bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ligand design for human acetylcholinesterase and nicotinic acetylcholine receptors, extending beyond the conventional and canonical
Authors: Taylor Palmer , Shyong Yan‐Jye , Samskey Nathan , Ho Kwok‐Yiu , Radic' Zoran , Fenical William , Sharpless K. Barry , Kovarik Zrinka , Camacho‐Hernandez Gisela‐Andrea 
Published: February 2021

AbstractWe detail here distinctive departures from lead classical cholinesterase re‐activators, the pyridinium aldoximes, to achieve rapid CNS penetration and reactivation of AChE in the CNS (brain and spinal cord). Such reactivation is consistent with these non‐canonical re‐activators enhancing survival parameters in both mice and macaques following exposure to organophosphates. Thus, the ideal cholinesterase re‐activator should show minimal toxicity, limited inhibitory activity in the absence of an organophosphate, and rapid CNS penetration, in addition to its nucleophilic potential at the target, the conjugated AChE active center. These are structural properties directed to reactivity profiles at the conjugated AChE active center, reinforced by the pharmacokinetic and tissue disposition properties of the re‐activator leads. In the case of nicotinic acetylcholine receptor (nAChR) agonists and antagonists, with the many existing receptor subtypes in mammals, we prioritize subtype selectivity in their design. In contrast to nicotine and its analogues that react with panoply of AChR subtypes, the substituted di‐2‐picolyl amine pyrimidines possess distinctive ionization characteristics reflecting in selectivity for the orthosteric site at the α7 subtypes of receptor. Here, entry to the CNS should be prioritized for the therapeutic objectives of the nicotinic agent influencing aberrant CNS activity in development or in the sequence of CNS ageing (longevity) in mammals, along with general peripheral activities controlling inflammation.
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Assessing the effectiveness of the combination therapy with fractional Er‐YAG laser and platelet‐rich plasma in treatment of periorbital dark circles patients: A clinical trial
Authors: Nilforoushzadeh Mohammad Ali , Heidari‐Kharaji Maryam , Alavi Shiva , Mahmoudbeyk Mona , Torkamaniha Elham , Peyrovan Aisan , Nouri Maryam , Zare Sona 
Published: February 2021

AbstractBackgroundNumerous therapeutic techniques for periorbital hyperpigmentation have been suggested.AimIn this comparative intrapatient study, the effectiveness of combination therapy included fractional Er: YAG laser and autologous platelet‐rich plasma (PRP) compared to Er: YAG laser in periorbital hyperpigmentation treatment.Patients/MethodsThirty‐two patients were enrolled. The right periorbital sides of patients received combination of Er: YAG laser and autologous platelet‐rich plasma (PRP) and the left side received Er: YAG laser (three sessions with 4 weeks' intervals). PRP was used in two ways included injection and topical. Patients were evaluated by biometric characteristics, patients, and physician assessments. Also, the patient's satisfaction was assessed and side effects were evaluated.ResultsThe mexameter results showed that the melanin content in the right side of the periorbital of the patients was significantly decreased compared to left side. Also, significant increase was observed in the skin lightness of the right side in compare to left. The visioface results showed the decrease in the percent change of the color and wrinkle in both sides, but in the right side these changes were significantly more than left side. The patients and physician assessment confirmed the measured results.ConclusionCombination of Er: YAG laser and PRP is significantly effective for periorbital hyperpigmentation.
Additively Manufactured Ingot for Interim Dental Restorations Fabrication Using a Chairside Milling Machine
Authors: Pérez‐Giugovaz Marcelo Gabriel , Mostafavi Delaram , Revilla‐León Marta 
Published: February 2021

AbstractThis manuscript describes a technique to fabricate additively manufactured ingots for producing tooth‐ and implant‐supported interim dental restorations using a chairside milling machine. The technique aimed to ease the additively manufactured interim restoration's manufacturing by using a chairside milling machine, optimize the manufacturing workflow time, and eliminate the surface roughness of additively manufactured restorations.
Night shift schedule causes circadian dysregulation of DNA repair genes and elevated DNA damage in humans
Authors: Koritala Bala S. C. , Porter Kenneth I. , Arshad Osama A. , Gajula Rajendra P. , Mitchell Hugh D. , Arman Tarana , Manjanatha Mugimane G. , Teeguarden Justin , Van Dongen Hans P. A. , McDermott Jason E. , Gaddameedhi Shobhan 
Published: February 2021

AbstractCircadian disruption has been identified as a risk factor for health disorders such as obesity, cardiovascular disease, and cancer. Although epidemiological studies suggest an increased risk of various cancers associated with circadian misalignment due to night shift work, the underlying mechanisms have yet to be elucidated. We sought to investigate the potential mechanistic role that circadian disruption of cancer hallmark pathway genes may play in the increased cancer risk in shift workers. In a controlled laboratory study, we investigated the circadian transcriptome of cancer hallmark pathway genes and associated biological pathways in circulating leukocytes obtained from healthy young adults during a 24‐hour constant routine protocol following 3 days of simulated day shift or night shift. The simulated night shift schedule significantly altered the normal circadian rhythmicity of genes involved in cancer hallmark pathways. A DNA repair pathway showed significant enrichment of rhythmic genes following the simulated day shift schedule, but not following the simulated night shift schedule. In functional assessments, we demonstrated that there was an increased sensitivity to both endogenous and exogenous sources of DNA damage after exposure to simulated night shift. Our results suggest that circadian dysregulation of DNA repair may increase DNA damage and potentiate elevated cancer risk in night shift workers.
IL‐1B(3954) polymorphism and red complex bacteria increase IL‐1β (GCF) levels in periodontitis
Authors: Pani Pinelopi , Tsilioni Irene , McGlennen Ronald , Brown Carrie A. , Hawley Charles E. , Theoharides Theoharis C. , Papathanasiou Evangelos 
Published: February 2021

AbstractObjectiveThe aim of this study was to compare IL‐1β levels in gingival crevicular fluid (GCF) from healthy and periodontitis sites of IL‐1B(3954)‐Single Nucleotide Polymorphism (SNP) positive and IL‐1B(3954)‐SNP negative periodontitis subjects in association with their bacterial profiles.BackgroundSusceptibility to periodontitis has been associated with several risk factors, including allelic variants at multiple gene loci. Variations in the IL‐1 gene cluster have been linked with increased risk for periodontitis. IL‐1B(3954)‐SNP has been previously associated with increased levels of IL‐1β in GCF or periodontal tissues in chronic periodontitis patients, as well as higher levels of specific periodontal pathogens. There is insufficient evidence to conclude if IL‐1B gene polymorphisms affect the susceptibility to periodontitis by ultimately modulating the levels of IL‐1β in GCF, the subgingival microbial profile or both.Materials and MethodsGCF, subgingival plaque, and buccal epithelial cells were collected from 32 individuals with periodontitis. GCF IL‐1β levels were measured by an enzyme‐linked immunosorbent assay (ELISA). Bacterial plaque samples were analyzed for 11 periodontal pathogens using polymerase chain reaction (PCR) analysis with specific primers for the 16SrRNA gene of each bacterium. IL‐1B(3954)‐SNP status was determined by identifying the carriers of the polymorphic T allele.ResultsA significant association was shown between IL‐1B(3954)‐SNP and IL‐1β GCF levels (amount and concentration). The concomitant presence of two or three red complex bacterial species was associated with increased IL‐1β GCF levels in periodontitis sites (site‐level analysis). The concurrent presence of all three red complex periodontal pathogens and IL‐1B(3954)‐SNP was associated with the highest IL‐1β GCF levels in periodontitis sites.ConclusionsOur results indicate an independent association of both IL‐1B(3954)‐SNP and red complex bacterial species with increased IL‐1β levels in GCF of periodontitis sites. A better understanding of the interaction between genetics, bacteria, and inflammation is essential to develop more effective diagnostic, prognostic, and therapeutic tools for periodontitis.
Heeding supply chain disruption warnings: When and how do cross‐functional teams ensure firm robustness?
Authors: de Vries Thomas A. , van der Vegt Gerben S. , Scholten Kirstin , van Donk Dirk Pieter 
Published: February 2021

AbstractFirms can adopt several strategies to increase their robustness to potential supply chain (SC) disruptions. One promising strategy is the use of a cross‐functional team with representatives from functional departments. Such a team may facilitate sharing relevant information, enabling the firm to respond effectively to SC disruption warnings. However, despite their potential, cross‐functional teams also differ in their ability to respond to SC disruption warnings and to ensure firm robustness. Extending insights from information‐processing theory and team research to the field of SC management, we propose that a cross‐functional team’s ability to handle high numbers of SC disruption warnings depends on the extent to which the team adopts centralized decision‐making, with one or two members orchestrating the decision‐making process. We also introduce internal integration problems as a mediating mechanism explaining why a cross‐functional team lacking centralized decision‐making may be unable to handle high numbers of SC disruption warnings. In two independent studies, we use multi‐source data on cross‐functional teams’ performance in dealing with SC disruption warnings during a realistic SC management simulation; the results support our predictions.
Small freshwater ecosystems with dissimilar microbial communities exhibit similar temporal patterns
Authors: David Gwendoline M. , López‐García Purificación , Moreira David , Alric Benjamin , Deschamps Philippe , Bertolino Paola , Restoux Gwendal , Rochelle‐Newall Emma , Thébault Elisa , Simon Marianne , Jardillier Ludwig 
Published: February 2021

AbstractDespite small freshwater ecosystems being biodiversity reservoirs and contributing significantly to greenhouse fluxes, their microbial communities remain largely understudied. Yet, microorganisms intervene in biogeochemical cycling and impact water quality. Because of their small size, these ecosystems are in principle more sensitive to disturbances, seasonal variation and pluri‐annual climate change. However, how microbial community composition varies over space and time, and whether archaeal, bacterial and microbial eukaryote communities behave similarly remain unanswered. Here, we aim to unravel the composition and intra/interannual temporal dynamic patterns for archaea, bacteria and microbial eukaryotes in a set of small freshwater ecosystems. We monitored archaeal and bacterial community composition during 24 consecutive months in four ponds and one brook from northwestern France by 16S rRNA gene amplicon sequencing (microbial eukaryotes were previously investigated for the same systems). Unexpectedly for oxic environments, bacterial Candidate Phyla Radiation (CPR) were highly diverse and locally abundant. Our results suggest that microbial community structure is mainly driven by environmental conditions acting over space (ecosystems) and time (seasons). A low proportion of operational taxonomic units (OTUs) (<1%) was shared by the five ecosystems despite their geographical proximity (2–9 km away), making microbial communities almost unique in each ecosystem and highlighting the strong selective influence of local environmental conditions. Marked and similar seasonality patterns were observed for archaea, bacteria and microbial eukaryotes in all ecosystems despite strong turnovers of rare OTUs. Over the 2‐year survey, microbial community composition varied despite relatively stable environmental parameters. This suggests that biotic associations play an important role in interannual community assembly.
Translingual and Transcultural Reflection in Study Abroad: The Case of a Vietnamese‐American Student in Guatemala
Authors: QUAN TRACY , MENARD–WARWICK JULIA 
Published: February 2021

AbstractHow multilinguals reflect on and interpret their experiences abroad as they acquire an additional language has been undertheorized in study abroad research. Multilinguals navigate multiple identities, cross linguistic and social boundaries, and employ an array of resources to make meaning—that is, they engage in translingual practice. This article presents the case of Terry—a Vietnamese‐American learner of Spanish—during a 13‐week stay in Guatemala as she navigates and reflects on her sense of self. Employing translingual practice and symbolic competence as theoretical frameworks, this study examines how Terry drew on her cultural and linguistic background to understand her experiences abroad and in turn, how an abroad experience encouraged critical self‐reflection. Through a thematic analysis of interviews, course assignments, and audio‐recorded classroom observations, the findings illustrate how an abroad curriculum that emphasized structured critical reflection and local engagement encouraged Terry's development of critical translingual competence; an awareness of the symbolic significance of meaning‐making resources across contexts; and the inextricable connections among identity, language, and culture.
The mechanism of sugar export from long conifer needles
Authors: Liesche Johannes , Vincent Christopher , Han Xiaoyu , Zwieniecki Maciej , Schulz Alexander , Gao Chen , Bravard Rodrigue , Marker Sean , Bohr Tomas 
Published: February 2021

Summary

The green leaves of plants are optimised for carbon fixation and the production of sugars, which are used as central units of carbon and energy throughout the plant. However, there are physical limits to this optimisation that remain insufficiently understood.

Here, quantitative anatomical analysis combined with mathematical modelling and sugar transport rate measurements were used to determine how effectively sugars are exported from the needle‐shaped leaves of conifers in relation to leaf length.

Mathematical modelling indicated that phloem anatomy constrains sugar export in long needles. However, we identified two mechanisms by which this constraint is overcome, even in needles longer than 20 cm: (1) the grouping of transport conduits, and (2) a shift in the diurnal rhythm of sugar metabolism and export in needle tips.

The efficiency of sugar transport in the phloem can have a significant influence on leaf function. The constraints on sugar export described here for conifer needles are likely to also be relevant in other groups of plants, such as grasses and angiosperm trees.
Tracing uptake and translocation of phosphorus in wheat using oxygen isotopes and mathematical modelling
Authors: Bauke Sara L. , Schnepf Andrea , von Sperber Christian , Orlowski Natalie , Lewandowski Hans , Selzner Tobias , Tamburini Federica , Amelung Wulf 
Published: February 2021

Summary

Understanding P uptake in soil–plant systems requires suitable P tracers. The stable oxygen isotope ratio in phosphate (expressed as δ18OP) is an alternative to radioactive labelling, but the degree to which plants preserve the δ18OP value of the P source is unclear. We hypothesised that the source signal will be preserved in roots rather than shoots.

In soil and hydroponic experiments with spring wheat (Triticum aestivum), we replaced irrigation water by 18O‐labelled water for up to 10 d. We extracted plant inorganic phosphates with trichloroacetic acid (TCA), assessed temporal dynamics of δ18OTCA‐P values after changing to 18O‐labelled water and combined the results with a mathematical model.

Within 1 wk, full equilibration of δ18OTCA‐P values with the isotope value of the water in the growth medium occurred in shoots but not in roots. Model results further indicated that root δ18OTCA‐P values were affected by back transport of phosphate from shoots to roots, with a greater contribution of source P at higher temperatures when back transport was reduced.

Root δ18OTCA‐P partially preserved the source signal, providing an indicator of P uptake sources. This now needs to be tested extensively for different species, soil and climate conditions to enable application in future ecosystem studies.
Ambiguous workarounds in policy piloting in the NHS: Tensions, trade‐offs and legacies of organisational change projects
Authors: Goff Mhorag , Hodgson Damian , Bailey Simon , Bresnen Michael , Elvey Rebecca , Checkland Katherine 
Published: February 2021

AbstractPilot projects are increasingly used as a mechanism to enact organisational change, particularly government policy. Information technology's centrality to organisations often makes it key to the introduction of new processes. However, it can give rise to workarounds as employees circumvent impediments it presents by rejecting its prescribed use. Workarounds tend to be conceptualised dichotomously, as either ‘good’ problem solving, or ‘bad’ subversion of the technology. In pilot projects, workarounds are more ambiguous because those that support projects' successful completion in the short‐term may undermine day to day operations longer term. We draw on interview data from a policy pilot in general practice in the National Health Service in England aimed at extending access to care. We problematise the dichotomous conceptualisation of workarounds, finding they can be simultaneously supportive and undermining of policy pilots. Workarounds thereby become political, as employees are required to trade‐off consequences for themselves and the wider organisation.
Diabetes, stroke, and neuroresilience: looking beyond hyperglycemia
Authors: Krinock Matthew J. , Singhal Neel S. 
Published: February 2021

AbstractIschemic stroke is a leading cause of morbidity and mortality among type 2 diabetic patients. Preclinical and translational studies have identified critical pathophysiological mediators of stroke risk, recurrence, and poor outcome in diabetic patients, including endothelial dysfunction and inflammation. Most clinical trials of diabetes and stroke have focused on treating hyperglycemia alone. Pioglitazone has shown promise in secondary stroke prevention for insulin‐resistant patients; however, its use is not yet widespread. Additional research into clinical therapies directed at diabetic pathophysiological processes to prevent stroke and improve outcome for diabetic stroke survivors is necessary. Resilience is the process of active adaptation to a stressor. In patients with diabetes, stroke recovery is impaired by insulin resistance, endothelial dysfunction, and inflammation, which impair key neuroresilience pathways maintaining cerebrovascular integrity, resolving poststroke inflammation, stimulating neural plasticity, and preventing neurodegeneration. Our review summarizes the underpinnings of stroke risk in diabetes, the clinical consequences of stroke in diabetic patients, and proposes hypotheses and new avenues of research for therapeutics to stimulate neuroresilience pathways and improve stroke outcome in diabetic patients.
Surgical extractions of wisdom teeth at Tufts University, USA according to UK’s NICE guidelines
Authors: Shah Parus Amit , Ahmed Bilal , Chang David Joey , Fakitsas Dimitrios 
Published: February 2021

AbstractAimsTo investigate the reasons for extraction of third molars (3Ms) at Tufts University School of Dental Medicine (TUSDM) and compare this to the UK’s NICE guidelines.MethodsData were collected at TUSDM retrospectively from 99 patients who underwent surgery in 2019 under American Dental Association (ADA) codes D7220, D7230, D7240 and D7241 (removal of impacted tooth in soft tissue, partially bony, completely bony and with unusual surgical complications). Patient details of age, location of 3M, Winter's classification of impaction, reason for extraction, need for bony removal, type of anaesthesia or sedation, prescribed medications and complications were recorded.ResultsA total of 274 surgical extractions of teeth were recorded. Ages ranged from 15 to 39, with an average age of 24. Intravenous sedation (IVS) was used in 80% of patients with an average of 3.6 3Ms extracted in each of these patients, when local anaesthetic was used alone an average of two 3Ms were extracted. Ninety per cent and 78.7% of maxillary and mandibular 3Ms, respectively, were extracted with no pathology. Thirteen per cent of mandibular 3Ms were extracted due to pericoronitis (usually a single episode), 4% due to caries and 2.3% due to distal second molar (2M) caries. There were five instances of post‐operative complications, the worst being hypoesthesia of the right inferior dental (ID) nerve for 3 months.ConclusionWisdom teeth are removed earlier at Tufts for prophylactic reasons with the intention of preventing future problems and caries in the adjacent tooth. More evidence is required to decide which patients would benefit from prophylactic extractions.
Policy preferences in response to negative economic prospects of COVID‐19: A survey‐experiment among local politicians in four European countries
Authors: van der Voet Joris 
Published: February 2021

AbstractThis study investigates how the negative economic prospects of the COVID‐19 pandemic affect local government politicians' policy preferences in the Netherlands, the United Kingdom, Switzerland, and Spain. The study examines to what extent politicians prefer increasing the role of government (directive state), transferring public tasks to private sector organizations (hollow state), transferring public tasks to third sector organizations (communitarian state), or downsizing and reducing the role of government without transferring tasks (coping state). The experiment primes decision‐makers on the pandemic's negative financial and economic prospects vis‐à‐vis its impact on health and well‐being. When negative economic prospects are emphasized, the study finds decreased preferences for a directive state and increased preferences for a coping state. The study concludes that how decision‐makers interpret the nature of a crisis determines their preferred response: An emphasis on the negative economic prospects of the COVID‐19 pandemic is likely to increase preferences for renewed policies of austerity.
There Are No Purely Aesthetic Obligations
Authors: Dyck John 
Published: February 2021

AbstractDo aesthetic reasons have normative authority over us? Could there be anything like an aesthetic ‘ought’ or an aesthetic obligation? I argue that there are no aesthetic obligations. We have reasons to act certain ways regarding various aesthetic objects – most notably, reasons to attend to and appreciate those objects. But, I argue, these reasons never amount to duties. This is because aesthetic reasons are merely evaluative, not deontic. They can only entice us or invite us – they can never compel us. Beauty gives us goods without shoulds.