bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Application of Coronary Computed Tomography Angiography in Patients with Suspected Coronary Artery Disease
Authors: Blad Jared N. , Smith Hayden L. , Hurdelbrink Jonathan R. , Craig Steven R. , Wolford Brent , Wendl Elizabeth , Telles-Garcia Nelson A. 
Published: June 2022

AbstractBackgroundCoronary computed tomography angiography (CCTA) has emerged as a helpful tool in the evaluation of patients with chest pain and suspected coronary artery disease (CAD). The study objective was to evaluate the clinical application of CCTA for assessment of patients presenting with chest pain at a large single urban tertiary health care center located in the US.MethodsA retrospective review of observational data from center was conducted. The study sample included outpatients aged 18 years or older who underwent CCTA during January 2018 through February 2020.ResultsThere were 158 patients in the study, with sixty-two percent having stress testing within 6-months prior to CCTA. Fifty-five percent of these patients had abnormal stress test findings but demonstrated no CAD on CCTA. Among the patients with normal stress tests, 24.4% demonstrated CAD on CCTA. Twenty-five patients underwent invasive coronary angiography (ICA) within the 6-months following CCTA. For these patients, the positive predictive value of CCTA was 91.3% (95% CI: 72.0%, 99.0%) and negative predictive value was 100.0% (95% CI: 15.8%, 100.0%) when compared to ICA results. In addition, CCTA demonstrated myocardial bridging in 10.0% and an anomalous coronary vessel in 8.8% of patients.ConclusionsThis study revealed that CCTA is being used as a diagnostic test in patients presenting with chest pain at the study center. Among patients with prior stress testing, these results were at times potentially inconsistent with the findings from the CCTA. In addition, the CCTA was able to identify variants in anatomical structures.
Inhibition of DNA-PKcs impairs the activation and cytotoxicity of CD4+ helper and CD8+ effector T cells
Authors: Azevedo-Pouly Ana C. , Appell Lauren E. , Burdine Lyle , Rogers Lora J. , Morehead Lauren C. , Barker Melanie , Waldrip Zachary J. , Koss Brian , Burdine Marie Schluterman 
Published: June 2022

AbstractModulation of T cell activity is an effective strategy for the treatment of autoimmune diseases, immune-related disorders and cancer. This highlights a critical need for continued investigation of proteins that regulate T cell function. The kinase DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is emerging as a potent regulator of the immune system spurring interest in its use as a therapeutic target for immune-related diseases. In murine models of autoimmune disease including asthma and rheumatoid arthritis, treatment with small molecule DNA-PKcs inhibitors, which are in clinical trials for cancer therapy, decreased disease severity. Additionally, DNA-PKcs inhibitors reduced T cell-mediated graft rejection and extended graft survival in a murine allogenic skin graft rejection model. These in vivo studies suggest the therapeutic use of DNA-PKcs inhibitors for autoimmune and T cell-mediated disorders. In this study, we sought to further characterize the effects of DNA-PKcs inhibitors on T cells to better understand their clinical potential. We determined that pharmacological inhibition of DNA-PKcs abrogated activation of murine and human CD4+ and CD8+ T cells as evident by reduced expression of the activation markers CD69 and CD25. Furthermore, inhibition of DNA-PKcs impeded metabolic pathways and proliferation of anti-CD3/CD28 activated CD4+ and CD8+ T cells as well as peptide-stimulated OTI-CD8+ T cells. This reduced the ability of OTI-CD8+ T cells to kill cancer cells and the expression of IFNγ and the cytotoxic genes eomes, perforin and granzyme B. These results suggest a novel role for DNA-PKcs in early T cell activation. Furthermore, our data support the therapeutic potential of DNA-PKcs inhibitors on diseases of immune dysregulation.
Quantification of Aquatic Unicellular Diazotrophs by Immunolabeled Flow Cytometry
Authors: Geisler Eyal , Siebner Hagar , Rahav Eyal , Bar-Zeev Edo 
Published: June 2022

AbstractQuantifying the number of aquatic diazotrophs is highly challenging and relies mainly on microscopical approaches and/or molecular tools that are based on nif genes. However, it is still challenging to count diazotrophs, especially the unicellular fraction, despite their significant contribution to the aquatic nitrogen cycle. In this study a new method was developed to quantify unicellular diazotrophs by immunolabeling the nitrogenase enzyme followed by identification and quantification via flow cytometry. The new quantification method was initially developed using a diazotrophic monoculture (Vibrio natriegens) and verified by various auxiliary approaches. It was found that only 15-20% of the total number of V. natriegens cells have synthesized the nitrogenase enzyme, even though the media was anaerobic, and N limited. This approach was further tested in samples from marine and freshwater environments. It was found that the ratio of diazotrophs to total bacteria was 0.1% in the Mediterranean Sea, while 4.7% along the Jordan River. In contrast, the specific N2 fixation per unicellular diazotrophs was highest in the Mediterranean Sea (88 attomole N cell-1 d-1) while the total N2 fixation rates were lowest in the lake and the river (0.2 nmole N L-1 d-1). Overall, we expect that this direct quantification approach will provide new insights on the number and contribution of unicellular diazotrophs to total N2 fixation in marine and freshwater environments under various conditions.
Unique Pakistani gut microbiota highlights population-specific microbiota signatures of type 2 diabetes mellitus
Authors: Saleem Afshan , Ikram Aamer , Dikareva Evgenia , Lahtinen Emilia , Matharu Dollwin , Pajari Anne-Maria , de Vos Willem M. , Hasan Fariha , Salonen Anne , Jian Ching 
Published: June 2022

AbstractBiogeographic variations in the gut microbiota reflect host and environmental factors delineating human populations, and are pivotal to understand global patterns of host-microbiota interactions in health and prevalent lifestyle-related diseases, such as type 2 diabetes mellitus (T2D). Pakistani adults, having an exceptionally high prevalence of T2D, are one of the most understudied populations in microbiota research to date. The aim of the present study is to examine the gut microbiota across individuals from Pakistan and other populations of non-industrialized and industrialized lifestyles with a focus on T2D. The fecal samples from 94 urban-dwelling Pakistani adults with and without T2D were profiled by 16S ribosomal RNA gene amplicon sequencing and qPCR, and plasma samples quantified for circulating levels of lipopolysaccharide binding protein (LBP) and the activation ability of Toll-like receptor (TLR)-signaling. Publicly available datasets generated with comparable molecular methods were retrieved for comparative analysis. Overall, urbanized Pakistanis’ gut microbiota was similar to that of transitional or non-industrialized populations, depleted in Akkermansiaceae and enriched in Prevotellaceae (dominated by the non-Westernized clades of Prevotella copri). The relatively high proportion of Atopobiaceae appeared to be a unique characteristic of the Pakistani gut microbiota. The Pakistanis with T2D had elevated levels of LBP and TLR-signaling in circulation as well as gut microbial signatures atypical of other populations e.g., increased relative abundance of Libanicoccus/Parolsenella, limiting the inter-population extrapolation of gut microbiota-based classifiers for T2D. Taken together, our findings call for more global representation of understudied populations to extend the applicability of microbiota-based diagnostics and therapeutics.
Wild-type allele of TaHRC suppresses calcium-mediated plant immune response by hijacking TaCAXIP4 to trigger FHB susceptibility in wheat
Authors: Chen Hui , Su Zhenqi , Tian Bin , Hao Guixia , Trick Harold N. , Bai Guihua 
Published: June 2022

SummaryFusarium head blight (FHB) is one of the most destructive diseases of wheat worldwide. Epidemics of FHB cause a serious reduction in grain yield and quality of wheat and result in significant economic losses to wheat producers. Recently, we have cloned a histidine-rich calcium-binding protein gene (TaHRC) as the causal gene for Fhb1 and demonstrated that the wild-type allele of TaHRC conditions FHB susceptibility and a large deletion including the start codon resulted in FHB resistance. However, the molecular mechanisms on how TaHRC regulating FHB susceptibility remains unknown. In this study, we conducted yeast two-hybrid screening (Y2H) against the wheat cDNA expression libraries using TaHRC as bait and identified a cation exchanger (CAX)-interacting protein 4 (TaCAXIP4) as the candidate protein that interacts with TaHRC to affect calcium transport activity. The strong interaction was further confirmed by Bimolecular fluorescence complementation (BiFC) assays. Using gene editing, we edited three different sites (one before and one within and one after the NLS domain) of TaHRC in a susceptible wheat cultivar ‘Bobwhite’ using the CRISPR/Cas9 gene editing technology and demonstrated the N-terminus carrying NLS domain of TaHRC plays a critical role for the interaction and conditions TaHRC function on FHB susceptibility. We determined that the interaction between TaCAXIP4 and TaHRC occurs in the nuclei of cells by subcellular colocalization assay. Intriguingly, we found TaHRC can sequester TaCAXIP4 to suppress the Ca2+ transporting activity of TaCAX1 (a H+/Ca2+ antiporter) through yeast calcium suppression assay and suggested wild-type TaHRC may hijack TaCAXIP4 to suppresses calcium-mediated plant immune response during Fusarium infection in wheat. Furthermore, we performed the reactive oxygen species (ROS) assays and further showed that TaHRC might suppress the chitin-triggered plant immune responses during Fusarium infection by sequestering TaCAXIP4 to trigger FHB susceptibility, which facilitates the pathogen spread within a wheat spike. This work provides first line of evidence to support wild type Fhb1 is a susceptible gene and how Fhb1 wild type allele regulate FHB susceptibility.
A Bivalent Omicron-containing Booster Vaccine Against Covid-19
Authors: Chalkias Spyros , Harper Charles , Vrbicky Keith , Walsh Stephen R. , Essink Brandon , Brosz Adam , McGhee Nichole , Tomassini Joanne E. , Chen Xing , Chang Ying , Sutherland Andrea , Montefiori David C. , Girard Bethany , Edwards Darin K. , Feng Jing , Zhou Honghong , Baden Lindsey R. , Miller Jacqueline M. , Das Rituparna 
Published: June 2022

ABSTRACTBackgroundUpdated vaccination strategies against acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern are needed. Interim results of the safety and immunogenicity of the bivalent omicron-containing mRNA-1273.214 booster candidate are presented.MethodsIn this ongoing, phase 2/3 trial, the 50-μg bivalent vaccine mRNA-1273.214 (25-μg each ancestral Wuhan-Hu-1 and omicron B.1.1.529 spike SARS-CoV-2 mRNAs) was compared to the authorized 50-μg mRNA-1273 booster in adults who previously received 2-dose primary series of 100-μg mRNA-1273 and a first booster dose of 50-μg mRNA-1273 at least 3 months prior. Primary objectives were safety and reactogenicity, and immunogenicity of 50-μg mRNA-1273.214 compared with 50-μg mRNA-1273. Immunogenicity data 28 days after the booster dose are presented.ResultsFour hundred thirty-seven and 377 participants received 50-μg of mRNA-1273.214, or mRNA-1273, respectively. Median time between first and second booster doses of mRNA-1273.214 and mRNA-1273 were similar (136 and 134 days, respectively). In participants with no prior SARS-CoV-2 infection, observed omicron neutralizing antibody geometric mean titers (GMTs [95% confidence interval]) after the mRNA-1273.214 and mRNA-1273 booster doses, were 2372.4 (2070.6−2718.2) and 1473.5 (1270.8−1708.4) respectively and the model-based GMT ratio (97.5% confidence interval) was 1.75 (1.49−2.04). All pre-specified non-inferiority (ancestral SARS-CoV-2 with D614G mutation [D614G] GMT ratio; ancestral SARS-CoV-2 [D614G] and omicron seroresponse rates difference) and superiority primary objectives (omicron GMT ratio) for mRNA-1273.214 compared to mRNA-1273 were met. Additionally, mRNA-1273.214 50-μg induced a potent neutralizing antibody response against omicron subvariants BA.4/BA.5 and higher binding antibody responses against alpha, beta, gamma, delta and omicron variants. Safety and reactogenicity profiles were similar and well-tolerated for both vaccines groups.ConclusionThe bivalent vaccine mRNA-1273.214 50-μg was well-tolerated and elicited a superior neutralizing antibody response against omicron, compared to mRNA-1273 50-μg, and a non-inferior neutralizing antibody response against the ancestral SARS-CoV-2 (D614G), 28 days after immunization, creating a new tool as we respond to emerging SARS-CoV-2 variants.
A novel time-lapse imaging method for studying developing bacterial biofilms
Authors: Futo Momir , Široki Tin , Koska Sara , Čorak Nina , Tušar Anja , Domazet-Lošo Mirjana , Domazet-Lošo Tomislav 
Published: June 2022

AbstractIn nature, bacteria prevailingly reside in the form of biofilms. These elaborately organized surface-bound assemblages of bacterial cells show numerous features of multicellular organization. We recently showed that biofilm growth is a true developmental process, which resembles developmental processes in multicellular eukaryotes. To study the biofilm growth, in a fashion of eukaryotic ontogeny, it is essential to define dynamics and critical transitional phases of this process. The first step in this endeavor is to record the gross morphological changes of biofilm ontogeny under standardized conditions. This visual information is instrumental in guiding the sampling strategy for the later omics analyses of biofilm ontogeny. However, none of the currently available visualizations methods is specifically tailored for recording gross morphology across the whole biofilm development. To address this void, here we present an affordable Arduino-based approach for time-lapse visualization of complete biofilm ontogeny. The major challenge in recording biofilm development on the air-solid interphase is water condensation, which compromises filming directly through the lid of a Petri dish. To overcome these trade-offs, we developed an Arduino microcontroller setup which synchronizes a robotic arm, responsible for opening and closing the Petri dish lid, with the activity of a stereomicroscope-mounted camera and lighting conditions. We placed this setup into microbiological incubator that maintains temperature and humidity during the biofilm growth. As a proof-of-principle, we recorded biofilm development of five Bacillus subtilis strains that show different morphological and developmental dynamics.
MYB and ELF3 differentially modulate labor-inducing gene expression in myometrial cells
Authors: Shchuka Virlana M. , Khader Nawrah , Dorogin Anna , Shynlova Oksana , Mitchell Jennifer A. 
Published: June 2022

AbstractSpontaneous uterine contractions are initiated when smooth muscle cells (SMCs) within the uterine muscle, or myometrium, transition from a functionally dormant to an actively contractile phenotype at the end of the pregnancy period. We know that this process is accompanied by gestational time point-specific differences in the SMC transcriptome, which can be modulated by the Activator protein 1 (AP-1), Nuclear factor kappa beta (Nf-κβ), Estrogen receptor (ER), and Progesterone receptor (PR) transcription factors. Less is known, however, about the additional proteins that might assist these factors in conferring the transcriptional changes observed at labor onset. Here, we present functional evidence for the roles of two proteins previously understudied in the SMC context – MYB and ELF3 – which can contribute to the regulation of labor-driving gene transcription. We show that the MYB and ELF3 genes exhibit elevated transcript expression levels in mouse and human myometrial tissues during spontaneous term labor. The expression of both genes was also significantly increased in mouse myometrium during preterm labor induced by the progesterone antagonist, mifepristone (RU486), but not during infection-simulating preterm labor induced by intrauterine infusion of Lipopolysaccharide (LPS). Furthermore, both MYB and ELF3 proteins affect labor-driving gene promoter activity, although in surprisingly opposing ways: Gja1 and Fos promoter activation increases in the presence of MYB and decreases in the presence of ELF3. Collectively, our study adds to the current understanding of the transcription factor network that defines the transcriptomes of SMCs during late gestation and implicates two new players in the control of labor timing.
Three-dimensional chromatin organisation shapes origin activation and replication fork directionality
Authors: Giles Katherine A. , Lamm Noa , Taberlay Phillippa C. , Cesare Anthony J. 
Published: June 2022

SummaryFaithful DNA replication requires the orderly firing of replication origins across the genome. At present, we lack details around how origins are selected for activation and the subsequent impact of this on replication dynamics. Here, we have investigated how chromatin organisation contributes to replication initiation and dynamics by intersecting ChIP-seq, Hi-C, Repli-seq, and OK-seq data from primary and tumour cells lines. We found replication initiation is significantly enriched at TAD boundaries, co-localizing with CTCF and cohesin in early and mid S-phase. Strong replication fork directionality (RFD) from initiation zones in TAD boundaries could occur in a bi- or uni-directional manner, which highly correlated with replication timing. While TAD boundaries were largely invariant, a minority of initiation zones were shared across cell lines, indicative of cell type specific regulation. These data are consistent with chromatin structure organizing replication initiation and dynamics, ensuring orderly completion of replication from TAD boundaries into TAD internal regions.
Phytochromes mediate germination inhibition under red, far-red, and white light in Aethionema arabicum
Authors: Mérai Zsuzsanna , Xu Fei , Musilek Andreas , Ackerl Florian , Khalil Sarhan , Soto-Jiménez Luz Mayela , Lalatović Katarina , Klose Cornelia , Tarkowská Danuše , Turečková Veronika , Strnad Miroslav , Scheid Ortrun Mittelsten 
Published: June 2022

AbstractThe view on the role of light during seed germination stems mainly from studies with Arabidopsis, where light is required to initiate this process. In contrast, white light is a strong inhibitor of germination in other plants, exemplified by accessions of Aethionema arabicum, another Brassicaceae. Their seeds respond to light with gene expression changes of key regulators converse to Arabidopsis, resulting in antipodal hormone regulation and prevention of germination. The photoreceptors involved in this process in A. arabicum were unknown. Screening the first mutant collection of A. arabicum, we identified koy-1, a mutant that lost light inhibition of germination, due to a deletion in the promoter of HEME OXYGENASE 1, the gene for a key enzyme in the biosynthesis of the phytochrome chromophore. koy-1 seeds are unresponsive to red- and far-red light and hyposensitive under white light. Comparison of hormone and gene expression between wild type and koy- 1 revealed that very low light fluence stimulates germination, while high irradiance of red and far-red light is inhibitory, indicating a dual role of phytochromes in light-regulated seed germination. The mutation also affects the ratio between the two fruit morphs of A. arabicum, suggesting that light reception via phytochromes can fine-tune several parameters of propagation in adaptation to conditions in the habitat.One sentence summaryCharacterization of a phytochrome chromophore biosynthesis mutant demonstrates an active role of phytochromes in the light-inhibited seed germination in Aethionema arabicum.
Artificial intelligence based decision-making in accounting and auditing: ethical challenges and normative thinking
Authors: Lehner Othmar Manfred , Ittonen Kim , Silvola Hanna , Ström Eva , Wührleitner Alena 
Published: June 2022

PurposeThis paper aims to identify ethical challenges of using artificial intelligence (AI)-based accounting systems for decision-making and discusses its findings based on Rest's four-component model of antecedents for ethical decision-making. This study derives implications for accounting and auditing scholars and practitioners.Design/methodology/approachThis research is rooted in the hermeneutics tradition of interpretative accounting research, in which the reader and the texts engage in a form of dialogue. To substantiate this dialogue, the authors conduct a theoretically informed, narrative (semi-systematic) literature review spanning the years 2015–2020. This review's narrative is driven by the depicted contexts and the accounting/auditing practices found in selected articles are used as sample instead of the research or methods.FindingsIn the thematic coding of the selected papers the authors identify five major ethical challenges of AI-based decision-making in accounting: objectivity, privacy, transparency, accountability and trustworthiness. Using Rest's component model of antecedents for ethical decision-making as a stable framework for our structure, the authors critically discuss the challenges and their relevance for a future human–machine collaboration within varying agency between humans and AI.Originality/valueThis paper contributes to the literature on accounting as a subjectivising as well as mediating practice in a socio-material context. It does so by providing a solid base of arguments that AI alone, despite its enabling and mediating role in accounting, cannot make ethical accounting decisions because it lacks the necessary preconditions in terms of Rest's model of antecedents. What is more, as AI is bound to pre-set goals and subjected to human made conditions despite its autonomous learning and adaptive practices, it lacks true agency. As a consequence, accountability needs to be shared between humans and AI. The authors suggest that related governance as well as internal and external auditing processes need to be adapted in terms of skills and awareness to ensure an ethical AI-based decision-making.