bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of chronic and acute enterotoxigenic E. coli challenge on growth performance, intestinal inflammation, microbiome, and metabolome of weaned piglets
Authors: Boeckman Justin X. , Sprayberry Sarah , Korn Abby M. , Suchodolski Jan S. , Paulk Chad , Genovese Kenneth , Rech Raquel R. , Giaretta Paula R. , Blick Anna K. , Callaway Todd , Gill Jason J. 
Published: March 2022

AbstractPost-weaning enteropathies in swine caused by pathogenic E. coli, such as post-weaning diarrhea (PWD) or edema disease (ED), remain a significant problem for the swine industry. Reduction in the use of antibiotics over concerns of antibiotic resistance and public health concerns, necessitate the evaluation of effective antibiotic alternatives to prevent significant loss of livestock and/or reductions in swine growth performance. For this purpose, an appropriate piglet model of pathogenic E. coli enteropathy is required. In this study, we attempted to induce clinical signs of post-weaning disease in a piglet model using a one-time acute or lower daily chronic dose of a pathogenic E. coli strain containing genes for both heat stable and labile toxins, as well as Shiga toxin. The induced disease state was monitored by determining fecal shedding and colonization of the challenge strain, animal growth performance, cytokine levels, fecal calprotectin, histology, fecal metabolomics, and fecal microbiome shifts. The most informative analyses were colonization and shedding of the pathogen, serum cytokines, metabolomics, and targeted metagenomics to determine dysbiosis. Histopathological changes of the gastrointestinal (GI) tract and tight junction leakage as measured by fecal calprotectin concentrations were not observed. Chronic dosing was similar to the acute regimen suggesting that a high dose of pathogen, as used in many studies, may not be necessary. The piglet disease model presented here can be used to evaluate alternative PWD treatment options.
Implementation of single-qubit measurement-based t-designs using IBM processors
Authors: Strydom Conrad , Tame Mark 
Published: March 2022

AbstractRandom unitary matrices sampled from the uniform Haar ensemble have a number of important applications both in cryptography and in the simulation of a variety of fundamental physical systems. Since the Haar ensemble is very expensive to sample, pseudorandom ensembles in the form of t-designs are frequently used as an efficient substitute, and are sufficient for most applications. We investigate t-designs generated using a measurement-based approach on superconducting quantum computers. In particular, we implemented an exact single-qubit 3-design on IBM quantum processors by performing measurements on a 6-qubit graph state. By analysing channel tomography results, we were able to show that the ensemble of unitaries realised was a 1-design, but not a 2-design or a 3-design under the test conditions set, which we show to be a result of depolarising noise during the measurement-based process. We obtained improved results for the 2-design test by implementing an approximate 2-design, in which measurements were performed on a smaller 5-qubit graph state, but the test still did not pass for all states. This suggests that the practical realisation of measurement-based t-designs on superconducting quantum computers will require further work on the reduction of depolarising noise in these devices.
How Spanish speakers express norms using generic person markers
Authors: Salvador Cristina E. , Orvell Ariana , Kross Ethan , Gelman Susan A. 
Published: March 2022

AbstractLanguage is one powerful vehicle for transmitting norms—a universal feature of society. In English, people use “you” generically (e.g., “You win some you lose some”) to express and interpret norms. Here, we examine how norms are conveyed and interpreted in Spanish, a language that—unlike English—has two forms of you (i.e., formal, informal), distinct generic person markers, and pro-drop, allowing for an examination of underlying conceptual tendencies in how the structure of language facilitates the transmission of norms. In Study 1a-b (N = 838) Spanish speakers used informal generic-you and the generic person marker “se” (but not formal-you) to express norms (vs. preferences). In Study 2 (N = 300), formal you, informal you, and impersonal “se” had persuasive force over personal endorsements (e.g., “I”), informing Spanish speaker’s interpretation of unfamiliar norms. Our findings add to a growing literature on how subtle linguistic shifts reflect and influence cognitive processes.
Atomistic mechanisms of human TRPA1 activation by electrophile irritants through molecular dynamics simulation and mutual information analysis
Authors: Habgood Matthew , Seiferth David , Zaki Afroditi-Maria , Alibay Irfan , Biggin Philip C. 
Published: March 2022

AbstractThe ion channel TRPA1 is a promiscuous chemosensor, with reported response to a wide spectrum of noxious electrophilic irritants, as well as cold, heat, and mechanosensation. It is also implicated in the inception of itch and pain and has hence been investigated as a drug target for novel analgesics. The mechanism of electrophilic activation for TRPA1 is therefore of broad interest. TRPA1 structures with the pore in both open and closed states have recently been published as well as covalent binding modes for electrophile agonists. However, the detailed mechanism of coupling between electrophile binding sites and the pore remains speculative. In addition, while two different cysteine residues (C621 and C665) have been identified as critical for electrophile bonding and activation, the bound geometry has only been resolved at C621. Here, we use molecular dynamics simulations of TRPA1 in both pore-open and pore-closed states to explore the allosteric link between the electrophile binding sites and pore stability. Our simulations reveal that an open pore is structurally stable in the presence of open ‘pockets’ in the C621/C665 region, but rapidly collapses and closes when these pockets are shut. Binding of electrophiles at either C621 or C665 provides stabilisation of the pore-open state, but molecules bound at C665 are shown to be able to rotate in and out of the pocket, allowing for immediate stabilisation of transient open states. Finally, mutual information analysis of trajectories reveals an informational path linking the electrophile binding site pocket to the pore via the voltage-sensing-like domain, giving a detailed insight into the how the pore is stabilized in the open state.
Interaction between a robot and Bunimovich stadium billiards
Authors: Vasconcelos J. V. A. , Miranda-Filho L. H. , de Souza A. J. F. , de C. Romaguera A. R. , Barbosa A. L. R. 
Published: March 2022

AbstractThe robot–environment–task triad provides many opportunities to revisit physical problems with fresh eyes. Hence, we develop a simple experiment to observe chaos in classical billiards with a macroscopic 3.38-m long setup. Using a digital video camera, one records the dynamic time evolution of the interaction between a robot and Bunimovich stadium billiards with specular reflection. From the experimental time series, we calculate the Lyapunov exponent $$\lambda$$
λ
as a function of a geometric parameter. The results are in concordance with theoretical predictions. In addition, we determine the Poincaré surface of section from the experimental data and check its sensitivity to the initial conditions as a function of time.
Differential volume reductions in the subcortical, limbic, and brainstem structures associated with behavior in Prader–Willi syndrome
Authors: Yamada Kenichi , Watanabe Masaki , Suzuki Kiyotaka 
Published: March 2022

AbstractIndividuals with Prader–Willi syndrome (PWS) exhibit complex behavioral characteristics, including hyperphagia, autistic features, and subsequent age-related maladaptive behaviors. While this suggests functional involvements of subcortical, limbic, and brainstem areas, developmental abnormalities in such structures remain to be investigated systematically. Twenty-one Japanese individuals with PWS and 32 healthy controls with typical development were included. T1-weighted three-dimensional structural magnetic resonance images were analyzed for subcortical, limbic, and brainstem structural volumes, with age as a covariate, using a model-based automatic segmentation tool. Correlations were determined between each volume measurement and behavioral characteristics as indexed by questionnaires and block test scores for hyperphagia (HQ), autistic and obsessional traits, non-verbal intelligence (IQ), and maladaptive behavior (VABS_mal). Compared with the control group, the PWS group showed significantly reduced relative volume ratios per total intracranial volume (TIV) in thalamus, amygdala, and brainstem structures, along with TIV and native volumes in all substructures. While the brainstem volume ratio was significantly lower in all age ranges, amygdala volume ratios were significantly lower during early adulthood and negatively correlated to HQ and VABS_mal but positively correlated to Kohs IQ. Thus, limbic and brainstem volume alterations and differential volume trajectories may contribute to the developmental and behavioral pathophysiology of PWS.
Down-regulation of the transcriptional repressor ZNF802 (JAZF1) reactivates fetal hemoglobin in β0-thalassemia/HbE
Authors: Wongborisuth Chokdee , Chumchuen Sukanya , Sripichai Orapan , Anurathaphan Usanarat , Sathirapongsasuti Nuankanya , Songdej Duantida , Tangprasittipap Amornrat , Hongeng Suradej 
Published: March 2022

AbstractReactivating of fetal hemoglobin (HbF; α2γ2) can ameliorate the severity of β-thalassemia disease by compensating for adult hemoglobin deficiency in patients. Previously, microarray analysis revealed that zinc finger protein (ZNF)802 (also known as Juxta-posed with another zinc finger gene-1 (JAZF1)) was upregulated in human erythroblasts derived from adult peripheral blood compared with fetal liver-derived cells, implying a potential role as a HbF repressor. However, deficiency in ZNF802 induced by lentiviral shRNA in β0-thalassemia/hemoglobinE erythroblasts had no effect on erythroblast proliferation and differentiation. Remarkably, the induction of HBG expression was observed at the transcriptional and translational levels resulting in an increase of HbF to 35.0 ± 3.5%. Interestingly, the embryonic globin transcripts were also upregulated but the translation of embryonic globin was not detected. These results suggest ZNF802 might be a transcriptional repressor of the γ-globin gene in adult erythroid cells.
Revealing key lncRNAs in cytogenetically normal acute myeloid leukemia by reconstruction of the lncRNA–miRNA–mRNA network
Authors: Sun Tao , Dong Lin , Guo Yan , Zhao Hai , Wang Manzhi 
Published: March 2022

AbstractCytogenetically normal acute myeloid leukemia (CN-AML) is a heterogeneous disease with different prognoses. Researches on prognostic biomarkers and therapy targets of CN-AML are still ongoing. Instead of protein-coding genes, more and more researches were focused on the non-coding RNAs especially long non-coding RNAs (lncRNAs) which may play an important role in the development of AML. Although a large number of lncRNAs have been found, our knowledge of their functions and pathological process is still in its infancy. The purpose of this research is to identify the key lncRNAs and explore their functions in CN-AML by reconstructing the lncRNA–miRNA–mRNA network based on the competitive endogenous RNA (ceRNA) theory. We reconstructed a global triple network based on the ceRNA theory using the data from National Center for Biotechnology Information Gene Expression Omnibus and published literature. According to the topological algorithm, we identified the key lncRNAs which had both the higher node degrees and the higher numbers of lncRNA–miRNA pairs and total pairs in the ceRNA network. Meanwhile, Gene Ontology (GO) and pathway analysis were performed using databases such as DAVID, KOBAS and Cytoscape plug-in ClueGO respectively. The lncRNA–miRNA–mRNA network was composed of 90 lncRNAs,33mRNAs,26 miRNAs and 259 edges in the lncRNA upregulated group, and 18 lncRNAs,11 mRNAs,6 miRNAs and 45 edges in the lncRNA downregulated group. The functional assay showed that 53 pathways and 108 GO terms were enriched. Three lncRNAs (XIST, TUG1, GABPB1-AS1) could possibly be selected as key lncRNAs which may play an important role in the development of CN-AML. Particularly, GABPB1-AS1 was highly expressed in CN-AML by both bioinformatic analysis and experimental verification in AML cell line (THP-1) with quantitative real‐time polymerase chain reaction. In addition, GABPB1-AS1 was also negatively correlated with overall survival of AML patients. The lncRNA–miRNA–mRNA network revealed key lncRNAs and their functions in CN-AML. Particularly, lncRNA GABPB1-AS1 was firstly proposed in AML. We believe that GABPB1-AS1 is expected to become a candidate prognostic biomarker or a potential therapeutic target.
NaCl exposure results in increased expression and processing of IL-1β in Meniere’s disease patients
Authors: Pathak Shresh , Vambutas Andrea 
Published: March 2022

AbstractMeniere’s disease (MD) is a chronic disease that causes episodic vertigo, fluctuating hearing loss, and aural fullness, initially managed by dietary salt reduction, and use of diuretics. Our prior research in autoimmune inner ear disease (AIED) demonstrated that in peripheral blood mononuclear cell (PBMC) from corticosteroid-resistant AIED patients, increased production, processing and release of interleukin-1β (IL-1β) is observed and hearing could be improved with use of anakinra, an interleukin-1 receptor antagonist. We have further identified that in these AIED patients, IL-1β is uniquely processed to a 28 kDa pro-inflammatory product by caspase-7. In the present study, we characterize the production, processing and release of the pro-inflammatory cytokines IL-1β and IL-6 from PBMC of MD (n = 14) patients in response to sodium chloride (NaCl), and determined the effect of the diuretic triamterene-hydrocholothiazide (T-HCTZ), or anakinra in these patients. We observed that PBMC cultured with NaCl from MD patients show processing of IL-1β to the 28 kDa product, and that this product is abrogated with T-HCTZ. Our observations are consistent with other autoimmune diseases where high concentrations of NaCl caused release of pro-inflammatory cytokines and may provide further insight as to the mechanism of disease progression in MD patients.
Electrocautery smoke exposure and efficacy of smoke evacuation systems in minimally invasive and open surgery: a prospective randomized study
Authors: Kocher Gregor J. , Koss Abigail R. , Groessl Michael , Schefold Joerg C. , Luedi Markus M. , Quapp Christopher , Dorn Patrick , Lutz Jon , Cappellin Luca , Hutterli Manuel , Lopez-Hilfiker Felipe D. , Al-Hurani Mohammad , Sesia Sergio B. 
Published: March 2022

AbstractWorldwide, health care professionals working in operating rooms (ORs) are exposed to electrocautery smoke on a daily basis. Aims of this study were to determine composition and concentrations of electrocautery smoke in the OR using mass spectrometry. Prospective observational study at a tertiary care academic center, involving 122 surgical procedures of which 84 were 1:1 computer randomized to smoke evacuation system (SES) versus no SES use. Irritating, toxic, carcinogenic and mutagenic VOCs were observed in OR air, with some exceeding permissible exposure limits (OSHA/NIOSH). Mean total concentration of harmful compounds was 272.69 ppb (± 189 ppb) with a maximum total concentration of harmful substances of 8991 ppb (at surgeon level, no SES). Maximum total VOC concentrations were 1.6 ± 1.2 ppm (minimally-invasive surgery) and 2.1 ± 1.5 ppm (open surgery), and total maximum VOC concentrations were 1.8 ± 1.3 ppm at the OR table ‘at surgeon level’ and 1.4 ± 1.0 ppm ‘in OR room air’ away from the operating table. Neither difference was statistically significant. In open surgery, SES significantly reduced maximum concentrations of specific VOCs at surgeon level, including aromatics and aldehydes. Our data indicate relevant exposure of health care professionals to volatile organic compounds in the OR. Surgical technique and distance to cautery devices did not significantly reduce exposure. SES reduced exposure to specific harmful VOC’s during open surgery.Trial Registration Number: NCT03924206 (clinicaltrials.gov).
Genetic variation in released gametes produces genetic diversity in the offspring of the broadcast spawning coral Acropora tenuis
Authors: Kitanobo Seiya , Toshino Sho , Morita Masaya 
Published: March 2022

AbstractAll coral species in the genus Acropora are broadcast-spawning hermaphrodites. Fertilization in the ocean requires sufficient numbers of gametes from conspecifics and the contact time for fertilization is thought to be limited by the rapid diffusion of sperm. Many studies have reported a positive correlation between sperm concentration and fertilization success, but it is not clear how gametes diffuse in seawater to produce mixtures of gametes from many colonies, leading to fertilization that improves genetic diversity. To elucidate this, we analyzed the changes in sperm concentration of A.tenuis in situ after spawning and genotyped sperm and fertilized eggs from seawater using seven microsatellite (MS) markers. Results showed that most of the eggs were fertilized at below 106 sperm/mL in situ. MS genotyping showed that the alleles of released sperm were diverse and those alleles also appeared in the fertilized eggs. The MS fragment peak height in released sperm, which presumably reflects the allele frequency of the sperm, was positively correlated with the allele frequencies of the fertilized eggs. Collectively, synchronous spawning populations composed of highly fecund and genetically diverse colonies potentially increases genetic diversity and the number of descendants.
Development and validation of a risk-score model for opioid overdose using a national claims database
Authors: Heo Kyu-Nam , Lee Ju-yeun , Ah Young-Mi 
Published: March 2022

AbstractOpioid overdose can be serious adverse effects of opioid analgesics. Thus, several strategies to mitigate risk and reduce the harm of opioid overdose have been developed. However, despite a marked increase in opioid analgesic consumption in Korea, there have been no tools predicting the risk of opioid overdose in the Korean population. Using the national claims database of the Korean population, we identified patients who were incidentally prescribed non-injectable opioid analgesic (NIOA) at least once from 2017 to 2018 (N = 1,752,380). Among them, 866 cases of opioid overdose occurred, and per case, four controls were selected. Patients were randomly allocated to the development (80%) and validation (20%) cohort. Thirteen predictive variables were selected via logistic regression modelling, and a risk-score was assigned for each predictor. Our model showed good performance with c-statistics of 0.84 in the validation cohort. The developed risk score model is the first tool to identify high-risk patients for opioid overdose in Korea. It is expected to be applicable in the clinical setting and useful as a national level surveillance tool due to the easily calculable and identifiable predictors available from the claims database.
Evidence of the role of the cerebellum in cognitive theory of mind using voxel-based lesion mapping
Authors: Beuriat Pierre-Aurélien , Cohen-Zimerman Shira , Smith Gretchen N. L. , Krueger Frank , Gordon Barry , Grafman Jordan 
Published: March 2022

AbstractTheory of Mind (ToM) is a social-cognitive skill that allows the understanding of the intentions, beliefs, and desires of others. There is a distinction between affective and cognitive ToM, with evidence showing that these processes rely on partially distinct neural networks. The role of the cerebellum in social cognition has only been rarely explored. In this study, we tested whether the cerebellum is necessary for cognitive and affective ToM performance. We investigated adults with traumatic brain injury (n = 193) and healthy controls (n = 52) using voxel-based lesion-symptom mapping (VLSM) and by measuring the impact on functional connectivity. First, we observed that damage to the cerebellum affected pure Cognitive ToM processing. Further, we found a lateralization effect for the role of the cerebellum in cognitive ToM with participants with left cerebellar injury performing worse than those with right cerebellar injury. Both VLSM and standard statistical analysis provided evidence that left cerebellar Crus I and lobule VI contributed to ToM processing. Lastly, we found that disconnection of the left thalamic projection and the left fronto-striatal fasciculus was associated with poor cognitive ToM performance. Our study is the first to reveal direct causal neuropsychological evidence for a role of the cerebellum in some but not all types of ToM, processing. It reinforces the idea that social cognition relies on a complex network functionally connected through white matter pathways that include the cerebellum. It supports evidence that the neural networks underpinning the different types of ToM can be differentiated.
The role of lysine palmitoylation/myristoylation in the function of the TEAD transcription factors
Authors: Mesrouze Yannick , Aguilar Gustavo , Meyerhofer Marco , Bokhovchuk Fedir , Zimmermann Catherine , Fontana Patrizia , Vissières Alexandra , Voshol Hans , Erdmann Dirk , Affolter Markus , Chène Patrick 
Published: March 2022

AbstractThe TEAD transcription factors are the most downstream elements of the Hippo pathway. Their transcriptional activity is modulated by different regulator proteins and by the palmitoylation/myristoylation of a specific cysteine residue. In this report, we show that a conserved lysine present in these transcription factors can also be acylated, probably following the intramolecular transfer of the acyl moiety from the cysteine. Using Scalloped (Sd), the Drosophila homolog of human TEAD, as a model, we designed a mutant protein (Glu352GlnSd) that is predominantly acylated on the lysine (Lys350Sd). This protein binds in vitro to the three Sd regulators—Yki, Vg and Tgi—with a similar affinity as the wild type Sd, but it has a significantly higher thermal stability than Sd acylated on the cysteine. This mutant was also introduced in the endogenous locus of the sd gene in Drosophila using CRISPR/Cas9. Homozygous mutants reach adulthood, do not present obvious morphological defects and the mutant protein has both the same level of expression and localization as wild type Sd. This reveals that this mutant protein is both functional and able to control cell growth in a similar fashion as wild type Sd. Therefore, enhancing the lysine acylation of Sd has no detrimental effect on the Hippo pathway. However, we did observe a slight but significant increase of wing size in flies homozygous for the mutant protein suggesting that a higher acylation of the lysine affects the activity of the Hippo pathway. Altogether, our findings indicate that TEAD/Sd can be acylated either on a cysteine or on a lysine, and suggest that these two different forms may have similar properties in cells.