bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin-1 Receptor Antagonist Gene (IL1RN) Variants Modulate the Cytokine Release Syndrome and Mortality of COVID-19
Authors: Attur Mukundan , Petrilli Christopher , Adhikari Samrachana , Iturrate Eduardo , Li Xiyue , Tuminello Stephanie , Hu Nan , Chakravarti Aravinda , Beck David , Abramson Steven B 
Published: June 2024

Abstract

Background
We examined effects of single-nucleotide variants (SNVs) of IL1RN, the gene encoding the anti-inflammatory interleukin 1 receptor antagonist (IL-1Ra), on the cytokine release syndrome (CRS) and mortality in patients with acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods
IL1RN CTA haplotypes formed from 3 SNVs (rs419598, rs315952, rs9005) and the individual SNVs were assessed for association with laboratory markers of inflammation and mortality. We studied 2589 patients hospitalized with SARS-CoV-2 between March 2020 and March 2021.

Results
Mortality was 15.3% and lower in women than men (13.1% vs 17.3%, P = .0003). Carriers of the CTA-1/2 IL1RN haplotypes exhibited decreased inflammatory markers and increased plasma IL-1Ra. Evaluation of the individual SNVs of the IL1RN, carriers of the rs419598 C/C SNV exhibited significantly reduced inflammatory biomarker levels and numerically lower mortality compared to the C/T-T/T genotype (10.0% vs 17.8%, P = .052) in men, with the most pronounced association observed in male patients ≤74 years old, whose mortality was reduced by 80% (3.1% vs 14.0%, P = .030).

Conclusions
The IL1RN haplotype CTA and C/C variant of rs419598 are associated with attenuation of the CRS and decreased mortality in men with acute SARS-CoV-2 infection. The data suggest that the IL1RN pathway modulates the severity of coronavirus disease 2019 (COVID-19) via endogenous anti-inflammatory mechanisms.
Plasma From Older Children in Malawi Inhibits Plasmodium falciparum Binding in 3-Dimensional Brain Microvessels
Authors: Joof Fatou , Hu Ruoqian , Saidi Alex , Seydel Karl B , Cohee Lauren M , Zheng Ying , Smith Joseph D 
Published: June 2024

Abstract
A hallmark of cerebral malaria is sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the brain microcirculation. Antibodies contribute to malaria immunity, but it remains unclear whether functional antibodies targeting parasite-expressed ligand can block cytoadhesion in the brain. Here, we screened the plasma of older children and young adults in Malawi to characterize the antibody response against the P. falciparum-IE surface and used a bioengineered 3-dimensional (3D) human brain microvessel model incorporating variable flow dynamics to measure adhesion-blocking responses. We found a strong correlation between surface antibody reactivity by flow cytometry and reduced P. falciparum-IE binding in 3D microvessels. Moreover, there was a threshold of surface antibody reactivity necessary to achieve robust inhibitory activity. Our findings provide evidence of the acquisition of adhesion-blocking antibodies against cerebral binding variants in people exposed to stable P. falciparum transmission and suggest the quality of the inhibitory response can be influenced by flow dynamics.
Adverse events reporting during the COVID-19 pandemic in a Danish region: a retrospective analysis
Authors: Uggerby Christian , Knudsen Søren Valgreen , Grøntved Simon , Sørensen Agnete Lund , Larsen Karen Lyng , Schmidt Charlotte Kaae , Jensen Tilde , Pedersen Jens Ravnholt , Mainz Jan 
Published: June 2024

Abstract
The 2020 onset of the COVID-19 pandemic globally strained healthcare. Healthcare systems worldwide had to rapidly reorganize, impacting service delivery, patient care, and care-seeking behaviors. This left little time to assess the pandemic’s effects on patient safety. This paper investigates COVID-19’s influence on patient safety in a Danish region, using data from the national reporting system for adverse events during the initial COVID-19 surge in early 2020. This retrospective analysis investigated how the early phase of the COVID-19 pandemic (January–September 2020) affected the incidence of adverse events in a Danish Region, comparing it to the same period in 2019. Data were sourced from the Danish Patient Safety Database and regional systems. Adverse events were reported numerically. Descriptive statistics were employed to describe the percentage difference in adverse events and hospital activity, as well as the rate of adverse events per 1000 activities. Additionally, COVID-19-specific adverse events from April 2020 to March 2021 were identified and analyzed, categorizing them into seven risk areas across various healthcare sectors. During Denmark’s initial COVID-19 surge in early 2020, the North Denmark Region’s hospitals reported a significant decrease in adverse events, with a 42.5% drop in March 2020 compared to March 2019. From January to September 2020, the number of adverse events dropped 8.5% compared to the same period in 2019. In the same period, hospital activity declined by 10.2%. The ratio of reported adverse events per 1000 hospital activities thus decreased in early 2020 but showed only a minor difference overall for January–September compared to 2019. Between April 2020 and March 2021, out of 5703 total adverse events, 324 (5.7%) were COVID-19 related. COVID-19-related events were categorized into seven distinct risk areas, reflecting diverse impacts across healthcare sectors including hospitals, general practices, pre-hospital care, and specialized services. The initial decline in reporting of adverse events likely resulted from rapid healthcare changes and under-prioritization of the reporting system during the acute phase. However, a near return to pre-pandemic reporting levels suggests a resilient reporting system despite the crisis. The study’s strength lies in the comprehensive data from Danish reporting systems, though it acknowledges potential underreporting and doesn’t measure the pandemic’s overall impact on patient safety.
An IR Textbook in the Interwar Period: Reflections on the Contents of a Quincy Wright “Time Capsule”
Authors: Beck Robert J 
Published: June 2024

Abstract
A recently opened “time capsule” from the 1930’s reveals how the marketing of a prominent textbook on International Relations (IR) was done then and how one opinion-leading scholar responded to that textbook’s marketing, but especially, to its overall approach. The textbook was Simonds and Emeny’s The Great Powers in World Politics (1935), putatively the “most widely sold book in its field.” The scholar was Quincy Wright, one of IR’s founders and most distinguished interwar figures. This essay shares the time capsule’s background, then assesses its fascinating contents, focusing particularly on Professor Wright’s scholarly response, which until now has remained undocumented. In the interwar period, higher education was a much smaller domain than it is today, and the IR field was in its nascency. Even so, IR textbooks were being written and their publishers were already manifesting aggressive and sophisticated advocacy. In that environment, Quincy Wright proved an engaged but critical audience, having by then developed quite robust views on his subject and how it should be studied. A review of this textbook episode offers compelling vignettes of both interwar IR’s milieu and one of its most intriguing personalities. More specifically, an examination of this incident underscores the importance of a discipline’s textbooks, enriches our understanding of Quincy Wright as intellectual, scholar, and teacher, and powerfully reminds us that the questions with which Wright and the IR discipline engaged almost a century ago remain salient and their answers highly contested. Moreover, revisionist accounts of Quincy Wright’s scholarship and IR’s early stages find strong support.
Active prokaryotic and eukaryotic viral ecology across spatial scale in a deep-sea brine pool
Authors: Minch Benjamin , Chakraborty Morgan , Purkis Sam , Rodrigue Mattie , Moniruzzaman Mohammad 
Published: June 2024

Abstract
Deep-sea brine pools represent rare, extreme environments, providing unique insight into the limits of life on Earth, and by analogy, the plausibility of life beyond it. A distinguishing feature of many brine pools is presence of thick microbial mats that develop at the brine–seawater interface. While these bacterial and archaeal communities have received moderate attention, viruses and their host interactions in these environments remain underexplored. To bridge this knowledge gap, we leveraged metagenomic and metatranscriptomic data from three distinct zones within the NEOM brine pool system (Gulf of Aqaba) to reveal the active viral ecology around the pools. We report a remarkable diversity and activity of viruses infecting microbial hosts in this environment, including giant viruses, RNA viruses, jumbo phages, and Polinton-like viruses. Many of these form distinct clades—suggesting presence of untapped viral diversity in this ecosystem. Brine pool viral communities exhibit zone-specific differences in infection strategy—with lysogeny dominating the bacterial mat further away from the pool’s center. We linked viruses to metabolically important prokaryotes—including association between a jumbo phage and a key manganese-oxidizing and arsenic-metabolizing bacterium. These foundational results illuminate the role of viruses in modulating brine pool microbial communities and biogeochemistry through revealing novel viral diversity, host associations, and spatial heterogeneity in viral dynamics.
Therapeutic drug monitoring of polymyxin B cerebrospinal fluid concentrations in patients with carbapenem-resistant Gram-negative bacteria-induced central nervous system infection
Authors: Wang Peile , Liu Shaohua , He Xia , Miao Wang , Sun Tongwen , Yang Jing 
Published: June 2024

AbstractObjectivesCentral nervous system (CNS) infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) present a major health and economic burden worldwide. This multicentre prospective study aimed to assess the feasibility and usefulness of CSF therapeutic drug monitoring (TDM) after intrathecal/intraventricular administration of polymyxin B in patients with CNS infections.MethodsForty-two patients treated with intrathecal/intraventricular administration of polymyxin B against CR-GNB-induced CNS infections were enrolled. CSF trough level (Cmin) was collected beginning on Day 2 post-polymyxin B initiation and thereafter. The primary outcomes were clinical cure and 28-day all-cause mortality.ResultsAll patients started with intrathecal/intraventricular administration of polymyxin B at a dose of 5 g/day, corresponding to a median CSF Cmin of 2.93 mg/L (range, 0.21–25.74 mg/L). Clinical cure was 71.4%, and the median CSF Cmin of this group was higher than that of clinical failure group [3.31 (IQR, 1.73–5.62) mg/L versus 2.25 (IQR, 1.09–4.12) mg/L; P = 0.011]. In addition, with MICs ≤ 0.5 mg/L, maintaining polymyxin B CSF Cmin above 2.0 mg/L showed a higher clinical cure rate (P = 0.041). The 28-day all-cause mortality rate was 31.0% and had no association with CSF Cmin.ConclusionsAfter intrathecal/intraventricular administration of polymyxin B, CSF concentrations fluctuated considerably inter- and intra-individual. Polymyxin B CSF Cmin above 2.0 mg/L was associated with clinical cure when MICs were ≤ 0.5 mg/L, and the feasibility of TDM warrants additional clinical studies.
A detection of quarantine scale pest Icerya seychellarum (Hemiptera: Monophlebidae) in South Korea
Authors: Kim Hyeongsu , Lee Sang-Bin , Lee Wonhoon 
Published: June 2024

Abstract
Icerya seychellarum (Westwood, 1855) (Hemiptera: Monophlebidae) is found in most tropical and subtropical regions worldwide and is a highly polyphagous pest that affects more than 140 genera of host plants. In 2023, I. seychellarum was discovered for the first time in Seogwipo-si, Jeju Island, South Korea. The specimen was found in heavily infested Cycas revoluta. Here, we provide information regarding the associated host damage, a description of the species, and details of sampling locations. The discovery of I. seychellarum is of agricultural and quarantine importance in South Korea; therefore, this study presents an opportunity to investigate new strategies geared toward advancing efforts to detect and eliminate threats in the future.
β-Amyloid species production and tau phosphorylation in iPSC-neurons with reference to neuropathologically characterized matched donor brains
Authors: Oakley Derek H , Chung Mirra , Abrha Sara , Hyman Bradley T , Frosch Matthew P 
Published: June 2024

Abstract
A basic assumption underlying induced pluripotent stem cell (iPSC) models of neurodegeneration is that disease-relevant pathologies present in brain tissue are also represented in donor-matched cells differentiated from iPSCs. However, few studies have tested this hypothesis in matched iPSCs and neuropathologically characterized donated brain tissues. To address this, we assessed iPSC-neuron production of β-amyloid (Aβ) Aβ40, Aβ42, and Aβ43 in 24 iPSC lines matched to donor brains with primary neuropathologic diagnoses of sporadic AD (sAD), familial AD (fAD), control, and other neurodegenerative disorders. Our results demonstrate a positive correlation between Aβ43 production by fAD iPSC-neurons and Aβ43 accumulation in matched brain tissues but do not reveal a substantial correlation in soluble Aβ species between control or sAD iPSC-neurons and matched brains. However, we found that the ApoE4 genotype is associated with increased Aβ production by AD iPSC-neurons. Pathologic tau phosphorylation was found to be increased in AD and fAD iPSC-neurons compared to controls and positively correlated with the relative abundance of longer-length Aβ species produced by these cells. Taken together, our results demonstrate that sAD-predisposing genetic factors influence iPSC-neuron phenotypes and that these cells are capturing disease-relevant and patient-specific components of the amyloid cascade.
Polymicrobial brain abscesses: A complex condition with diagnostic and therapeutic challenges
Authors: Eichorn Frances-Claire , Kameda-Smith Michelle , Fong Crystal , Graham Alice K , Main Cheryl , Lu Jian-Qiang 
Published: June 2024

Abstract
Brain abscesses (BA) are focal parenchymal infections that remain life-threatening conditions. Polymicrobial BAs (PBAs) are complex coinfections of bacteria or bacterial and nonbacterial pathogens such as fungi or parasites, with diagnostic and therapeutic challenges. In this article, we comprehensively review the prevalence, pathogenesis, clinical manifestations, and microbiological, histopathological, and radiological features of PBAs, as well as treatment and prognosis. While PBAs and monomicrobial BAs have some similarities such as nonspecific clinical presentations, PBAs are more complex in their pathogenesis, pathological, and imaging presentations. The diagnostic challenges of PBAs include nonspecific imaging features at early stages and difficulties in identification of some pathogens by routine techniques without the use of molecular analysis. Imaging of late-stage PBAs demonstrates increased heterogeneity within lesions, which corresponds to variable histopathological features depending on the dominant pathogen-induced changes in different areas. This heterogeneity is particularly marked in cases of coinfections with nonbacterial pathogens such as Toxoplasma gondii. Therapeutic challenges in the management of PBAs include initial medical therapy for possibly underrecognized coinfections prior to identification of multiple pathogens and subsequent broad-spectrum antimicrobial therapy to eradicate identified pathogens. PBAs deserve more awareness to facilitate prompt and appropriate treatment.
Phase-separated super-enhancers confer an innate radioresistance on genomic DNA
Authors: Matsumoto Koki , Ikliptikawati Dini Kurnia , Makiyama Kei , Mochizuki Kako , Tobita Maho , Kobayashi Isao , Voon Dominic Chih-Cheng , Lim Keesiang , Ogawa Kazuma , Kashiwakura Ikuo , Suzuki Hiroshi I , Yoshino Hironori , Wong Richard W , Hazawa Masaharu 
Published: June 2024

Abstract
Recently, biomolecular condensates formed through liquid–liquid phase separation have been widely reported to regulate key intracellular processes involved in cell biology and pathogenesis. BRD4 is a nuclear protein instrumental to the establishment of phase-separated super-enhancers (SEs) to direct the transcription of important genes. We previously observed that protein droplets of BRD4 became hydrophobic as their size increase, implying an ability of SEs to limit the ionization of water molecules by irradiation. Here, we aim to establish if SEs confer radiation resistance in cancer cells. We established an in vitro DNA damage assay that measures the effect of radicals provoked by the Fenton reaction on DNA integrity. This revealed that DNA damage was markedly reduced when BRD4 underwent phase separation with DNA. Accordingly, co-focal imaging analyses revealed that SE foci and DNA damage foci are mutually exclusive in irradiated cells. Lastly, we observed that the radioresistance of cancer cells was significantly reduced when irradiation was combined with ARV-771, a BRD4 de-stabilizer. Our data revealed the existence of innately radioresistant genomic regions driven by phase separation in cancer cells. The disruption of these phase-separated components enfolding genomic DNA may represent a novel strategy to augment the effects of radiotherapy.
Appreciating animal induced pluripotent stem cells to shape plant cell reprogramming strategies
Authors: Wittmer Jana , Heidstra Renze 
Published: June 2024

Abstract
Animals and plants have developed resilience mechanisms to effectively endure and overcome physical damage and environmental challenges throughout their life span. To sustain their vitality, both animals and plants employ mechanisms to replenish damaged cells, either directly, involving the activity of adult stem cells, or indirectly, via dedifferentiation of somatic cells that are induced to revert to a stem cell state and subsequently redifferentiate. Stem cell research has been a rapidly advancing field in animal studies for many years, driven by its promising potential in human therapeutics, including tissue regeneration and drug development. A major breakthrough was the discovery of induced pluripotent stem cells (iPSCs), which are reprogrammed from somatic cells by expressing a limited set of transcription factors. This discovery enabled the generation of an unlimited supply of cells that can be differentiated into specific cell types and tissues. Equally, a keen interest in the connection between plant stem cells and regeneration has been developed in the last decade, driven by the demand to enhance plant traits such as yield, resistance to pathogens, and the opportunities provided by CRISPR/Cas-mediated gene editing. Here we discuss how knowledge of stem cell biology benefits regeneration technology, and we speculate on the creation of a universal genotype-independent iPSC system for plants to overcome regenerative recalcitrance.
Satellite lines from auto-ionizing states of Fe xvi and the problems with the X-ray Fe xvii lines
Authors: Del Zanna G , Badnell N R , Storey P J 
Published: June 2024

ABSTRACT
We present new calculations of atomic data needed to model auto-ionizing states of Fe xvi. We compare the state energies, radiative and excitation data with a sample of results from previous literature. We find a large scatter of results, the most significant ones in the auto-ionization rates, which are very sensitive to the configuration interaction and state mixing. We find relatively good agreement between the auto-ionization rates and the collisional excitation rates calculated with the R-matrix suite of programs and autostructure. The largest model, which includes J-resolved states up to $n=10$, produces ab-initio wavelengths and intensities of the satellite lines which agree well with solar high-resolution spectra of active regions, with few minor wavelength adjustments. We review previous literature, finding many incorrect identifications, most notably those in the NIST data base. We provide several new tentative identifications in the 15–15.7 Å range, and several new ones at shorter wavelengths, where previous lines were unidentified. Compared to the previous CHIANTI model, the present one has an increased flux in the 15–15.7 Å range at 2 MK of a factor of 1.9, resolving the discrepancies found in the analysis of the Marshall Grazing Incidence X-Ray Spectrometer observation. It appears that the satellite lines also resolve the long-standing discrepancy in the intensity of the important Fe xvii 3D line at 15.26 Å.
A fast-cadenced search for gamma-ray burst orphan afterglows with the Deeper, Wider, Faster programme
Authors: Freeburn James , Cooke Jeff , Möller Anais , Dobie Dougal , Zhang Jielai , Salafia Om Sharan , Siellez Karelle , Auchettl Katie , Goode Simon , Abbott Timothy M C , Andreoni Igor , Allen Rebecca , Van Bemmel Natasha , Webb Sara 
Published: June 2024

ABSTRACT
The relativistic outflows that produce long gamma-ray bursts (LGRBs) can be described by a structured jet model where prompt $\gamma$-ray emission is restricted to a narrow region in the jet’s core. Viewing the jet off-axis from the core, a population of afterglows without an associated GRB detection can be predicted. In this work, we conduct an archival search for these ‘orphan’ afterglows (OAs) with minute-cadence, deep ($g\sim 23$) data from the Dark Energy Camera (DECam) taken as part of the Deeper, Wider, Faster programme (DWF). We introduce a method to select fast-evolving OA candidates within DWF data that comprises a machine learning model, based on a realistic synthetic population of OAs. Using this classifier, we recover 51 OA candidates. Of these candidates, 42 are likely flare events from M-class stars. The remaining nine possess quiescent, coincident sources in archival data with angular profiles consistent with a star and are inconsistent with the expected population of LGRB host galaxies. We therefore conclude that these are likely Galactic events. We calculate an upper limit on the rate of OAs down to $g\lt 22$ AB mag of 7.46 deg$^{-2}$yr$^{-1}$ using our criteria and constrain possible jet structures. We also place an upper limit of the characteristic angle between the $\gamma$-ray-emitting region and the jet’s half-opening angle. For a smooth power law and a power law with core jet model, respectively, these values are $58.3^{\circ }$ and $56.6^{\circ }$, for a power-law index of 0.8 and $75.3^{\circ }$ and $76.8^{\circ }$ for a power-law index of 1.2.
Intrinsically disordered regions regulate RhlE RNA helicase functions in bacteria
Authors: Hausmann Stéphane , Geiser Johan , Allen George Edward , Geslain Sandra Amandine Marie , Valentini Martina 
Published: June 2024

Abstract
RNA helicases—central enzymes in RNA metabolism—often feature intrinsically disordered regions (IDRs) that enable phase separation and complex molecular interactions. In the bacterial pathogen Pseudomonas aeruginosa, the non-redundant RhlE1 and RhlE2 RNA helicases share a conserved REC catalytic core but differ in C-terminal IDRs. Here, we show how the IDR diversity defines RhlE RNA helicase specificity of function. Both IDRs facilitate RNA binding and phase separation, localizing proteins in cytoplasmic clusters. However, RhlE2 IDR is more efficient in enhancing REC core RNA unwinding, exhibits a greater tendency for phase separation, and interacts with the RNase E endonuclease, a crucial player in mRNA degradation. Swapping IDRs results in chimeric proteins that are biochemically active but functionally distinct as compared to their native counterparts. The RECRhlE1-IDRRhlE2 chimera improves cold growth of a rhlE1 mutant, gains interaction with RNase E and affects a subset of both RhlE1 and RhlE2 RNA targets. The RECRhlE2-IDRRhlE1 chimera instead hampers bacterial growth at low temperatures in the absence of RhlE1, with its detrimental effect linked to aberrant RNA droplets. By showing that IDRs modulate both protein core activities and subcellular localization, our study defines the impact of IDR diversity on the functional differentiation of RNA helicases.