bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional lung imaging identifies peripheral ventilation changes in mice with muco-obstructive lung disease
Authors: Reyne Nicole , Smith Ronan , Cmielewski Patricia , Eikelis Nina , Nilsen Kris , Louise Jennie , Duerr Julia , Mall Marcus A. , Lawrence Mark , Parsons David , Donnelley Martin 
Published: July 2024

Abstractβ-ENaC-Tg mice serve as a relevant model of muco-obstructive lung disease, with impaired mucociliary clearance, mucus obstruction, chronic airway inflammation, structural lung damage, and altered lung function. The aim of this study was to undertake a comprehensive lung function and mechanics analysis of the adult β-ENaC-Tg model. β-ENaC-Tg and wild-type littermates underwent X-ray Velocimetry (XV) scans using a Permetium XV scanner (4DMedical, Melbourne, Australia). For comparative lung mechanics, lung function assessments were conducted with a flexiVent system. XV imaging demonstrated elevated ventilation defect percentage, mean specific ventilation, and ventilation heterogeneity in β-ENaC-Tg mice. Spatial analysis of ventilation maps indicated increased ventilation variability in the peripheral lung regions, as well as an increased proportion of under-ventilated areas. The flexiVent analysis indicated that compared to wild-types, β-ENaC-Tg mice have a significantly more compliant lungs with increased inspiratory capacity, reduced tissue elastance and increased hysteresivity (heterogeneity), suggesting loss of parenchymal integrity. This research highlights the utility of XV imaging in evaluating ventilation defects in the β-ENaC-Tg model and provides a comprehensive lung function analysis.
Parallelism between phylogeny and ontogeny
Authors: Bergman Juraj , Bakarić Robert , Brčić-Kostić Krunoslav 
Published: July 2024

ABSTRACTHaeckel’s biogenetic law, or the recapitulation theory remains a controversial subject to this day. Currently, the modern version of biogenetic law is the hourglass model with its phylotypic period. Importantly, the hourglass model is nothing more than a model of development, and it does not provide any evidence that ontogeny recapitulates phylogeny. However, the hourglass model and biogenetic law are not mutually exclusive, and there are several examples of recapitulation-like processes observable after the phylotypic period of ontogeny. At the level of transcriptomics, all attempts to demonstrate recapitulation failed. Using a novel approach, combining transcriptomics with phylostratigraphy, we demonstrate that recapitulation, or parallelism between phylogeny and ontogeny, exists. We show that the mean indispensability of genes decreases for phylogenetically younger genes, as well as genes expressed during later stages of ontogeny. We also define the ontotypic period of phylogeny, an analog to the phylotypic period of ontogeny. Since it starts from the beginning of phylogeny, it is reasonable to hypothesize that recapitulation starts from the phylotypic period. We conclude that parallelism, or recapitulation, is explainable by the fact that genes that emerged later in phylogeny have tendencies to be expressed during later stages of ontogeny.
Detecting epidemic-driven selection: a simulation-based tool to optimize sampling design and analysis strategies
Authors: Santander Cindy G. , Moltke Ida 
Published: July 2024

AbstractThroughout history, populations from numerous species have been decimated by epidemic outbreaks, like the 19th-century rinderpest outbreak in Cape buffalo (≈90% mortality) and Black Death in humans (≈50% mortality). Recent studies have raised the enticing idea that such epidemic outbreaks have led to strong natural selection acting on disease-protective variants in the host populations. However, so far there are few, if any, clear examples of such selection having taken place. This could be because so far studies have not had sufficient power to detect the type of selection an epidemic outbreak must induce: strong but extremely short-term selection on standing variation. We present here a simulation-framework that allows users to explore under what circumstances it is possible to detect epidemic-driven selection using standard selection scan methods likeFSTand iHS. Using two examples, we illustrate how the framework can be used. Furthermore, via these examples, we show that comparing survivors to the dead has the potential to render higher power than more commonly used sampling schemes. And importantly, we show that even for outbreaks with high mortality, like the Black Death, strong selection may have led to only modest shifts in allele frequency, suggesting large sample sizes are required to obtain appropriate power to detect the selection. We hope this framework can help in designing well-powered future studies and thus lead to a clarification of the role epidemic-driven selection has played in the evolution of different species.Significance StatementOur study introduces a simulation-based framework,SimOutbreakSelection(SOS), which enables researchers to design studies that have power to detect epidemic-driven selection while taking sampling time points and demographic history into account. We use rinderpest in African Buffalo and the Black Death in Medieval Sweden as examples to showcase the framework. Via these examples we also show that large sample sizes are needed even for severe epidemics like the Black Death and that the often used sampling strategy where samples from before the epidemic and samples from after are compared is not always optimal.
Live-cell RNA imaging with the inactivated endonuclease Csy4 enables new insights into plant virus transport through plasmodesmata
Authors: Burnett David , Hussein Mohamed , Barr Zoe Kathleen , Näther Laura Newsha , Wright Kathryn M. , Tilsner Jens 
Published: July 2024

AbstractPlant-infecting viruses spread through their hosts by transporting their infectious genomes through intercellular nano-channels called plasmodesmata. This process is mediated by virus-encoded movement proteins, which bind nucleic acids and target and dilate plasmodesmata. Whilst the sub-cellular localisations of movement proteins have been intensively studied, live-cell RNA imaging systems have so far not been able to detect viral genomes inside the plasmodesmata. Here, we describe a new, highly sensitive RNA live-cell reporter based on an enzymatically inactive form of the small bacterial endonuclease Csy4, which binds to its cognate stem-loop with nanomolar affinity. This system allows imaging of plant viral RNA genomes inside plasmodesmata and shows thatPotato virus XRNA remains accessible within the channels and is therefore not fully encapsidated during movement. We also combine Csy4-based RNA-imaging with interspecies movement complementation to show that an unrelated movement protein fromTobacco mosaic viruscan recruitPotato virus Xreplication complexes to plasmodesmata entrances. Therefore, recruitment of replication complexes is mediated non-specifically, likely by indirect coupling of movement proteins and viral replicaseviathe viral RNA or co-compartmentalisation, potentially contributing to transport specificity. Lastly, we show that a ‘self-tracking’ virus can express the Csy4-based reporter during the progress of infection. However, expression of the RNA-binding proteinin cisinterferes with viral movement by an unidentified mechanism when cognate stem-loops are present in the viral RNA.
Whole Genome Landscape Analysis of Homologous Recombination Deficiency in a Pan-Cancer Cohort
Authors: Al Assaad Majd , Hadi Kevin , Levine Max F. , Guevara Daniela , Patel Minal , Tranquille Marvel , King Abigail , Otilano John , Semaan Alissa , Gundem Gunes , Medina-Martínez Juan S. , Sigouros Michael , Manohar Jyothi , Kuo Hui-Hsuan , Wilkes David C. , Andreopoulou Eleni , Chapman-Davis Eloise , Tagawa Scott T. , Sboner Andrea , Ocean Allyson J. , Shah Manish , Papaemmanuil Elli , Sternberg Cora N. , Holcomb Kevin , Nanus David M. , Elemento Olivier , Mosquera Juan Miguel 
Published: July 2024

AbstractPurposeHomologous recombination deficiency (HRD) impacts cancer treatment strategies, particularly the effectiveness of PARP inhibitors. However, the variability different HRD assays has hampered the selection of oncology patients who may benefit from these therapies. Our study aims to assess the whole genome landscape to better define HRD in a pan-cancer cohort and to contribute to harmonization of HRD detection.MethodsWe employed a whole-genome sequencing WGS HRD classifier that included genome-wide features associated with HRD to analyze 580 tumor/normal paired pan-cancer samples. The HRD results were correlated retrospectively with treatment responses and were compared with commercial HRD tests in a subset of cases.ResultsHRD phenotype was identified in 62 samples across various cancers including breast (19%), pancreaticobiliary (17%), gynecological (15%), prostate (8%), upper gastrointestinal (GI) (2%), and other cancers (1%). HRD cases were not confined toBRCA1/2mutations; 24% of HRD cases wereBRCA1/2wild-type. A diverse range of HRR pathway gene alterations involved in HRD were elucidated, including biallelic mutations inFANCF, XRCC2, andFANCC, and deleterious structural variants. Comparison with results from commercial HRD assays suggests a better performance of WGS to detect HRD, based on treatment response.ConclusionHRD is a biomarker used to determine which cancer patients would benefit from PARPi and platinum-based chemotherapy. However, a lack of harmonization of tests to determine HRD status makes it challenging to interpret their results. Our study highlights the use of comprehensive WGS analysis to predict HRD in a pan-cancer cohort, elucidates new genomic mechanisms associated with HRD, and enables an accurate identification of this phenotype, paving the way for improved outcomes in oncology care.
GABAergic modulation of beta power enhances motor adaptation in frontotemporal lobar degeneration
Authors: Hughes Laura E. , Adams Natalie E. , Rouse Matthew A. , Naessens Michelle , Shaw Alexander , Murley Alexander G. , Cope Thomas E. , Holland Negin , Nesbitt David , Street Duncan , Whiteside David J. , Rowe James B. 
Published: July 2024

AbstractThe impairment of behavioural control is a characteristic feature of disorders associated with frontotemporal lobar degeneration (FTLD). Behavioural disinhibition and impulsivity in these disorders are linked to abnormal neurophysiology of the frontal lobe, such as the loss beta-band power and changes in prefrontal GABAergic neurotransmission. Here we test the hypothesis that a pharmacological increase of GABA would concurrently improve cortical beta-band power and adaptive behavioural control in people with behavioural-variant frontotemporal dementia (bvFTD), and progressive supranuclear palsy (PSP, Richardson’s syndrome). We recorded magnetoencephalography during a visuomotor task that measures participants’ ability to adapt motor responses to visual feedback. Tiagabine, a GABA re-uptake inhibitor, was used as a pharmacological probe in a double-blind placebo controlled crossover design. The study included 11 people with bvFTD, 11 people with PSP and 20 healthy age-matched controls. Behavioural performance and beta power were examined with linear mixed models examined changes in, to estimate motor learning over time and the response to tiagabine. Significant beta power differences were source-localised using linear-constraint minimum variance beamformer. As predicted, participants with bvFTD and PSP were impaired behaviourally, and the beta power associated with movement, learning and accuracy, was diminished compared to controls. Tiagabine facilitated partial recovery of the impairments in behaviour and beta power over trials, moderated by executive function, such that the greatest improvements were seen in those with higher cognitive scores. The beamformer localised the physiological effects of disease and tiagabine treatment to frontal cortices, and confirmed the right prefrontal cortex as a key site of drug by group interaction. We interpret the differential response to tiagabine between bvFTD and PSP as a function of baseline differences in atrophy and physiology. In summary, behavioural and neurophysiological deficits can be mitigated by enhancement of GABAergic neurotransmission. Clinical trials are warranted to test for enduring clinical benefits from this restorative-psychopharmacology strategy.
Risk reduction in SARS-CoV-2 infection and reinfection conferred by humoral antibody levels among essential workers during Omicron predominance
Authors: Hollister James , Porter Cynthia , Sprissler Ryan , Beitel Shawn C , Romine James K. , Uhrlaub Jennifer L. , Grant Lauren , Yoo Young M. , Fowlkes Ashley , Britton Amadea , Olsho Lauren E.W. , Newes-Adeyi Gabriella , Fuller Sammantha , Zheng Pearl Q. , Gaglani Manjusha , Rose Spencer , Dunnigan Kayan , Naleway Allison L. , Gwynn Lisa , Caban-Martinez Alberto , Schaefer Solle Natasha , Tyner Harmony L. , Philips Andrew L. , Hegmann Kurt T , Yoon Sarang , Lutrick Karen , Burgess Jefferey L. , Ellingson Katherine D. 
Published: July 2024

AbstractThe extent to which semi-quantitative antibody levels confer protection against SARS-CoV-2 infection in populations with heterogenous immune histories is unclear. Two nested case-control studies were designed within the multisite HEROES/RECOVER prospective cohort of frontline workers to study the relationship between antibody levels and protection against first-time post-vaccination infection and reinfection with SARS-CoV-2 from December 2021 to January 2023. All participants submitted weekly nasal swabs for rRT-PCR testing and blood samples quarterly and following infection or vaccination. Cases of first-time post-vaccination infection following a third dose of monovalent (origin strain WA-1) mRNA vaccine (n=613) and reinfection (n=350) were 1:1 matched to controls based on timing of blood draw and other potential confounders. Conditional logistic regression models were fit to estimate infection risk reductions associated with 3-fold increases in end titers for receptor binding domain (RBD). In first-time post-vaccination and reinfection study samples, most were female (67%, 57%), non-Hispanic (82%, 68%), and without chronic conditions (65%, 65%). The odds of first-time post-vaccination infection were reduced by 21% (aOR=0.79, 95% CI=[0.66-0.96]) for each 3-fold increase in RBD end titers. The odds of reinfection associated with a 3-fold increase in RBD end titers were reduced by 23% (aOR=0.77, 95% CI=[0.65-0.92] for unvaccinated individuals and 58% (aOR=0.42, 95% CI=0.22-0.84) for individuals with three mRNA vaccine doses following their first infection. Frontline workers with higher antibody levels following a third dose of mRNA COVID-19 vaccine were at reduced risk of SARS-CoV-2 during Omicron predominance. Among those with previous infections, the point estimates of risk reduction associated with antibody levels was greater for those with three vaccine doses compared to those who were unvaccinated.
Does time awareness coaching support hybrid workers’ wellbeing?: Protocol for a pilot randomized controlled trial
Authors: Young Anna Navin , Blasi Zelda Di , Foley Sarah , Hunt Eithne 
Published: July 2024

AbstractBackgroundHigh rates of poor employee mental health and wellbeing have spurred growing demands for initiatives that support wellbeing in the workplace. The promotion of positive mental health and wellbeing is an essential component of workplace wellbeing initiatives, focusing on enhancing positive aspects of work, workers’ capacities, and positive behaviors. As one of the fastest growing practices in personal and professional development, coaching is found to improve workers’ wellbeing and performance through reflection, awareness, and meaningful goal pursuit. As time-related challenges exacerbate workplace stressors and threaten wellbeing, specific time-focused coaching approaches are essential to the promotion of positive mental health and wellbeing in the workplace. Effectively addressing work-time challenges is especially critical for hybrid workers, who divide their work-time across multiple onsite and remote locations.MethodsThe current paper is a protocol for a pilot three-armed randomized controlled trial that aims to evaluate the effectiveness of a time awareness coaching (TAC) intervention to support hybrid workers’ wellbeing. Sixty hybrid working participants will be randomized to either the TAC intervention, reflective time tracking (active control), or a passive control group. Professional coaches will be recruited and trained to facilitate the TAC intervention. Pre-post intervention measures of chronic time pressure, perceived control of time, perceived stress, wellbeing, and self-efficacy will be evaluated and compared across intervention arms. Qualitative feedback from participants and coaches will be collected to assess the intervention’s acceptability and implementation.DiscussionThe results of the study will offer insights into intervention effectiveness as well as the feasibility of critical intervention elements such as recruitment, retention, and implementation. The findings will inform recommendations for the use of TAC in future research studies and workplace wellbeing initiatives.
Human Papilloma Virus Circulating Cell-Free DNA Kinetics in Cervical Cancer Patients Undergoing Definitive Chemoradiation
Authors: Seo Aaron , Xiao Weihong , Gjyshi Olsi , Yoshida-Court Kyoko , Wei Peng , Swanson David , Napravnik Tatiana Cisneros , Grippin Adam , Venkatesan Aradhana M , Jacobsen Megan C , Fuentes David T , Lynn Erica , Sammouri Julie , Jhingran Anuja , Joyner Melissa , Lin Lilie L , Colbert Lauren E , Gillison Maura L , Klopp Ann H 
Published: July 2024

ABSTRACTPurposeThe human papillomavirus (HPV) is a significant cause of cervical cancer. We hypothesized that detecting viral cell-free HPV DNA (cfDNA) before, during, and after chemoradiation (chemoRT) could provide insights into disease extent, clinical staging, and treatment response.Experimental DesignSixty-six patients with locally advanced cervical cancer were enrolled between 2017 and 2023, with 49 receiving standard-of-care (SOC) treatment and 17 participating in a clinical trial combining a therapeutic HPV vaccine (PDS0101; IMMUNOCERV). Plasma samples were collected at baseline, during weeks 1, 3, and 5 of chemoRT, and 3-4 months after chemoRT. HPV cfDNA was quantified using droplet digital PCR targeting the HPV E6/E7 oncogenes of 13 high-risk types. MRI was performed at baseline and before brachytherapy.ResultsThe median follow-up was 23 months, with recurrence-free survival (RFS) of 78.4% at 2 years. Baseline nodal disease extent correlated with HPV cfDNA levels. HPV cfDNA levels peaked in week 1 of radiation and decreased through treatment. Patients receiving the PDS0101 vaccine had a higher rate of undetectable HPV type 16 cfDNA compared to SOC. HPV cfDNA clearance correlated with better 2-yr RFS (92.9% vs. 30%, log-rank p=0.0067). The strongest predictor of RFS was HPV cfDNA clearance in follow-up achieving a concordance index (CI) 0.83, which improved when combined with MRI response (CI 0.88).ConclusionsHPV cfDNA levels change dynamically during chemoRT. HPV cfDNA levels at first follow-up predict RFS, and the therapeutic HPV vaccine was linked to rapid HPV cfDNA decline. Monitoring HPV cfDNA during and after chemoRT may guide tailoring of personalized treatment.
A Split-Belt Instrumented Treadmill with Uneven Terrain
Authors: Hosseini-Yazdi Seyed Saleh , Kuo Arthur D. 
Published: July 2024

AbstractThe biomechanics of walking are far less understood for uneven terrain than flat or even surfaces. This is due in part to a lack of ground reaction force and moment recordings from each leg. These are often obtained with split-belt instrumented treadmills, which are currently incompatible with uneven terrain, making it difficult to perform biomechanics analyses such as inverse dynamics. Here we show how a standard split-belt instrumented treadmill (Bertec, Inc., Columbus, OH) can be modified to accommodate a variety of uneven terrains. The principal design considerations are structural clearance to allow passage of an uneven treadmill belt and fabrication of the terrain. We designed mechanical components with sufficient clearance for terrains up to 0.045 m high, and formed the terrain from uneven strips of polystyrene. Measured ground reaction forces from each leg at typical walking speeds agreed well with an intact benchmark treadmill (minimum interclass cross correlation score = 0.97). The modifications had negligible effect on the treadmill’s structural strength. The terrain produced some noise-like vibrations, but at much higher frequencies than fundamental to human locomotion. The uneven terrain treadmill can record many steps of the full complement of ground reaction forces and moments from individual legs.
Motor adaptation is reduced by symbolic compared to sensory feedback
Authors: Chen Yifei , Abram Sabrina J. , Ivry Richard B. , Tsay Jonathan S. 
Published: July 2024

AbstractMotor adaptation – the process of reducing motor errors through feedback and practice – is an essential feature of human competence, allowing us to move accurately in dynamic and novel environments. Adaptation typically results from sensory feedback, with most learning driven by visual and proprioceptive feedback that arises with the movement. In humans, motor adaptation can also be driven by symbolic feedback. In the present study, we examine how implicit and explicit components of motor adaptation are modulated by symbolic feedback. We conducted three reaching experiments involving over 400 human participants to compare sensory and symbolic feedback using a task in which both types of learning processes could be operative (Experiment 1) or tasks in which learning was expected to be limited to only an explicit process (Experiments 2 and 3). Adaptation with symbolic feedback was dominated by explicit strategy use, with minimal evidence of implicit recalibration. Even when matched in terms of information content, adaptation to rotational and mirror reversal perturbations was slower in response to symbolic feedback compared to sensory feedback. Our results suggest that the abstract and indirect nature of symbolic feedback disrupts strategic reasoning and/or refinement, deepening our understanding of how feedback type influences the mechanisms of sensorimotor learning.