bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of xenon and argon inhalation on erythropoiesis and steroidogenesis: a systematic review
Authors: Bezuglov Eduard , Morgans Ryland , Khalikov Ruslan , Bertholz Vladislav , Emanov Anton , Talibov Oleg , Astakhov Evgeniy , Lazarev Artemii , Shoshorina Maria 
Published: April 2022

AbstractBackgroundXenon and argon inhalation were included in the WADA Prohibited List in 2014 due to the reported positive effects on erythropoiesis and steroidogenesis occurs as a result of the use of these substances. Currently, xenon is on the WADA Prohibited List notable affecting erythropoiesis as a Hypoxia-inducible factor (HIF) activating agent. At the same time, argon inhalation was allowed again in 2019. Thus, the systematic review of studies supporting these notions is of interest.MethodsA thorough search for articles on the effects of xenon and argon inhalation on erythropoiesis and steroidogenesis, as well as their negative effects on human health and methods of their detection in body fluids was conducted. Pubmed, Google Scholar databases and the Cochrane Library were researched, as well as the special research section of the WADA website. The search was conducted in accordance with PRISMA guidelines. All articles in English published between 2000 and 2021 were analyzed, as well as reference studies meeting the search criteria.ResultsAt present, there are only two publications in healthy human subjects evaluating the effects of xenon inhalation on erythropoiesis were found with no conclusive evidence of a positive effect on erythropoiesis. Both articles were published after 2014 when the gases were included on the WADA Prohibited List. Both articles had a high risk of bias. There were no studies on the effect of argon inhalation on erythropoiesis. No studies were found on the effect of xenon or argon inhalation on steroidogenesis in healthy subjects. No studies related to the effects of xenon or argon inhalation on erythropoiesis and steroidogenesis were found on the WADA website.ConclusionThere is still inconclusive evidence to support the administration of xenon and argon inhalations on erythropoiesis and steroidogenesis and their positive effects on health. Further research is needed to establish the effects of these gases. Additionally, improved communication between the anti-doping authorities and all key stakeholders is required to support the inclusion of various substances on the Prohibited List.
Safety and Efficacy of Dupilumab for the Treatment of Hospitalized Patients with Moderate to Severe COVID 19: A Phase IIa Trial
Authors: Sasson Jennifer , Donlan Alexandra N. , Ma Jennie Z. , Haughey Heather M. , Coleman Rachael , Nayak Uma , Mathers Amy J. , Laverdure Sylvain , Dewar Robin , Jackson Patrick E. H. , Heysell Scott K. , Sturek Jeffrey M. , Petri William A. 
Published: April 2022

ABSTRACTBackgroundA profound need remains to develop further therapeutics for treatment of those hospitalized with COVID-19. Based on data implicating the type 2 cytokine interleukin (IL)-13 as a significant factor leading to critical COVID-19, this trial was designed to assess dupilumab, a monoclonal antibody that blocks IL-13 and IL-4 signaling, for treatment of inpatients with COVID-19.MethodsWe conducted a phase IIa randomized double-blind placebo-controlled trial to assess the safety and efficacy of dupilumab plus standard of care versus placebo plus standard of care in mitigating respiratory failure and death in those hospitalized with COVID-19. Subjects were followed prospectively for 60 days. The primary endpoint was the proportion of patients alive and free of invasive mechanical ventilation at 28 days.FindingsForty eligible subjects were enrolled from June to November of 2021. There was no difference in adverse events nor in ventilator free survival at day 28 between study arms. However, for the secondary endpoint of mortality at day 60, subjects randomized to dupilumab had a higher survival rate compared to the placebo group (89.5% vs 76.2%, adjusted HR 0.05, 95% CI: 0.0-0.72, p=0.03). There were fewer subjects admitted to the ICU in the dupilumab group compared to placebo (33.3% vs 66.7%; adjusted HR 0.44, 95% CI: 0.09-2.09, p=0.30). Lastly, we saw downstream evidence of IL-4 and IL-13 signaling blockade in the dupilumab group through analysis of immune biomarkers over time.InterpretationDupilumab was well tolerated and improved 60-day survival in patients hospitalized with moderate to severe COVID-19.Trial RegistrationThis trial is registered with ClinicalTrials.gov, NCT04920916.FundingVirginia Biosciences Health Research Corporation, PBM C19, Henske Family Foundation, National Institutes of Health, National Cancer Institute
Age at cancer diagnosis by breed, weight, sex, and cancer type in a cohort of over 3,000 dogs: determining the optimal age to initiate cancer screening in canine patients
Authors: Rafalko Jill M. , Kruglyak Kristina M. , McCleary-Wheeler Angela L. , Goyal Vidit , Phelps-Dunn Ashley , Wong Lilian K. , Warren Chelsea D. , Brandstetter Gina , Rosentel Michelle C. , McLennan Lisa M. , Grosu Daniel S. , Chibuk Jason , Tsui Dana W.Y. , Chorny Ilya , Flory Andi 
Published: April 2022

AbstractThe goal of cancer screening is to detect disease at an early stage when treatment may be more effective. Until recently, cancer screening in dogs has relied upon annual physical examinations and routine laboratory tests, which are largely inadequate for detecting preclinical disease. With the introduction of non-invasive “liquid biopsy” cancer detection methods, the discussion is shifting from “Howto screen dogs for cancer” to “Whento screen dogs for cancer”. To address this question, data from 3,452 cancer-diagnosed subjects were analyzed to determine the age at which dogs of certain breeds and weights are typically diagnosed with cancer. In the study population, the median age at cancer diagnosis was 8.8 years, with males diagnosed at younger ages than females, and spayed/neutered dogs diagnosed at significantly later ages than intact dogs. Overall, weight was inversely correlated with age at cancer diagnosis, and purebred dogs were diagnosed at significantly younger ages than mixed-breed dogs. For breeds with 10 or more subjects, a breed-based median age at diagnosis was calculated. A weight-based linear regression model was developed to predict the median age at diagnosis for breeds represented by fewer than 10 subjects and for mixed-breed dogs. The study findings support a general recommendation to start cancer screening for all dogs at the age of 7, and as early as 4 years of age for breeds with a lower median age at cancer diagnosis, in order to increase the chances of early detection and treatment.
Spatial, transcriptomic and epigenomic analyses link dorsal horn neurons to chronic pain genetic predisposition
Authors: Arokiaraj Cynthia M. , Leone Michael J. , Kleyman Michael , Chamessian Alexander , Phan BaDoi N. , Lopes Bettega C. , Cherupally Vijay Kiran , Noh Myung-Chul , Corrigan Kelly A. , Yeramosu Deepika , Franusich Michael E. , Podder Riya , Lele Sumitra , Shiers Stephanie , Kang Byungsoo , Kennedy Meaghan M , Chen Viola , Chen Ziheng , Dum Richard P. , Lewis David A. , Qadri Yawar , Price Theodore J. , Pfenning Andreas R. , Seal Rebecca P. 
Published: April 2022

SummaryKey mechanisms underlying chronic pain occur within the neural circuitry of the dorsal horn. Recent genome-wide association studies (GWAS) have identified genetic variants associated with the predisposition to chronic pain. However, most of these variants lie in regulatory non-coding regions that have so far not been linked to spinal cord function. Here, we take a multi-species approach to determine whether chronic pain variants impact regulatory elements of dorsal horn neurons. We first built a more comprehensive single cell atlas; filling gaps by generating a high-quality Rhesus macaque atlas and integrating it with human and mouse. With cellular-resolution spatial transcriptomics, we mapped the laminar distributions of the resulting species-conserved neuron subtypes, uncovering an unexpected organization. Lastly, we generated a mouse single-nucleus open chromatin atlas to partition the heritability of chronic pain traits. From this, we identified strong, selective associations between specific, conserved neuron subtypes and major forms of chronic pain.
Reproducible stool metagenomic biomarkers linked to the melanoma immunotherapy positive outcome
Authors: Olekhnovich Evgenii I. , Ivanov Artem B. , Babkina Anna A. , Sokolov Arseniy A. , Ulyantsev Vladimir I. , Fedorov Dmitry E. , Ilina Elena N. 
Published: April 2022

AbstractThe human gut microbiome plays an important role both in human’s health and disease. Recent studies have shown the undeniable influence of gut microbiota composition on cancer immunotherapy efficacy. However, these researches show a lack of consensus in defining reproducible metagenomic markers for a positive immunotherapy outcome. Accordingly, extended published data re-analysis may help reveal clearer associations between the composition of the gut microbiota and treatment response. In this study, we analyzed 358 stool metagenomes from 5 studies published earlier: 210 metagenomes from melanoma patients with positive immunotherapy outcome, 148 metagenomes from melanoma patients with negative immunotherapy outcome. The biomarkers were selected by the group comparison of patients’ stool samples with different treatment responses (47 responders vs 55 non-responders, 102 metagenomes). Selected biomarkers were verified using the available data describing the influence of the fecal microbiota transplantation on melanoma immunotherapy outcomes (9 donors, 6 responders, 19 non-responders, 256 metagenomes). According to our analysis, the resulting cross-study reproducible taxonomic biomarkers correspond to 12 Firmicutes, 4 Bacteroidetes, and 3 Actinobacteria. 140 gene groups were identified as reproducible functional biomarkers, including those potentially involved in production of immune-stimulating molecules and metabolites. In addition, we ranked taxonomic biomarkers by the number of functional biomarkers found in their metagenomic context. In other words, we predicted a list of the potential “most beneficial” bacteria for a positive response to melanoma immunotherapy. The obtained results can be used to make recommendations for the gut microbiota correction in cancer immunotherapy, and the resulting list of biomarkers can be considered for potential diagnostic ways for predicting melanoma immunotherapy outcome. Another important point is the functional biomarkers of positive immunotherapy outcome are distributed in different bacterial species that can explain the lack of consensus of defining melanoma immunotherapy beneficial species between different studies.
Newfoundland and Labrador: A mosaic founder population of an Irish and British diaspora from 300 years ago
Authors: Gilbert Edmund , Zurel Heather , MacMillan Margaret E. , Demiriz Sedat , Mirhendi Sadra , Merrigan Michael , O’Reilly Seamus , Molloy Anne M. , Brody Lawrence C. , Bodmer Walter , Leach Richard A. , Scott Roderick E. M. , Mugford Gerald , Randhawa Ranjit , Stephens J. Claiborne , Symington Alison L. , Cavalleri Gianpiero L. , Phillips Michael S. 
Published: April 2022

AbstractThe founder population of Newfoundland and Labrador (NL) is a unique genetic resource, in part due to geographic and cultural isolation, where historical records describe a migration of European settlers primarily from Ireland and England to NL in the 18th and 19th centuries. Whilst its historical isolation, and increase prevalence of certain monogenic disorders, have been appreciated, the fine-scale genetic structure and ancestry of the population has not been well described. Understanding the genetic background on which functional, disease causing, genetic variation resides on would aid informed genetic mapping efforts in the Province. Here, we leverage dense genome-wide SNP data on 1,807 NL individuals to reveal fine-scale genetic structure in NL that is clustered around coastal communities and correlated with Christian denomination. We show that the majority of NL European ancestry can be traced back to the south-east and south-west of Ireland and England, respectively. We date a substantial population size bottleneck approximately 10-15 generations ago in NL, associated with increased haplotype sharing and autozygosity. Our results elucidate novel insights into the population history of NL and demonstrate evidence of a population conducive to further genetic studies and biomarker discovery.Significance StatementNewfoundland and Labrador (NL) has been identified as a founder population, though evidence of its magnitude and subsequent isolation is unclear. Here, analysis of 1,807 NL individuals demonstrates population structure associated with geographical isolation in coastal communities and religious denomination (Catholic or Protestant Christian). Further, NL European ancestry primarily descends from settlers from south-east Ireland and south-west England. This history is associated with increased sharing of longer haplotypes in NL, and NL-specific drift in some communities more than others, providing strong evidence of a founder event occurring about 10-15 generations ago. This study elucidates the detailed population structure of NL and shows enrichment for otherwise low frequency functional variants due to genetic drift useful for potential future biomarker discovery studies.
Microstructural alterations in tract development in college football: a longitudinal diffusion MRI study
Authors: Goubran Maged , Mills Brian D. , Georgiadis Marios , Karimpoor Mahta , Mouchawar Nicole , Sami Sohrab , Dennis Emily L. , Akers Carolyn , Mitchell Lex A. , Boldt Brian , Douglas David , DiGiacomo Phil , Rosenberg Jarrett , Grant Gerald , Wintermark Max , Camarillo David , Zeineh Michael 
Published: April 2022

AbstractBackground and ObjectivesRepeated concussive and sub-concussive impacts in high-contact sports can affect the brain’s microstructure, which can be studied using diffusion MRI. Most prior imaging studies, however, employ a cross-sectional design, do not include low-contact players as controls, or use traditional diffusion tensor imaging without investigating novel tractspecific microstructural metrics.MethodsWe examined brain microstructure in 63 high-contact (American football) and 34 low-contact (volleyball) collegiate athletes with up to 4 years of follow-up (315 total scans) using advanced diffusion MRI, a comprehensive set of multi-compartment models, and automated fiber quantification tools. We investigated diffusion metrics along the length of tracts using nested linear mixed-effects models to ascertain the acute and chronic effects of sub-concussive and concussive impacts, as well as associations between diffusion changes with clinical, behavioral, and sports-related measures.ResultsSignificant longitudinal increases in fractional anisotropy and axonal water fraction were detected in volleyball players, but not in football players, along with decreases in radial and mean diffusivity as well as orientation dispersion index (all findings absolute T-statistic > 3.5, p < .0001). This pattern was present in the callosum forceps minor, left superior longitudinal fasciculus, left thalamic radiation, and right cingulum hippocampus. Longitudinal group differences were more prominent and observed in a larger number of tracts in concussed (previously or in-study) football players (p < .0001), while smaller effects were noted in un-concussed players. An analysis of immediate-post concussion scans in football players demonstrated a transient localized increase in axial diffusivity, mean and radial kurtosis in the left uncinate and right cingulum hippocampus (p < .0001). Finally, football players with high position-based sub-concussive risk demonstrated increased orientation dispersion index over time (p < .0001).DiscussionThe observed longitudinal changes in our volleyball cohort likely reflect normal development in this age range, while the relative attenuation of these effects seen in football, and especially concussed athletes, could possibly reveal diminished myelination, altered axonal calibers, or depressed pruning processes leading to a static, non-decreasing axonal dispersion. This prospective longitudinal study demonstrates significantly divergent tract-specific trajectories of brain microstructure, possibly reflecting a concussive and/or repeated sub-concussive impact-related alteration of normal white matter development in football athletes.
Visuo-tactile integration in texture perception: A replication and extension study
Authors: Kangur Karina , Giesel Martin , Harris Julie M. , Hesse Constanze 
Published: April 2022

AbstractEmploying a sensory conflict paradigm, previous research has found that vision and touch contribute, on average, equally to the visuo-tactile perception of surface texture. Our study aimed to, firstly, replicate the original findings using a comparable setup and stimulus set; secondly, examine whether equal modality contributions can also be observed on an individual basis (using a within-subject design); and thirdly, explore how visuo-tactile integration is affected by illumination angle (top vs. oblique). Participants explored a discrepant standard consisting of different abrasive papers by vision, touch, and using both modalities simultaneously, and subsequently had to find the closest visual, tactile, and visuo-tactile match from a set of matching stimuli. We replicated equal contribution from vision and touch across the whole sample in both illumination conditions. We also found considerable inter-individual variations in the modality contributions when the stimuli were illuminated from the top. Interestingly, this variation decreased under oblique illumination, with most participants showing an about-equal contribution from both modalities to the combined texture percept. These findings are consistent with the assumption that the perceived discrepancy between vision and touch was reduced under oblique illumination suggesting overall that visual and tactile information are only weighted equally within a certain range of experienced discrepancy. Outside this individual range, one of the modalities is weighted higher with no clear preference for either modality.
hemispheR: an R package for fisheye canopy image analysis
Authors: Chianucci Francesco , Macek Martin 
Published: April 2022

AbstractHemispherical photography is a relevant tool to estimate canopy attributes such as leaf area index (LAI). Advancements in digital photography and image processing tools have supported long-lasting use of digital hemispherical photography (DHP). While some open-source tools have been made available for DHP, very few solutions have been made available in R programming packages, and none of these allows a full processing workflow to retrieve LAI and other canopy attributes from fisheye images.To fill this gap, we developed an R package (hemispheR) to support the whole processing of DHP images in an automated, fast, and reproducible way. The package functions, which are designed for step-by-step single-image analysis, can be performed sequentially in a pipeline, while allowing inspecting the quality of each image processing step. The package allows to analyze both circular and fullframe fisheye images, collected either with upward facing (forest canopies) or downward facing (short canopies and crops) camera orientation. In addition, the package allows to implement two consolidated LAI methods (LAI-2000/2200 and 57° method).A case study is presented to demonstrate the reliability of canopy attributes derived from hemispheR in temperate deciduous forests with variable canopy density and structure. Canopy attributes were validated against either results obtained from a reference proprietary software, either by benchmarking measurements obtained from terrestrial laser scanning. Results indicated hemispheR provide reliable openness and leaf area index values in forest canopies as compared with reference values.By providing a simple, transparent, and flexible image processing procedure, hemispheR supported the use of DHP for routine measurements and monitoring of forest canopy attributes. Hosting the package in a Git repository will further support development of the package, through either collaborative coding or forking projects.
A deep hierarchy of predictions enables assignment of semantic roles in online speech comprehension
Authors: Su Yaqing , MacGregor Lucy J. , Olasagasti Itsaso , Giraud Anne-Lise 
Published: April 2022

AbstractUnderstanding speech requires mapping fleeting and often ambiguous soundwaves to meaning. While humans are known to exploit their capacity to contextualize to facilitate this process, how internal knowledge is deployed on-line remains an open question. Here, we present a model that extracts multiple levels of information from continuous speech online. The model applies linguistic and nonlinguistic knowledge to speech processing, by periodically generating top-down predictions and incorporating bottom-up incoming evidence in a nested temporal hierarchy. We show that a nonlinguistic context level provides semantic predictions informed by sensory inputs, which are crucial for disambiguating among multiple meanings of the same word. The explicit knowledge hierarchy of the model enables a more holistic account of the neurophysiological responses to speech compared to using lexical predictions generated by a neural-network language model (GPT-2). We also show that hierarchical predictions reduce peripheral processing via minimizing uncertainty and prediction error. With this proof-of-concept model we demonstrate that the deployment of hierarchical predictions is a possible strategy for the brain to dynamically utilize structured knowledge and make sense of the speech input.
Western spotted skunks provide important food web linkages in forest of the Pacific Northwest
Authors: Tosa Marie I. , Lesmeister Damon B. , Allen Jennifer M. , Levi Taal 
Published: April 2022

AbstractThere are increasing concerns about the decreasing population trends of small mammalian carnivores around the world. With limited knowledge about their ecology and natural history, small mammal conservation and management remains difficult. To address one of these deficiencies for western spotted skunks (Spilogale gracilis), we investigated their diet in the Oregon Cascades of the Pacific Northwest during 2017 – 2019. We collected 130 spotted skunk scats opportunistically and with detection dog teams and identified prey items using DNA metabarcoding and mechanical sorting. Western spotted skunk diet consisted of invertebrates such as wasps, millipedes, and gastropods, vertebrates such as small mammals, amphibians, and birds, and plants such as Gaultheria, Rubus, and Vaccinium. Diet also consisted of items such as black-tailed deer that were likely scavenged. Comparison in diet by season revealed that spotted skunks consumed more insects during the dry season (June - August) and marginally more mammals during the wet season (September – May). We observed similar diet in areas with no record of human disturbance and areas with a history of logging. Western spotted skunks provide important food web linkages between aquatic, terrestrial, and arboreal systems by facilitating energy and nutrient transfer, and serve important functional roles of seed dispersal and scavenging. Through prey-switching, western spotted skunks may dampen the effects of irruptions of prey, such as wasps during dry springs and summers, which could then provide ecosystem resilience to environmental change.