bluuebunny/crossref_metadata_2025_split huggingface dataset:
An automated respiratory data pipeline for waveform characteristic analysis
Authors: Lusk Savannah , Ward Christopher S. , Chang Andersen , Twitchell-Heyne Avery , Fattig Shaun , Allen Genevera , Jankowsky Joanna , Ray Russell 
Published: December 2022

AbstractComprehensive and accurate analysis of respiratory and metabolic data is crucial to modelling congenital, pathogenic, and degenerative diseases converging on autonomic control failure. A lack of tools for high-throughput analysis of respiratory datasets remains a major challenge. We present Breathe Easy, a novel open-source pipeline for processing raw recordings and associated metadata into operative outcomes, publication-worthy graphs, and robust statistical analyses including QQ and residual plots for assumption queries and data transformations. This pipeline uses a facile graphical user interface for uploading data files, setting waveform feature thresholds, and defining experimental variables. Breathe Easy was validated against manual selection by experts, which represents the current standard in the field. We demonstrate Breathe Easy’s utility by examining a 2-year longitudinal study of an Alzheimer’s Disease mouse model to assess contributions of forebrain pathology in disordered breathing. Whole body plethysmography has become an important experimental outcome measure for a variety of diseases with primary and secondary respiratory indications. Respiratory dysfunction, while not an initial symptom in many of these disorders, often drives disability or death in patient outcomes. Breathe Easy provides an open-source respiratory analysis tool for all respiratory datasets and represents a necessary improvement upon current analytical methods in the field.
Deep mutational scanning to predict antibody escape in SARS-CoV-2 Omicron subvariants
Authors: Alcantara Mellissa C , Higuchi Yusuke , Kirita Yuhei , Matoba Satoaki , Hoshino Atsushi 
Published: December 2022

AbstractThe major concern of COVID-19 therapeutic monoclonal antibodies is the loss of efficacy to continuously emerging SARS-CoV-2 variants. To predict the antibodies efficacy to the future Omicron subvariants, we conducted deep mutational scanning (DMS) encompassing all single mutations in the receptor binding domain of BA.2 strain. In case of bebtelovimab that preserves neutralization activity against BA.2 and BA.5, broad range of amino acid substitutions at K444, V445 and G446 and some substitutions at P499 and T500 were indicated to achieve the antibody escape. Among currently increasing subvariants, BA2.75 carrying G446S partly and XBB with V445P and BQ.1 with K444T completely evade the neutralization of bebtelovimab, consistent with the DMS results. DMS can comprehensively characterize the antibody escape for efficient and effective management of future variants.
Single-Cell Imaging Maps Inflammatory Cell Subsets to Pulmonary Arterial Hypertension Vasculopathy
Authors: Ferrian Selena , Cao Aiqin , Mccaffrey Erin F. , Saito Toshie , Greenwald Noah F. , Nicolls Mark R. , Bruce Trevor , Zamanian Roham T. , Rosario Patricia Del , Rabinovitch Marlene , Angelo Michael 
Published: December 2022

ABSTRACTRationaleElucidating the immune landscape within and surrounding pulmonary arteries (PAs) is critical in understanding immune-driven vascular pathology in pulmonary arterial hypertension (PAH). Although more severe vascular pathology is often observed in hereditary (H)PAH patients withBMPR2mutations, the involvement of specific immune cell subsets remains unclear.MethodsWe used cutting-edge multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to compare PAs and adjacent tissue in PAH lungs (idiopathic (I)PAH and HPAH) with unused donor lungs.MeasurementsWe quantified immune cells’ proximity and abundance, focusing on those linked to vascular pathology, and evaluated their impact on pulmonary arterial smooth muscle cells (SMCs) and endothelial cells (ECs).ResultsDistinct immune infiltration patterns emerged between PAH subtypes, with intramural involvement independently linked to PA occlusive changes. Notably, we identified monocyte-derived dendritic cells (mo-DCs) within PA subendothelial and adventitial regions, influencing vascular remodeling by promoting SMC proliferation and suppressing endothelial gene expression across PAH subtypes. In HPAH patients, pronounced immune dysregulation encircled PA walls, characterized by heightened perivascular inflammation involving TIM-3+ T cells. This correlated with an expanded DC subset expressing IDO-1, TIM-3, and SAMHD1, alongside increased neutrophils, SMCs, and α-SMA+ECs, reinforcing the severity of pulmonary vascular lesions.ConclusionsThis study presents the first architectural map of PAH lungs, connecting immune subsets not only with specific PA lesions but also with heightened severity in HPAH compared to IPAH. Our findings emphasize the therapeutic potential of targeting mo-DCs, neutrophils, cellular interactions, and immune responses to alleviate severe vascular pathology in IPAH and HPAH.
Inducible non-human primate models of retinal degeneration for testing end stage therapies and understanding disease mechanisms
Authors: Ail Divya , Nava Diane , Hwang In Pyo , Brazhnikova Elena , Nouvel-Jaillard Céline , Dentel Alexandre , Joffrois Corentin , Rousseau Lionel , Dégardin Julie , Bertin Stephane , Sahel José-Alain , Goureau Olivier , Picaud Serge , Dalkara Deniz 
Published: December 2022

AbstractThe anatomical differences between the retinas of humans and most animal models pose a challenge for testing novel therapies. Non-human primate (NHP) retina is anatomically closest to the human retina with the presence of a high acuity region called the fovea. However, there is a lack of relevant NHP models for retinal degeneration that can be used for preclinical studies of vision restoration. To address this unmet need we aimed to generate inducible NHP models of photoreceptor degeneration. We generated three cynomolgus macaque models using distinct strategies. We used two genetically targeted strategies using optogenetics and Crispr-Cas9 to ablate specifically rods to mimic rod-cone dystrophy. Additionally, we created an acute model by physical separation of the photoreceptors and retinal pigment epithelium using a polymer patch. Retinal degeneration was evaluated in all three models by in-life exams such as fundus imaging, optical coherence tomography, adaptive optics and electroretinography. In the genetic models we observed punctuate areas of degeneration in the injected area marked by disorganization of outer segments, loss of rod photoreceptors and thinning of the outer nuclear layer. In the acute model, the degeneration was faster and involved both rods and cones. Among the three distinct NHP models, the Crispr-Cas9 based approach was the most advantageous model in view of recapitulating disease specific features and its ease of implementation. The acute model however resulted in the fastest degeneration making it the most relevant model for testing end-stage vision restoration therapies such as stem cell transplantation.
Enhanced Protection from SARS-CoV-2 Variants by MVA-Based Vaccines Expressing Matched or Mismatched S Proteins Administered Intranasally to hACE2 Mice
Authors: Cotter Catherine A. , Americo Jeffrey L. , Earl Patricia L. , Moss Bernard 
Published: December 2022

ABSTRACTThe continuous evolution of SARS-CoV-2 strains is contributing to the prolongation of the global pandemic. We previously reported the prevention or more rapid clearance of SARS-CoV-2 from the nasal turbinates and lungs of susceptible K18-hACE2 mice that had been vaccinated intranasally (IN) rather than intramuscularly (IM) with a recombinant MVA (rMVA) expressing a modified S protein of the ancestor SARS-CoV-2 strain. Here, we constructed additional rMVAs and pseudoviruses expressing modified S protein of SARS-CoV-2 variants and compared the ability of vaccines with S proteins that were matched or mismatched to neutralize variants, bind to S proteins and protect K18-hACE2 mice against SARS-CoV-2 challenge. Although vaccines with matched S proteins induced higher neutralizing antibodies, vaccines with mismatched S proteins still protected against severe disease and reduced virus and mRNAs in the lungs and nasal turbinates, though not as well as vaccines with matched S proteins. In mice earlier primed and boosted with rMVA expressing ancestral S, antibodies to the latter increased after one immunization with rMVA expressing Omicron S, but neutralizing antibody to Omicron required a second immunization. Passive transfer of Wuhan immune serum with Omicron S binding but undetectable neutralizing activities reduced infection of the lungs by the variant. Notably, the reduction in infection of the nasal turbinates and lungs was significantly greater when the rMVAs were administered IN rather than IM and this held true for vaccines that were matched or mismatched to the challenge SARS-CoV-2.
Single-cell transcriptomic analysis of human pleura reveals stromal heterogeneity and informs in vitro models of mesothelioma
Authors: Obacz Joanna , Nibhani Reshma , Adams Taylor S. , Schupp Jonas C. , Valer Jose Antonio , Veale Niki , Aresu Giuseppe , Coonar Aman S. , Peryt Adam , Biffi Giulia , Kaminski Naftali , Francies Hayley , Rassl Doris M. , Garnett Matthew J , Rintoul Robert C. , Marciniak Stefan J. 
Published: December 2022

ABSTRACTThe pleural lining of the thorax regulates local immunity, inflammation and repair. A variety of conditions, both benign and malignant including pleural mesothelioma, can affect this tissue. A lack of knowledge concerning the mesothelial and stromal cells comprising the pleura has hampered the development of targeted therapies. Here we present the first comprehensive single cell transcriptomic atlas of the human parietal pleura and demonstrate its utility in elucidating pleural biology. We confirm the presence of known universal fibroblasts and describe novel, potentially pleural-specific, fibroblast subtypes. We also present transcriptomic characterisation of multiplein vitromodels of benign and malignant mesothelial cells, and characterise these through comparison within vivotranscriptomic data. While bulk pleural transcriptomes have been reported previously, this is the first study to provide resolution at single cell level. We expect our pleural cell atlas will prove invaluable to those studying pleural biology and disease. For example, it has already enabled us to shed light on the transdifferentiation of mesothelial cells allowing us to develop a simple method for prolonging mesothelial cell differentiation in vitro.
EEG is better left alone
Authors: Delorme Arnaud 
Published: December 2022

AbstractAutomated preprocessing methods are critically needed to process the large publicly-available EEG databases, but the optimal approach remains unknown because we lack data quality metrics to compare them. Here, we designed a simple yet robust EEG data quality metric assessing the percentage of significant channels between two experimental conditions within a 100 ms post-stimulus time range. Because of volume conduction in EEG, given no noise, most brain-evoked related potentials (ERP) should be visible on every single channel. Using three publicly available collections of EEG data, we showed that, with the exceptions of high-pass filtering and bad channel interpolation, automated data corrections had no effect on or significantly decreased the percentage of significant channels. Referencing and advanced baseline removal methods were significantly detrimental to performance. Rejecting bad data segments or trials could not compensate for the loss in statistical power. Automated Independent Component Analysis rejection of eyes and muscles failed to increase performance reliably. We compared optimized pipelines for preprocessing EEG data maximizing ERP significance using the leading open-source EEG software: EEGLAB, FieldTrip, MNE, and Brainstorm. Only one pipeline performed significantly better than high-pass filtering the data.
A Unitary Mechanism Underlies Adaptation to Both Local and Global Environmental Statistics in Time Perception
Authors: Wang Tianhe , Luo Yingrui , Ivry Richard B. , Tsay Jonathan S. , Pöppel Ernst , Bao Yan 
Published: December 2022

AbstractOur sense of the passage of time flexibly adapts to the statistical properties of the temporal context. Humans and non-human species exhibit a perceptual bias towards the mean of durations previously observed as well as serial dependence, a perceptual bias towards the duration of recently processed events. Here we asked whether those two phenomena arise from a unitary mechanism or reflect the operation of two distinct systems that adapt separately to the global and local statistics of the environment. We employed a set of duration reproduction tasks in which the target duration was sampled from distributions with different variances and means. The central tendency and serial dependence biases were jointly modulated by the range and the variance of the prior. These effects were well-captured by a unitary mechanism model in which temporal expectancies are updated after each trial based on perceptual observations. Alternative models that assume separate mechanisms for global and local contextual effects failed to capture the empirical results.TeaserTime perception of humans is shaped by a common mechanism that is sensitive to short-term and long-term environmental changes.
COVID-19 vaccine coverage targets to inform reopening plans in a low incidence setting
Authors: Conway Eamon , Walker Camelia , Baker Chris , Lydeamore Michael , Ryan Gerard E. , Campbell Trish , Miller Joel C. , Yeung Max , Kabashima Greg , Wood James , Rebuli Nic , McCaw James M. , McVernon Jodie , Golding Nick , Price David J. , Shearer Freya M. 
Published: December 2022

ABSTRACTSince the emergence of SARS-CoV-2 in 2019 through to mid-2021, much of the Australian population lived in a COVID-19 free environment. This followed the broadly successful implementation of a strong suppression strategy, including international border closures. With the availability of COVID-19 vaccines in early 2021, the national government sought to transition from a state of minimal incidence and strong suppression activities to one of high vaccine coverage and reduced restrictions but with still-manageable transmission. This transition is articulated in the national “re-opening” plan released in July 2021. Here we report on the dynamic modelling study that directly informed policies within the national re-opening plan including the identification of priority age groups for vaccination, target vaccine coverage thresholds and the anticipated requirements for continued public health measures — assuming circulation of the Delta SARS-CoV-2 variant. Our findings demonstrated that adult vaccine coverage needed to be at least 70% to minimise public health and clinical impacts following the establishment of community transmission. They also supported the need for continued application of test-trace-isolate-quarantine and social measures during the vaccine roll-out phase and beyond.
Trends and Relationships in Opioid Prescribing Rates and Overdose Rates in the United States 2013-2019
Authors: Enthoven Luke F. 
Published: December 2022

AbstractThe opioid epidemic began more than two decades ago and continues to increase in severity with the rate of overdose death increasing steadily. The epidemic was born in problematic claims about opioids and aggressive prescribing. After initial analysis of the first decade of the epidemic it became clear that actions would need to be taken to curtail overprescribing and many states passed legislation tracking and limiting opioid prescribing. Since then opioid prescribing has declined, but overdose has continued to increase at an alarming rate. This analysis is focused on evaluating more recent trends in opioid prescribing and overdose to see if the close positive correlation that existed between these values prior to 2010 holds true for the following decade. My findings indicate that between 2013 and 2019 that there is no relationship, or possibly a negative relationship, between opioid prescribing and overdose. Between 2013 and 2019 there was a 25% decrease in opioid prescribing rate yet a 96% increase in opioid overdose deaths. The close relationship that existed between prescribing and overdose appears to have diverged to the point where overdose increases as prescribing decreases. Linear regression on both national and state data revealed a significant negative relationship between overdose and prescribing for national data between 2013 and 2019 (R2value of 0.84 and a p-value of 0.003) and no relationship between overdose and prescribing for state data between 2014 and 2019 (R2value of 0.04 and a p-value of < 0.001). This questions the value of further efforts to reduce prescribing in preventing overdose and supports the hypothesis that restriction of prescription opioids can contribute to increased use of dangerous illicit opioids.
Nitrate Assimilation Underlying Kleptoplasty
Authors: Maruyama Moe , Kagamoto Tsuyoshi , Matsumoto Yuga , Onuma Ryo , Miyagishima Shin-ya , Tanifuji Goro , Nakazawa Masami , Kashiyama Yuichiro 
Published: December 2022

AbstractWhile photoautotrophic organisms utilize inorganic nitrogen as the nitrogen source, heterotrophic organisms utilize organic nitrogen and thus do not generally have an inorganic nitrogen assimilation pathway. Here we focused on the nitrogen metabolism ofRapaza viridis, a unicellular eukaryote exhibiting kleptoplasty. Although belonging to the lineage of essentially heterotrophic flagellates,R. viridisexploits the photosynthetic products of the kleptoplasts and was therefore suspected to potentially utilize inorganic nitrogen. From the transcriptome data ofR. viridis, we identified the gene RvNaRL, which had sequence similarity to nitrate reductases found in plants. Phylogenetic analysis revealed that RvNaRLwas acquired by a horizontal gene transfer event. To verify its function of the protein productRvNaRL, we established a RNAi mediated knockdown and a CRISPR-Cas9-mediated knockout experiments for the first time inR. viridisand applied them to this gene. The RvNaRLknockdown and knockout cells exhibited significant growth only when ammonium was supplied but, in contrast to the wild-type cells, no substantial growth when nitrate was supplied. Such arrested growth in absence of ammonium was attributed to impaired amino acid synthesis due to the deficiency of nitrogen supply from the nitrate assimilation pathway; this in turn resulted in the accumulation of excess photosynthetic products in the form of cytosolic polysaccharide grains as observed. These results indicate thatRvNaRL is certainly involved in nitrate assimilation byR. viridis. Thus, we infer thatR. viridisachieved its advanced kleptoplastic strategy owing to a posteriori acquisition of the nitrate assimilation pathway the horizontal gene transfer.
Elucidation of Amyloid-Beta’s Gambit in Oligomerization: Truncated Aβ fragments of residues Aβ1-23, Aβ1-24 and Aβ1-25 rapidly seed to form SDS-stable, LMW Aβ oligomers that impair synaptic plasticity
Authors: Gil Beatriz , Rose Jamie , Demurtas Davide , Mancini Gian-Filippo , Sordet-Dessimoz Jessica , Sorrentino Vincenzo , Rudinskiy Nikita , Frosch Matthew P. , Hyman Bradley T. , Moniatte Marc , Spires-Jones Tara. L. , Herron Caroline E. , Schmid Adrien W. 
Published: December 2022

AbstractIn Alzheimer’s disease (AD), Amyloid-beta (Aβ) oligomers are considered an appealing therapeutic- and diagnostic target. However, to date, the molecular mechanisms associated with the pathological accumulation or structure of Aβ oligomers remains an enigma to the scientific community. Here we demonstrate the strong seeding properties of unique Aβ fragment signatures and show that the truncated Aβ peptides of residues Aβ1-23, Aβ1-24 and Aβ1-25, rapidly seed to form small, SDS-PAGE stable assemblies of ∼5kDa to ∼14kDa molecular mass range. Mass spectrometry analysis of SDS-PAGE fractionated and gel extracted oligomers revealed that the truncated Aβ isoforms of residues 1-23 to 1-25 form stable entities with low molecular weight (LMW) oligomers, which strongly resemble the regularly reported Aβ entities of putative dimeric or trimeric assemblies found in human post-mortem AD and Tg mouse brain extracts. Furthermore, electrophysiological recordings in the mouse hippocampus indicate that LMW Aβ assemblies formed by fragments Aβ1-23 to Aβ1-25 significantly impair long-term-potentiation (LTP) in the absence of full-length Aβ1-42. Extensive antibody screening highlights the important observation, that the LMW Aβ assemblies formed by these truncated Aβ peptides escape immuno-detection using conventional, conformation specific antibodies but, more importantly, the clinical antibody aducanumab. Our novel findings suggest that there are new Aβ target “loopholes” which can be exploited for the development of therapeutic antibodies with binding properties against stable target hotspots present in Aβ oligomers. We provide here a first example of a new class of monoclonal antibody with unique binding properties against LMW Aβ oligomers, in the absence of binding to large fibrillar Aβ assemblies, or dense amyloid plaques. Our research supports a novel, unparalleled approach for targeting early, pathological Aβ species during the insidious phase of AD and prior to the appearance of large oligomeric or protofibrilar assemblies.
A scoping review on the use of consumer-grade EEG devices for research
Authors: Sabio Joshua , Williams Nikolas S , McArthur Genevieve M , Badcock Nicholas A 
Published: December 2022

AbstractBACKGROUNDCommercial electroencephalography (EEG) devices have become increasingly available over the last decade. These devices have been used in a wide variety of fields ranging from engineering to cognitive neuroscience.PURPOSEThe aim of this study was to chart peer-review articles that used currently available consumer-grade EEG devices to collect neural data. We provide an overview of the research conducted with these relatively more affordable and user-friendly devices. We also inform future research by exploring the current and potential scope of consumer-grade EEG.METHODSWe followed a five-stage methodological framework for a scoping review that included a systematic search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. We searched the following electronic databases: PsycINFO, MEDLINE, Embase, Web of Science, and IEEE Xplore. We charted study data according to application (BCI, experimental research, validation, signal processing, and clinical) and location of use as indexed by the first author’s country.RESULTSWe identified 916 studies that used data recorded with consumer-grade EEG: 531 were reported in journal articles and 385 in conference papers. Emotiv devices were most used, followed by the NeuroSky MindWave, OpenBCI, interaXon Muse, and MyndPlay Mindband. The most common use was for brain-computer interfaces, followed by experimental research, signal processing, validation, and clinical purposes.CONCLUSIONSConsumer-grade EEG has proven to be a useful tool for neuroscientific research and will likely continue to be used well into the future. Our study provides a comprehensive review of their application, as well as future directions for researchers who wish to use these devices.