bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population level consumption of cephalosporins and macrolides may select for reduced antimicrobial susceptibility to unrelated antimicrobials in Neisseria gonorrhoeae: an ecological analysis
Authors: Kenyon Chris 
Published: July 2020

AbstractAimsPrevious studies have found positive associations between population level consumption of macrolides/cephalosporins/floroquinolones and Neisseria gonorrhoeae sensitivity to the same class of antimicrobial. We hypothesized that these associations may also apply to different classes of antimicrobials.MethodsUsing susceptibility data from 24 countries in the European Gonococcal Antimicrobial Surveillance Programme and antimicrobial consumption data from the IMS Health MIDAS database we built mixed effects linear regression models with country-level cephalosporin, quinolone and macrolide consumption (standard doses/ 1000 population/ year) as the explanatory variables (from 2009 to 2015) and 1-year lagged ceftriaxone, azithromycin and ciprofloxacin geometric mean minimum inhibitory concentrations and percent resistance as the outcome variables (2010 to 2016).ResultsPositive associations were found between the consumption of cephalosporins and geometric mean MIC ceftriaxone, cefixime and ciprofloxacin. Macrolide consumption was associated with cefixime and ciprofloxacin geometric mean MIC as well as the prevalence of antimicrobial resistance to ciprofloxacin and cefixime.ConclusionsPopulation level consumption of cephalosporins and macrolides may select for reduced antimicrobial susceptibility to unrelated antimicrobials.
Decline of humoral responses against SARS-CoV-2 Spike in convalescent individuals
Authors: Beaudoin-Bussières Guillaume , Laumaea Annemarie , Anand Sai Priya , Prévost Jérémie , Gasser Romain , Goyette Guillaume , Medjahed Halima , Perreault Josée , Tremblay Tony , Lewin Antoine , Gokool Laurie , Morrisseau Chantal , Bégin Philippe , Tremblay Cécile , Martel-Laferrière Valérie , Kaufmann Daniel E. , Richard Jonathan , Bazin Renée , Finzi Andrés 
Published: July 2020

ABSTRACTIn the absence of effective vaccines and with limited therapeutic options, convalescent plasma is being collected across the globe for potential transfusion to COVID-19 patients. The therapy has been deemed safe and several clinical trials assessing its efficacy are ongoing. While it remains to be formally proven, the presence of neutralizing antibodies is thought to play a positive role in the efficacy of this treatment. Indeed, neutralizing titers of ≥1:160 have been recommended in some convalescent plasma trials for inclusion. Here we performed repeated analyses at one-month interval on 31 convalescent individuals to evaluate how the humoral responses against the SARS-CoV-2 Spike, including neutralization, evolve over time. We observed that receptor-binding domain (RBD)-specific IgG slightly decreased between six and ten weeks after symptoms onset but RBD-specific IgM decreased much more abruptly. Similarly, we observed a significant decrease in the capacity of convalescent plasma to neutralize pseudoparticles bearing SARS-CoV-2 S wild-type or its D614G variant. If neutralization activity proves to be an important factor in the clinical efficacy of convalescent plasma transfer, our results suggest that plasma from convalescent donors should be recovered rapidly after symptoms resolution.
Embryonic Protein NODAL Regulates the Breast Tumour Microenvironment by Reprogramming Cancer-Derived Secretomes
Authors: Dieters-Castator Dylan , Dantonio Paola Marino , Piaseczny Matt , Zhang Guihua , Liu Jiahui , Kuljanin Miljan , Sherman Stephen , Jewer Michael , Quesnel Katherine , Kang Eun Young , Köbel Martin , Siegers Gabrielle M. , Leask Andrew , Hess David , Lajoie Gilles , Postovit Lynne-Marie 
Published: July 2020

AbstractThe tumour microenvironment (TME) is an important mediator of breast cancer progression. Cancer-associated fibroblasts (CAFs) constitute a major component of the TME and may originate from tissue-associated fibroblasts or infiltrating mesenchymal stromal cells (MSCs). The mechanisms by which cancer cells activate fibroblasts and recruit MSCs to the TME are largely unknown, but likely include deposition of a pro-tumourigenic secretome. The secreted embryonic protein NODAL is clinically associated with breast cancer stage and promotes tumour growth, metastasis, and vascularization. Herein, we show that NODAL expression correlates with the presence of activated fibroblasts in human triple negative breast cancers and that it directly induces CAF phenotypes. We further show that NODAL reprograms cancer cell secretomes by simultaneously altering levels of chemokines (e.g. CXCL1), cytokines (e.g. IL-6) and growth factors (e.g. PDGFRA), leading to alterations in MSC chemotaxis. We therefore demonstrate a hitherto unappreciated mechanism underlying the dynamic regulation of the TME.
Expression attenuation as a mechanism of robustness to gene duplication in protein complexes
Authors: Ascencio Diana , Diss Guillaume , Gagnon-Arsenault Isabelle , Dubé Alexandre K , DeLuna Alexander , Landry Christian R. 
Published: July 2020

AbstractGene duplication is ubiquitous and a major driver of phenotypic diversity across the tree of life, but its immediate consequences are not fully understood. Deleterious effects would decrease the probability of retention of duplicates and prevent their contribution to long term evolution. One possible detrimental effect of duplication is the perturbation of the stoichiometry of protein complexes. Here, we measured the fitness effects of the duplication of 899 essential genes in the budding yeast using high-resolution competition assays. At least ten percent of genes caused a fitness disadvantage when duplicated. Intriguingly, the duplication of most protein complex subunits had small to non-detectable effects on fitness, with few exceptions. We selected four complexes with subunits that had an impact on fitness when duplicated and measured the impact of individual gene duplications on their protein-protein interactions. We found that very few duplications affect both fitness and interactions. Furthermore, large complexes such as the 26S proteasome are protected from gene duplication by attenuation of protein abundance. Regulatory mechanisms that maintain the stoichiometric balance of protein complexes may protect from the immediate effects of gene duplication. Our results show that a better understanding of protein regulation and assembly in complexes is required for the refinement of current models of gene duplication.
Development of hybrid fire testing by real-time subdivision of physical and numerical substructures
Authors: Pinoteau Nicolas , Pham Duc Toan , Nguyen Hong Hai , Mège Romain 
Published: July 2020

Purpose
This study aims to evaluate the feasibility of a hybrid fire testing by real-time subdivision of physical and numerical substructures (NSs) on simplified structures as a milestone in the development of the method.

Design/methodology/approach
An interface where the data was exchanged between a finite element software and a hydraulic jack regulator using text files has been developed and applied to perform two experimental campaigns of nine tests on simple steel frame structures with different thermal loading conditions. In the first experimental campaign, the physical substructure (PS) was assumedly protected by insulating material, while the NS was uniformly exposed to ISO 834 fire on all sides. The difference of the second experimental campaign from the first one was that the PS was heated on one side.

Findings
The experimental results showed how a gap between the determined equilibrium position and the “real” position caused by the time lag, as well as an overshoot phenomenon due to the non-synchronized action of both substructures, may occur. From the identification of the overshoot, two paths of development spring to mind to reduce the delay of the NS.

Originality/value
In the context that the number of proposal theoretical algorithms continues to increase with the absence of real experimental adjustments, such experimental results and the associated analysis constitute additional understandings to identify possible paths of improvements that might have been missed or could not be accessed through previous studies.
Surgical Locker room Environment: Understanding the Hazards (SLEUTH) study
Authors: David Rowan , Heijkoop Bridget , A. Kahokehr Arman 
Published: July 2020

AbstractBackgroundAnecdotal evidence reveals that medical equipment are easily found in hospital changing rooms. Access to potentially lethal drugs and intravenous access equipment may put vulnerable medical staff at risk. The aims are to quantify the burden of medical equipment found in this environment, calculate the associated cost burden and to raise clinician awareness about a potential health hazard.MethodsWe prospectively collected data on the medical paraphernalia found in surgical changing rooms from one private and two public hospitals in South Australia over 2 months. We systematically searched open surgical lockers, benches and floors in male and female lockers rooms. Item costs were calculated from Imprest and the Pharmacy Department.ResultsDuring the study period, we found a total of 537 items. There were 280 sharps, including 185 scalpels found in one open locker. There were 78 items of intravenous paraphernalia, 38 surgical tapes, 70 bandages and 73 miscellaneous items. In addition, there were six medications found including 3 × 5 mL vials of 1% lignocaine, one vial of lignocaine with adrenaline, one ketorolac suppository and 5 mL fentanyl. There were 529 (98.5%) items within their date of expiry. The total cost of the items was 2358 Australian dollars (AUD), with an estimated annual cost of 14 148 AUD over the three sites and 424 400 AUD over South Australia.ConclusionThe burden of available medical supplies found in the theatre changing room is high and worrisome. Strategies for appropriate disposal and safe storage of medical equipment are required.
Orthodontic therapy teaching review at Trinity College Dublin
Authors: Wall Aoibheann , Sagheri Darius , Burns Angus 
Published: July 2020

AbstractIntroductionThe aim of this teaching review was to obtain feedback from graduates of the Orthodontic Therapy course from the School of Dental Science, Trinity College Dublin, which was established in 2014.Materials and MethodsA focus group, comprising of one to two graduates from each of the five years of the orthodontic therapy course, convened to obtain feedback. Thematic analysis was used to analyse the feedback transcribed from the focus group.ResultsMultiple themes emerged including enthusiasm, commitment, educational support, peer support and satisfaction. The graduates found the course challenging but very rewarding, helped by support from the university, mentors and peers. Satisfaction was very high from all participants with 100% reporting they would recommend the course. Suggestions emerged regarding the delivery of specific didactic components of the course and increased engagement with the specialist orthodontic mentors to ensure teaching is standardised for all trainees.ConclusionThe course is rated very highly by the graduates and completion of this training has had a positive impact on their job satisfaction. Members of the focus group provided constructive feedback on the delivery of the course, which will contribute to its refinement for future trainees.
Mentorship availability and needs for junior faculty members at the United States and Australian dental schools
Authors: Bartle Emma K. , Crivello Brandon J. , Bullock Jeri L. , Ogbureke Ezinne I. 
Published: July 2020

AbstractObjectivesThe aims of this study were to understand the experiences junior faculty have during their professional socialisation as educators and how they perceive the need and value of mentorship.MethodsA cross‐sectional qualitative study design was used. Data were collected in 2019 through a pre‐survey and focus groups with junior faculty (defined as 0‐5 years) across four institutions in Australia and the United States of America. Framework analysis was used to identify themes in the data, based on our defined research questions, and socio‐cognitive career theory was applied to guide our analysis.ResultsA total of 22 junior faculty participated in the study. Only one of the four institutions had a formal mentoring programme for junior dental faculty. At this institution, 83% of participants indicated they were likely/extremely likely to remain in dental education. Across the three institutions where formal mentoring for junior dental faculty was not available, only 40% of participants indicated they were likely/extremely likely to remain in dental education. We identified five themes in the qualitative data: motivation for career choice, the importance of relationships, personal goals and the need for self‐direction, expectations of the role, and institutional effects.ConclusionOur findings suggest that mentoring is a critical factor in a junior faculty member's experience entering and socialising into a career in dental education. The perceived value of mentoring emerged across all themes, both from the perspective of participants who had received formal mentoring and those who had not.
Application of simultaneous selective pressures slows adaptation
Authors: Merlo Lauren M. F. , Sprouffske Kathleen , Howard Taylor C. , Gardiner Kristin L. , Caulin Aleah F. , Blum Steven M. , Evans Perry , Bedalov Antonio , Sniegowski Paul D. , Maley Carlo C. 
Published: July 2020

AbstractBeneficial mutations that arise in an evolving asexual population may compete or interact in ways that alter the overall rate of adaptation through mechanisms such as clonal or functional interference. The application of multiple selective pressures simultaneously may allow for a greater number of adaptive mutations, increasing the opportunities for competition between selectively advantageous alterations, and thereby reducing the rate of adaptation. We evolved a strain of Saccharomyces cerevisiae that could not produce its own histidine or uracil for ~500 generations under one or three selective pressures: limitation of the concentration of glucose, histidine, and/or uracil in the media. The rate of adaptation was obtained by measuring evolved relative fitness using competition assays. Populations evolved under a single selective pressure showed a statistically significant increase in fitness on those pressures relative to the ancestral strain, but the populations evolved on all three pressures did not show a statistically significant increase in fitness over the ancestral strain on any single pressure. Simultaneously limiting three essential nutrients for a population of S. cerevisiae effectively slows the rate of evolution on any one of the three selective pressures applied, relative to the single selective pressure cases. We identify possible mechanisms for fitness changes seen between populations evolved on one or three limiting nutrient pressures by high‐throughput sequencing. Adding multiple selective pressures to evolving disease like cancer and infectious diseases could reduce the rate of adaptation and thereby may slow disease progression, prolong drug efficacy and prevent deaths.
Hibernating ribosomes exhibit chaperoning activity but can resist unfolded protein‐mediated subunit dissociation
Authors: Ferdosh Sehnaz , Banerjee Senjuti , Pathak Bani K. , Sengupta Jayati , Barat Chandana 
Published: July 2020

Ribosome hibernation is a prominent cellular strategy to modulate protein synthesis during starvation and the stationary phase of bacterial cell growth. Translational suppression involves the formation of either factor‐bound inactive 70S monomers or dimeric 100S hibernating ribosomal complexes, the biological significance of which is poorly understood. Here, we demonstrate that the Escherichia coli 70S ribosome associated with stationary phase factors hibernation promoting factor or protein Y or ribosome‐associated inhibitor A and the 100S ribosome isolated from both Gram‐negative and Gram‐positive bacteria are resistant to unfolded protein‐mediated subunit dissociation and subsequent degradation by cellular ribonucleases. Considering that the increase in cellular stress is accompanied by accumulation of unfolded proteins, such resistance of hibernating ribosomes towards dissociation might contribute to their maintenance during the stationary phase. Analysis of existing structures provided clues on the mechanism of inhibition of the unfolded protein‐mediated disassembly in case of hibernating factor‐bound ribosome. Further, the factor‐bound 70S and 100S ribosomes can suppress protein aggregation and assist in protein folding. The chaperoning activity of these ribosomes is the first evidence of a potential biological activity of the hibernating ribosome that might be crucial for cell survival under stress conditions.
Does having insurance change individuals' self‐confidence?
Authors: Guber Raphael , Kocher Martin G. , Winter Joachim 
Published: July 2020

AbstractRecent research in contract theory on the effects of behavioral biases implicitly assumes that they are stable, in the sense of not being affected by the contracts themselves. In this paper, we provide evidence that this is not necessarily the case. We show that in an insurance context, being insured against losses that may be incurred in a real‐effort task changes subjects' self‐confidence. Our novel experimental design allows us to disentangle selection into insurance from the effects of being insured by randomly assigning coverage after subjects revealed whether they want to be insured or not. We find that uninsured subjects are underconfident while those that obtain insurance have well‐calibrated beliefs. Our results suggest that there might be another mechanism through which insurance affects behavior than just moral hazard.
Mountain linguistics
Authors: Urban Matthias 
Published: July 2020

AbstractLanguage use in mountainous areas often exhibits special social dynamics. This contribution sketches some of the most salient patterns of language use in upland Southeast Asia ,the greater Himalayas, the Caucasus, the Central Andes, the New Guinea highlands, and touches upon the Alps and some highland areas of Africa and North America. Accumulated over long time, such patterns of use yield particular—often highly diverse, fragmented, and discontinuous—distributions of languages and language families in geographical space the precise characteristics of which also depend on prevailing local sociolinguistic and socioeconomic conditions. Generalization are still difficult since most observations are anecdotal rather than systematic: as far as language structure is concerned, languages spoken in mountainous regions are traditionally often attributed a “conservative” or “archaic” character, preserving inherited traits and patterns that are lost elsewhere; the inaccessibility of the terrain and the resulting relative social isolation are commonly invoked to explain this situation. More recently, mountain languages have also been claimed to feature peaks in the distribution of some typological properties, whether due to sociogeographical factors or, more controversially, even direct influences of the environment: ejectives, grammatical encoding of elevational or topographic information, and overall high levels of structural complexity.
Alendronic acid‐induced oral mucosal ulceration: two case reports
Authors: McLean S. , Kelly R. , Rajlawat B. , Field A. 
Published: July 2020

AbstractAlendronic acid is generally a well‐tolerated medication, however, there are well‐established adverse effects known within dentistry, such as medication‐related osteonecrosis of the jaw and upper gastro‐intestinal disturbances, particularly erosive oesophagitis. There is growing evidence of bisphosphonate‐induced oral ulcerations and this diagnosis needs to be considered for patients presenting with unexplained oral ulceration. An 84‐year‐old female patient with dementia presented at our emergency dental department with severe, painful oromucosal ulceration. Haematological investigation, including Indirect‐immunofluorescence demonstrated no abnormalities. Therefore, the likely diagnosis was that of chemically induced traumatic ulceration. The patient was managed through the cessation of alendronic acid, and the use of both topical and systemic corticosteroids. A 68‐year‐old female patient with learning difficulties presented with ulceration in the lower buccal sulcus following an urgent referral. The patients carer reported persistent difficulty in the swallowing of medicines, with medications regularly ‘pouched’ in the patients cheeks. Due to patient distress no further investigations were completed. Clinically, the lesion was characteristic of chemically induced traumatic ulceration. We therefore encouraged the continuation of liquid form alendronic acid. At a 2 week review, the ulceration had fully resolved. Alendronic acid‐induced ulceration should be considered for patients presenting with oral ulceration, particularly in those with cognitive impairments. There needs to be increased awareness of alendronic acid‐induced oral ulceration among prescribers, particularly in patients ‘at risk’. Alternate preparations of this medication such as dispersible tablets and an oral solution are available.
Amplification of Operational Uncertainty Induced by Nonideal Flows in Supersonic Turbine Cascades
Authors: Romei Alessandro , Vimercati Davide , Guardone Alberto , Persico Giacomo 
Published: July 2020

Abstract
In high-temperature transcritical organic Rankine cycles (ORCs), the expansion process may take place in the neighborhood of the thermodynamic critical point. In this region, many organic fluids feature a value of the fundamental derivative of gas dynamics Γ that is less than unity. As a consequence, severe nonideal gas-dynamic effects can be possibly observed. Examples of these nonideal effects are the nonmonotonic variation of the Mach number along an isentropic expansion, oblique shocks featuring an increase of the Mach number, and a significant dependence of the flow field on the upstream total state. To tackle this latter nonideal effect, an uncertainty-quantification strategy combined with Reynolds-averaged flow simulations is devised to evaluate the turbine performance in presence of operational uncertainty. The results clearly indicate that a highly nonideal expansion process leads to an amplification of the operational uncertainty. Specifically, given an uncertainty in the order of 1% in cycle nominal conditions, the mass flow rate and cascade losses vary ±4% and ±0.75 percentage points, respectively. These variations are four and six times larger than those prompted by an ideal-like expansion process. The flow delivered to the first rotating cascade is severely altered as well, leading to local variations in the rotor incidence angle up to 10 deg. A decomposition of variance contributions reveals that the uncertainty in the upstream total temperature is mainly responsible for these variations. Finally, the understanding of the physical mechanism behind these changes allows us to generalize the present findings to other organic-fluid flows.