bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Kingella kingae causing prosthetic joint infection in an adult
Authors: Wensley Katherine , McClelland Damian , Grocott Natalie , Manoharan Gopikanthan , Desai Seema 
Published: January 2023

Introduction

Kingella kingae (K. kingae) is a gram-negative microorganism that is rare in the adult population, apart from occasional reports in those who are immunocompromised. Although widely reported to affect prosthetic heart valves, to our knowledge, there have been no previously reported cases of K. kingae infecting prosthetic joints.
Case:
A 61 year-old patient with a history of rheumatoid arthritis since 1986, presented to the rheumatology clinic with insidious onset of pain and swelling in her right shoulder, which had progressed to a discharging sinus. The patient had undergone a total shoulder replacement 11 years previously and had not had any post-operative complications or previous infections in the shoulder. The patient subsequently underwent a two stage revision procedure. In the first stage, the implant was removed, the sinus excised and an extensive debridement and washout was performed. A temporary antibiotic loaded spacer was implanted. Tissue samples and culture swabs were sent for microbiological culture and grew K. Kingae at 5 days post-operatively. The patient was commenced on intravenous ceftriaxone for 14 days, followed by a further 28 days of oral ciprofloxacin. A second stage was undertaken at 10 months following the first stage and the patient made a good recovery with satisfactory return of function.

Conclusion

The authors suggest that clinicians should be attuned to K. kingae as a potential cause of periprosthetic joint infection, particularly in patients with immune compromise. Adherence to specific culture and isolation techniques can facilitate diagnosis of this fastidious organism, ensuring prompt and appropriate treatment.
Productivity costs associated with reactive school closures related to influenza or influenza-like illness in the United States from 2011 to 2019
Authors: Park Joohyun , Joo Heesoo , Maskery Brian A. , Zviedrite Nicole , Uzicanin Amra 
Published: January 2023

AbstractIntroductionSchools close in reaction to seasonal influenza outbreaks and, on occasion, pandemic influenza. The unintended costs of reactive school closures associated with influenza or influenza-like illness (ILI) has not been studied previously. We estimated the costs of ILI-related reactive school closures in the United States over eight academic years.MethodsWe used prospectively collected data on ILI-related reactive school closures from August 1, 2011 to June 30, 2019 to estimate the costs of the closures, which included productivity costs for parents, teachers, and non-teaching school staff. Productivity cost estimates were evaluated by multiplying the number of days for each closure by the state- and year-specific average hourly or daily wage rates for parents, teachers, and school staff. We subdivided total cost and cost per student estimates by school year, state, and urbanicity of school location.ResultsThe estimated productivity cost of the closures was $476 million in total during the eight years, with most (90%) of the costs occurring between 2016−2017 and 2018−2019, and in Tennessee (55%) and Kentucky (21%). Among all U.S. public schools, the annual cost per student was much higher in Tennessee ($33) and Kentucky ($19) than any other state ($2.4 in the third highest state) or the national average ($1.2). The cost per student was higher in rural areas ($2.9) or towns ($2.5) than cities ($0.6) or suburbs ($0.5). Locations with higher costs tended to have both more closures and closures with longer durations.ConclusionsIn recent years, we found significant heterogeneity in year-to-year costs of ILI-associated reactive school closures. These costs have been greatest in Tennessee and Kentucky and been elevated in rural or town areas relative to cities or suburbs. Our findings might provide evidence to support efforts to reduce the burden of seasonal influenza in these disproportionately impacted states or communities.
Degree of immunoglobulin kappa light chain glycosylation of anti-spike SARS CoV-2 antibodies correlates with COVID-19 severity
Authors: Grigaite Raminta , Iles Jason K , Harding Stephen , Patel Roshani , Wallis Gregg , Iles Ray K 
Published: January 2023

AbstractGlycosylation of antibodies and the effects this has on inflammatory responses has concentrated predominately on the study of glycosylation moieties found in the Fc region of heavy chains. Light chain glycosylation and their ratios are relatively understudied. Nevertheless, variable glycosylation and ratio of κ and λ light chains have been associated with worse prognosis in myeloma and in tissue deposition – amyloidosis.The κ & λ light chains, of antibodies binding to SARS-CoV2 nucleocapsid and spike protein were analysed, using MALDI-ToF MS, in respect to their intensity, ratios, glycosylation patterns and any pattern changes correlating with COVID-19 severity. The molecular masses and signal intensity of κ and λ glycosylated and non-glycosylated light chains were measured for immunoglobulins isolated from plasma of sero-positive and sero-negative health care workers (HCW), and convalescent patients who had suffered from acute respiratory distress syndrome (ARDS).Overall, there was no significant changes in κ to λ ratio of total IgG (via protein G capture) antibodies between the groups. A non-statistically significant trend towards λ light chains was found in antibodies against SARS CoV-2 Nucleocapsid and Spike proteins. However, detailed analysis of the molecular forms found a significant increase and bias towards un-glycosylated light chains and in particular un-glycosylated κ light chains, in antibodies against SAR-CoV-2 spike protein, from convalescent COVID-ARDS patients.Here we have demonstrated a bias towards un-glycosylated κ chains in anti-spike antibodies in those who suffered from ARDS as a result of SARS-CoV2 infection 3 months after recovery. How this relates to the immunopathology of COVID-19 requires further study.
Improved biorepository to support sickle cell disease genomics and clinical research: A practical approach to link patient data and biospecimens from Muhimbili Sickle Cell Program, Tanzania
Authors: Masamu Upendo , Sangeda Raphael Z , Mgaya Josephine , Nkya Siana , Octavian Beatrice , Mtiiye Frank R , Nduguru Joyce , Jonathan Agnes , Kandonga Daniel , Minja Irene K , Rugajo Paschal , Balandya Emmanuel , Makani Julie 
Published: January 2023

AbstractGenetic modifiers underlying various sickle cell disease phenotypic expressions are largely unexplored in Africa due to lack of databases linking biospecimens with demographic and clinical data. The problem may be compounded by a complete lack of biorepositories in these settings. This article aims to document the physical verification of biospecimens stored in the biorepository and link them to patient clinical and demographic information to facilitate plans for genomic and related clinical research studies. We reviewed and updated the existing biorepository infrastructure at Muhimbili Sickle Cell Programme in Dar es Salaam, Tanzania. The database of archived biospecimens was updated with the location information of respective biospecimens following the physical verification of biospecimens and then mapping the patient demographic and clinical data with the biospecimen data using sickle cell patients’ demographic identifiers. Three freezers maintained at -80°C store a total of 74,079 biospecimens, of which 63,345 were from 5,159 patients registered in the Muhimbili Sickle Cohort from 2004 to 2016. Out of stored biospecimens, follow-ups were 46,915 (74.06%), control 8,067 (12.74%), admission 5,517 (8.71%) and entry 2,846 (4.49%). Of these registered patients, females were 2,521 (48.87%) and males were 2,638 (51.13%). The age distribution was 1 to 59 years, with those above 18 years being 577 (11.18%) and children 4,582 (88.82%) of registered patients. The notable findings during the process include a lack of automated biospecimen checks, laboratory information management system and standardization of equipment used, biospecimens not linked to clinical and demographic data, date format inconsistencies, lack of regular updating of a database on exhausted biospecimens and updates when biospecimens are moved between positions within freezers. Well-organized biorepository plays a crucial role in answering future research questions. Enforcing strict standard operating procedures and quality control standards will ensure that laboratory scientists and other users adhere to the best biospecimen management procedures.
Effect of experimentally introduced interaural frequency mismatch on sentence recognition in bilateral cochlear-implant listeners
Authors: Cleary Miranda , DeRoy Milvae Kristina , Nguyen Nicole , Bernstein Joshua G. W. , Goupell Matthew J. 
Published: January 2023

AbstractBilateral cochlear-implant users experience interaural frequency mismatch because of asymmetries in array insertion and frequency-to-electrode assignment. To explore the acute perceptual consequences of such mismatch, sentence recognition in quiet was measured in nine bilateral cochlear-implant listeners as frequency allocations in the poorer ear were shifted by ±1.5, ±3 and ±4.5 mm using experimental programs. Shifts in frequency allocation >3 mm were found to reduce bilateral sentence scores below those for the better ear alone, suggesting that the poorer ear interfered with better-ear perception. This was not a result of fewer active channels; deactivating electrodes without frequency shifting had minimal effect.
Insufficiency of PCR diagnostics for Detection of DiarrhoeagenicEscherichia coliin Ibadan, Nigeria
Authors: Akinlabi Olabisi C. , Dada Rotimi A. , Nwoko El-shama Q. , Okeke Iruka N. 
Published: January 2023

AbstractUnderstanding the contribution of different diarrhoeagenicEscherichia colipathotypes to disease burden is critical to mapping risk and informing vaccine development. Targeting select virulence genes by PCR is the diagnostic approach of choice in high-burden, least-resourced African settings. We compared the performance of a commonly-used multiplex protocol to whole genome sequencing (WGS).PCR was applied to 3,815E. coliisolates from 120 children with diarrhoea and 357 healthy controls. Three or more isolates per specimen were also Illumina-sequenced. Following quality assurance, ARIBA and Virulencefinder database were used to identify virulence targets. Root cause analysis of deviant PCR results was performed by examining target sensitivity using BLAST, Sanger sequencing false-positive amplicons, and identifying lineages prone to false-positivity using in-silico multilocus sequence typing and a Single Nucleotide Polymorphism phylogeny constructed using IQTree.The sensitivity and positive predictive value of PCR compared to WGS ranged from 0-77.8% while specificity ranged from 74.5-94.7% for different pathotypes. WGS identified more enteroaggregativeE. coli(EAEC), fewer enterotoxigenicE. coli(ETEC) and none of the Shiga toxin-producingE. colidetected by PCR, painting a considerably different epidemiological picture. Use of the CVD432 target resulted in EAEC under-detection, and enteropathogenicE. coli eaeprimers mismatched more recently described intimin alleles common in our setting. False positive ETEC were over-represented among West Africa-predominant ST8746 complex strains. PCR precision varies with pathogen genome so primers optimized for use in one part of the world may have noticeably lower sensitivity and specificity in settings where different pathogen lineages predominate.
Fine-mapping across diverse ancestries drives the discovery of putative causal variants underlying human complex traits and diseases
Authors: Yuan Kai , Longchamps Ryan J. , Pardiñas Antonio F. , Yu Mingrui , Chen Tzu-Ting , Lin Shu-Chin , Chen Yu , Lam Max , Liu Ruize , Xia Yan , Guo Zhenglin , Shi Wenzhao , Shen Chengguo ,   The Schizophrenia Workgroup of Psychiatric Genomics Consortium, Daly Mark J. , Neale Benjamin M. , Feng Yen-Chen A. , Lin Yen-Feng , Chen Chia-Yen , O’Donovan Michael , Ge Tian , Huang Hailiang 
Published: January 2023

AbstractGenome-wide association studies (GWAS) of human complex traits or diseases often implicate genetic loci that span hundreds or thousands of genetic variants, many of which have similar statistical significance. While statistical fine-mapping in individuals of European ancestries has made important discoveries, cross-population fine-mapping has the potential to improve power and resolution by capitalizing on the genomic diversity across ancestries. Here we present SuSiEx, an accurate and computationally efficient method for cross-population fine-mapping, which builds on the single-population fine-mapping framework, Sum of Single Effects (SuSiE). SuSiEx integrates data from an arbitrary number of ancestries, explicitly models population-specific allele frequencies and LD patterns, accounts for multiple causal variants in a genomic region, and can be applied to GWAS summary statistics. We comprehensively evaluated SuSiEx using simulations, a range of quantitative traits measured in both UK Biobank and Taiwan Biobank, and schizophrenia GWAS across East Asian and European ancestries. In all evaluations, SuSiEx fine-mapped more association signals, produced smaller credible sets and higher posterior inclusion probability (PIP) for putative causal variants, and captured population-specific causal variants.
Modeling of growth ofUlvasp. macroalgae in a controlled photobioreactor based on nitrogen accumulation dynamics
Authors: Zollmann Meiron , Liberzon Alexander , Golberg Alexander 
Published: January 2023

AbstractMacroalgae biomass production models that capture nutrient dynamics, temperature, light, and salinity are important for the design and operation of large-scale farms. The goal of this study is to understand how the nitrogen fertilizing regime, relating to fertilizing dose (μM N week-1), amplitude (μM N), and duration (hours), affects the dynamics of nitrogen content and biomass production of theUlvasp. macroalgae. We hypothesize that the nitrogen fertilizing regime controls theUlvaNitrogen Use Efficiency (NUE), defined here as the fraction of fertilizer nitrogen that is utilized and allocated to yield N, and, accordingly, also nitrogen assimilation in the biomass and the growth rate. We test this hypothesis by measuring internal nitrogen and biomass weight and by calculating NUE under various fertilization regimes in controlled photobioreactors. Based on this experimental data, we developed a biomass productivity model that predicts nitrogen and biomass dynamics in time over three weeks of cultivation. This study points out efficient fertilizing regimes and enables the development of a comprehensive understanding of the dynamic relationship between external N, internal N, and biomass production of theUlvasp. macroalgae under varying external N levels, which is important for real-world agricultural applications. This study provides a better understanding of the external N-internal N-biomass triangle followed by an improved dynamic cultivation model, enabling better control of nutrient application and biomass production in macroalgae farming for a sustainable marine bioeconomy.
Transient septin sumoylation steers a Fir1-Skt5 protein complex between the split septin ring
Authors: Müller Judith , Furlan Monique , Settele David , Grupp Benjamin , Johnsson Nils 
Published: January 2023

AbstractUbiquitylation and phosphorylation control composition and architecture of the cell separation machinery in yeast and other eukaryotes. The significance of septin sumoylation on cell separation remained an enigma. Septins form an hourglass structure at the bud neck of yeast cells that transforms into a split septin double ring during mitosis. We discovered that sumoylated septins recruit the cytokinesis checkpoint protein Fir1 to the peripheral side of the septin hourglass. Subsequent de-sumoylation and synchronized binding to the scaffold Spa2 relocate Fir1 in a seamless transition between the split septin rings. Fir1 binds and carries Skt5 on its route to the division plane where the Fir1-Skt5 complex serves as receptor for chitin synthase III. We propose that the opposite positioning of the sumoylated septins and Spa2 creates a tension across the ring that upon de-sumoylation tunnels the membrane-bound Fir1-Skt5 complex through a transiently permeable septin diffusion barrier.
Phage-Assisted, Active Site-Directed Ligand Evolution with a Genetically EncodedNε-Butyryl-L-Lysine to Identify a Cellularly Potent and Selective Inhibitor for the ENL YEATS Domain as an Anti-Leukemia Agent
Authors: Chen Peng-Hsun Chase , Guo Xuejiao Shirley , Zhang Hanyuan Eric , Geng Zhi Zachary , Dubey Gopal K. , Fierke Carol A. , Xu Shiqing , Liu Wenshe Ray 
Published: January 2023

AbstractEleven-nineteen leukemia protein (ENL) plays pivotal roles in the leukemogenesis. As a YEATS domain protein, ENL reads histone acylation marks and recruits key transcription factors to leukemic drivers such asHOXA9, MEIS1, andMYBand therefore promotes leukemia development. The histone-reading function of ENL has been proven essential in the onset and progression of several acute leukemias, suggesting a putative therapeutic window for ENL inhibition. In this study, we developed a phage-assisted, active site-directed ligand evolution (PADLE) approach for the identification of potent and selective ENL inhibitors, whereNε-butyryl-l-lysine (BuK) that possesses known target-protein interactions with the ENL YEATS domain was genetically incorporated into a phage display library to serve as a warhead to direct displayed peptides to the active site of ENL YEATS for enrichment. Using this novel strategy in combination with structure-activity relationship that replaced BuK with other ncAAs for de novo π-π-π stacking interactions with two aromatic residues in ENL YEATS, selective and potent ENL inhibitors with aKdvalue as low as 2.0 nM were identified. One pentapeptide inhibitortENL-S1fdisplayed selective inhibition of ENL over other YEATS domains as well as strong cellular target engagement and on-target effects in inhibiting leukemia cell growth and suppressing the expression of ENL target genes. As the first of its kind study, the current work opens a large avenue of research of using PADLE to develop selective and potent peptidyl inhibitors for a large variety of epigenetic reader proteins.
Cortical astrocyte N-Methyl-D-Aspartate receptors influence whisker barrel activity and sensory discrimination
Authors: Ahmadpour Noushin , Kantroo Meher , Stobart Michael J. , Salamovska Tania , O’Hara Finnegan , Erickson Dustin , Carrion-Falgarona Sofia , Stobart Jillian L. 
Published: January 2023

AbstractCortical astrocytes encode sensory information through their calcium dynamics, but it remains unclear if modulation of astrocyte calcium transients can change somatosensory circuits and behaviourin vivo. Here, we used a novel knockdown approach to selectively reduce astrocyte N-methyl-D-aspartate receptors (NMDAR). We found that these ionotropic receptors contribute to astrocyte Ca2+transients encoding sensory information. This was essential for the optimal processing of sensory information in nearby neurons, since a reduction in astrocyte NMDARs caused circuit dysfunction and impaired neuronal responses to stimulation. This led to sensory discrimination deficits in the animal. Overall, our findings show that astrocytes can rapidly respond to glutamatergic transmission via their NMDAR and these receptors are an important component for astrocyte-neuron interactions that regulate cortical sensory discriminationin vivo.
Demonstration ofin vivoengineered tandem duplications of varying sizes using CRISPR and recombinases inDrosophila melanogaster
Authors: Loehlin David W. , McClain Georgia L. , Xu Manting , Kedia Ria , Root Elise 
Published: January 2023

AbstractTandem gene duplicates are important parts of eukaryotic genome structure, yet the phenotypic effects of new tandem duplications are not well-understood, in part owing to a lack of techniques to build and modify them. We introduce a method, Recombinase-Mediated Tandem Duplication (RMTD), to engineer specific tandem duplicationsin vivousing CRISPR and recombinases. We describe construction of four different tandem duplications of theAlcohol Dehydrogenase(Adh) gene inDrosophila melanogaster, with duplicated block sizes ranging from 4.2 kb to 20.7 kb. Flies with theAdhduplications show elevated ADH enzyme activity over unduplicated single copies. This approach to engineering duplications is combinatoric, opening the door to systematic study of the relationship between the structure of tandem duplications and their effects on expression.
EngineeringEscherichia colito produce aromatic chemicals from ethylene glycol
Authors: Panda Smaranika , Zhou Jie Fu J , Feigis Michelle , Harrison Emma , Ma Xiaoqiang , Yuen Vincent Fung Kin , Mahadevan Radhakrishnan , Zhou Kang 
Published: January 2023

AbstractMicrobial overproduction of aromatic chemicals has gained considerable industrial interest and various metabolic engineering approaches have been employed in recent years to address the associated challenges. So far, most studies have used sugars (mostly glucose) or glycerol as the primary carbon source. In this study, we used ethylene glycol (EG) as the main carbon substrate. EG could be obtained from the degradation of plastic and cellulosic wastes. As a proof of concept,Escherichia coliwas engineered to transform EG into L-tyrosine, a valuable aromatic amino acid. Under the best fermentation condition, the strain produced 2 g/L L-tyrosine from 10 g/L EG at approximately 50% of the theoretical yield, outperforming glucose (the most common sugar feedstock) in the same experimental conditions. To prove the concept that EG can be converted into different aromatic chemicals,E. coliwas further engineered with a similar approach to synthesize other valuable aromatic chemicals, L-phenylalanine andp-coumaric acid. Finally, waste polyethylene terephthalate (PET) bottles were degraded using acid hydrolysis and the resulting monomer EG was transformed into L-tyrosine using the engineeredE. coli, yielding a comparable titer to that obtained using commercial EG. The strains developed in this study should be valuable to the community for producing valuable aromatics from EG.