infections among adult 391 patients admitted to ICU from 2017 to 2019 GC at Addis Ababa Public Governmental Hospital, Addis Ababa, Ethiopia, June-December 2020.Data had manually checked and entered to Epi-data manager version 4.6 and statistical analyses have been performed using SPSS version 23 software program. Strength of association between dependent and independent variables is assessed using crude odds ratio (COR) and adjusted odds ratio (AOR) with confidence Interval (CI) of 95%. Variables that had a value of P < 0.25 on bi-variate analysis were directly forward to be analyzed by multi variable analysis. Goodness of fit test had also computed for logistic regression using Hosmer and Lemeshow test resulted in (sig=0.073), finally having P-values < 0.05 is considered as statistically significant.Resultthe study find that the prevalence of Healthcare Associated Urinary Tract Infection among ICU admitted patients was 91(23.3%) 95%CI ;(19.2-27.4), While length of stay, Having tracheostomy, patients on Mechanical Ventilation and taking Proton pump inhibitor drugs were associated with HAUTI in the study area.ConclusionHealthcare-associated Urinary Tract infection is highly emerging clinical condition among ICU admitted patients in the study areas.
Endolysin B as a new archetype inM. tuberculosistreatment
Authors: Griego Anna , Antinori Beatrice , Spitaleri Andrea , Muzzolini Ilaria , Muzzioli Stefano , Calò Luca , Moschetti Giorgia , Genta Marianna , Scarpa Edoardo , Matteis Valeria De , Miggiano Riccardo , Ricagno Stefano , Rizzello Loris 
Published: December 2023

SummarySo far it is thanks to antibiotics that illnesses, such as Tuberculosis (TB), are treatable. However, antimicrobial misuse combined withMycobacterium tuberculosisphenotypic plasticity are nullifying the effects of the existing therapies. As a result, increasingly people are dying (one person dies of TB every 20 seconds), especially due to the rise of multi-and extensively drug-resistant strains. There is indeed a urgent need for new and more effective therapies, which should match the requirement of avoiding the rise in drug resistance. Among them, the use of bacteriophage – bacteria-restricted viruses – or simply phage lytic enzyme (i.e.,endolysin) represents one of the most promising alternatives. All phages encode for the endolysin A (LysA), which degrades the bacteria cell wall, finally leading to the release of the newly synthesized virions. Nevertheless, mycobacteriophages (bacterial viruses selectively infecting mycobacteria), evolved the additional endolysin B (LysB) to selectively damage the complex mycobacteria cell wall, and to evade from their host. LysB, owing a lipolytic enzyme, can degrade the thick mycolic acid layer, and hence disrupt the integrity of the mycobacterial membrane. Despite its key role in mediating mycobacteria lysis, the molecular mechanism regulating LysB binding to its target remains poorly characterized. Herein, we selected Ms6LysB and created a fluorescent engineered version as a proxy to analyze LysB binding qualitatively and quantitatively to both the fast-growing non-pathogenicMycobacterium smegmatisand the slow-growing pathogenicM. tuberculosis.Additionally, we shed light on LysB antimicrobial activity uponM. tuberculosisinfection, by using alveolar-like mouse macrophages (mAMs) as a cellular model that closely recapitulates the natural niche ofM. tuberculosisinfection. Our study provides the proof-of-principle that Ms6 LysB binding to the outer mycobacterial membrane can impairM. tuberculosisgrowth homeostasis and that LysB retain its lytic properties even when internalized by mAMs. This lays the groundwork for the use of LysB as a new therapeutic strategy to undermineM. tuberculosisinfection.
Sex specific regulation of the cortical transcriptome in response to sleep deprivation
Authors: Shi Tianyi , Shah Ishani , Dang Quang , Taylor Lewis , Jagannath Aarti 
Published: December 2023

ABSTRACTMultiple studies have documented sex differences in sleep behaviour, however the molecular determinants of such differences remain unknown. Furthermore, most studies addressing molecular mechanisms have been performed only in males, leaving the current state of knowledge biased towards the male sex. To address this, we studied the differences in the transcriptome of the cerebral cortex of male and female C57Bl/6J mice after six hours of sleep deprivation. We found that several genes, including the neurotrophin growth factorBdnf, immediate early genesFosbandFosl2, and the adenylate cyclaseAdcy7are differentially upregulated in males compared to females. We identified the androgen-receptor activating transcription factor EZH2 as the upstream regulatory element specifying sex differences in the sleep deprivation transcriptome. We propose that the pathways downstream of these transcripts, which impact on cellular re-organisation, synaptic signalling and learning may underpin the differential response to sleep deprivation in the two sexes.
Escherichia coliacid phosphatase AphA expression is upregulated under carbon and phosphate starvations and inhibited by CytR
Authors: Kronborg Kristina , Zhang Yong Everett 
Published: December 2023

AbstractThis study investigates the regulation ofE. coli aphAexpression under nutrient starvation. Using transcriptional reporters with truncatedaphApromoter sequences, we found that starvation of carbon and phosphate, but not amino acid, stimulatedaphAexpression through distinct promoter regions. Deletions ofcrporcyaAreducedaphAexpression, confirming their importance inaphAregulation during carbon starvation. Conversely, CytR deletion increasedaphAexpression, suggesting CytR’s role as a repressor ofaphAexpression. Collectively, these data imply a potential connection between CytR,aphAexpression, and the broader context of natural competence evolution and bacterial nutrient absorption.
Non-invasive homogeneous targeted blood-brain barrier disruption using acoustic holography with a clinical focused ultrasound system
Authors: McDannold Nathan , Zhang Yongzhi , Fletcher Stecia-Marie , Livingstone Margaret 
Published: December 2023

AbstractHolographic methods can be used with phased array transducers to shape an ultrasound field. We tested a simple method to create holograms with a 1024-element phased array transducer. With this method, individual acoustic simulations for each element of the transducer were simultaneously loaded into computer memory. Each element’s phase was systematically modulated until the combined field matched a desired pattern. The method was evaluated with a 220 kHz hemispherical transducer being tested clinically to enhance drug delivery via blood-brain barrier disruption. The holograms were evaluated in a tissue-mimicking phantom andin vivoin experiments disrupting the blood-brain barrier in rats and in a macaque. This approach can enlarge the focal volume in a patient-specific manner and could reduce the number of sonication targets needed to disrupt large volumes, improve the homogeneity of the disruption, and improve our ability to detect microbubble activity in tissues with low vascular density.TeaserHolography can shape the focal region of a clinical focused ultrasound system developed for targeted drug delivery in the brain.
Microbial Reduction of Geogenic and Synthetic Goethite and Hematite
Authors: O’Loughlin Edward J. 
Published: December 2023

AbstractThe microbial reduction of Fe(III) is a major component of Fe cycling in terrestrial and aquatic environments and is affected by the Fe(III) mineralogy of the system. The majority of the research examining the bioreduction of Fe(III) oxides by Fe(III)-reducing bacteria (IRB) has focused on the reduction of poorly crystalline Fe(III) phases, primarily ferrihydrite; however, crystalline Fe(III) oxides like goethite (α-FeOOH) and hematite (α-Fe2O3) comprise the majority of Fe(III) oxides in soils. This study examined the bioreduction of goethite and hematite of geogenic and synthetic origin byShewanella putrefaciensCN2, a well-studied model IRB, in laboratory incubations. Overall, the rate and extent of Fe(II) production were greater for goethite than for hematite, and for geogenic Fe(III) oxides relative to their synthetic analogs. Although there was substantial production of Fe(II) (i.e., > 5 mM Fe(II)) in many of the systems, X-ray diffraction analysis of the solids at the end of the incubation did not indicate the formation of any Fe(II)-bearing secondary minerals (e.g., magnetite, siderite, green rust, etc.). The results of this study demonstrate the variability in the extent of bioreduction of geogenic goethite and hematite, and furthermore, that synthetic goethite and hematite may not be good analogs for the biogeochemical behavior of Fe(III) oxides in aquatic and terrestrial environments.