bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential use of antibodies to provide an earlier indication of lymphatic filariasis resurgence in post-mass drug administration surveillance, American Samoa
Authors: Cadavid Restrepo Angela M. , Gass Katherine , Won Kimberly Y. , Sheel Meru , Robinson Keri , Graves Patricia M. , Fuimaono Saipale , Lau Colleen L 
Published: December 2021

AbstractObjectivesUnder the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted seven rounds of mass drug administration between 2000 and 2006. The territory passed transmission assessment surveys (TAS) in 2011 (TAS-1) and 2015 (TAS-2) based on World Health Organization guidelines. In 2016, the territory failed TAS-3, indicating resurgence. This study aims to determine if antibodies (Ab) may have provided a timelier indication of LF resurgence in American Samoa.MethodsWe examined school-level Ag and Ab status (presence/absence of Ag- and Ab- positive children) and prevalence of single and combined Ab responses to Wb123, Bm14, Bm33 Ags at each TAS. Pearson’s chi-squared tests and logistic regression were used to examine associations between school-level Ab prevalence in TAS-1 and TAS-2 and school-level Ag status in TAS-3.ResultsSchools with higher prevalence of Wb123 Ab in TAS-2 had higher odds of being Ag-positive in TAS-3 (odds ratio [OR] 24.5, 95% CI:1.2-512.7). Schools that were Ab-positive for WB123 plus Bm14, Bm33 or both Bm14 and Bm33 in TAS-2 had higher odds of being Ag-positive in TAS-3 (OR 16.0-24.5).ConclusionAnti-filarial Abs could provide earlier signals of resurgence and enable a timelier response. The promising role of Abs in post-MDA surveillance and decision making should be further investigated in other settings.
Ambiguous Body Ownership Experience Caused by Feeling–judgement Conflict: Evidence from Subjective Measurement in Rubber Hand Illusion using Integrated Information Theory
Authors: Niizato Takayuki , Nishiyama Yuta , Sakamoto Kotaro , Kazama Takumi , Okabayashi Tatsuya , Yamaguchi Taiki 
Published: December 2021

AbstractHuman body awareness is malleable and adaptive to changing contexts. The illusory sense of body-ownership has been studied since the publication of the rubber hand illusion, where ambiguous body ownership feeling, expressed as “the dummy hand is my hand even though that is not true”, was first defined. Phenomenologically, the ambiguous body ownership is attributed to a conflict between feeling and judgement; in other words, it characterises a discrepancy between first-person (i.e. bottom-up) and third-person (i.e. top-down) processes. Although Bayesian inference can explain this malleability of body image sufficiently, the theory does not provide a good illustration of why we have different experiences to the same stimuli – the difficulty lies in the uncertainty regarding the concept of judgement in their theory.This study attempts to explain subjective experience during rubber hand illusions using integrated information theory (IIT). The integrated information Φ in IIT measures the difference between the entire system and its subsystems. This concept agrees with the phenomenological interpretation – that is, there is conflict between judgement and feeling. By analysing the seven nodes of a small body– brain system, we demonstrate that the integrity of the entire system during the illusion decreases with increasing integrity of its subsystems. These general tendencies agree well with many brain-image analyses and subjective reports; furthermore, we found that subjective ratings were associated with the Φs. Our result suggests that IIT can explain the general tendency of the sense of ownership illusions and individual differences in subjective experience during the illusions.
SR Ca2+ handling in unbranched, immediately post-necrotic fast-twitch mdx fibres is similar to wt littermates
Authors: Chan Stephen , Kueh Sindy L. L. , Morley John W. , Head Stewart I. 
Published: December 2021

AbstractThere is a lack of consensus in the literature regarding the effects of dystrophin deficiency on the Ca2+-handling properties of the SR in mdx mice, an animal model of Duchenne muscular dystrophy. One possible reason for this is that only a few studies control for the presence of branched fibres. Fibre branching, a consequence of degenerative-regenerative processes such as muscular dystrophy, has in itself a significant influence on the function of the SR. In our present study we attempt to detect early effects of dystrophin deficiency on SR Ca2+ handling by using unbranched fibres from the immediate post-necrotic stage in mdx mice (just regenerated following massive necrosis). Using kinetically-corrected Fura-2 fluorescence signals measured during twitch and tetanus, we analysed the amplitude, rise time and decay time of Δ[Ca2+]i in unfatigued and fatigued fibres. Decay was also resolved into SR pump and SR leak components. Fibres from mdx mice were similar in all respects to fibres from wt littermates apart from: (i) a longer rise time and slower rate of rise of [Ca2+]i during a tetanus; and (ii) a mitigation of the fall in Δ[Ca2+]i amplitude during the course of fatigue. Our findings suggest that the early effects of a loss of dystrophin on SR Ca2+ handling are only slight, and differ from the widely held view that there is significant Ca2+ pathology in mdx mice. It may be that Ca2+ pathology is magnified by progressive branching and degeneration.New findingsCentral question: What are the early effects of dystrophin deficiency on SR Ca2+ handling in the mdx mouse?Main finding: In the mdx mouse, Ca2+ handling by the SR is little affected by the absence of dystrophin when looking at fibres without branches that have just regenerated following massive myonecrosis. This has important implications for the traditional view that Ca2+ pathology is significant in the mdx mouse.
Proteomics Indicates Lactate Dehydrogenase is Prognostic in Acetaminophen-induced Acute Liver Failure Patients and Reveals a Role for LKB1-AMPK Signaling
Authors: Vazquez Joel H. , Kennon-McGill Stefanie , Byrum Stephanie D. , Mackintosh Samuel G. , Jaeschke Hartmut , Williams D. Keith , Lee William M. , Dranoff Jonathan A. , McGill Mitchell R. ,   Acute Liver Failure Study Group
Published: December 2021

ABSTRACTBetter biomarkers to predict death early in acute liver failure (ALF) are needed. To that end, we obtained early (study day 1) and later (day 3) serum samples from transplant-free survivors (n=28) and non-survivors (n=30) of acetaminophen (APAP)-induced ALF from the NIH-sponsored Acute Liver Failure Study Group, and from control volunteers (n=10). To identify proteins that increase early in serum during ALF, we selected individuals from this cohort for whom ALT was lower on day 1 than day 3, indicating a time point before the peak of injury (n=10/group). We then performed untargeted proteomics on their day 1 samples. Out of 1,682 quantifiable proteins, 79 were elevated ≥4-fold in ALF patients vs. controls and 23 of those were further elevated ≥4-fold in non-survivors vs. survivors, indicating potential to predict death. Interestingly, the biomarker with best performance was LDH. To confirm the prognostic potential of LDH, we measured activity in all day 1 and 3 samples from all 58 ALF patients. LDH was elevated in the non-survivors vs. survivors on both days. In addition, receiver operating characteristic (ROC) curve analyses revealed that LDH alone performed similarly to the model for end-stage liver disease (MELD), while a combination of MELD and LDH outperformed either alone. Finally, Upstream Analysis of our proteomics data indicated activation of LKB1-AMPK signaling in liver regeneration after APAP overdose and we confirmed that in mice. Overall, we conclude LDH can predict death in APAP-induced ALF and that LKB1-AMPK signaling may be a promising therapeutic target to improve survival.
Machine learning for prediction of immunotherapy efficacy in non-small cell lung cancer from simple clinical and biological data
Authors: Benzekry Sébastien , Grangeon Mathieu , Karlsen Mélanie , Alexa Maria , Bicalho-Frazeto Isabella , Chaleat Solène , Tomasini Pascale , Barbolosi Dominique , Barlesi Fabrice , Greillier Laurent 
Published: December 2021

ABSTRACTBackgroundImmune checkpoint inhibitors (ICIs) are now a therapeutic standard in advanced non-small cell lung cancer (NSCLC), but strong predictive markers for ICIs efficacy are still lacking. We evaluated machine learning models built on simple clinical and biological data to individually predict response to ICIs.MethodsPatients with metastatic NSCLC who received ICI in second line or later were included. We collected clinical and hematological data and studied the association of this data with disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Multiple machine learning (ML) algorithms were assessed for their ability to predict response.ResultsOverall, 298 patients were enrolled. The overall response rate and DCR were 15.3 % and 53%, respectively. Median PFS and OS were 3.3 and 11.4 months, respectively. In multivariable analysis, DCR was significantly associated with performance status (PS) and hemoglobin level (OR 0.58, p<0.0001; OR 1.8, p<0.001). These variables were also associated with PFS and OS and ranked top in random forest-based feature importance. Neutrophils-to-lymphocytes ratio was also associated with DCR, PFS and OS. The best ML algorithm was a random forest. It could predict DCR with satisfactory efficacy based on these three variables. Ten-fold cross-validated performances were: accuracy 0.68 ± 0.04, sensitivity 0.58 ± 0.08; specificity 0.78 ± 0.06; positive predictive value 0.70 ± 0.08; negative predictive value 0.68 ± 0.06; AUC 0.74 ± 0.03.ConclusionCombination of simple clinical and biological data could accurately predict disease control rate at the individual level.Highlights-Machine learning applied to a large set of NSCLC patients could predict efficacy of immunotherapy with a 69% accuracy using simple routine data-Hemoglobin levels and performance status were the strongest predictors and significantly associated with DCR, PFS and OS-Neutrophils-to-lymphocyte ratio was also associated with outcome-Benchmark of 8 machine learning models
Network Assisted Analysis ofDe NovoVariants Using Protein-Protein Interaction Information Identified 46 Candidate Genes for Congenital Heart Disease
Authors: Xie Yuhan , Jiang Wei , Dong Weilai , Li Hongyu , Jin Sheng Chih , Brueckner Martina , Zhao Hongyu 
Published: December 2021

AbstractDe novovariants (DNVs) with deleterious effects have proved informative in identifying risk genes for early-onset diseases such as congenital heart disease (CHD). A number of statistical methods have been proposed for family-based studies or case/control studies to identify risk genes by screening genes with more DNVs than expected by chance in Whole Exome Sequencing (WES) studies. However, the statistical power is still limited for cohorts with thousands of subjects. Under the hypothesis that connected genes in protein-protein interaction (PPI) networks are more likely to share similar disease association status, we develop a Markov Random Field model that can leverage information from publicly available PPI databases to increase power in identifying risk genes. We identified 46 candidate genes with at least 1 DNV in the CHD study cohort, including 18 known human CHD genes and 35 highly expressed genes in mouse developing heart. Our results may shed new insight on the shared protein functionality among risk genes for CHD.
Single-cell physical phenotyping of mechanically dissociated tissue biopsies for fast diagnostic assessment
Authors: Soteriou Despina , Kubánková Markéta , Schweitzer Christine , López-Posadas Rocío , Pradhan Rashmita , Thoma Oana-Maria , Györfi Andrea-Hermina , Matei Alexandru-Emil , Waldner Maximilian , Distler Jörg H. W. , Scheuermann Stefan , Langejürgen Jens , Schneider-Stock Regine , Atreya Raja , Neurath Markus F. , Hartmann Arndt , Guck Jochen 
Published: December 2021

AbstractRapid and accurate histopathological diagnosis during surgery is critical for clinical decision-making. The prevalent method of intraoperative consultation pathology is time, labour and cost intensive and requires the expertise of trained pathologists. Here, we present an alternative technique for the rapid, label-free analysis of biopsy samples by sequentially assessing the physical phenotype of singularized, suspended cells in high-throughput. This new diagnostic pipeline combines enzyme-free, mechanical dissociation of tissues with real-time deformability cytometry at measurement rates of 100 – 1,000 cells/sec, and machine learning-based analysis. We show that physical phenotype parameters extracted from brightfield images of single cells can be used to distinguish subpopulations of cells in various tissues, without prior knowledge or the need for molecular markers. Further, we demonstrate the potential of our method for inflammatory bowel disease diagnostics. Using unsupervised dimensionality reduction and logistic regression, we accurately differentiate between healthy and tumorous tissue in both mouse and human biopsy samples. The method delivers results within 30 minutes, laying the groundwork for a fast and marker-free diagnostic pipeline to detect pathological changes in solid biopsies.
Accessibility of Canadian COVID-19 Testing Locations for People with Disabilities During the Third Wave of the COVID-19 Pandemic
Authors: Rotenberg Sara , Cooper Jane , Downer Matthew B. 
Published: December 2021

AbstractBackgroundCanadians with disabilities make up nearly a quarter of the population yet face barriers in accessing information about COVID-19 testing accessibility across the country.ObjectiveNo known studies evaluate the online information about the accessibility of COVID-19 testing locations. This study aimed to understand the accessibility of COVID-19 testing sites in Canada based on online information in March 2021.MethodsKey accessibility features were identified to evaluate COVID-19 testing websites information on accessibility and data were extracted from the website to simulate the user experience of booking a COVID-19 test.ResultsAll provinces and territories provided minimal accessibility information on their COVID-19 testing websites, except for Ontario. Out of 170 testing locations in Ontario, few had information about accessibility, with only 8.2% listing at least 3 of the 5 key accessibility features measured on their websites.ConclusionsThis paper demonstrates that more than a year into the pandemic, there existed a clear lack of accessibility information for Canadian testing locations for people with disabilities.
Cytolysin-positive Enterococcus faecalis is elevated in patients with chronic alcoholic pancreatitis
Authors: Perrin Clara , Rebours Vinciane , Trainel Nicolas , Voican Cosmin Sebastian , Perlemuter Gabriel , Cassard Anne-Marie , Ciocan Dragos 
Published: December 2021

ABSTRACTIntroductionPatients with alcoholic hepatitis have an increase in cytolysin-producing Enterococcus faecalis that correlates with disease severity and mortality.AimTo determine whether patients with chronic alcoholic pancreatitis have an elevated abundance of cytolysin-producing E. faecalis.MethodsQuantification by qPCR of cytolysin-producing E. faecalis in controls and patients with alcoholic hepatitis or pancreatitis.ResultsPatients with alcoholic pancreatitis had a higher proportion of intestinal cytolysin-positive E. faecalis than healthy controls and patients with alcoholic hepatitis.ConclusionCytolytic E. faecalis may also be involved in this other alcohol-related complication and benefit from targeted microbiota editing strategies.
AP2/ERF transcription factor NbERF-IX-33 is involved in the regulation of phytoalexin production for the resistance ofNicotiana benthamianatoPhytophthora infestans
Authors: Imano Sayaka , Fushimi Mayuka , Camagna Maurizio , Tsuyama-Koike Akiko , Mori Hitoshi , Ashida Akira , Tanaka Aiko , Sato Ikuo , Chiba Sotaro , Kawakita Kazuhito , Ojika Makoto , Takemoto Daigo 
Published: December 2021

ABSTRACTPlants recognize molecular patterns unique to a certain group of microbes to induce effective resistance mechanisms. Elicitins are secretory proteins produced by plant pathogenic oomycete genera includingPhytophthoraandPythium. Treatment of INF1 (an elicitin produced byP. infestans) induces a series of defense responses inNicotianaspecies, including reactive oxygen species (ROS) production, transient induction of ethylene production, hypersensitive cell death and accumulation of the sesquiterpenoid phytoalexin capsidiol. In this study, we analyzed the expression profiles ofN. benthamianagenes after INF1 treatment by RNAseq analysis. Based on their expression patterns,N. benthamianagenes were categorized into 20 clusters and 4,761 (8.3%) out of 57,140 genes were assigned to the clusters for INF1-induced genes. All genes encoding enzymes dedicated to capsidiol production, 5-epi-aristolochene (EA) synthase (NbEAS, 10 copies) and EA dehydrogenase (NbEAH, 6 copies), and some genes for ethylene production, such as 1-aminocyclopropane 1-carboxylate (ACC) synthase (NbACS) and ACC oxidase (NbACO), were significantly upregulated by INF1 treatment. Analysis ofNbEAS1andNbEAS4promoters revealed that AGACGCC (GCC box-like motif) is the essential cis-element required for INF1-induced expression ofNbEASgenes. Given that the GCC box is known to be targeted by ERF (ethylene-responsive factor) transcription factors, we created a complete list ofN. benthamianagenes encoding AP2/ERF family transcription factors, and identified 45 out of 337AP2/ERFgenes in the clusters for INF1-induced genes. Among INF1-inducedNbERFgenes, silencing ofNbERF-IX-33compromised resistance againstP. infestansand INF1-induced production of capsidiol. Recombinant NbERF-IX-33 protein can bind to the promoter sequence ofNbEAS4, suggesting that NbERF-IX-33 is a transcription factor directly regulating the expression of genes for phytoalexin production.
A phylogenetic and proteomic reconstruction of eukaryotic chromatin evolution
Authors: Grau-Bové Xavier , Navarrete Cristina , Chivas Cristina , Pribasnig Thomas , Antó Meritxell , Torruella Guifré , Galindo Luis Javier , Lang Bernd Franz , Moreira David , López-Garcia Purificación , Ruiz-Trillo Iñaki , Schleper Christa , Sabidó Eduard , Sebé-Pedrós Arnau 
Published: December 2021

AbstractHistones and associated chromatin proteins have essential functions in eukaryotic genome organization and regulation. Despite this fundamental role in eukaryotic cell biology, we lack a phylogenetically-comprehensive understanding of chromatin evolution. Here, we combine comparative proteomics and genomics analysis of chromatin in eukaryotes and archaea. Proteomics uncovers the existence of histone post-translational modifications in Archaea. However, archaeal histone modifications are scarce, in contrast with the highly conserved and abundant marks we identify across eukaryotes. Phylogenetic analysis reveals that chromatin-associated catalytic functions (e.g., methyltransferases) have pre-eukaryotic origins, whereas histone mark readers and chaperones are eukaryotic innovations. We show that further chromatin evolution is characterized by expansion of readers, including capture by transposable elements and viruses. Overall, our study infers detailed evolutionary history of eukaryotic chromatin: from its archaeal roots, through the emergence of nucleosome-based regulation in the eukaryotic ancestor, to the diversification of chromatin regulators and their hijacking by genomic parasites.
Stimulus dependence of theta rhythmic activity in primate V1 and its potential relevance for visual perception
Authors: Fanyiwi Prasakti Tenri , Agayby Beshoy , Kienitz Ricardo , Haag Marcus , Schmid Michael C. 
Published: December 2021

AbstractA growing body of psychophysical research reports theta (3-8 Hz) rhythmic fluctuations in visual perception that are often attributed to an attentional sampling mechanism arising from theta rhythmic neural activity in mid- to high-level cortical association areas. However, it remains unclear to what extent such neuronal theta oscillations might already emerge at early sensory cortex like the primary visual cortex (V1), e.g. from the stimulus filter properties of neurons. To address this question, we recorded multi-unit neural activity from V1 of two macaque monkeys viewing a static visual stimulus with variable sizes, orientations and contrasts. We found that among the visually responsive electrode sites, more than 50 % showed a spectral peak at theta frequencies. Theta power varied with varying basic stimulus properties. Within each of these stimulus property domains (e.g. size), there was usually a single stimulus value that induced the strongest theta activity. In addition to these variations in theta power, the peak frequency of theta oscillations increased with increasing stimulus size and also changed depending on the stimulus position in the visual field. Further analysis confirmed that this neural theta rhythm was indeed stimulus-induced and did not arise from small fixational eye movements (microsaccades). When the monkeys performed a detection task of a target embedded in a theta-generating visual stimulus, reaction times also tended to fluctuate at the same theta frequency as the one observed in the neural activity. The present study shows that a highly stimulus-dependent neuronal theta oscillation can be elicited in V1 that appears to influence the temporal dynamics of visual perception.
Chronic adolescent exposure to cannabis in mice leads to sex-biased changes in gene expression networks across brain regions
Authors: Zuo Yanning , Iemolo Attilio , Montilla-Perez Patricia , Li Hai-Ri , Yang Xia , Telese Francesca 
Published: December 2021

AbstractDuring adolescence, frequent and heavy cannabis use can lead to serious adverse health effects and cannabis use disorders (CUD). Rodent models of adolescent exposure to the main psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC), mimic the behavioral alterations observed in adolescent users. However, the underlying molecular mechanisms remain largely unknown. Here, we treated female and male mice with high doses of THC during early adolescence and assessed their memory and social behaviors in late adolescence. We then profiled the transcriptome of five brain regions involved in cognitive and addiction-related processes. We applied gene coexpression network analysis and identified gene coexpression modules, termed cognitive modules, that simultaneously correlated with THC treatment and memory traits reduced by THC. The cognitive modules were related to endocannabinoid signaling in the female dorsal medial striatum, inflammation in the female ventral tegmental area, and synaptic transmission in the male nucleus accumbens. Moreover, cross-brain region module-module interaction networks uncovered intra- and inter-region molecular circuitries influenced by THC. Lastly, we identified key driver genes of gene networks associated with THC in mice and genetic susceptibility to CUD in humans. This analysis revealed a common regulatory mechanism linked to CUD vulnerability in the nucleus accumbens of females and males, which shared four key drivers (Hapln4, Kcnc1, Elav12, Zcchc12). These genes regulate transcriptional subnetworks implicated in addiction processes, synaptic transmission, brain development, and lipid metabolism. Our study provides novel insights into disease mechanisms regulated by adolescent exposure to THC in a sex- and brain region-specific manner.