bluuebunny/crossref_metadata_2025_split huggingface dataset:
AadT, a new weapon inAcinetobacter’sfight against antibiotics
Authors: Naidu Varsha , Shah Bhumika , Maher Claire , Paulsen Ian T. , Hassan Karl A. 
Published: January 2023

AbstractA novel multidrug efflux pump, AadT from the Drug:H+antiporter 2 family, was discovered inAcinetobactermultidrug resistance plasmids. Here, we profiled the antimicrobial resistance potential and examined the distribution of this gene. Putative homologs of this efflux pump were encoded in manyAcinetobacterspecies and other Gram-negative species, and were genetically associated with novel variants ofadeAB(C), which encodes a major tripartite efflux pump inAcinetobacter. The AadT pump conferred decreased susceptibility to at least eight diverse antimicrobials, including antibiotics erythromycin, tetracycline; biocides chlorhexidine; and dyes ethidium bromide and DAPI. These results show that AadT is a new determinant in theAcinetobacterresistance arsenal and may cooperate with variants of AdeAB(C).
Efficient gene knockout and genetic interactions: the IN4MER CRISPR/Cas12a multiplex knockout platform
Authors: Anvar Nazanin Esmaeili , Lin Chenchu , Ma Xingdi , Wilson Lori L. , Steger Ryan , Sangree Annabel K. , Colic Medina , Wang Sidney H. , Doench John G. , Hart Traver 
Published: January 2023

AbstractGenetic interactions mediate the emergence of phenotype from genotype, but initial technologies for combinatorial genetic perturbation in mammalian cells suffer from inefficiency and are challenging to scale. Recent focus on paralog synthetic lethality in cancer cells offers an opportunity to evaluate different approaches and improve on the state of the art. Here we report a meta-analysis of CRISPR genetic interactions screens, identifying a candidate set of background-independent paralog synthetic lethals, and find that the Cas12a platform provides superior sensitivity and assay replicability. We demonstrate that Cas12a can independently target up to four genes from a single guide array, and we build on this knowledge by constructing a genome-scale library that expresses arrays of four guides per clone, a platform we call ‘in4mer’. Our genome-scale human library, with only 49k clones, is substantially smaller than a typical CRISPR/Cas9 monogenic library while also targeting more than four thousand paralog pairs, triples, and quads. Proof of concept screens in four cell lines demonstrate discrimination of core and context-dependent essential genes similar to that of state-of-the-art CRISPR/Cas9 libraries, as well as detection of synthetic lethal and masking/buffering genetic interactions between paralogs of various family sizes, a capability not offered by any extant library. Importantly, the in4mer platform offers a fivefold reduction in the number of clones required to assay genetic interactions, dramatically improving the cost and effort required for these studies.
An RNA seq-based reference landscape of human normal and neoplastic brain
Authors: Arora Sonali , Szulzewsky Frank , Jensen Matt , Nuechterlein Nicholas , Pattwell Siobhan S , Holland Eric C 
Published: January 2023

ABSTRACTIn order to better understand the relationship between normal and neoplastic brain, we combined five publicly available large-scale datasets, correcting for batch effects and applying Uniform Manifold Approximation and Projection (UMAP) to RNA-seq data. We assembled a reference Brain-UMAP including 702 adult gliomas, 802 pediatric tumors and 1409 healthy normal brain samples, which can be utilized to investigate the wealth of information obtained from combining several publicly available datasets to study a single organ site. Normal brain regions and tumor types create distinct clusters and because the landscape is generated by RNA seq, comparative gene expression profiles and gene ontology patterns are readily evident. To our knowledge, this is the first meta-analysis that allows for comparison of gene expression and pathways of interest across adult gliomas, pediatric brain tumors, and normal brain regions. We provide access to this resource via the open source, interactive online tool Oncoscape, where the scientific community can readily visualize clinical metadata, gene expression patterns, gene fusions, mutations, and copy number patterns for individual genes and pathway over this reference landscape.
IsoAnalytics: A Single-cell Proteomics Web Server
Authors: Palmer Suzette N. , Koh Andrew Y. , Zhan Xiaowei 
Published: January 2023

AbstractMotivationSingle-cell proteomics provide unprecedented resolution to examine biological processes. Customized data analysis and facile data visualization are crucial for scientific discovery. Further, userfriendly data analysis and visualization software that is easily accessible for the general scientific community is essential.ResultsWe have created a web server,IsoAnalytics, that gives users without computational or bioinformatics background the ability to directly analyze and interactively visualize data obtained from the Isoplexis single cell technology platform. We envision this open-sourced web server will increase research productivity and serve as a free, competitive alternative for single-cell proteomics research.ContactAndrew.Koh@utsouthwestern.eduandXiaowei.Zhan@utsouthwestern.eduAvailabilityIsoAnalytics is free and available at:https://cdc.biohpc.swmed.edu/isoplexis/and is implemented in Python, with all major browsers supported. Code for IsoAnalytics is free and available at:https://github.com/zhanxw/Isoplexis_Data_Analysis.Supplementary InformationSupplementary data are available atBioinformaticsonline.
The gut metagenome harbors metabolic and antibiotic resistance signatures of moderate-to-severe asthma
Authors: Wilson Naomi G. , Hernandez-Leyva Ariel , Schwartz Drew J. , Bacharier Leonard B. , Kau Andrew L. 
Published: January 2023

AbstractAsthma is a common allergic airway disease that develops in association with the human microbiome early in life. Both the composition and function of the infant gut microbiota have been linked to asthma risk, but functional alterations in the gut microbiota of older patients with established asthma remain an important knowledge gap. Here, we performed whole metagenomic shotgun sequencing of 95 stool samples from 59 healthy and 36 subjects with moderate-to-severe asthma to characterize the metagenomes of gut microbiota in children and adults 6 years and older. Mapping of functional orthologs revealed that asthma contributes to 2.9% of the variation in metagenomic content even when accounting for other important clinical demographics. Differential abundance analysis showed an enrichment of long-chain fatty acid (LCFA) metabolism pathways which have been previously implicated in airway smooth muscle and immune responses in asthma. We also observed increased richness of antibiotic resistance genes (ARGs) in people with asthma. One differentially abundant ARG was a macrolide resistance marker,ermF, which significantly co-occurred with theBacteroides fragilistoxin, suggesting a possible relationship between enterotoxigenicB. fragilis, antibiotic resistance, and asthma. Lastly, we found multiple virulence factor (VF) and ARG pairs that co-occurred in both cohorts suggesting that virulence and antibiotic resistance traits are co-selected and maintained in the fecal microbiota of people with asthma. Overall, our results show functional alterations via LCFA biosynthetic genes and increases in antibiotic resistance genes in the gut microbiota of subjects with moderate-to-severe asthma and could have implications for asthma management and treatment.
Altered hierarchical auditory predictive processing after lesions to the orbitofrontal cortex
Authors: Asko Olgerta , Blenkmann Alejandro O. , Leske Sabine L. , Foldal Maja Dyhre , Llorens Anaïs , Funderud Ingrid , Meling Torstein R. , Knight Robert T. , Endestad Tor , Solbakk Anne-Kristin 
Published: January 2023

AbstractOrbitofrontal cortex (OFC) is classically linked to inhibitory control, emotion regulation and reward processing. Recent perspectives propose that the OFC also generates predictions about perceptual events, actions, and their outcomes. We tested the role of the OFC in detecting violations of prediction at two levels of abstraction (i.e., hierarchical predictive processing) by studying the event-related potentials (ERPs) of patients with focal OFC lesions (n = 12) and healthy controls (n = 14) while they detected deviant sequences of tones in a Local-Global paradigm. The structural regularities of the tones were controlled at two hierarchical levels by rules defined at a local (i.e.,between tones within sequences)and at a global (i.e.,between sequences) level. In OFC patients, ERPs elicited by standard tones were unaffected at both local and global levels compared to controls. However, patients showed an attenuated mismatch negativity (MMN) and P3a to local prediction violation, as well as a diminished MMN followed by a delayed P3a to the combined local and global level prediction violation. The subsequent P3b component to conditions involving violations of prediction at the level of global rules was preserved in the OFC group. Comparable effects were absent in patients with lesions restricted to the lateral PFC, which lends a degree of anatomical specificity to the altered predictive processing resulting from OFC lesion. Overall, the altered magnitudes and time courses of MMN/P3a responses after lesions to the OFC indicate that the neural correlates of detection of auditory regularity violation is impacted at two hierarchical levels of rule abstraction.HighlightsOrbitofrontal lesions reduce auditory MMN to unpredicted tones at the local level (between tones within sequences) of the rule hierarchy in the Local-Global paradigm.Orbitofrontal lesions also impact combined local and global (between sequences) level auditory deviance response, as manifested by diminished and delayed MMN and delayed P3a.
Assessment of Immunogenicity and Efficacy of CV0501 mRNA-based Omicron COVID-19 Vaccination in Small Animal Models
Authors: Roth Nicole , Gergen Janina , Kovacikova Kristina , Mueller Stefan O. , Ulrich Lorenz , Schön Jacob , Halwe Nico Joel , Fricke Charlie , Corleis Björn , Dorhoi Anca , Hoffmann Donata , Beer Martin , Maione Domenico , Petsch Benjamin , Rauch Susanne 
Published: January 2023

AbstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron and its subvariants (BA.2, BA.4, BA.5) represent the most commonly circulating variants of concern (VOC) in the coronavirus disease 2019 (COVID-19) pandemic in 2022. Despite high vaccination rates with approved SARS-CoV-2 vaccines encoding the ancestral spike (S) protein, these Omicron subvariants have collectively resulted in increased viral transmission and disease incidence. This necessitates the development and characterization of vaccines incorporating later emerging S proteins to enhance protection against VOC. In this context, bivalent vaccine formulations may induce broad protection against VOC and potential future SARS-CoV-2 variants. Here, we report preclinical data for a lipid nanoparticle (LNP)-formulated RNActive® N1-methylpseudouridine (N1mΨ) modified mRNA vaccine (CV0501) based on our second-generation SARS-CoV-2 vaccine CV2CoV, encoding the S protein of Omicron BA.1.The immunogenicity of CV0501, alone or in combination with a corresponding vaccine encoding the ancestral S protein (ancestral N1mΨ), was first measured in dose-response and booster immunization studies performed in Wistar rats. Both monovalent CV0501 and bivalent CV0501/ancestral N1mΨ immunization induced robust neutralizing antibody titers against the BA.1, BA.2 and BA.5 Omicron subvariants, in addition to other SARS-CoV-2 variants in a booster immunization study.The protective efficacy of monovalent CV0501 against live SARS-CoV-2 BA.2 infection was then assessed in hamsters. Monovalent CV0501 significantly reduced SARS-CoV-2 BA.2 viral loads in the airways, demonstrating protection induced by CV0501 vaccination. CV0501 has now advanced into human Phase 1 clinical trials (ClinicalTrials.govIdentifier:NCT05477186).
scRNA-seq analysis of hemocytes of penaeid shrimp under virus infection
Authors: Koiwai Keiichiro , Kondo Hidehiro , Hirono Ikuo 
Published: January 2023

AbstractThe classification of cells in non-model organisms has lagged behind that of model organisms using established cluster of differentiation marker sets. To reduce fish diseases, research is needed to better understand immune-related cells, or hemocytes, in non-model organisms like shrimp and other marine invertebrates. In this study, we used Drop-seq to examine how virus infection affected the populations of hemocytes in kuruma shrimp,Penaeus japonicus, which had been artificially infected with a virus. The findings demonstrated that virus infection reduced particular cell populations in circulating hemolymph and inhibited the expression of antimicrobial peptides. We also identified the gene sets that are likely to be responsible for this reduction. Additionally, we identified functionally unknown genes as novel antimicrobial peptides, and we supported this assumption by the fact that these genes were expressed in the population of hemocytes that expressed other antimicrobial peptides. In addition, we aimed to improve the operability of the experiment by conducting Drop-seq with fixed cells as a template and discussed the impact of methanol fixation on Drop-seq data in comparison to previous results obtained without fixation. These results not only deepen our understanding of the immune system of crustaceans but also demonstrate that single-cell analysis can accelerate research on non-model organisms.
Personalized alpha-tACS targeting left posterior parietal cortex modulates visuo-spatial attention and posterior evoked EEG activity
Authors: Radecke Jan-Ole , Fiene Marina , Misselhorn Jonas , Herrmann Christoph S. , Engel Andreas K. , Wolters Carsten H. , Schneider Till R. 
Published: January 2023

AbstractBackgroundCovert visuo-spatial attention is marked by the anticipatory lateralization of neuronal alpha activity in the posterior parietal cortex. Previous applications of transcranial alternating current stimulation (tACS) at the alpha frequency, however, were inconclusive regarding the causal contribution of oscillatory activity during visuo-spatial attention.ObjectiveAttentional shifts of behavior and electroencephalography (EEG) after-effects were assessed in a cued visuo-spatial attention paradigm. We hypothesized that parietal alpha-tACS facilitates attention in the ipsilateral visual hemifield. Furthermore, we assumed that modulations of behavior and neurophysiology are related to individual electric field simulations.MethodsWe applied personalized tACS at alpha and gamma frequencies to elucidate the role of oscillatory neuronal activity for visuo-spatial attention. Personalized tACS montages were algorithmically optimized to target individual left and right parietal regions that were defined by an EEG localizer.ResultsBehavioral performance in the left hemifield was specifically increased by alpha-tACS compared to gamma-tACS targeting the left parietal cortex. This hemisphere-specific effect was observed despite the symmetry of simulated electric fields. In addition, visual event-related potential (ERP) amplitudes showed a reduced lateralization over posterior sites induced by left alpha-tACS. Neuronal sources of this effect were localized in the left premotor cortex. Interestingly, accuracy modulations induced by left parietal alpha-tACS were directly related to electric field magnitudes in the left premotor cortex.ConclusionOverall, results corroborate the notion that alpha lateralization plays a causal role in covert visuo-spatial attention and indicate an increased susceptibility of parietal and premotor brain regions of the left dorsal attention network to subtle tACS-neuromodulation.
Cell-type-specific propagation of visual flicker
Authors: Schneider Marius , Tzanou Athanasia , Uran Cem , Vinck Martin 
Published: January 2023

AbstractRhythmic flicker stimulation has gained interest as a treatment for neurodegenerative diseases and a method for frequency tagging neural activity in human EEG/MEG recordings. Yet, little is known about the way in which flicker-induced synchronization propagates across cortical levels and impacts different cell types. Here, we used Neuropixels to simultaneously record from LGN, V1, and CA1 while presenting visual flicker stimuli at different frequencies. LGN neurons showed strong phase locking up to 40Hz, whereas phase locking was substantially weaker in V1 units and absent in CA1 units. Laminar analyses revealed an attenuation of phase locking at 40Hz for each processing stage, with substantially weaker phase locking in the superficial layers of V1. Gamma-rhythmic flicker predominantly entrained fast-spiking interneurons. Optotagging experiments showed that these neurons correspond to either PV+ or narrow-waveform Sst+ neurons. A computational model could explain the observed differences in phase locking based on the neurons’ capacitative low-pass filtering properties. In summary, the propagation of synchronized activity and its effect on distinct cell types strongly depend on its frequency.
Understanding and evaluating ambiguity in single-cell and single-nucleus RNA-sequencing
Authors: He Dongze , Soneson Charlotte , Patro Rob 
Published: January 2023

Recently, a new modification has been proposed by Hjörleifsson and Sullivanet al. to the model used to classify the splicing status of reads (as spliced (mature), unspliced (nascent), or ambiguous) in single-cell and single-nucleus RNA-seq data. Here, we evaluate both the theoretical basis and practical implementation of the proposed method. The proposed method is highly-conservative, and therefore, unlikely to mischaracterize reads as spliced (mature) or unspliced (nascent) when they are not. However, we find that it leaves a large fraction of reads classified as ambiguous, and, in practice, allocates these ambiguous reads in an all-or-nothing manner, and differently between single-cell and single-nucleus RNA-seq data. Further, as implemented in practice, the ambiguous classification is implicit and based on the index against which the reads are mapped, which leads to several drawbacks compared to methods that consider both spliced (mature) and unspliced (nascent) mapping targets simultaneously — for example, the ability to use confidently assigned reads to rescue ambiguous reads based on shared UMIs and gene targets. Nonetheless, we show that these conservative assignment rules can be obtained directly in existing approaches simply by altering the set of targets that are indexed. To this end, we introduce thespliceureference and show that its use withalevin-fryrecapitulates the more conservative proposed classification.We also observe that, on experimental data, and under the proposed allocation rules for ambiguous UMIs, the difference between the proposed classification scheme and existing conventions appears much smaller than previously reported. We demonstrate the use of the newpiscemindex for mapping simultaneously against spliced (mature) and unspliced (nascent) targets, allowing classification against the full nascent and mature transcriptome in human or mouse in <3GB of memory. Finally, we discuss the potential of incorporating probabilistic evidence into the inference of splicing status, and suggest that it may provide benefits beyond what can be obtained from discrete classification of UMIs as splicing-ambiguous.
Determinants of high school students’ digital reading flow experience: an experimental study
Authors: Chen Jingjun , Tang Xiwen , Xia Yuan , Bao Shangfei , Shen Jianting 
Published: January 2023

PurposeThis study aims to explore the influence of information presentation conditions on the flow experience of digital reading for high school students.Design/methodology/approachFirstly, a survey determines the preferred reading medium and the types of texts that high school students frequently read. Secondly, Experiment 1 focuses on the effects of the text type and reading medium on flow experience and reading comprehension. Finally, Experiment 2 addresses a narrative text presented on a smartphone, and discusses the influence of advance organizer, presentation format and page layout on flow experience and reading comprehension.FindingsIn digital reading, the narrative text has a stronger flow experience than explanatory text; the flow experience of reading narration on smartphones is more evident than on computers. The advance organizer and text combined with pictures are more conducive to a flow experience when a smartphone is used as a reading medium. From the perspective of reading comprehension, scrolling is more suitable for reading text combined with pictures and paging best suits pure text.Originality/valueThrough experimental methods, this study reveals the influence of information presentation conditions on the digital reading flow experience, which is a meaningful and innovative topic. The findings can provide more enlightenment and reference for the design and promotion of digital resources and digital reading by teenagers.
Post-pandemic adopted learning approach to promote architectural education: statistical approach
Authors: El-Mowafy Basma N. , Hassan Asmaa M. 
Published: January 2023

PurposeOnline learning has many limitations in studio-based courses, such as architectural design courses, considering the challenges during post-pandemic. Therefore, this study aims to propose a post-pandemic adopted learning approach, which integrates flipped classrooms (FC) with project-based learning (PBL). In addition, this study evaluates the perceptions of students based on and the effects of the proposed learning approach in architectural design.Design/methodology/approachThis study provides a mixed methodology based on a literature review on the topic to bridge the gaps in previous studies regarding the FC and PBL. In addition, a case study survey including semi-structured interviews, observations questionnaire recruited undergraduate students to generate both qualitative and quantitative data to investigate the perceptions of students based on post-pandemic adopted learning approach.FindingsThis study has highlighted the significance of post-pandemic adopted hybrid learning method, especially in architectural education, whereas the research finds that FC is an appropriate solution to improve design courses with online technologies.Practical implicationsThe proposed approach provides specialists to develop and integrate proposals and strategies to enable a better online practice for students and instructors. The proposed approach can enhance the students' interpersonal skills, hence active online learning related architectural design projects.Originality/valueRecognizing the significance of e-learning in response to the post-pandemic scenario, this study developed and assessed new learning technique that combines online learning with traditional design studios via hybrid learning method.