bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune complexes, innate immunity, and NETosis in ChAdOx1 vaccine-induced thrombocytopenia
Authors: Holm Sverre , Kared Hassen , Michelsen Annika E , Kong Xiang Yi , Dahl Tuva B , Schultz Nina H , Nyman Tuula A , Fladeby Cathrine , Seljeflot Ingebjørg , Ueland Thor , Stensland Maria , Mjaaland Siri , Goll Guro Løvik , Nissen-Meyer Lise Sofie , Aukrust Pål , Skagen Karolina , Gregersen Ida , Skjelland Mona , Holme Pål A , Munthe Ludvig A , Halvorsen Bente 
Published: August 2021

Abstract

Aims
We recently reported five cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) 7–10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against corona virus disease 2019 (COVID-19). We aimed to investigate the pathogenic immunological responses operating in these patients.

Methods and results
We assessed circulating inflammatory markers by immune assays and immune cell phenotyping by flow cytometry analyses and performed immunoprecipitation with anti-platelet factor (PF)4 antibody in plasma samples followed by mass spectrometry from all five patients. A thrombus was retrieved from the sinus sagittal superior of one patient and analysed by immunohistochemistry and flow cytometry. Precipitated immune complexes revealed multiple innate immune pathway triggers for platelet and leucocyte activation. Plasma contained increased levels of innate immune response cytokines and markers of systemic inflammation, extensive degranulation of neutrophils, and tissue and endothelial damage. Blood analyses showed activation of neutrophils and increased levels of circulating H3Cit, dsDNA, and myeloperoxidase–DNA complex. The thrombus had extensive infiltration of neutrophils, formation of neutrophil extracellular traps (NETs), and IgG deposits.

Conclusions
The results show that anti-PF4/polyanion IgG-mediated thrombus formation in VITT patients is accompanied by a massive innate immune activation and particularly the fulminant activation of neutrophils including NETosis. These results provide novel data on the immune response in this rare adenoviral vector-induced VITT.
Long-term prognosis of patients undergoing radiofrequency catheter ablation for atrial fibrillation: comparison between heart failure subtypes based on left ventricular ejection fraction
Authors: Fujimoto Hajime , Doi Naofumi , Okayama Satoshi , Naito Masaki , Kobori Atsushi , Kaitani Kazuaki , Inoue Koichi , Kurotobi Toshiya , Morishima Itsuro , Yamaji Hirosuke , Matsui Yumie , Nakazawa Yuko , Kusano Kengo , Hirai Kaeko , Nakai Takehito , Suzuki Megumi , Yano Hiroki , Sakai Satoshi , Kimura Takeshi , Shizuta Satoshi , Saito Yoshihiko ,   the KPAF investigators
Published: August 2021

Abstract

Aims
Heart failure (HF) prognosis has been reported similar in patients with preserved vs. reduced left ventricular ejection fraction (LVEF). This study compared the long-term prognosis of HF patients undergoing radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF).

Methods and results
Among 5010 patients undergoing RFCA in Kansai Plus AF registry, 656 patients (13.1%) with a documented history of HF were enrolled in the study before RFCA. The primary endpoint was a composite of all-cause death, HF hospitalization, and stroke or systemic embolism. Patients with reduced (&lt;40%), mid-range (40–49%), and preserved (≥50%) LVEF were 98 (14.9%), 107 (16.3%), and 451 (68.8%) patients, respectively. The prevalence of ischaemic heart disease and cardiomyopathies was higher among patients with reduced as compared with preserved LVEF (27.6% vs. 10.0%, P &lt; 0.05 and 36.7% vs. 15.3%, P &lt; 0.05, respectively). The median follow-up period was 2.9 years. The 3-year cumulative risk for the primary endpoint was higher in patients with reduced LVEF (32.7%) compared to those with mid-range (11.7%) or preserved (11.6%) LVEF (P &lt; 0.001). Reduced LVEF was the most significant independent risk factor for primary endpoint (hazard ratio, 2.83; 95% confidence interval 1.74–4.61, P &lt; 0.001). The 3-year arrhythmia recurrence rate was similar among the groups (48.2%, 42.8%, and 47.3%, respectively, P = 0.75).

Conclusion
This study raises hypothesis that patients with HFrEF and AF had approximately three times higher risk for a composite of all-cause death, HF hospitalization, and stroke or systemic embolism after AF ablation compared with patients with HFmrEF or HFpEF.
MicroRNAs and extracellular vesicles in the gut: new host modulators of the microbiome?
Authors: Du Xiaochen , Ley Ruth , Buck Amy H 
Published: August 2021

ABSTRACTThe gut microbiota plays an integral role in human health and its dysbiosis is associated with many chronic diseases. There are still large gaps in understanding the host and environmental factors that directly regulate the gut microbiota, and few effective strategies exist to modulate the microbiota in therapeutic applications. Recent reports suggest that certain microRNAs (miRNAs) released by mammalian cells can regulate bacterial gene expression to influence the microbiome composition and propose extracellular vesicles as one natural mechanism for miRNA transport in the gut. These new findings interface with a burgeoning body of data showing that miRNAs are present in a stable form in extracellular environments and can mediate cell-to-cell communication in mammals. Here, we review the literature on RNA-mediated modulation of the microbiome to bring cross-disciplinary perspective to this new type of interaction and its potential implications in biology and medicine.
Socioemotional Selectivity Theory: The Role of Perceived Endings in Human Motivation
Authors: Carstensen Laura L 
Published: August 2021

Abstract
Socioemotional selectivity theory (SST) is a theory of life-span development grounded in the uniquely human ability to monitor time. SST maintains that the approach of endings—whether due to aging or other endings such as geographic relocations and severe illness—elicits motivational changes in which emotionally meaningful goals are prioritized over exploration. Research guided by SST has informed preferences, social networks, and emotional experience and led to the discovery of the positivity effect in cognitive processing. This article, based on my 2015 Robert W. Kleemeier Award Lecture, describes the development of SST and its related program of empirical research.
X-factors in human disease: impact of gene content and dosage regulation
Authors: Fang He , Deng Xinxian , Disteche Christine M 
Published: August 2021

Abstract
The gene content of the X and Y chromosomes has dramatically diverged during evolution. The ensuing dosage imbalance within the genome of males and females has led to unique chromosome-wide regulatory mechanisms with significant and sex-specific impacts on X-linked gene expression. X inactivation or silencing of most genes on one X chromosome chosen at random in females profoundly affects the manifestation of X-linked diseases, as males inherit a single maternal allele, while females express maternal and paternal alleles in a mosaic manner. An additional complication is the existence of genes that escape X inactivation and thus are ubiquitously expressed from both alleles in females. The mosaic nature of X-linked gene expression and the potential for escape can vary between individuals, tissues, cell types and stages of life. Our understanding of the specialized nature of X-linked genes and of the multilayer epigenetic regulation that influence their expression throughout the organism has been helped by molecular studies conducted by tissue-specific and single-cell-specific approaches. In turn, the definition of molecular events that control X silencing has helped develop new approaches for the treatment of some X-linked disorders. This review focuses on the peculiarities of the X chromosome genetic content and epigenetic regulation in shaping the manifestation of congenital and acquired X-linked disorders in a sex-specific manner.
Intrapulmonary pharmacokinetic profile of cefiderocol in mechanically ventilated patients with pneumonia
Authors: Katsube Takayuki , Nicolau David P , Rodvold Keith A , Wunderink Richard G , Echols Roger , Matsunaga Yuko , Menon Anju , Portsmouth Simon , Wajima Toshihiro 
Published: August 2021

AbstractObjectivesLung penetration of cefiderocol, a novel siderophore cephalosporin approved for treatment of nosocomial pneumonia, has previously been evaluated in healthy subjects. This study assessed the intrapulmonary pharmacokinetic profile of cefiderocol at steady state in hospitalized, mechanically ventilated pneumonia patients.MethodsPatients received cefiderocol 2 g (or ≤1.5 g if renally impaired), administered IV q8h as a 3 h infusion, or 2 g q6h if patients had augmented renal function (estimated CLCR &gt; 120 mL/min). After multiple doses, each patient underwent a single bronchoalveolar lavage (BAL) procedure either at the end of the infusion or at 2 h after the end of infusion. Plasma samples were collected at 1, 3, 5 and 7 h after the start of infusion. After correcting for BAL dilution, cefiderocol concentrations in epithelial lining fluid (ELF) for each patient and the ELF/unbound plasma concentration ratio (RC, E/P) were calculated. Safety was assessed up to 7 days after the last cefiderocol dose.ResultsSeven patients received cefiderocol. Geometric mean ELF concentration of cefiderocol was 7.63 mg/L at the end of infusion and 10.40 mg/L at 2 h after the end of infusion. RC, E/P was 0.212 at the end of infusion and 0.547 at 2 h after the end of infusion, suggesting delayed lung distribution. There were no adverse drug reactions.ConclusionsThe results suggest that cefiderocol penetrates the ELF in critically ill pneumonia patients with concentrations that are sufficient to treat Gram-negative bacteria with an MIC of ≤4 mg/L.
Crohn’s and Colitis Canada’s 2021 Impact of COVID-19 and Inflammatory Bowel Disease in Canada: Children and Expectant Mothers With Inflammatory Bowel Disease
Authors: Benchimol Eric I , Carroll Matthew W , Geist Rose , Griffiths Anne M , Huang James Guoxian , Mack David R , Bernstein Charles N , Bitton Alain , Jones Jennifer L , Kaplan Gilaad G , Kuenzig M Ellen , Lee Kate , Mukhtar Mariam S , Murthy Sanjay K , Tandon Parul , Targownik Laura E , Windsor Joseph W , Seow Cynthia H 
Published: August 2021

Abstract
Coronavirus disease 2019 (COVID-19) in children with inflammatory bowel disease (IBD) typically results in a mild infection, similar to those without IBD. Children and adolescents have less severe manifestations of COVID-19 compared to older people, whether or not they have IBD. However, some IBD medications (in particular, corticosteroids) are associated with more severe COVID-19. During the first year of the global pandemic, more IBD care was provided with online technology, necessitated by efforts to reduce hospital and clinic visits. Additionally, non-endoscopic monitoring of inflammation has been required due to the cancellation of non-urgent procedures, resulting in longer endoscopy wait-times. In contrast, pregnant people (with and without IBD) who contract COVID-19 are at increased risk of severe manifestations, death and preterm delivery, making them a priority for severe acute respiratory syndrome coronavirus 2 protective measures and vaccination. Few studies have examined effect of COVID-19 on IBD-related disease activity in pregnant people with IBD. The pandemic has significantly affected the mental health and sense of well-being of children and their families, as well as pregnant people with IBD. These groups were much more likely to experience anxiety and depression compared with prior to the pandemic, even while concern has mostly abated regarding the effect of IBD medications and COVID-19 severity. Unfortunately, the availability of mental health care providers who specialize in people with IBD has not kept pace with the increasing demand.
MAMP and DAMP signaling contributes resistance to Fusarium graminearum in Arabidopsis
Authors: Manes Nimrat , Brauer Elizabeth K , Hepworth Shelley , Subramaniam Rajagopal 
Published: August 2021

Abstract
Plants perceive externally produced microbe-associated molecular patterns (MAMPs) and endogenously produced danger-associated molecular patterns (DAMPs) to activate inducible immunity. While several inducible immune responses have been observed during Fusarium graminearum infection, the identity of the signaling pathways involved is only partly known. We screened 227 receptor kinase and innate immune response genes in Arabidopsis to identify nine genes with a role in F. graminearum resistance. Resistance-promoting genes included the chitin receptors LYK5 and CERK1, and the reactive oxygen species (ROS)-producing NADPH oxidase RbohF, which were required for full inducible immune responses during infection. Two of the genes identified in our screen, APEX and the PAMP-induced peptide 1 (PIP1) DAMP receptor RLK7, repressed F. graminearum resistance. Both RbohF and RLK7 were required for full chitin-induced immune responses and PIP1 precursor expression was induced by chitin and F. graminearum infection. Together, this indicates that F. graminearum resistance is mediated by MAMP and DAMP signaling pathways and that chitin-induced signaling is enhanced by PIP1 perception and ROS production.
fuPCR as diagnostic method for the detection of rare fungal pathogens, such as Trichosporon, Cryptococcus and Fusarium
Authors: Scharf Sebastian , Bartels Anna , Kondakci Mustafa , Haas Rainer , Pfeffer Klaus , Henrich Birgit 
Published: August 2021

Abstract
Fungal respiratory tract colonization is a common finding in patients with hematologic neoplasms due to immunosuppression inherent in the diseases and exacerbated by therapy. This greatly increases the risk of fungal infections of the lungs, which is associated with significant mortality. Therefore, reliable diagnostic methods with rapidly available results are needed to administer adequate antifungal therapy. We have established an improved method for fungal DNA extraction and amplification that allows simultaneous detection of fungal families based on a set of multiplexed real-time PCR reactions (fuPCR). We analyzed respiratory rinses and blood of 94 patients with hematological systemic diseases by fuPCR and compared it with the results of culture and serological diagnostic methods. 40 healthy subjects served as controls.
Regarding Candida species, the highest prevalence resulted from microbiological culture of respiratory rinses and from detection of antibodies in blood serum in patients (61 and 47%, respectively) and in the control group (29 and 51%, respectively). Detection of other pathogenic yeasts, such as Cryptococcus and Trichosporon, and molds, such as Fusarium, was only possible in patients by fuPCR from both respiratory rinses and whole blood and serum. These fungal species were found statistically significantly more frequent in respiratory rinses collected from patients after myeloablative therapy for stem cell transplantation compared to samples collected before treatment (P &lt; 0.05i). The results show that fuPCR is a valuable complement to culturing and its inclusion in routine mycological diagnostics might be helpful for early detection of pathophysiologically relevant respiratory colonization for patients with hematologic neoplasms.
Antifungal susceptibility testing with YeastONE™ is not predictive of clinical outcomes of Cryptococcus neoformans var. grubii fungemia
Authors: Yang Jeng-How , Huang Po-Yen , Cheng Chun-Wen , Shie Shian-Sen , Lin Zhong-Fu , Yang Lan-Yan , Lee Chia-Hui , Wu Ting-Shu 
Published: August 2021

Abstract
Mortality rates due to Cryptococcus neoformans var. grubii fungemia remain significant despite treatment with antifungal drugs. The predictive function of antifungal susceptibility and its correlation with treatment outcome remains controversial. A retrospective study was conducted from January 1, 2009, to December 31, 2016, on 85 patients with C. neoformans var. grubii fungemia confirmed by matrix-assisted laser desorption ionization–time-of-flight mass spectrometry. Antifungal drug susceptibility was determined using the YeastONE™ colorimetric broth microdilution method coupled with Vizion™ System following the Clinical and Laboratory Standards Institute guidelines. Six antifungal agents—amphotericin B, fluconazole, flucytosine, itraconazole, posaconazole, and voriconazole—were tested. The patients’ demographic data and clinical information were abstracted for further analyses. Antifungal regimens consisting of amphotericin B with or without fluconazole or flucytosine were administered for induction treatment of these patients, followed with intravenous or oral fluconazole for maintenance therapy. Clinical outcomes were defined by 14- and 30-day mortality rates. Risk factors associated with outcomes were fitted in a logistic regression model by univariate or multivariate method. Eighty-five patients with C. neoformans var. grubii fungemia were enrolled in the study. The Sequential Organ Failure Assessment Score, Glasgow Coma Scale, Charlson comorbidity score, and adequate duration of therapy for amphotericin B were predictors for mortality in univariate analysis. Antifungal susceptibility testing with YeastONE™ does not predict clinical outcomes of C. neoformans var. grubii fungemia. Greater disease severity, high comorbidities, poor consciousness level, and inappropriate treatment were associated with increased mortality in cryptococcemia cases.
The origin of the soft X-ray excess in the narrow-line Seyfert 1 galaxy SBS 1353 + 564
Authors: Xu Xinpeng , Ding Nan , Gu Qiusheng , Guo Xiaotong , Contini E 
Published: August 2021

ABSTRACT
We present for the first time the timing and spectral analyses for a narrow-line Seyfert 1 galaxy, SBS 1353 + 564, using XMM-Newton and Swift multiband observations from 2007 to 2019. Our main results are as follows: (1) The temporal variability of SBS 1353+564 is random, while the hardness ratio is relatively constant over a time span of 13 yr; (2) We find a prominent soft X-ray excess feature below 2 keV that cannot be well described by a simple blackbody component; (3) After comparing the two most prevailing models for interpreting the origin of the soft X-ray excess, we find that the relativistically smeared reflection model is unable to fit the data above 5 keV well and the X-ray spectra do not show any reflection features, such as the Fe K α emission line. However, the warm corona model can obtain a good fitting result. For the warm corona model, we try to use three different sets of spin values to fit the data and derive different best-fitting parameter sets; (4) We compare the UV/optical spectral data with the extrapolated values of the warm corona model to determine which spin value is more appropriate for this source, and we find that the warm corona model with non-spin can sufficiently account for the soft X-ray excess in SBS 1353 + 564.
Detecting globular cluster tidal extensions with Bayesian inference – I. Analysis of ω Centauri with Gaia EDR3
Authors: Kuzma P B , Ferguson A M N , Peñarrubia J 
Published: August 2021

ABSTRACT
The peripheral regions of globular clusters (GCs) are extremely challenging to study due to their low surface brightness nature and the dominance of Milky Way contaminant populations along their sightlines. We have developed a probabilistic approach to this problem through utilizing a mixture model in spatial and proper motion space that separately models the cluster, extra-tidal, and contaminant stellar populations. We demonstrate the efficacy of our method through application to Gaia third early data release photometry and astrometry in the direction of NGC 5139 (ω Centauri, hereafter ω Cen), a highly challenging target on account of its Galactic latitude (b ≈ 15○) and low proper motion contrast with the surrounding field. We recover the spectacular tidal extensions, spanning the 10○ on the sky explored here, seen in earlier work and quantify the star count profile and ellipticity of the system out to a cluster-centric radius of 4○. We show that both RR Lyrae and blue horizontal branch stars consistent with belonging to ω Cen are found in the tidal tails, and calculate that these extensions contain at least ≈0.1 per cent of the total stellar mass in the system. Our high-probability members provide prime targets for future spectroscopic studies of ω Cen out to unprecedented radii.
Formation of massive disc galaxies in the IllustrisTNG simulation
Authors: Zeng Guangquan , Wang Lan , Gao Liang 
Published: August 2021

ABSTRACT
We investigate the formation history of massive disc galaxies in hydrodynamical simulation – the IllustrisTNG, to study why massive disc galaxies survive through cosmic time. 83 galaxies in the simulation are selected with M*,z = 0 &gt; 8 × 1010 M⊙ and kinematic bulge-to-total ratio less than 0.3. We find that 8.4 per cent of these massive disc galaxies have quiet merger histories and preserve disc morphology since formed. 54.2 per cent have a significant increase in bulge components in history, then become discs again till present time. The rest 37.3 per cent experience prominent mergers but survive to remain discy. While mergers and even major mergers do not always turn disc galaxies into ellipticals, we study the relations between various properties of mergers and the morphology of merger remnants. We find a strong dependence of remnant morphology on the orbit type of major mergers. Specifically, major mergers with a spiral-in falling orbit mostly lead to disc-dominant remnants, and major mergers of head-on galaxy–galaxy collision mostly form ellipticals. This dependence of remnant morphology on orbit type is much stronger than the dependence on cold gas fraction or orbital configuration of merger system as previously studied.
Logit function in stochastic categorizations
Authors: Wang Kai 
Published: August 2021

Abstract
Binary categorizations refer to the behaviour for which a decision maker puts the alternatives from a menu into binary categories (authorization category and rejection category). For example, a judge approves/denies parole for inmates, a doctor administers/withholds treatment to patients, and a teacher passes/fails essays. Categorizations are observed to exhibit randomness in various contexts, but the stochasticity in categorizations has received little attention in economic studies. We consider stochastic categorizations using a logit categorization function, which expresses the probability of authorizing an alternative from a menu in a ‘logit-like’ form. We characterize the model from a simple condition on authorization frequencies. Furthermore, we derive an empirical version of our model, which not only provides insight into applications of the model, but also gives an intuitive interpretation of the stochasticity in categorizations. We use simple examples to show that our model can bring new insights and research possibilities in the economic studies.
Task-Irrelevant Semantic Properties of Objects Impinge on Sensory Representations within the Early Visual Cortex
Authors: Nah Joseph C , Malcolm George L , Shomstein Sarah 
Published: August 2021

Abstract
Objects can be described in terms of low-level (e.g., boundaries) and high-level properties (e.g., object semantics). While recent behavioral findings suggest that the influence of semantic relatedness between objects on attentional allocation can be independent of task-relevance, the underlying neural substrate of semantic influences on attention remains ill-defined. Here, we employ behavioral and functional magnetic resonance imaging measures to uncover the mechanism by which semantic information increases visual processing efficiency. We demonstrate that the strength of the semantic relatedness signal decoded from the left inferior frontal gyrus: 1) influences attention, producing behavioral semantic benefits; 2) biases spatial attention maps in the intraparietal sulcus, subsequently modulating early visual cortex activity; and 3) directly predicts the magnitude of behavioral semantic benefit. Altogether, these results identify a specific mechanism driving task-independent semantic influences on attention.