bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine Augmentation Reverses Transplant Recipient Neutrophil Dysfunction Against the Human Fungal Pathogen Candida albicans
Authors: Barros Nicolas , Alexander Natalie , Viens Adam , Timmer Kyle , Atallah Natalie , Knooihuizen Sally A I , Hopke Alex , Scherer Allison , Dagher Zeina , Irimia Daniel , Mansour Michael K 
Published: January 2021

Abstract

Background
Solid organ transplant (SOT) and stem cell transplant (SCT) recipients are at increased risk of invasive fungal disease despite normal neutrophil counts. Here, we measure neutrophil anti-Candida activity.

Methods
Twenty-one SOT and 19 SCT recipients were enrolled 2–4 months posttransplant and compared to 23 healthy control patients (HC). Neutrophils were coincubated with Candida albicans, and percentage killing and swarming responses were measured.

Results
Neutrophils from transplant patients had decreased fungicidal capacity compared to HC (42%, 43%, and 72% for SCT, SOT, and HC, respectively; SCT vs HC: P &lt; .0001; SOT vs HC: P &lt; .0001; SOT vs SCT: P = .8), including diminished ability to control hyphal growth (HC vs SOT: 0.1455 vs 0.3894, P ≤ .001; HC vs SCT: 0.1455 vs 0.6295, P ≤ .0001, respectively). Serum from SCT, but not SOT, recipients, inhibited the ability of HC neutrophils to control C. albicans (37%, 45%, and 55% for SCT, SOT, and HC, respectively). Neutrophils’ control of hyphal growth was partially restored with granulocyte colony-stimulating factor or granulocyte macrophage colony-stimulating factor.

Conclusions
Despite normal circulating numbers, our data suggest that neutrophils from SOT and SCT recipients mount dysfunctional responses against C. albicans. Intrinsic neutrophil changes and extrinsic serum factors may be responsible for the dysfunction, which is partially reversed with cytokine augmentation.
Characteristics and Long-term Prognosis of Danish Patients With Varicella Zoster Virus Detected in Cerebrospinal Fluid Compared With the Background Population
Authors: Omland Lars H , Vestergaard Hanne T , Dessau Ram B , Bodilsen Jacob , Andersen Nanna S , Christiansen Claus B , Ellermann-Eriksen Svend , Nielsen Lene , Andersen Christian Ø , Lebech Anne-Mette , Obel Niels 
Published: January 2021

Abstract

Background
Risk factors for, and long-term outcomes following, detection of varicella zoster virus (VZV) DNA in the cerebrospinal fluid (CSF) are unknown.

Methods
We performed a nationwide population-based cohort study of all Danish residents who had VZV DNA detected in the CSF by polymerase chain reaction (PCR) between 1 January 1997 and 1 March 2016 (VZV cohort; n = 517) and an age- and sex- matched comparison cohort from the general Danish population (n = 9823). We examined potential risk factors and mortality, neurologic morbidity, psychiatric morbidity, redemptiom of prescriptions for nervous system medicine prescribed for the nervous system, and social outcomes.

Results
Prior hospital admission, redemption of immunosuppressive medicine, comorbidity, and immunosuppressive conditions were associated with detection of VZV DNA in the CSF. Mortality was increased in the VZV cohort, especially during the first year of observation and among patients with encephalitis. Patients in the VZV cohort had an increased risk of dementia and epilepsy. The redemption of antiepileptics and antidepressants was increased in the VZV cohort.

Conclusions
Immunosuppression and comorbidity are associated with increased risk of detection of VZV DNA in the CSF and the condition is associated with increased mortality and neurological morbidity.
Emergence of MDR invasive Neisseria meningitidis in El Salvador, 2017–19
Authors: Marín José Eduardo Oliva , Villatoro Esmeralda , Luna María Jose , Barrientos Ana María , Mendoza Elmer , Lemos Ana Paula S , Camargo Carlos H , Sacchi Claudio T , Cunha Marcos Paulo V , Galas Marcelo , Gabastou Jean-Marc 
Published: January 2021

Abstract

Background
Invasive meningococcal disease (IMD) is an acute, highly transmissible and potentially fatal disease caused by Neisseria meningitidis. Prompt antimicrobial therapy and prophylaxis are recommended, where penicillin or ciprofloxacin are the available choices. However, the emergence of resistant isolates of N. meningitidis poses a challenge for antimicrobial therapy.

Objectives
To describe the clinical, epidemiological and biological characteristics of six penicillin- and ciprofloxacin-resistant, culture-confirmed IMD cases reported in El Salvador, Central America, between 2017 and 2019.

Methods
Following the detection of six patients presenting with IMD in El Salvador, clinical data were collected and epidemiological action plans conducted. Isolates were subjected to antimicrobial susceptibility testing by broth microdilution and WGS for genotyping and molecular characterization analysis, including phylogeny comparison with global sequences available from public databases.

Results
A total of six IMD cases caused by N. meningitidis serogroup Y, resistant to both penicillin (MIC &gt;8.0 mg/L) and ciprofloxacin (MIC 0.125 mg/L), were detected from 2017 to 2019. Genomic analysis showed that penicillin resistance was mediated by the production of β-lactamase ROB-1. Ciprofloxacin resistance was attributed to an amino acid substitution in DNA gyrase (T91I). All isolates were classified as ST3587, clonal complex 23, and were genetically highly similar, based on core-genome SNP analysis.

Conclusions
To the best of our knowledge, we report the first cases of MDR N. meningitidis causing IMD in Latin America. Our findings highlight the emergence of this potential public health threat, with a profound impact on the efficacy of IMD treatment and prophylaxis protocols.
The case for ‘conservative pharmacotherapy’
Authors: Jorgensen Sarah C J , Stewart Jackson J , Dalton Bruce R 
Published: January 2021

Abstract
In the modern era of rapid advances in the field of antimicrobial ‘precision dosing’ through therapeutic drug monitoring (TDM), there is growing pressure to adopt new technologies and expand the number of antimicrobials managed with TDM and/or the complexity of TDM methods. For many clinicians, it may seem inevitable that TDM must improve patient outcomes. However, based on the evidence to date, this concept remains largely a hypothesis. Conversely, it is plausible that focusing on TDM may distract from careful clinical monitoring of the patient for efficacy and drug-related toxicities and shift finite resources from other valuable interventions. In this article we make the case for embracing critical appraisal of precision dosing, remaining skeptical until persuaded by compelling evidence, and adopting new technologies only when they have proven their value over competing priorities; that is, we make the case for using ‘conservative pharmacotherapy’.
Quanta prudentia et usus administrandæ reipublicæ: Quiccheberg and Mylaeus on the utility of techne
Authors: Meadow Mark A 
Published: January 2021

Abstract
Two mid-sixteenth-century treatises, by Samuel Quiccheberg (1565) and Christophorus Mylaeus (1551), provide important insights into how early modern collections were understood in their own day to be useful. This essay argues that both authors conceptualize utility in relation to the Aristotelian concept of prudence: the kind of practical wisdom required to govern effectively. Although the two texts were written on very different topics – respectively, how to create a Kunstkammer and how to write history – Quiccheberg and Mylaeus share an understanding of wisdom that posits ‘techne’, in the form of collected works of artistry, as a necessary aspect of prudential governance.
Clinical approach to re-irradiation for recurrent diffuse intrinsic pontine glioma
Authors: Krishnatry Rahul , Manjali Jifmi Jose , Chinnaswamy Girish , Chatterjee Abhishek , Goda Jayant Sastri , Janu Amit , Sahu Arpita , Jalali Rakesh , Gupta Tejpal 
Published: January 2021

Abstract

Background
We present our institutional approach for re-irradiation in diffuse intrinsic pontine glioma and their outcomes.

Methods
Consecutive patients of recurrent diffuse intrinsic pontine glioma treated with re-irradiation (January 2015–September 2019) were reviewed retrospectively to describe the clinical-response-based approach followed for the dose and volume decision. Outcomes were defined with clinical and steroid response criteria and survival endpoints included progression-free survival and overall survival as cumulative(c) overall survival and re-irradiation overall survival (re-irradiation starting to death). The Kaplan–Meier method and log-rank test were used for survival analysis.

Results
Twenty-patient cohort with a median (m) age of 7.5 years, m-progression-free survival of 8.4 months and m-Lansky performance score of 50 received re-irradiation of which 17 (85%) were called clinical responders. The median re-irradiation-overall survival with 39.6–41.4, 43.2 and 45 Gy were 5.8, 7 and 5.3 months, respectively. One-month post-re-irradiation steroid independent status was a significant predictor of better survival outcomes (overall survival, P≤0.004). No ≥ grade 3 toxicities were noticed. Two patients succumbed to intra-tumoral hemorrhage.

Conclusions
Higher doses of re-irradiation based on a clinical-response-based approach show improvement in survival and steroid dependence rates with acceptable toxicity. Steroid independent status at 1-month post-re-irradiation predicts better outcomes. Prospective studies may validate this with quality of life data.
Kidney injury molecule-1 is a potential receptor for SARS-CoV-2
Authors: Yang Chen , Zhang Yu , Zeng Xia , Chen Huijing , Chen Yuchen , Yang Dong , Shen Ziwei , Wang Xiaomu , Liu Xinran , Xiong Mingrui , Chen Hong , Huang Kun 
Published: January 2021

Abstract
COVID-19 patients present high incidence of kidney abnormalities, which are associated with poor prognosis and mortality. The identification of SARS-CoV-2 in the kidney of COVID-19 patients suggests renal tropism of SARS-CoV-2. However, whether there is a specific target of SARS-CoV-2 in the kidney remains unclear. Herein, by using in silico simulation, coimmunoprecipitation, fluorescence resonance energy transfer, fluorescein isothiocyanate labeling, and rational design of antagonist peptides, we demonstrate that kidney injury molecule-1 (KIM1), a molecule dramatically upregulated upon kidney injury, binds with the receptor-binding domain (RBD) of SARS-CoV-2 and facilitates its attachment to cell membrane, with the immunoglobulin variable Ig-like (Ig V) domain of KIM1 playing a key role in this recognition. The interaction between SARS-CoV-2 RBD and KIM1 is potently blockaded by a rationally designed KIM1-derived polypeptide AP2. In addition, our results also suggest interactions between KIM1 Ig V domain and the RBDs of SARS-CoV and MERS-CoV, pathogens of two severe infectious respiratory diseases. Together, these findings suggest KIM1 as a novel receptor for SARS-CoV-2 and other coronaviruses. We propose that KIM1 may thus mediate and exacerbate the renal infection of SARS-CoV-2 in a ‘vicious cycle’, and KIM1 could be further explored as a therapeutic target.
Developmental and water deficit-induced changes in hydraulic properties and xylem anatomy of tomato fruit and pedicels
Authors: Li Hao , Zhang Xianbo , Hou Xuemin , Du Taisheng 
Published: January 2021

AbstractXylem water transport from the parent plant plays a crucial role in fruit growth, development, and the determination of quality. Attempts have been made to partition the hydraulic resistance of the pathway over the course of development, but no consensus has been reached. Furthermore, the issue has not been addressed in the context of changing plant and fruit water status under water deficit conditions. In this study, we have conducted a rigorous investigation into the developmental changes that occur in the hydraulic properties of tomato fruits and their pedicels under well-irrigated and water deficit conditions, based on hydraulic measurements, fruit rehydration, dye-tracing, light and electron microscopy, and flow modeling. We found that a decline in water transport capacity during development did not occur in the xylem pathway leading up to the fruit, but within the fruit itself, where the effect might reside either inside or outside of the xylem pathway. The developmental pattern of the hydraulic resistance of the xylem pathway was not significantly influenced by water deficit. The changes in xylem flow between the fruit and the parent plant resulting from the reduced driving force under water deficit could explain the reduced accumulation of water in the fruit. This study provides new insights that aid our understanding of xylem water transport in fleshy fruits and its sensitivity to water deficit from a hydraulic perspective.
Winds from fast rotating stars
Authors: Bogovalov S V , Petrov M A , Timofeev V A 
Published: January 2021

ABSTRACT
Numerical modelling of an isothermal wind from a fast rotating star is performed. Excitation of hydrodynamical turbulence and deviation of the shape of the stellar surface from a sphere are taken into account. Rotation and turbulence result in a dramatic increase of the mass flow rate from the star in comparison with a non-rotating one. The outflow occurs predominantly from a region on the stellar surface located at the equator. This flow expands rapidly due to thermal pressure. However, a disc-like flow at the equator is formed. The flow is more complicated near the pole. At large distances from the star a radially expanding wind is formed while close to the star some fraction of the outflow from the equatorial region falls down on to the stellar surface, producing a huge vortex. The dependence of the mass loss rate on the parameters of the star is presented.
Cross-correlating radio continuum surveys and CMB lensing: constraining redshift distributions, galaxy bias, and cosmology
Authors: Alonso David , Bellini Emilio , Hale Catherine , Jarvis Matt J , Schwarz Dominik J 
Published: January 2021

ABSTRACT
We measure the harmonic-space auto-power spectrum of the galaxy overdensity in the LOFAR Two-metre Sky Survey (LoTSS) first data release and its cross-correlation with the map of the lensing convergence of the cosmic microwave background (CMB) from the Planck collaboration. We report a ∼5σ detection of the cross-correlation. We show that the combination of the clustering power spectrum and CMB lensing cross-correlation allows us to place constraints on the high-redshift tail of the redshift distribution, one of the largest sources of uncertainty in the use of continuum surveys for cosmology. Our analysis shows a preference for a broader redshift tail than that predicted by the photometric redshifts contained in the LoTSS value-added catalogue, as expected, and more compatible with predictions from simulations and spectroscopic data. Although the ability of CMB lensing to constrain the width and tail of the redshift distribution could also be valuable for the analysis of current and future photometric weak lensing surveys, we show that its performance relies strongly on the redshift evolution of the galaxy bias. Assuming the redshift distribution predicted by the Square Kilometre Array Design simulations, we use our measurements to place constraints on the linear bias of radio galaxies and the amplitude of matter inhomogeneities σ8, finding $\sigma _8=0.69^{+0.14}_{-0.21}$ assuming the galaxy bias scales with the inverse of the linear growth factor, and $\sigma _8=0.79^{+0.17}_{-0.32}$ assuming a constant bias.
Far and extreme ultraviolet radiation fields and consequent disc destruction in star-forming regions
Authors: Parker Richard J , Nicholson Rhana B , Alcock Hayley L 
Published: January 2021

ABSTRACT
The first stages of planet formation usually occur when the host star is still in a (relatively) dense star-forming region, where the effects of the external environment may be important for understanding the outcome of the planet formation process. In particular, star-forming regions that contain massive stars have strong far-ultraviolet (FUV) and extreme ultraviolet (EUV) radiation fields, which can induce mass-loss from protoplanetary discs due to photoevaporation. In this paper, we present a parameter-space study of the expected FUV and EUV fields in N-body simulations of star-forming regions with a range of initial conditions. We then use recently published models to determine the mass-loss due to photoevaporation from protoplanetary discs. In particular, we focus on the effects of changing the initial degree of spatial structure and initial virial ratio in the star-forming regions, as well as the initial stellar density. We find that the FUV fields in star-forming regions are much higher than in the interstellar medium, even when the regions have stellar densities as low as in the Galactic field, due to the presence of intermediate-mass, and massive, stars (&gt;5 M⊙). These strong radiation fields lead to the destruction of the gas component in protoplanetary discs within 1 Myr, implying that gas giant planets must either form extremely rapidly (&lt;1 Myr), or that they exclusively form in star-forming regions like Taurus, which contain no intermediate-mass or massive stars. The latter scenario is in direct tension with meteoritic evidence from the Solar system that suggests the Sun and its protoplanetary disc was born in close proximity to massive stars.
Photoionized Herbig–Haro objects in the Orion Nebula through deep high-spectral resolution spectroscopy – I. HH 529 II and III
Authors: Méndez-Delgado J E , Esteban C , García-Rojas J , Henney W J , Mesa-Delgado A , Arellano-Córdova K Z 
Published: January 2021

ABSTRACT
We present the analysis of physical conditions, chemical composition, and kinematic properties of two bow shocks – HH 529 II and HH 529 III – of the fully photoionized Herbig–Haro object HH 529 in the Orion Nebula. The data were obtained with the Ultraviolet and Visual Echelle Spectrograph at the 8.2m Very Large Telescope and 20 yr of Hubble Space Telescope imaging. We separate the emission of the high-velocity components of HH 529 II and III from the nebular one, determining ne and Te in all components through multiple diagnostics, including some based on recombination lines (RLs). We derive ionic abundances of several ions, based on collisionally excited lines and RLs. We find a good agreement between the predictions of the temperature fluctuation paradigm (t2) and the abundance discrepancy factor (ADF) in the main emission of the Orion Nebula. However, t2 cannot account for the higher ADF found in HH 529 II and III. We estimate 6 per cent of Fe in the gas phase of the Orion Nebula, while this value increases to 14 per cent in HH 529 II and between 10 and 25 per cent in HH 529 III. We find that such increase is probably due to the destruction of dust grains in the bow shocks. We find an overabundance of C, O, Ne, S, Cl, and Ar of about 0.1 dex in HH 529 II and III that might be related to the inclusion of H-deficient material from the source of the HH 529 flow. We determine the proper motions of HH 529 finding multiple discrete features. We estimate a flow angle with respect to the sky plane of 58° ± 4° for HH 529.
Dinucleotides as simple models of the base stacking-unstacking component of DNA ‘breathing’ mechanisms
Authors: Beyerle Eric R , Dinpajooh Mohammadhasan , Ji Huiying , von Hippel Peter H , Marcus Andrew H , Guenza Marina G 
Published: January 2021

AbstractRegulatory protein access to the DNA duplex ‘interior’ depends on local DNA ‘breathing’ fluctuations, and the most fundamental of these are thermally-driven base stacking-unstacking interactions. The smallest DNA unit that can undergo such transitions is the dinucleotide, whose structural and dynamic properties are dominated by stacking, while the ion condensation, cooperative stacking and inter-base hydrogen-bonding present in duplex DNA are not involved. We use dApdA to study stacking-unstacking at the dinucleotide level because the fluctuations observed are likely to resemble those of larger DNA molecules, but in the absence of constraints introduced by cooperativity are likely to be more pronounced, and thus more accessible to measurement. We study these fluctuations with a combination of Molecular Dynamics simulations on the microsecond timescale and Markov State Model analyses, and validate our results by calculations of circular dichroism (CD) spectra, with results that agree well with the experimental spectra. Our analyses show that the CD spectrum of dApdA is defined by two distinct chiral conformations that correspond, respectively, to a Watson–Crick form and a hybrid form with one base in a Hoogsteen configuration. We find also that ionic structure and water orientation around dApdA play important roles in controlling its breathing fluctuations.
PTEN deficiency leads to proteasome addiction: a novel vulnerability in glioblastoma
Authors: Benitez Jorge A , Finlay Darren , Castanza Anthony , Parisian Alison D , Ma Jianhui , Longobardi Ciro , Campos Alex , Vadla Raghavendra , Izurieta Alejandro , Scerra Gianluca , Koga Tomoyuki , Long Tao , Chavez Lukas , Mesirov Jill P , Vuori Kristiina , Furnari Frank 
Published: January 2021

Abstract

Background
Glioblastoma (GBM) is the most common primary brain tumor in adults with a median survival of approximately 15 months; therefore, more effective treatment options for GBM are required. To identify new drugs targeting GBMs, we performed a high-throughput drug screen using patient-derived neurospheres cultured to preferentially retain their glioblastoma stem cell (GSC) phenotype.

Methods
High-throughput drug screening was performed on GSCs followed by a dose-response assay of the 5 identified original “hits.” A PI3K/mTOR dependency to a proteasome inhibitor (carfilzomib), was confirmed by genetic and pharmacologic experiments. Proteasome Inhibition Response Signatures were derived from proteomic and bioinformatic analysis. Molecular mechanism of action was determined using three-dimensional (3D) GBM-organoids and preclinical orthotopic models.

Results
We found that GSCs were highly sensitive to proteasome inhibition due to an underlying dependency on an increased protein synthesis rate, and loss of autophagy, associated with PTEN loss and activation of the PI3K/mTOR pathway. In contrast, combinatory inhibition of autophagy and the proteasome resulted in enhanced cytotoxicity specifically in GSCs that did express PTEN. Finally, proteasome inhibition specifically increased cell death markers in 3D GBM-organoids, suppressed tumor growth, and increased survival of mice orthotopically engrafted with GSCs. As perturbations of the PI3K/mTOR pathway occur in nearly 50% of GBMs, these findings suggest that a significant fraction of these tumors could be vulnerable to proteasome inhibition.

Conclusions
Proteasome inhibition is a potential synthetic lethal therapeutic strategy for GBM with proteasome addiction due to a high protein synthesis rate and autophagy deficiency.
Private Equity Buyouts and Workplace Safety
Authors: Cohn Jonathan , Nestoriak Nicole , Wardlaw Malcolm 
Published: January 2021

AbstractThis paper presents evidence of a large, persistent decline in establishment-level workplace injury rates after private equity (PE) buyouts of publicly traded U.S. firms. We find that firms experience fewer OSHA safety violations after buyouts and that a larger decline in injury rates is associated with an increased probability of exit via IPO. Employment reductions after buyouts are concentrated in relatively low-injury-risk establishments. Overall, our results suggest that buyouts improve workplace safety and that PE acquirers benefit from this improvement. We explore possible causes of these changes through interviews with executives of companies acquired in buyouts and through cross-sectional analysis.