bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increasing Biosimilar Utilization at a Pediatric Inflammatory Bowel Disease Center and Associated Cost Savings: Show Me the Money
Authors: Morris Grant A , McNicol Megan , Boyle Brendan , Donegan Amy , Dotson Jennifer , Michel Hilary K , Maltz Ross M 
Published: May 2021

Abstract

Background
Tumor necrosis factor-alpha inhibitors (anti-TNFs) are a primary treatment for inflammatory bowel disease. Pharmaceutical expenditures and usage of specialty drugs are increasing. In the United States, biosimilars continue to be underutilized, despite opportunities for health care cost savings. Through quality improvement (QI) methodology, we aimed to increase biosimilar utilization among eligible patients initiating intravenous (IV) anti-TNF therapy and describe patient outcomes and associated cost savings.

Methods
Beginning in July 2019, all patients initiating IV anti-TNF therapy were identified and tracked. Using the Institute of Healthcare Improvement Plan-Do-Study-Act cycle, a four-stage problem-solving model used for carrying out change, we trialed interventions to increase biosimilar utilization, including provider, staff, and family education, and utilization of a clinical pharmacist and insurance specialist. Statistical process control charts were used to show improvement over time. Patients’ clinical outcome and cost savings were reviewed.

Results
Using QI methodology, we increased biosimilar utilization from a baseline of 1% in June 2019 to 96% by February 2021, with sustained improvement. The originator (infliximab) was the insurance company’s preferred product for 20 patients (20%). Patient outcomes (IV anti-TNF levels, absence of antidrug antibodies, and physician global assessment) between biosimilars and originators were similar. Estimated cost savings over the project duration were nearly $381,000 (average sales price) and $651,000 (wholesale acquisition cost).

Conclusions
Through QI methodology, we increased biosimilar utilization from 1% to 96% with sustained improvement, without compromising patient outcomes or safety. Estimated cost savings were substantial. Similar methodology could be implemented at other institutions to increase biosimilar utilization and potentially decrease health care costs.
Blow-up Dynamics for L2-Critical Fractional Schrödinger Equations
Authors: Lan Yang 
Published: May 2021

Abstract
In this paper, we consider the $L^2$-critical fractional Schrödinger equation $iu_t-|D|^{\beta }u+|u|^{2\beta }u=0$ with initial data $u_0\in H^{\beta /2}(\mathbb{R})$ and $\beta $ close to $2$. We show that if the initial data have negative energy and slightly supercritical mass, then the solution blows up in finite time. We also give a specific description for the blow-up dynamics. This is an extension of the works of F. Merle and P. Raphaël for $L^2$-critical Schrödinger equations. However, the nonlocal structure of this equation and the lack of some symmetries make the analysis more complicated, hence some new strategies are required.
The Evolutionary History of Siphonophore Tentilla: Novelties, Convergence, and Integration
Authors: Damian-Serrano A , Haddock S H D , Dunn C W 
Published: May 2021

Abstract
Synopsis Siphonophores are free-living predatory colonial hydrozoan cnidarians found in every region of the ocean. Siphonophore tentilla (tentacle side branches) are unique biological structures for prey capture, composed of a complex arrangement of cnidocytes (stinging cells) bearing different types of nematocysts (stinging capsules) and auxiliary structures. Tentilla present an extensive morphological and functional diversity across species. While associations between tentillum form and diet have been reported, the evolutionary history giving rise to this morphological diversity is largely unexplored. Here we examine the evolutionary gains and losses of novel tentillum substructures and nematocyst types on the most recent siphonophore phylogeny. Tentilla have a precisely coordinated high-speed strike mechanism of synchronous unwinding and nematocyst discharge. Here we characterize the kinematic diversity of this prey capture reaction using high-speed video and find relationships with morphological characters. Since tentillum discharge occurs in synchrony across a broad morphological diversity, we evaluate how phenotypic integration is maintaining character correlations across evolutionary time. We found that the tentillum morphospace has low dimensionality, identified instances of heterochrony and morphological convergence, and generated hypotheses on the diets of understudied siphonophore species. Our findings indicate that siphonophore tentilla are phenotypically integrated structures with a complex evolutionary history leading to a phylogenetically-structured diversity of forms that are predictive of kinematic performance and feeding habits.
In vitroactivity of cefiderocol and comparators against isolates of Gram-negative pathogens from a range of infection sources: SIDERO-WT-2014–2018 studies in France
Authors: Naas Thierry , Lina Gerard , Santerre Henriksen Anne , Longshaw Christopher , Jehl Francois 
Published: May 2021

AbstractObjectivesOver recent years, France has experienced an increase of infections caused by carbapenem-resistant Gram-negative (GN) pathogens. Cefiderocol is approved in Europe for the treatment of aerobic GN infections in adults with limited treatment options. This study evaluated the in vitro activity of cefiderocol and comparators against GN clinical isolates from France.MethodsMICs were determined by broth microdilution, according to International Organization for Standardization guidelines. Cefiderocol was tested using iron-depleted CAMHB. Susceptibility rates were based on EUCAST breakpoints. In the absence of a species-specific breakpoint, pharmacokinetic/pharmacodynamic breakpoints were used.ResultsOf 2027 isolates, 1344 (66.3%) were Enterobacterales and 683 (33.7%) were non-fermenters. The most common pathogen was Pseudomonas aeruginosa (16.8%), followed by Escherichia coli (16.0%), Klebsiella pneumoniae (13.1%), Acinetobacter baumannii (7.9%) and Stenotrophomonas maltophilia (5.1%). Isolates represented a range of infection sources including nosocomial pneumonia (33.6%), complicated urinary tract infection (24.3%), bloodstream infection (13.1%) and complicated intra-abdominal infection (18.0%). In total, 135/2027 (6.7%) isolates were meropenem resistant (MIC &gt;8 mg/L); 133/135 (98.5%) were non-fermenters. Overall, 1330/1344 (99.0%) Enterobacterales and 681/683 (99.7%) non-fermenters were cefiderocol susceptible, including 100% of meropenem-resistant S. maltophilia (n = 98) and P. aeruginosa (n = 18) isolates. Susceptibility to cefiderocol was significantly higher (P &lt; 0.01) in nosocomial pneumonia isolates (681/682 [99.9%]) than susceptibility to meropenem (586/682 [85.9%]), ceftolozane/tazobactam (593/682 [87.0%]), ceftazidime/avibactam (612/682 [89.7%]) and colistin (538/682 [78.9%]).ConclusionsCefiderocol demonstrated high in vitro susceptibility rates against a wide range of Gram-negative pathogens, including meropenem-resistant strains, and was significantly more active than comparators against pneumonia isolates.
Development and randomized controlled trial of an animated film aimed at reducing behaviours for acquiring antibiotics
Authors: Wilding Sarah , Kettu Virpi , Thompson Wendy , Howard Philip , Jeuken Lars J C , Pownall Madeleine , Conner Mark , Sandoe Jonathan A T 
Published: May 2021

Abstract

Background
Antimicrobial resistance (AMR) is a global health crisis but reducing antibiotic use can help. Some antibiotic use is driven by patient demand.

Objectives
To develop an intervention to discourage antibiotic-seeking behaviour in adults.

Methods
Literature reviewed to identify behaviours for acquiring antibiotics among adults in the community. Behaviour change wheel approach was used to select the target behaviour and behaviour change techniques. An intervention in the form of a short animated film was developed and its potential impact evaluated in a randomized, controlled, online questionnaire study.

Results
Asking a general medical/dental practitioner for antibiotics was identified as the target behaviour. A short stop-motion animated film was chosen to deliver several behaviour-change techniques. Education and persuasion were delivered around information about the normal microbial flora, its importance for health, the negative effect of antibiotics, and about AMR. 417 UK-based individuals completed the questionnaire; median age 34.5 years, 71% female, 91% white ethnicity. 3.8% of participants viewing the test film intended to ask for antibiotics compared with 7.9% viewing the control film. Test film viewers had significantly higher knowledge scores. At 6 week follow up, knowledge scores remained significantly different, while most attitude and intention scores were not different.

Conclusions
Some patients continue to ask for antibiotics. The film increased knowledge and reduced intentions to ask for antibiotics. At 6 weeks, knowledge gains remained but intentions not to ask for antibiotics had waned. Evaluation in the clinical environment, probably at the point of care, is needed to see if antibiotic prescribing can be impacted.
Antibiotic prescribing patterns in patients hospitalized with COVID-19: lessons from the first wave
Authors: O’Kelly Brendan , Cronin Colm , Connellan David , Griffin Sean , Connolly Stephen Peter , McGrath Jonathan , Cotter Aoife G , McGinty Tara , Muldoon Eavan G , Sheehan Gerard , Cullen Walter , Doran Peter , McHugh Tina , Vidal Louise , Avramovic Gordana , Lambert John S 
Published: May 2021

Abstract

Background
A high proportion of hospitalized patients with COVID-19 receive antibiotics despite evidence to show low levels of true bacterial coinfection.

Methods
A retrospective cohort study examining antibiotic prescribing patterns of 300 patients sequentially diagnosed with COVID-19. Patients were grouped into 3 sub-cohorts: Group 1 received no antibiotics, Group 2 received antibiotics for microbiologically confirmed infections and Group 3 was empirically treated with antibiotics for pneumonia. The primary aim was to identify factors that influenced prescription and continuation of antibiotics in Group 3. Secondary aims were to examine differences in outcomes between groups.

Results
In total, 292 patients were included (63 Group 1, 35 Group 2, 194 Group 3), median age was 60 years (IQR 44–76) and the majority were ethnically Irish (62%). The median duration of antibiotics was 7 days (IQR 5–10). In Group 3, factors associated with prescription IV antibiotics on admission were raised C-reactive protein (CRP) (P = 0.024), increased age (P = 0.023), higher quick SOFA (P = 0.016) score and fever &gt;37.5 °C (P = 0.011). Factors associated with duration of antibiotic course were duration of hypoxia (P &lt; 0.001) and maximum respiratory support requirement (P = 0.013). Twenty-one patients in Group 3 had one or more antibiotic escalation events, most (n = 139) had no escalation or de-escalation of therapy.

Conclusions
Duration of hypoxia and need for respiratory support may have acted as surrogate measures of improvement where usual response measures (CRP, neutrophilia, culture clearance) were absent. Continuous review of antibiotic prescriptions should be at the forefront of clinical management of hospitalized patients with COVID-19.
Novel welding distortion analysis method for large welded structures using orthotropic thermal expansion coefficients
Authors: Seo Hyun-Duk , Lee Jae Min 
Published: May 2021

Abstract
This paper proposes an effective numerical method to predict welding distortion for large welded structures. To predict welding distortions, inherent strain-based methods are computationally efficient and widely used in engineering fields. However, there are some drawbacks such as the generation of undesirable longitudinal forces and the use of vector-type input variables. Equivalent loads are derived through finite element formulation considering orthotropic thermal expansion conditions. Unlike previous methods, the proposed method predicts transverse shrinkage and angular distortion accurately, removing the undesirable longitudinal forces. In addition, scalar-type input variables are employed, which results in a convenient design procedure. The performance of the proposed method is verified through various examples including complex and large welded structures.
Charismatic Entrainment: How Brand Leaders and Consumers Co-Create Charismatic Authority in the Marketplace
Authors: Wieser Verena E , Luedicke Marius K , Hemetsberger Andrea 
Published: May 2021

AbstractHow do CEOs, entrepreneurs, managers, celebrity bloggers, and other brand leaders acquire charismatic authority in the marketplace? Grounded in a multi-perspective, in-depth case study of the charismatic CEO of an Austrian shoe manufacturer, this article introduces a sociocultural mechanism called charismatic entrainment. Charismatic entrainment involves brand leaders staging charismatic authority by promoting polarized worldviews and taking personal risks to demonstrate their ability to lead social change. It further involves consumer-followers publicly validating and consumer-critics challenging brand leaders’ claims to charismatic authority, encouraging further entrainment via their support, but also their criticism. Brand leaders, consumer-followers, and consumer-critics draw on social media, marketplace sentiments, and brand manifestations as entrainment resources to more effectively endow brand leaders with charismatic authority in the marketplace. The article contributes a market-based, multi-stakeholder—versus an organizational, leader-centric—theory of charisma co-creation to the literature on charismatic authority. It also adds to theories of iconic branding, risk consumption, and societal morality plays, sensitizing readers to the constructive but also destructive potential of market-based charisma co-creation.
Legal Pluralism and the Future of Personal Family Laws in Africa
Authors: Diala Anthony Chima 
Published: May 2021

Abstract
A notable aspect of Africa’s struggle with its colonial legacies is the co-existence of indigenous laws that emerged in agrarian settings with state laws that emerged in industrial settings. Given the dissonance in their origins, clashes frequently occur between traditionalists and change agents, especially over the property and succession rights of women, girls, and younger male children. Spurred by the judicial handling of these clashes, scholars categorise African customary laws into ‘official’ and ‘living’ versions. However, this categorisation does not account properly for the influence of globalisation on the normative behaviour of Africans. Based on multi-country field research, this article introduces adaptive legal pluralism as the framework for managing the co-existence of indigenous laws and state laws in sub-Saharan Africa. By explaining the influence of globalisation on the behaviour of people subject to indigenous laws, the article draws attention to the imitative character of normative interaction in this region. It presents adaptive legal pluralism as not only a crystal bowl for charting the future of indigenous family laws, but also the theoretical pathway to integrated state and indigenous laws.
Hubble Space Telescope[O iii] emission-line kinematics in two nearby QSO2s: a case for X-ray feedback
Authors: Trindade Falcão Anna , Kraemer S B , Fischer T C , Crenshaw D M , Revalski M , Schmitt H R , Maksym W P , Vestergaard M , Elvis M , Gaskell C M , Hamann F , Ho L C , Hutchings J , Mushotzky R , Netzer H , Storchi-Bergmann T , Turner T J , Ward M J 
Published: May 2021

ABSTRACTWe present a dynamical study of the narrow-line regions in two nearby type 2 quasars (QSO2s). We construct dynamical models based on detailed photoionization models of the emission-line gas, including the effects of internal dust, to apply to observations of large-scale outflows from these active galactic nuclei (AGNs). We use Mrk 477 and Mrk 34 in order to test our models against recent Hubble Space Telescope (HST) Space Telescope Imaging Spectrograph (STIS) observations of [O iii] emission-line kinematics, since these AGNs possess more energetic outflows than found in Seyfert galaxies. We find that the outflows within 500 pc are consistent with radiative acceleration of dusty gas, however the outflows in Mrk 34 are significantly more extended and may not be directly accelerated by radiation. We characterize the properties of X-ray winds found from the expansion of [O iii]-emitting gas close to the black hole. We show that such winds possess the kinetic energy density to disturb [O iii] gas at ∼1.8 kpc, and have sufficient energy to entrain the [O iii] clouds at ∼1.2 kpc. Assuming that the X-ray wind possesses the same radial mass distribution as the [O iii] gas, we find that the peak kinetic luminosity for this wind is 2 per cent of Mrk 34’s bolometric luminosity, which is in the 0.5–5 per cent range required by some models for efficient feedback. Our work shows that, although the kinetic luminosity as measured from [O iii]-emitting gas is frequently low, X-ray winds may provide more than one order of magnitude higher kinetic power.
Mechanistic insights into translation inhibition by aminoglycoside antibiotic arbekacin
Authors: Parajuli Narayan Prasad , Mandava Chandra Sekhar , Pavlov Michael Y , Sanyal Suparna 
Published: May 2021

Abstract
How aminoglycoside antibiotics limit bacterial growth and viability is not clearly understood. Here we employ fast kinetics to reveal the molecular mechanism of action of a clinically used, new-generation, semisynthetic aminoglycoside Arbekacin (ABK), which is designed to avoid enzyme-mediated deactivation common to other aminoglycosides. Our results portray complete picture of ABK inhibition of bacterial translation with precise quantitative characterizations. We find that ABK inhibits different steps of translation in nanomolar to micromolar concentrations by imparting pleotropic effects. ABK binding stalls elongating ribosomes to a state, which is unfavorable for EF-G binding. This prolongs individual translocation step from ∼50 ms to at least 2 s; the mean time of translocation increases inversely with EF-G concentration. ABK also inhibits translation termination by obstructing RF1/RF2 binding to the ribosome. Furthermore, ABK decreases accuracy of mRNA decoding (UUC vs. CUC) by ∼80 000 fold, causing aberrant protein production. Importantly, translocation and termination events cannot be completely stopped even with high ABK concentration. Extrapolating our kinetic model of ABK action, we postulate that aminoglycosides impose bacteriostatic effect mainly by inhibiting translocation, while they become bactericidal in combination with decoding errors.
Integration of single-cell datasets reveals novel transcriptomic signatures of β-cells in human type 2 diabetes
Authors: Bosi Emanuele , Marselli Lorella , De Luca Carmela , Suleiman Mara , Tesi Marta , Ibberson Mark , Eizirik Decio L , Cnop Miriam , Marchetti Piero 
Published: May 2021

AbstractPancreatic islet β-cell failure is key to the onset and progression of type 2 diabetes (T2D). The advent of single-cell RNA sequencing (scRNA-seq) has opened the possibility to determine transcriptional signatures specifically relevant for T2D at the β-cell level. Yet, applications of this technique have been underwhelming, as three independent studies failed to show shared differentially expressed genes in T2D β-cells. We performed an integrative analysis of the available datasets from these studies to overcome confounding sources of variability and better highlight common T2D β-cell transcriptomic signatures. After removing low-quality transcriptomes, we retained 3046 single cells expressing 27 931 genes. Cells were integrated to attenuate dataset-specific biases, and clustered into cell type groups. In T2D β-cells (n = 801), we found 210 upregulated and 16 downregulated genes, identifying key pathways for T2D pathogenesis, including defective insulin secretion, SREBP signaling and oxidative stress. We also compared these results with previous data of human T2D β-cells from laser capture microdissection and diabetic rat islets, revealing shared β-cell genes. Overall, the present study encourages the pursuit of single β-cell RNA-seq analysis, preventing presently identified sources of variability, to identify transcriptomic changes associated with human T2D and underscores specific traits of dysfunctional β-cells across different models and techniques.
Cystatin C kidney functional reserve: a simple method to predict outcome in chronic kidney disease
Authors: Christiadi Daniel , Simpson Charles , O’brien Kate , Taylor Kylie , Luxton Grant , Rossleigh Monica , Erlich Jonathan , Endre Zoltán H 
Published: May 2021

Abstract

Background
Kidney functional reserve (KFR), the only clinical kidney stress test, is not routinely measured because the complexity of measurement has limited clinical application. We investigated the utility of plasma cystatin C (CysC) after oral protein loading (PL) to determine KFR in Stages 3 and 4 chronic kidney disease (CKD).

Methods
Following a 24-h low-protein diet, KFR was measured after oral protein by hourly plasma CysC and compared with simultaneous creatinine clearance (CrCl) and radionuclide 99technetium diethylenetriaminepentaacetatic acid (Tc-99m-DTPA) measured glomerular filtration rate (mGFR) measurement in an observational, single-centre cohort study of adults with CKD Stages 3 and 4. Subjects were followed for 3 years for fast (F) or slow (S) CKD progression, dialysis requirement or death or a combination of major adverse kidney events (MAKEs).

Result
CysC, CrCl and Tc-99m-DTPA mGFR measurements of KFR in 19 CKD Stage 3 and 21 CKD Stage 4 patients yielded good agreement. KFR was not correlated with baseline kidney function. Eight CKD Stage 3 (42%) and 11 CKD Stage 4 (52%) subjects reached their lowest serum CysC concentration 4 h after PL. CysC KFR and baseline serum creatinine (sCr) predicted death or dialysis or MAKE-F with a respective area under the curve (AUC)  of 0.73 [95% confidence interval (CI) 0.48–0.89] and 0.71 (95% CI 0.51–0.84). Including CysC KFR, age, baseline sCr and nadir CysC predicted a decrease in sCr-estimated GFR &gt;1.2 mL/min/year (MAKE-S) with an AUC of 0.89.

Conclusions
Serial CysC avoided timed urine collection and radionuclide exposure and yielded equivalent estimates of KFR. Serial CysC may facilitate monitoring of KFR in clinical practice.