bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Basis for Accommodation of Emerging B.1.351 and B.1.1.7 Variants by Two Potent SARS-CoV-2 Neutralizing Antibodies
Authors: Cerutti Gabriele , Rapp Micah , Guo Yicheng , Bahna Fabiana , Bimela Jude , Reddem Eswar R. , Yu Jian , Wang Pengfei , Liu Lihong , Huang Yaoxing , Ho David D. , Kwong Peter D. , Sheng Zizhang , Shapiro Lawrence 
Published: February 2021

SummaryEmerging SARS-CoV-2 strains, B.1.1.7 and B.1.351, from the UK and South Africa, respectively show decreased neutralization by monoclonal antibodies and convalescent or vaccinee sera raised against the original wild-type virus, and are thus of clinical concern. However, the neutralization potency of two antibodies, 1-57 and 2-7, which target the receptor-binding domain (RBD) of spike, was unaffected by these emerging strains. Here, we report cryo-EM structures of 1-57 and 2-7 in complex with spike, revealing each of these antibodies to utilize a distinct mechanism to bypass or accommodate RBD mutations. Notably, each antibody represented a response with recognition distinct from those of frequent antibody classes. Moreover, many epitope residues recognized by 1-57 and 2-7 were outside hotspots of evolutionary pressure for both ACE2 binding and neutralizing antibody escape. We suggest the therapeutic use of antibodies like 1-57 and 2-7, which target less prevalent epitopes, could ameliorate issues of monoclonal antibody escape.
Illustrating Potential Effects of Alternate Control Populations on Real-World Evidence-based Statistical Analyses
Authors: Huang Yidi , Yuan William , Kohane Isaac S. , Beaulieu-Jones Brett K. 
Published: February 2021

AbstractCase-control study designs are commonly used in retrospective analyses of Real-World Evidence (RWE). Due to the increasingly wide availability of RWE, it can be difficult to determine whether findings are robust or the result of testing multiple hypotheses. We investigate the potential effects of modifying cohort definitions in a case-control association study between depression and Type 2 Diabetes Mellitus (T2D). We found that small permutations to the criteria used to define the control population result in significant shifts in both the demographic structure of the identified cohort as well as the odds ratio of association. These differences remain present when testing against age and sex-matched controls. We believe this offers strong support for the need for robust guidelines, best practices and regulations around the use of observational RWE for clinical or regulatory decision making.
Chemical rescue of mutant proteins in living cells by naturally occurring small molecules
Authors: Hassell Daniel S. , Steingesser Marc G. , Denney Ashley S. , Johnson Courtney R. , McMurray Michael A. 
Published: February 2021

AbstractIntracellular proteins function in a complex milieu wherein small molecules influence protein folding and act as essential cofactors for enzymatic reactions. Thus protein function depends not only on amino acid sequence but also on the concentrations of such molecules, which are subject to wide variation between organisms, metabolic states, and environmental conditions. We previously found evidence that exogenous guanidine reverses the phenotypes of specific budding yeast septin mutants by binding to a WT septin at the former site of an Arg side chain that was lost during fungal evolution. Here we used a combination of targeted and unbiased approaches to look for other cases of “chemical rescue” by naturally occurring small molecules. We reportin vivorescue of hundreds of yeast mutants representing a variety of genes, including likely examples of Arg or Lys side chain replacement by the guanidinium ion. Failed rescue of targeted mutants highlight features required for rescue, as well as key differences between thein vitroandin vivoenvironments. Some non-Arg mutants rescued by guanidine likely result from “off-target” effects on specific cellular processes in WT cells. Molecules isosteric to guanidine and known to influence protein folding had a range of effects, from essentially none for urea, to rescue of a few mutants by DMSO. Strikingly, the osmolyte trimethylamine-N-oxide rescued ∼20% of the mutants we tested, likely reflecting combinations of direct and indirect effects on mutant protein function. Our findings illustrate the potential of natural small molecules as therapeutic interventions and drivers of evolution.
Restoration of BDNF-TrkB signaling rescues deficits in a mouse model of SCA6
Authors: Cook Anna A. , Jayabal Sriram , Sheng Jacky , Fields Eviatar , Leung Tsz Chui Sophia , Quilez Sabrina , McNicholas Eileen , Lau Lois , Watt Alanna J. 
Published: February 2021

AbstractSpinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease resulting in motor coordination deficits and cerebellar pathology. Expression of brain-derived neurotrophic factor (BDNF) is reduced in several neurodegenerative diseases, including in post-mortem tissue from SCA6 patients. Here, we show that cerebellar BDNF levels are reduced at an early disease stage in a mouse model of SCA6 (SCA684Q/84Q). One month of voluntary exercise was sufficient to elevate BDNF expression, as well as rescue both motor coordination and cerebellar Purkinje cell firing rate deficits. A BDNF mimetic, 7,8-dihydroxyflavone (7,8-DHF) likewise improved motor coordination and reversed Purkinje cell firing rate deficits, suggesting that exercise acts via BDNF-TrkB signaling. Prolonged chronic 7,8-DHF administration rescued ataxia when treatment commenced near disease onset, but was ineffective when treatment was started late. These data suggest that 7,8-DHF, which is orally bioavailable and crosses the blood-brain barrier, is a promising therapeutic for SCA6 and argue for the importance of early intervention for SCA6.
High-level representations in human occipito-temporal cortex are indexed by distal connectivity
Authors: Walbrin Jon , Almeida Jorge 
Published: February 2021

AbstractHuman object recognition is dependent on occipito-temporal cortex, but a complete understanding of the complex functional architecture of this area must account for how it is connected to the wider brain. Converging functional magnetic resonance imaging evidence shows that univariate responses to different categories of information (e.g. faces, bodies, & non-human objects) are strongly related to, and potentially shaped by, functional and structural connectivity to the wider brain. However, to date, there have been no systematic attempts to determine how distal connectivity and complex local high-level responses in occipito-temporal cortex (i.e. multivoxel response patterns) are related. Here, we show that distal functional connectivity is related to, and can reliably index, high-level representations for several visual categories (i.e. tools, faces, & places) within occipito-temporal cortex; that is, voxels sets that are strongly connected to distal brain areas show higher pattern discriminability than less well-connected sets do. We further show that, in several cases, pattern discriminability is higher in sets of well-connected voxels than sets defined by ‘local’ activation (e.g. strong amplitude responses to faces in fusiform face area). Together, these findings demonstrate the important relationship between the complex functional organization of occipito-temporal cortex and wider brain connectivity.Significance statementHuman object recognition relies strongly on occipito-temporal cortex (OTC), yet responses in this broad area are often considered in relative isolation to the rest of the brain. We employ a novel ‘connectivity-guided’ voxel selection approach with functional MRI data to show higher sensitivity to information (i.e. higher multivoxel pattern discriminability) in voxel sets that share strong connectivity to distal brain areas, relative to: 1) voxel sets that are less-strongly connected; and in several cases 2) voxel sets that are defined by strong ‘local’ response amplitude. These findings underscore the importance of distal contributions to local processing in OTC.
Nitroxide radicals appended to phthalonitriles: synthesis, structural characterization and photophysical properties
Authors: Fidan Ismail , Onal Emel , Hirel Catherine 
Published: February 2021

The syntheses of 4-[4-(4,4,5,5-tetramethyl-2-imidazoline-3-oxide-1-oxyl-2-yl)phenoxy]phthalonitrile (3, C21H19N4O3) and 4-[4-(4,4,5,5-tetramethyl-2-imidazoline-1-oxyl-2-yl)phenoxy]phthalonitrile (4) were carried out by microwave-assisted nucleophilic aromatic substitution of 4-nitrophthalonitrile (2) by the pre-formed 2-(4-hydroxyphenyl)-4,4,5,5-tetramethyl-2-imidazoline-3-oxide-1-oxyl (1). Compounds 3 and 4 were characterized unambiguously by a rich array of analyses, such as melting point, FT–IR, MALDI–TOF MS, elemental analysis, UV–Vis, CV, EPR, magnetic measurements and single-crystal X-ray diffraction. Structural studies demonstrate that the C—H...X and C—X...π (X = O and N) interactions in the radical nitronyl nitroxide groups play an important role in the assembly of the crystal structures. Moreover, cyclic voltammetry analyses show that the phthalonitrile substituent retains the redox properties of the Ullman radicals.
Alcohol versus sponsorship: effectiveness in sports posters
Authors: Alonso Dos Santos Manuel , Huertas-Serrano Maria , Sánchez-Franco Manuel J. , Torres-Moraga Eduardo I. 
Published: February 2021

PurposeThe academic literature debates the desirability of sponsoring alcohol products at sporting events, a discussion that increases as major sporting events approach. This study aims to examine the influence that sponsorship of an alcoholic product such as beer has on the sports spectator, and the level of efficacy with respect to congruent, alcohol, and incongruent sponsorship.Design/methodology/approachThe experiment was performed on 180 subjects considering three variables 3 × 3 × 2 (congruency type vs alcohol; sport discipline; placement). The experiment consisted of exposure to sponsored sports posters. Visual attention was recorded through eye tracking and then a self-reported questionnaire.FindingsThrough an experiment using eye tracking the results showed that the recall variable is higher among alcohol sponsorships and incongruent sponsorship, but it cannot be concluded either that the intention to buy or the attitude toward the brand differ among the sponsorships analyzed.Practical implicationsAlcohol brand is perceived as an incongruous brand in the context of sports sponsorship. Congruent sponsors attract more attention and recall, but no differences in terms of intention to buy. If purchase intent and consumption does not increase, perhaps sports sponsorship by alcohol brands should be reconsidered.Originality/valueThis research makes at least three relevant contributions to the scientific literature. (1) It examines the response to sponsorship in the media of the sports poster. (2) It analyses the consumer's response using neurophysiological means and provides new indicators in this area and (3) It compares performance indicators such as purchase intent, recall and brand attitude for alcoholic and non-alcoholic brand sponsors. These contributions could introduce new information about sponsorship performance.
Expectations and tensions in school leadership regarding the 2014 Danish school reform: emerging perspectives linking school leadership, learning and well-being
Authors: Carlsson Monica 
Published: February 2021

PurposeThe purpose of this paper is to explore the expectations of and possible tensions in school leadership regarding the implementation of the 2014 Danish school reform and, by extension, to address emerging perspectives linking school leadership, learning and well-being.Design/methodology/approachAn analysis of central policy documents in the reform as well as research reports examining the role of leadership in the implementation of the reform offers insights into the new expectations of and tensions in school leadership. Drawing on theories of school leadership, the analysis highlights the various forms and aspects of school leadership that are at play in the reform.FindingsThe analysis identifies expectations regarding school leadership, ranging from aspects of strategic leadership that focus on management by objectives and results to aspects that are closer to teaching, such as curriculum and instructional leadership. It furthermore highlights barriers with regard to realizing policy intentions of strengthening instructional leadership, such as encroaching upon pedagogical and curriculum leadership, which have traditionally been the domain of teachers. Meanwhile, the kind of leadership that can be practiced through data-based management by objectives and results seems to have been perceived as a more viable approach in the implementation of the reform.Research limitations/implicationsThe papers' theoretical and empirical foundation is rooted in Danish and Scandinavian perspectives on schooling, and thus the generalizability of the findings may be limited to countries with similar perspectives or “packages of expectations” on linking school leadership, learning and well-being.Originality/valueThe paper provides an original contribution through its engagement with the tensions inherent in the specific “package of expectations” and new demands on school leadership in the 2014 school reform.
Educational innovation: trends for higher education in Brazil
Authors: Riccomini Fernanda Edileuza , Cirani Claudia Brito Silva , Carvalho Carolina Corrêa de , Storopoli José Eduardo 
Published: February 2021

PurposeThe purpose of this paper is to characterize the trends for educational innovation in higher education in Brazil, constructing a conceptual model of innovation trends in the sector.Design/methodology/approachA preliminary profile online was done with 76 experts in university education, and 17 were contacted for in-depth perceptions. The analysis of the content was made of all material and, as a result, the critical analysis of the results, which culminated in the development of a conceptual model and characterization of trends, dimensions and subdimensions to innovation in higher education.FindingsThe dimension universal design of accessibility and learning had major considerations, contributing to implementation of new innovative practices for higher education. Some subdimensions emerged, namely, governance, risk management, curricular extension and affirmative policies.Research limitations/implicationsThe difficulty in performing the deepening of all dimensions involved in terms of plurality of specialties involved.Practical implicationsThe use of the model and characterization of trends could serve as tools to support the strategic planning of HEI, and the trends allow planning innovation practices, favoring improvements of higher education institutions (HEI), students, employees and community to learning organization.Social implicationsThe identification of trends for higher education, highlighting innovation indicators or successful practices, and the characterization of the dimensions and subdimensions trends, and undeniable contribution to measure the educational innovation in higher education.Originality/valueEncourages researchers, in partnership with institutions, to develop scientific projects with other institutions and researchers, to meet interests not only of HEI as a whole but also of countries that prioritize education with quality, to reach the real educational objectives.
Sociodemographic aspects and their relationship with motivations, satisfaction and loyalty in ecotourism: a study in Costa Rica
Authors: Carvache-Franco Mauricio , Carvache-Franco Orly , Víquez-Paniagua Ana Gabriela , Carvache-Franco Wilmer , Perez-Orozco Allan 
Published: February 2021

PurposeThe objectives of this study were to (a) analyze the relationship between sociodemographic aspects and motivations in ecotourism and (b) identify the relationship between sociodemographic aspects and satisfaction and loyalty variables.Design/methodology/approachThe research was carried out in the Arenal National Park and the Caño Negro National Wildlife Refuge in Costa Rica, an ecologically important ecotourism destination. The sample consisted of 310 surveys obtained in situ. For data analysis, factor analysis and the multiple regression method were used.FindingsThe results show that younger tourists tend to be more motivated by self-development, whereas older tourists and lower-income tourists are more motivated toward strengthening interpersonal relationships with family and friends. In contrast, tourists with lower education levels are highly motivated by novelty, feel more satisfied with the visit and are more willing to recommend and say positive things about the destination. Besides, repeat visitors are most likely to return.Research limitations/implicationsThe present study was limited by the timing in which it was carried out. Among the future lines of research, studies that address the relationship between sociodemographic variables in the different ecotourism segments should be conducted.Practical implicationsRegarding the practical implications, this study helps companies related to tourism to pay attention to the sociodemographic characteristics of tourists to design activities and services according to their motivations, satisfaction and loyalty. For younger tourists who are motivated by self-development, activities and services related to learning about nature can be planned to encourage their personal growth, new abilities and individual skills. Regarding elderly and lower-income tourists, who are motivated to be with family and friends, recreational activities to improve family and friendship relationships can be promoted.Social implicationsThese findings will serve to plan attractions and services in protected areas, benefiting the destinations and the communities sustainably.Originality/valueOne of the contributions of this study is to find a negative relationship between the level of education and other variables such as satisfaction, intentions to recommend and intentions to say positive things about the destination. This research also identified a negative relationship between age and the self-development motivational dimension, a positive relationship between age and being with family and friends dimension, a negative relationship between income and being with family and friends dimension and a negative relationship between the number of visits and the novelty dimension.
Corona crisis chronicle: Fang Fang's Wuhan Diary (2020) as an act of sousveillance
Authors: Fedtke Jana , Ibahrine Mohammed , Wang Yuting 
Published: February 2021

PurposeThis paper analyzes Fang Fang's 2020 Wuhan Diary‐Dispatches from a Quarantined City, to show how the author communicates the coronavirus crisis in Wuhan in a global information ecosystem. The success of the diary showcases how the actual health emergency has been transformed into a communication issue.Design/methodology/approachThis study is exploratory and qualitative in nature. The authors conducted a thematic analysis (TA) of Wuhan Diary, in which we decided to focus on the aspects of sousveillance and solidarity. For the purposes of our paper, we used the English translation of the text by Dr. Michael Berry.FindingsThe authors focus on two major themes in their exploration of the corona crisis as a global communication issue: sousveillance and solidarity. The authors argue that the diary's ways of seeing perform a version of “sousveillance” or “undersight” in juxtaposition to surveillance or “oversight” (Mann, 2017). Fang Fang calls for solidarity as an effective measure for individuals, communities and societies to contain the pandemic and a potential misinfodemic.Originality/valueSince Wuhan was the early epicenter of the COVID-19 pandemic, Wuhan Diary presents an unprecedented narrative account of life under quarantine that could function as a litmus test for other cities and countries. Fang Fang's diary provides a countermeasure to official accounts of the pandemic in Wuhan, which has resonated both with people in China and abroad.
A powerful diagnostic tool for 21st Century management
Authors: Denning Stephen 
Published: February 2021

Purpose
The author offers The Principles, Processes, Practices (PPP) Worksheet, an analytic tool that can help firms diagnose their current status in relation to the transformation from 20th Century to 21st Century management.

Design/methodology/approach
The author posits that there are currently two strikingly different ways of running a corporation in a coherent and consistent fashion. The predominant mode of 20th Century management refined over the last 50 years has the goal of maximizing shareholder value. 10;By contrast, for 21st Century management–the pioneering mode of Agile enterprises and of leading Silicon Valley firms, the goal leads to principles and processes that enable agility. The principles and processes help firms mobilize talent to create instant, intimate, incremental value for customers. 10;

Findings
The Principles, Processes, Practices (PPP) Worksheet an be applied either to the entire organization or to any part of that organization, such as the leadership team, or any department, or any team, at any point in time.

Practical implications
Leaders using the PPP worksheet will become, in effect, what Richard Sheridan, CEO of Menlo Innovations, calls “a high tech anthropologist” probing what is going on.

Originality/value
This is the first description of a potent analytical tool that can help a firm plan and implement a management transformation to 21st Century Agile practices.
Skill or will? The respective contribution of motivational and behavioural characteristics to secondary school students' reading comprehension
Authors: Van Ammel Kim , Aesaert Koen , De Smedt Fien , Van Keer Hilde 
Published: February 2021

BackgroundA significant number of secondary school students struggle with comprehending texts proficiently. Enhancing their reading comprehension requires knowledge about how this ability is related to various motivational and behavioural characteristics. The central aim of this study was therefore to investigate the (in)direct relationships between ninth‐grade students' motivational (i.e., reading motivation and reading self‐concept) and behavioural characteristics (i.e., reading strategy use, reading engagement and reading frequency) and their reading comprehension. Furthermore, differential relationships across educational tracks are investigated.MethodsA total of 2,485 ninth‐grade students completed a standardised reading comprehension test and an online questionnaire to operationalise the motivational and behavioural reading variables. Data were analysed using multigroup structural equation modelling to study potential differential relationships across educational tracks (i.e., academic, technical and vocational track).ResultsMotivational and behavioural characteristics were directly related to students' reading comprehension. Moreover, the relationships between motivational characteristics and reading comprehension were mediated by behavioural characteristics. As to differences across educational tracks, not all of the relationships were corroborated similarly for each track.ConclusionGenerally, the results emphasise the importance of considering the ‘bigger picture’, taking into account the respective contribution of both behavioural and motivational characteristics to secondary school students' reading comprehension and concurrently considering differences across educational tracks.