bluuebunny/crossref_metadata_2025_split huggingface dataset:
A finite element error analysis for axisymmetric mean curvature flow
Authors: Barrett John W , Deckelnick Klaus , Nürnberg Robert 
Published: August 2020

Abstract
We consider the numerical approximation of axisymmetric mean curvature flow with the help of linear finite elements. In the case of a closed genus-1 surface we derive optimal error bounds with respect to the $L^2$- and $H^1$-norms for a fully discrete approximation. We perform convergence experiments to confirm the theoretical results and also present numerical simulations for some genus-0 and genus-1 surfaces, including for the Angenent torus.
The Exceptional Locus in the Bertini Irreducibility Theorem for a Morphism
Authors: Poonen Bjorn , Slavov Kaloyan 
Published: August 2020

Abstract
We introduce a novel approach to Bertini irreducibility theorems over an arbitrary field, based on random hyperplane slicing over a finite field. Extending a result of Benoist, we prove that for a morphism $\phi \colon X \to{\mathbb{P}}^n$ such that $X$ is geometrically irreducible and the nonempty fibers of $\phi $ all have the same dimension, the locus of hyperplanes $H$ such that $\phi ^{-1} H$ is not geometrically irreducible has dimension at most ${\operatorname{codim}}\ \phi (X)+1$. We give an application to monodromy groups above hyperplane sections.
Central Limit Theorem for Mesoscopic Eigenvalue Statistics of the Free Sum of Matrices
Authors: Bao Zhigang , Schnelli Kevin , Xu Yuanyuan 
Published: August 2020

AbstractWe consider random matrices of the form $H_N=A_N+U_N B_N U^*_N$, where $A_N$ and $B_N$ are two $N$ by $N$ deterministic Hermitian matrices and $U_N$ is a Haar distributed random unitary matrix. We establish a universal central limit theorem for the linear eigenvalue statistics of $H_N$ on all mesoscopic scales inside the regular bulk of the spectrum. The proof is based on studying the characteristic function of the linear eigenvalue statistics and consists of two main steps: (1) generating Ward identities using the left-translation invariance of the Haar measure, along with a local law for the resolvent of $H_N$ and analytic subordination properties of the free additive convolution, allows us to derive an explicit formula for the derivative of the characteristic function; (2) a local law for two-point product functions of resolvents is derived using a partial randomness decomposition of the Haar measure. We also prove the corresponding results for orthogonal conjugations.
PBW Property for Associative Universal Enveloping Algebras Over an Operad
Authors: Khoroshkin Anton 
Published: August 2020

AbstractGiven a symmetric operad $\mathcal{P}$ and a $\mathcal{P}$-algebra $V$, the associative universal enveloping algebra ${\textsf{U}_{\mathcal{P}}}$ is an associative algebra whose category of modules is isomorphic to the abelian category of $V$-modules. We study the notion of PBW property for universal enveloping algebras over an operad. In case $\mathcal{P}$ is Koszul a criterion for the PBW property is found. A necessary condition on the Hilbert series for $\mathcal{P}$ is discovered. Moreover, given any symmetric operad $\mathcal{P}$, together with a Gröbner basis $G$, a condition is given in terms of the structure of the underlying trees associated with leading monomials of $G$, sufficient for the PBW property to hold. Examples are provided.
Evaluation of Serological Tests for SARS-CoV-2: Implications for Serology Testing in a Low-Prevalence Setting
Authors: Bond Katherine , Nicholson Suellen , Lim Seok Ming , Karapanagiotidis Theo , Williams Eloise , Johnson Douglas , Hoang Tuyet , Sia Cheryll , Purcell Damian , Mordant Francesca , Lewin Sharon R , Catton Mike , Subbarao Kanta , Howden Benjamin P , Williamson Deborah A 
Published: August 2020

Abstract

Background
Robust serological assays are essential for long-term control of the COVID-19 pandemic. Many recently released point-of-care (PoCT) serological assays have been distributed with little premarket validation.

Methods
Performance characteristics for 5 PoCT lateral flow devices approved for use in Australia were compared to a commercial enzyme immunoassay (ELISA) and a recently described novel surrogate virus neutralization test (sVNT).

Results
Sensitivities for PoCT ranged from 51.8% (95% confidence interval [CI], 43.1%–60.4%) to 67.9% (95% CI, 59.4%–75.6%), and specificities from 95.6% (95% CI, 89.2%–98.8%) to 100.0% (95% CI, 96.1%–100.0%). ELISA sensitivity for IgA or IgG detection was 67.9% (95% CI, 59.4%–75.6%), increasing to 93.8% (95% CI, 85.0%–98.3%) for samples &gt;14 days post symptom onset. sVNT sensitivity was 60.9% (95% CI, 53.2%–68.4%), rising to 91.2% (95% CI, 81.8%–96.7%) for samples &gt;14 days post symptom onset, with specificity 94.4% (95% CI, 89.2%–97.5%).

Conclusions
Performance characteristics for COVID-19 serological assays were generally lower than those reported by manufacturers. Timing of specimen collection relative to onset of illness or infection is crucial in reporting of performance characteristics for COVID-19 serological assays. The optimal algorithm for implementing serological testing for COVID-19 remains to be determined, particularly in low-prevalence settings.
SARS-CoV-2–Specific Antibody Detection for Seroepidemiology: A Multiplex Analysis Approach Accounting for Accurate Seroprevalence
Authors: den Hartog Gerco , Schepp Rutger M , Kuijer Marjan , GeurtsvanKessel Corine , van Beek Josine , Rots Nynke , Koopmans Marion P G , van der Klis Fiona R M , van Binnendijk Robert S 
Published: August 2020

Abstract

Background
The COVID-19 pandemic necessitates better understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high-throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population.

Methods
Spike protein subunits S1 and receptor binding domain, and nucleoprotein were coupled to microspheres. Sera collected before emergence of SARS-CoV-2 (n = 224) and of non-SARS-CoV-2 influenza-like illness (n = 184), and laboratory-confirmed cases of SARS-CoV-2 infection (n = 115) with various severities of COVID-19 were tested for SARS-CoV-2–specific IgG concentrations.

Results
Our assay discriminated SARS-CoV-2–induced antibodies and those induced by other viruses. The assay specificity was 95.1%–99.0% with sensitivity 83.6%–95.7%. By merging the test results for all 3 antigens a specificity of 100% was achieved with a sensitivity of at least 90%. Hospitalized COVID-19 patients developed higher IgG concentrations and the rate of IgG production increased faster compared to nonhospitalized cases.

Conclusions
The bead-based serological assay for quantitation of SARS-CoV-2–specific antibodies proved to be robust and can be conducted in many laboratories. We demonstrated that testing of antibodies against multiple antigens increases sensitivity and specificity compared to single-antigen–specific IgG determination.
Fc receptor-like 4 and 5 define human atypical memory B cells
Authors: Li Huifang , Dement-Brown Jessica , Liao Pei-Jyun , Mazo Ilya , Mills Frederick , Kraus Zachary , Fitzsimmons Sean , Tolnay Mate 
Published: August 2020

Abstract
Atypical memory B cells accumulate in chronic infections and autoimmune conditions, and commonly express FCRL4 and FCRL5, respective IgA and IgG receptors. We characterized memory cells from tonsils on the basis of both FCRL4 and FCRL5 expression, defining three subsets with distinct surface proteins and gene expression. Atypical FCRL4+FCRL5+ memory cells had the most discrete surface protein expression and were enriched in cell adhesion pathways, consistent with functioning as tissue-resident cells. Atypical FCRL4−FCRL5+ memory cells expressed transcription factors and immunoglobulin genes that suggest poised differentiation into plasma cells. Accordingly, the FCRL4−FCRL5+ memory subset was enriched in pathways responding to endoplasmic reticulum stress and IFN-γ. We reconstructed ongoing B-cell responses as lineage trees, providing crucial in vivo developmental context. Each memory subset typically maintained its lineage, denoting mechanisms enforcing their phenotypes. Classical FCRL4−FCRL5− memory cells were infrequently detected in lineage trees, suggesting the majority were in a quiescent state. FCRL4−FCRL5+ cells were the most represented memory subset in lineage trees, indicating robust participation in ongoing responses. Together, these differences suggest FCRL4 and FCRL5 are unlikely to be passive markers but rather active drivers of human memory B-cell development and function.
From intensive care to step-down units: Managing patients throughput in response to COVID-19
Authors: AGNOLETTI Vanni , RUSSO Emanuele , CIRCELLI Alessandro , BENNI Marco , BOLONDI Giuliano , MARTINO Costanza , SANTONASTASO Domenico P , BROGI Etrusca , PRATICÒ Beniamino , COCCOLINI Federico , FUGAZZOLA Paola , ANSALONI Luca , GAMBERINI Emiliano 
Published: August 2020

Abstract

Quality problem or issue
The on-going COVID-19 pandemic may cause the collapse of healthcare systems because of unprecedented hospitalization rates.

Initial assessment
A total of 8.2 individuals per 1000 inhabitants have been diagnosed with COVID-19 in our province. The hospital predisposed 110 beds for COVID-19 patients: on the day of the local peak, 90% of them were occupied and intensive care unit (ICU) faced unprecedented admission rates, fearing system collapse.

Choice of solution
Instead of increasing the number of ICU beds, the creation of a step-down unit (SDU) close to the ICU was preferred: the aim was to safely improve the transfer of patients and to relieve ICU from the risk of overload.

Implementation
A nine-bed SDU was created next to the ICU, led by intensivists and ICU nurses, with adequate personal protective equipment, monitoring systems and ventilators for respiratory support when needed. A second six-bed SDU was also created.

Evaluation
Patients were clinically comparable to those of most reports from Western Countries now available in the literature. ICU never needed supernumerary beds, no patient died in the SDU, and there was no waiting time for ICU admission of critical patients. SDU has been affordable from human resources, safety and economic points of view.

Lessons learned
COVID-19 is like an enduring mass casualty incident. Solutions tailored on local epidemiology and available resources should be implemented to preserve the efficiency and adaptability of our institutions and provide the adequate sanitary response.
Pharmacokinetics and renal safety of tenofovir alafenamide with boosted protease inhibitors and ledipasvir/sofosbuvir
Authors: Brooks Kristina M , Castillo-Mancilla Jose R , Morrow Mary , MaWhinney Samantha , Blum Joshua , Wyles David L , Rowan Sarah E , Ibrahim Mustafa E , Zheng Jia-Hua , Johnson Bethany , Gomez Joe , Choi Ye Ji , Cendali Francesca , Haas Hannah , Roon Laura , Bushman Lane R , Anderson Peter L , Kiser Jennifer J 
Published: August 2020

Abstract

Background
Ledipasvir/sofosbuvir increases tenofovir plasma exposures by up to 98% with tenofovir disoproxil fumarate (TDF), and exposures are highest with boosted PIs. There are currently no data on the combined use of the newer tenofovir prodrug, tenofovir alafenamide (TAF), boosted PIs and ledipasvir/sofosbuvir.

Objectives
To compare the plasma and intracellular pharmacokinetics and renal safety of TAF with ledipasvir/sofosbuvir when co-administered with boosted PIs.

Methods
Persons with HIV between 18 and 70 years and on a boosted PI with TDF were eligible. The study was comprised of four phases: (1) TDF 300 mg with boosted PI; (2) TAF 25 mg with boosted PI; (3) TAF 25 mg with boosted PI and ledipasvir/sofosbuvir; and (4) TAF 25 mg with boosted PI. Pharmacokinetic sampling, urine biomarker collection [urine protein (UPCR), retinol binding protein (RBP) and β2 microglobulin (β2M) normalized to creatinine] and safety assessments occurred at the end of each phase. Plasma, PBMCs and dried blood spots were collected at each visit.

Results
Ten participants were enrolled. Plasma tenofovir exposures were 76% lower and tenofovir-diphosphate (TFV-DP) concentrations in PBMCs increased 9.9-fold following the switch to TAF. Neither of these measures significantly increased with ledipasvir/sofosbuvir co-administration, nor did TAF plasma concentrations. No significant changes in estimated glomerular filtration rate or UPCR occurred, but RBP:creatinine and β2M:creatinine improved following the switch to TAF.

Conclusions
Ledipasvir/sofosbuvir did not significantly increase plasma tenofovir or intracellular TFV-DP in PBMCs with TAF. These findings provide reassurance that the combination of TAF, boosted PIs and ledipasvir/sofosbuvir is safe in HIV/HCV-coinfected populations.
β-Lactam antimicrobial pharmacokinetics and target attainment in critically ill patients aged 1 day to 90 years: the ABDose study
Authors: Lonsdale Dagan O , Kipper Karin , Baker Emma H , Barker Charlotte I S , Oldfield Isobel , Philips Barbara J , Johnston Atholl , Rhodes Andrew , Sharland Mike , Standing Joseph F 
Published: August 2020

AbstractBackgroundThe pharmacokinetics of β-lactam antibiotics in critical illness remain poorly characterized, particularly in neonates, children and the elderly. We undertook a pharmacokinetic study of commonly used β-lactam antibiotics in critically ill patients of all ages. The aims were to produce a whole-life β-lactam pharmacokinetic model and describe the extent to which standard doses achieve pharmacokinetic/pharmacodynamic targets associated with clinical cure.Patients and methodsA total of 212 critically ill participants with an age range from 1 day (gestational age 24 weeks) to 90 years were recruited from a UK hospital, providing 1339 pharmacokinetic samples. Population pharmacokinetic analysis was undertaken using non-linear mixed-effects modelling (NONMEM) for each drug. Pooled data were used to estimate maturation and decline of β-lactam pharmacokinetics throughout life.ResultsPharmacokinetic models for eight drugs were described, including what is thought to be the first benzylpenicillin model in critically ill adults. We estimate that 50% of adult β-lactam clearance is achieved by 43 weeks post-menstrual age (chronological plus gestational age). Fifty percent of decline from peak adult clearance occurs by 71 years. Paediatric participants were significantly less likely than adults to achieve pharmacokinetic/pharmacodynamic targets with standard antibiotic doses (P &lt; 0.01).ConclusionsWe believe this to be the first prospective whole-life antibiotic pharmacokinetic study in the critically ill. The study provides further evidence that standard antibiotic doses fail to achieve pharmacokinetic/pharmacodynamic targets associated with clinical success in adults, children and neonates. Maturation and decline parameters estimated from this study could be adopted as a standard for future prospective studies.
Colonization with multiresistant bacteria in acute hospital care: the association of prior antibiotic consumption as a risk factor
Authors: Dualleh Nasra , Chanchiri Iman , Skjøt-Arkil Helene , Pedersen Andreas Kristian , Rosenvinge Flemming S , Johansen Isik Somuncu 
Published: August 2020

Abstract

Background
Antibiotic resistance poses a worldwide threat and knowledge concerning risk factors for colonization with multiresistant bacteria (MRB) is limited.

Objectives
To examine the impact of prior antibiotic consumption on MRB colonization, with focus on type of antibiotic and timeline between antibiotic prescription and MRB colonization.

Methods
A nationwide case–control study was conducted and adults visiting emergency departments were invited to participate. All patients were swabbed in the throat, nose and rectum, and analysed for colonization with ESBL-producing Enterobacteriaceae (ESBL-E), MRSA, carbapenemase-producing enterobacteria and VRE. Antibiotic history 2 years prior to enrolment was collected at an individual level through a national register. Multivariate analyses were performed to examine the association between antibiotic consumption and MRB status. A subgroup analysis of ESBL-E-colonized cases was made.

Results
We included 256 patients colonized with MRB and 4763 controls. In the 2 years prior to study inclusion, 77% of cases and 68% of controls had at least one antibiotic prescription (P = 0.002). We found a significant increase in risk of colonization with ESBL-E if penicillins (OR = 1.58–1.65) or fluoroquinolones (OR = 2.25–6.15) were prescribed. The analysis of all MRB-colonized patients showed similar results. An assessment of the timeline showed a significant increase in risk of colonization up to 2 years after exposure to penicillins, fluoroquinolones and macrolides.

Conclusions
The prevalence of ESBL-E colonization was related to fluoroquinolone, macrolide and penicillin consumption for at least 2 years after antibiotic treatment.
In vitroactivity of rifabutin against 293 contemporary carbapenem-resistantAcinetobacter baumanniiclinical isolates and characterization of rifabutin mode of action and resistance mechanisms
Authors: Trebosc Vincent , Schellhorn Birgit , Schill Julian , Lucchini Valentina , Bühler Jacqueline , Bourotte Marilyne , Butcher Jonathan J , Gitzinger Marc , Lociuro Sergio , Kemmer Christian , Dale Glenn E 
Published: August 2020

AbstractBackgroundRifabutin, an oral drug approved to treat Mycobacterium avium infections, demonstrated potent activity against Acinetobacter baumannii in nutrient-limited medium enabled by rifabutin cellular uptake through the siderophore receptor FhuE.ObjectivesTo determine rifabutin in vitro activity and resistance mechanisms in a large panel of A. baumannii isolates.MethodsTwo hundred and ninety-three carbapenem-resistant A. baumannii clinical isolates collected from Europe, the USA and Asia during 2017–19 were used for MIC determination. Sequencing/genotyping of fhuE, rpoB and arr-2 genes in isolates with elevated rifabutin MIC combined with genetic engineering and gene expression quantification was used to characterize rifabutin’s mode of action and resistance mechanisms.ResultsRifabutin showed excellent activity on the strain panel, with an MIC50/90 of 0.008/1 mg/L, and was superior to all other antibiotics tested, including colistin, tigecycline and cefiderocol (MIC90 of 8 mg/L). Rifabutin remained active on resistant subpopulations, including strains resistant to the siderophore–drug conjugate cefiderocol (MIC90 of 2 mg/L, n = 23). At least two independent resistance mechanisms were required to abolish rifabutin activity, which is in line with the dose-dependent mutational resistance frequency reaching 10−9 at rifabutin concentrations at or above 2 mg/L.ConclusionsThis study demonstrated the potent activity of rifabutin against carbapenem-resistant A. baumannii. We propose that FhuE-mediated active uptake of rifabutin enables activity against rifampicin-resistant isolates. To achieve clinically meaningful strain coverage and to avoid rapid resistance development, rifabutin concentrations ≥2 mg/L are required, something rifabutin oral formulations cannot deliver.
Time- and Site-Dependent Postmortem Redistribution of Antidepressants and Neuroleptics in Blood and Alternative Matrices
Authors: Brockbals Lana , Staeheli Sandra N , Gascho Dominic , Ebert Lars C , Kraemer Thomas , Steuer Andrea E 
Published: August 2020

Abstract
Postmortem redistribution (PMR) leads to challenges in postmortem case interpretation. Particularly antidepressants and neuroleptics are expected to undergo PMR based on their physico-chemical properties. For the current study, time- and site-dependent PMR of 20 antidepressants and neuroleptics were investigated in humans (authentic cases); five of which are discussed in detail (citalopram, mirtazapine, quetiapine, risperidone and venlafaxine) along with two metabolites (9-OH-risperidone and O-desmethylvenlafaxine). Blood [femoral (pB) and heart blood (HB)] and tissue biopsy samples (lung, kidney, liver, spleen, thigh muscle and adipose tissue) were collected upon admission to the institute utilizing a computed tomography-guided sample collection workflow (t1). Approximately 24 h later (t2; mean 23 ± 9.3 h), samples from the same body regions were collected manually. Liquid chromatography–tandem mass spectrometry was used for quantification. Most antidepressants and neuroleptics showed significant time-dependent concentration changes indicating the occurrence of PMR. For the first time, two phases of redistribution in pB for quetiapine were proposed (concentration decreases in the early postmortem phase, followed by concentration increases) and contrasting existing literature, both concentration increases and decreases in pB overtime were observed for risperidone and 9-OH-risperidone. Venlafaxine and its metabolite only showed minimal concentration changes, while citalopram exhibited a trend for concentration increases and mirtazapine for concentration decreases in pB overtime. Based on time-dependent tissue data, passive diffusion processes along the muscle-to-pB, liver-to-HB and lung-to-HB concentration gradients could be proposed along with bacterial degradation. Overall, no case interpretation had to be adjusted, which suggests that PMR changes of antidepressants and neuroleptics do not seem to be relevant for forensic case interpretation within the 24 h period that was investigated. However, limitations of the current study (e.g., temperature-controlled storage of the bodies) could have led to an underestimation of occurring postmortem changes, hence, interpretation of postmortem results should always be conducted with care, considering PMR phenomena and inter-individual variability.
Determining the Effect of Postharvest Cold Storage Treatment on the Survival of Immature Drosophila suzukii (Diptera: Drosophilidae) in Small Fruits
Authors: Kraft Laura J , Yeh D Adeline , Gómez Miguel I , Burrack Hannah J 
Published: August 2020

AbstractWe evaluated the effect of postharvest cold storage temperature (0.0–2.2°C) and duration (3–5 d) on pupal emergence of single life stage populations of laboratory-generated Drosophila suzukii (Matsumura) and mixed-age populations collected in the field from blackberries, blueberries, strawberries, and raspberries. For field-infested fruit, cold storage at any temperature and duration resulted in less pupal emergence compared with the control held at 20°C, but D. suzukii subjected to higher temperatures and shorter storage durations in caneberries had higher survival. When a single life stage of D. suzukii was exposed to cold storage, pupal emergence was significantly reduced across all fruit types held at 0°C and for most life stages and fruit types held at 1.5 and 2.2°C, dependent on the substrate. Freshly laid eggs exposed to cold storage produced the lowest pupal emergence. Our results suggest using cold storage treatment is an effective postharvest management strategy for small-fruit growers to use on-farm as part of an integrated program to manage D. suzukii infestation. An economic assessment was made to examine the profit implications of an investment in cold storage units to counter pest pressure. Results suggest that investment in a cold storage unit would breakeven in about 4 yr. On farms that already have cold storage installed, we estimated a $0.11/kg decrease in blueberry market price for holding fruit for 3 d. Together, this cost assessment will provide growers with the knowledge to make decisions based on infestation risk and the seasonal sale price of blueberries.