bluuebunny/crossref_metadata_2025 huggingface dataset:
Z-DNA as a Touchstone for Additive Empirical Force Fields and a Refinement of the Alpha/Gamma DNA torsions for AMBER
Authors: Zgarbová Marie , Šponer Jiří , Jurečka Petr
Published: July 2021

Although current AMBER force fields are relatively accurate for canonical B-DNA, many non-canonical structures are still described incorrectly. As non-canonical motifs are attracting increasing attention due to the role they play in living organisms, further improvement is desirable. Here, we have chosen Z-DNA molecule, can be considered a touchstone of the universality of empirical force fields, since the non-canonical α and γ backbone conformations native to Z-DNA are also found in protein-DNA complexes, i-motif DNA and other non-canonical DNAs. We show that spurious α/γ conformations occurring in simulations with current AMBER force fields, OL15 and bsc1, are largely due to inaccurate α/γ parameterization. Moreover, stabilization of native Z-DNA substates involving γ = trans conformations appears to be in conflict with the correct description of the canonical B-DNA structure. Because the balance of the native and spurious conformations is influenced by non-additive effects, this is a difficult case for an additive dihedral energy scheme such as AMBER. We propose new α/γ parameters, denoted OL21, and show that they improve the stability of native α/γ Z-DNA substates while keeping the canonical DNA description virtually unchanged, and thus represent a reasonable compromise within the additive force field framework. Although further extensive testing is needed, the new modification appears to be a promising step towards a more reliable description of non-canonical DNA motifs and provides the best performance for Z-DNA molecules among current AMBER force fields.
SARS-CoV-2 Spike Protein Mutations and Escape from Antibodies: a Computational Model of Epitope Loss in Variants of Concern
Authors: Triveri Alice , Serapian Stefano A. , Marchetti Filippo , Doria Filippo , Pavoni Silvia , Cinquini Fabrizio , Moroni Elisabetta , Rasola Andrea , Frigerio Francesco , Colombo Giorgio
Published: July 2021

The SARS-CoV-2 spike (S) protein is exposed on the viral surface and is the first point of contact between the virus and the host. For these reasons it represents the prime target for Covid-19 vaccines. In recent months, variants of this protein have started to emerge. Their ability to reduce or evade recognition by S-targeting antibodies poses a threat to immunological treatments and raises concerns for their consequences on vaccine efficacy.

To develop a model able to predict the potential impact of S-protein mutations on antibody binding sites, we performed unbiased multi-microsecond molecular dynamics of several glycosylated S-protein variants and applied a straightforward structure-dynamics-energy based strategy to predict potential changes in immunogenic regions on each variant. We recover known epitopes on the reference D614G sequence. By comparing our results, obtained on isolated S-proteins in solution, to recently published data on antibody binding and reactivity in new S variants, we directly show that modifications in the S-protein consistently translate into the loss of potentially immunoreactive regions. Our findings can thus be qualitatively reconnected to the experimentally characterized decreased ability of some of the Abs elicited against the dominant S-sequence to recognize variants. While based on the study of SARS-CoV-2 Spike variants, our computational epitope-prediction strategy is portable and could be applied to study immunoreactivity in mutants of proteins of interest whose structures have been characterized, helping the development/selection of vaccines and antibodies able to control emerging variants.
Crystal structure and Hirshfeld surface analysis of (3aR,4S,7S,7aS)-4,5,6,7,8,8-hexachloro-2-{6-[(3aR,4R,7R,7aS)-4,5,6,7,8,8-hexachloro-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-4,7-methanoisoindol-2-yl]hexyl}-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione
Authors: Alikhanova Aygun I. , Atioğlu Zeliha , Akkurt Mehmet , Mlowe Sixberth
Published: July 2021

The molecule of the title compound, C24H16Cl12N2O4, is generated by a crystallographic inversion centre at the midpoint of the central C—C bond. A kink in the molecule is defined by a torsion angle of −169.86 (15)° about this central bond of the alkyl bridge. The pyrrolidine ring is essentially planar [max. deviation = 0.014 (1) Å]. The cyclohexane ring has a boat conformation, while both cyclopentane rings adopt an envelope conformation. In the crystal structure, molecules are linked by intermolecular C—H...O, C—H...Cl and C—Cl...π interactions, and short intermolecular Cl...O and Cl...Cl contacts, forming a three-dimensional network.
Gamification effects on users' motivation to contribute knowledge in a Portuguese Q&A community
Authors: Oliveira Jordao do Amaral Isabel , Kang Minhyung
Published: July 2021

Purpose

This research investigates the detailed mechanisms of how gamification affordances influence intrinsic and internalized extrinsic motivation and ultimately improve the quality and quantity of knowledge contribution.

Design/methodology/approach

Survey responses from 154 users of Stack Overflow in Portuguese were analyzed by the partial least squares–structural equation modeling approach to validate the research model.

Findings

Challenge and goal setting influence individuals to reach the flow state, which increases the quantity of knowledge contribution. Rewards enhance the quality of knowledge contribution through perceived self-worth. Social comparison increases perceived reputation, but its impact does not ultimately lead to knowledge contribution.

Originality/value

The current study differentiated types of motivation and dimensions of knowledge contribution when exploring the effects of gamification affordances. This perspective was proven helpful to understand the various gamification affordances' influence on knowledge contribution.
What matters for the future? Comparing Globe's future orientation with Hofstede's long-term orientation
Authors: Alipour Ali
Published: July 2021

Purpose

This paper aims to compare the future orientation (FO) society practices dimension of the Globe model with Hofstede's long-term orientation (LTO) by testing their causal effects on three firm-level variables: cash holdings, long-term investments and acquisitions. In doing so, this research challenges the already taken-for-granted assumption in the empirical research that the two dimensions are equivalent.

Design/methodology/approach

Hierarchical linear modeling (HLM) was used to test the hypotheses on 7,065 firms across 49 countries between 2000 and 2017.

Findings

The findings show that the causal impacts of FO society practices and LTO on a given construct are not consistent. Although LTO increases cash holdings, the impact of FO society practices on this variable is insignificant. Additionally, unlike FO society practices, which significantly increases long-term investments and acquisitions, LTO does not influence long-term investments and decreases acquisitions.

Originality/value

This study is valuable since it addresses the confusion surrounding the similarities and differences between FO society practices and LTO. Despite the dissimilarity also emphasized by Globe, Hofstede claims that they are equivalent, and the great majority of the empirical literature has assumed them to be equivalent in their analyses. Addressing this confusion, this research provides further empirical evidence that these two dimensions are dissimilar. The additional important contribution of the study is theorizing and examining the impact of FO society practices and LTO on the firm-level outcomes that reflect their temporal orientation (i.e. long-term investments and acquisitions), which is surprisingly neglected in the literature.
Downside systematic risk in Pakistani stock market: role of corporate governance, financial liberalization and investor sentiment
Authors: Hussain Shahzad , Akbar Muhammad , Malik Qaisar Ali , Ahmad Tanveer , Abbas Nasir
Published: July 2021

Purpose

The purpose of this paper is to examine the impact of corporate governance, investor sentiment and financial liberalization on downside systematic risk and the interplay of socio-political turbulence on this relationship through static and dynamic panel estimation models.

Design/methodology/approach

The evidence is based on a sample of 230 publicly listed non-financial firms from Pakistan Stock Exchange (PSX) over the period 2008–2018. Furthermore, this study analyzes the data through Blundell and Bond (1998) technique in the full sample as well sub-samples (big and small firms).

Findings

The authors document that corporate governance mechanism reduces the downside risk, whereas investor sentiment and financial liberalization increase the investors’ exposure toward downside risk. Particularly, the results provide some new insights that the socio-political turbulence as a moderator weakens the impact of corporate governance and strengthens the effect of investor sentiment and financial liberalization on downside risk. Consistent with prior studies, the analysis of sub-samples reveals some statistical variations in large and small-size sampled firms. Theoretically, the findings mainly support agency theory, noise trader theory and the Keynesians hypothesis.

Originality/value

Stock market volatility has become a prime area of concern for investors, policymakers and regulators in emerging economies. Primarily, the existence of market volatility is attributed to weak governance, irrational behavior of market participants, the liberation of financial policies and sociopolitical turbulence. Therefore, the present study provides simultaneous empirical evidence to determine whether corporate governance, investor sentiment and financial liberalization hinder or spur downside risk in an emerging economy. Furthermore, the work relates to a small number of studies that examine the role of socio-political turbulence as a moderator on the relationship of corporate governance, investor sentiment and financial liberalization with downside systematic risk.
Perspectives, progress and prospects; researching women’s entrepreneurship in emerging economies
Authors: Anderson Alistair , Ojediran Funmi
Published: July 2021

Purpose

The purpose of this paper is to review the literature on women’s entrepreneurship in emerging economies. This is a thematic review to identify patterns and trends to better understand this literature. From the analysis, this study offers ideas for useful and theoretically informed research. In addition, this paper proposes the concept of restricted agency that helps to explain the practice.

Design/methodology/approach

This study identifies the nature, what is interesting, what it sees as important and considers what is neglected in this literature. The analysis sought important issues, interesting directions and the potential for useful future work. Thematic analysis is ideal for messy and unstructured material such as the literature used in this study as the data set. The process is qualitative, iterative and inductive but ontologically appropriate for the socially produced knowledge of the literature.

Findings

This paper finds the literature tends towards descriptive papers. Few papers make substantial contributions to theory. Many papers reported the barriers women to encounter, reporting general and typical processes of responding to obstacles and the implications for practice. Interestingly this study perceives overcoming and sometimes using, the cultural and physical restraints of gendered entrepreneurship. This paper proposes the concept of restricted agency explaining the gendering of entrepreneurs and explains what they can do. Moreover, the concept helps explain why and what. Most promising theoretically, is how the application of this agency is slowly and contextually differently changing the rules of the game.

Research limitations/implications

This study covers a large and extensive literature, so might have missed themes.

Originality/value

This paper starts with the notion of the “otherness” of women’s entrepreneurship. The literature is good at explaining both how and why women’s entrepreneurship is different and in effect, marginalised. This study conceptualises this gendering process as a restricted agency. Moreover, the concept helps explain why and what. Most promising theoretically, is how the application of this agency is slowly and contextually differently changing the rules of the game. It may be the mechanism for emancipation.
Introduction of a new AAC symbol classification system: the multidimensional quaternary symbol continuum (MQSC)
Authors: Pampoulou Eliada , Fuller Donald R.
Published: July 2021

Purpose

When the augmentative and alternative communication (ACC) model (Lloyd et al., 1990) was proposed, these components of symbols were not considered, nor were they contemplated when superordinate (Lloyd and Fuller, 1986) and subordinate levels (Fuller et al., 1992) of AAC symbol taxonomy were developed. The purpose of this paper is to revisit the ACC model and propose a new symbol classification system called multidimensional quaternary symbol continuum (MQSC)

Design/methodology/approach

The field of AAC is evolving at a rapid rate in terms of its clinical, social, research and theoretical underpinnings. Advances in assessment and intervention methods, technology and social issues are all responsible to some degree for the significant changes that have occurred in the field of AAC over the last 30 years. For example, the number of aided symbol collections has increased almost exponentially over the past couple of decades. The proliferation of such a large variety of symbol collections represents a wide range of design attributes, physical attributes and linguistic characteristics for aided symbols and design attributes and linguistic characteristics for unaided symbols.

Findings

Therefore, it may be time to revisit the AAC model and more specifically, one of its transmission processes referred to as the means to represent.

Originality/value

The focus of this theoretical paper then, is on the current classification of symbols, issues with respect to the current classification of symbols in terms of ambiguity of terminology and the evolution of symbols, and a proposal for a new means of classifying the means to represent.

Peer review

The peer review history for this article is available at: https://publons.com/publon10.1108/JET-04-2021-0024
Innovation in pandemics: a netnographic approach to the sharing economy contributions
Authors: Belezas Fernando , Daniel Ana
Published: July 2021

Purpose

Pandemics are a serious challenge for humanity, as their social and economic impacts can be tremendous. This study aims to understand how innovation based in the sharing economy (SE) business models can contribute to overcoming the challenges arising from the Covid-19 pandemic.

Design/methodology/approach

Following a netnographic approach, the authors studied the computer-mediated social interactions of internet-based virtual innovation communities.

Findings

This study found that the SE business models contribute to overcome the challenges of the Covid-19 pandemic by redistributing idle resources to lessen the impacts of confinement. This was achieved through process innovations and an innovative use of the network, which enabled fast-open and decentralized innovation processes, and quick implementation of innovations. This innovation process is based on a decentralized decision-making approach, clear rules, informal relationship among community members and open communication channels, as well as in evasive strategies to avoid facing challenges, institutional restrictions and barriers in the adoption of innovations.

Research limitations/implications

This study was limited to a virtual innovation community of highly specialized and educated experts and nine community projects focused on institutional contexts of a developed country. Future research should focus on the institutional contexts of less specialized communities and developing countries and study other community innovation projects in pandemics to understand the processes of fast-open, decentralized and evasive innovation and the importance of relational capabilities for innovation in digital contexts.

Practical implications

The findings can guide innovation managers and public policymakers in implementing effective strategies and policies to overcome pandemic challenges using SE business models. This research also provides important insights into the types and processes of innovation in organizations that create solutions to overcome social and business challenges during pandemics. In addition, this study highlights the contributions of netnographic approaches to conducting research on innovation and in pandemic periods when measures of confinement are in place.

Originality/value

This study uses an innovative framework to map the types of innovation and highlights two different types of innovation processes.
The social role of open spaces in informal settlements in Jordan
Authors: Alja'afreh Aseel , Al Tal Raed , Ibrahim Anwar
Published: July 2021

Purpose

The study hypothesized that the absence of the governing authority during the growth and expansion of informal settlements caused a highly randomized dense social fabric that shaped their characteristics.

Design/methodology/approach

This research employs urban tactics and social theories to understand dynamic relationships in social consolidation in informal settlements in Jordan. The research adopted a mixed-methods approach, deploying qualitative and quantitative methods to understand the concepts, terms, perspectives, means and functions of open spaces in informal settlements.

Findings

The results identified that the land ownership of open spaces, gender and age have a significant impact on the relationships and social interaction of people. The results suggested that despite the informal morphology of studied areas being random, unplanned and chaotic, there is often an underlying logic to meet occupants’ needs.

Research limitations/implications

This research explores informal spatiality to help understand the mechanisms of how marginal communities create and interact with each other in public spaces. This study is limited to the investigation of socio-cultural practices in public spaces, without an in-depth consideration of the roles of physical elements and features in the spatial configuration of these spaces.

Originality/value

The importance of the research is that the exploration of informal spatiality of this neighborhood morphology will enable to understand the mechanism of how marginal communities create and interact among each other and their public spaces in different cities.
Citric acid as environment friendly crease-resistance finishing agent for silk fabric combined by ß-cyclodextrin
Authors: Zare Abolfazl
Published: July 2021

Purpose

The purpose of this paper is to assess the possibility of cross-linking silk fabric using citric acid (CA) as the cross-linking agent and nano-TiO2 (NTO) particles as a catalyst at low temperature and under UV irradiation. This paper also assesses the possibility of treated samples with suitable combinations of CA and NTO to impart multiple functional properties such as self-cleaning and antimicrobial properties.

Design/methodology/approach

In this research, ß-cyclodextrin (ß-CD) grafted onto silk fabric using CA as a crosslinking agent and NTO particles as a catalyst through a pad-dry-cure technique and with UVA irradiation. The effects of different concentrations of CA, ß-CD and NTO particles on some properties of the treated samples are evaluated, and the optimum finishing conditions are obtained. The author also investigated the washing durability of the modified product after ten times of washing.

Findings

The results showed that CA plays the role of a linking agent through an esterification reaction with the hydroxyl groups of both ß-CD and silk fabrics and improves the durability of materials on the textile surface. Also, the silk fabrics treated with CA only were found to have excellent photocatalytic properties and better antibacterial activity than the control sample and the fabrics treated with a mixture of ß-CD/CA.

Originality/value

This study was conducted to achieve multiple functions such as antibacterial and photocatalytic activities, good dry crease recovery angle and wet crease recovery angle behavior without a significant adverse effect on the Yellowness index and tensile properties for treated silk fabrics.
Eldercare helpline: connecting with older people to mitigate the effects of the Covid-19 crisis in Jaipur, India
Authors: Raina Roshan Lal , Gupta Asheesh , Gupta Umesh , Singh Upasana , Jain Divanshu
Published: July 2021

Purpose

The purpose of this study is to identify the needs and concerns of older people in Jaipur, Rajasthan, India during the lockdown phase of the Covid-19 crisis. The study also aims to present a viable model for extending needed support through a telephone helpline run by a team of young student volunteers.

Design/methodology/approach

The study uses a thematic analysis of the interaction between callers (service users) and volunteers.

Findings

The study shows that the main reasons that motivate the use of the helpline are to seek medical advice and to request medical services and medical supplies free of charge. However, the study also shows that other reasons for calling the helpline are feelings of loneliness and the need for psychological support, especially due to insufficient assistance from families.

Practical implications

The study shows the benefits of providing this type of service for older people during a time of national health crisis. The service is cost-effective and offers a one-stop assistance point.

Social implications

The service also constitutes an avenue for building intergenerational solidarity and empathy between younger and older people. This is especially important for citizens who feel socially isolated and disconnected from the rest of society.

Originality/value

The study offers a model for an easily created resource that could usefully be exported to other geographic settings.
Diversity of co‐flowering plants at field margins potentially sustains an abundance of insects visiting buckwheat, Fagopyrum esculentum, in an agricultural landscape
Authors: Nagano Yuta , Miyashita Tadashi , Taki Hisatomo , Yokoi Tomoyuki
Published: July 2021

Pollinators have been declining in recent years due to changes in land use, and the negative impacts on food production are concern. Wildflowers play an important role in maintaining pollinators and pollination services in agricultural landscapes, but little is known about the effects of wildflowers at field margins on crop pollinators. We aimed to clarify the relationship between crop pollination and the species richness of wildflowers at field margins through sharing of flower visitors. We focused on insects that visit the flowers of buckwheat, Fagopyrum esculentum, in fields in Japan. Field surveys were conducted to investigate flower‐visiting insect communities in both the pre‐blooming and blooming periods of buckwheat in summer and autumn. The community structure of flower‐visiting insects differed between buckwheat and wildflowers in both seasons, but buckwheat shared beetles with co‐flowering plants in autumn. The abundance of insects visiting buckwheat increased with species richness of co‐flowering plants in autumn but was not related to wildflowers in summer. The morphological similarity of floral traits would not be important for these positive effects of wildflowers. Thus, co‐flowering plants have positive or neutral effects on the insects visiting buckwheat, which may contribute to the enhancement of buckwheat yields.
Influence of FSC certification on the governance of the logging sector in the Congo basin
Authors: Lescuyer Guillaume , Tsanga Raphaël , Nziengui Samir , Forni Eric , Romero Claudia
Published: July 2021

The performance of private forest governance systems, such as the standard and approach developed by the Forest Stewardship Council (FSC), is often assessed at the local level although they also have an indirect influence on public policies at the national level. Such spillover effects must be understood to assess the effectiveness of certification in contributing to improved forest governance. With this purpose, this article analyses the influences of the implementation of FSC standards on changes in forest governance in Cameroon, Congo and Gabon based on perceptions of 43 “knowledgeable” actors of FSC natural forest management. The information was collected through the use of semi‐open and open interviews, and rankings. Findings show that perceived FSC influence on forest governance has followed two pathways: (a) a clear impact on stakeholder participation and timber traceability; and (b) a limited impact on improving national governance, as illustrated by the lack of global improvement in resource management practices or in biodiversity conservation. Moreover, interviewees agreed that struggles against corruption and transparency have not been impacted by the FSC certification in the Congo Basin. This mitigated influence of FSC on forest governance is first explained by a limited spillover effect of the virtuous practices of the seven FSC‐certified companies on the national logging sector. Secondly, progress in FSC certification has been little taken up by public policies, which remain the main leverage for action on forest governance in producing countries.
Are food price promotions predictable? The hazard function of supermarket discounts
Authors: Lan Hao , Lloyd Tim , Morgan Wyn , Dobson Paul W.
Published: July 2021

Is the timing of food products going on sale, in the form of temporary price reductions, random or predictable? More specifically, are products more likely to go on sale the longer they remain non‐promoted? We investigate the nature and timing of sales discounts using a large database based on weekly supermarket scanner prices covering 500 products for 137 weeks in the largest seven national retail chains in the UK. Our duration analysis of regular price spells reveals that discounting for a wide range of food products is more likely the longer they remain without a sale. However, critical differences exist between retailers following Hi‐Lo or every‐day‐low‐pricing policies, while the time‐dependent pattern varies considerably across product categories, brand status and discount depth.
The management of gallstone pancreatitis in pregnancy: A systematic review of the literature on this clinical dilemma
Authors: Merali Nabeel , Reis Ines , Singh Gautam , Shirol Sunil , Singh Sukphal , Veeramootoo Darmarajah
Published: July 2021

Background

Acute gallstone pancreatitis in pregnancy (GSPP) is a challenging clinical problem; associated with high maternal mortality and foetal loss if not treated appropriately. There are no current UK management guidelines. Our study therefore aims to review published evidence‐based strategies on the management of GSPP and suggest a rational approach.

Method

The PRISMA Guidelines were used to undertake this comprehensive systematic literature review. Electronic literature search of the databases (PubMed/ MEDLINE, Cochrane database, UpToDate and Google Scholar) was started on 19 November 2019 and completed on 1 March 2020. The key words used were “gallstone pancreatitis in pregnancy”, “biliary pancreatitis” and “laparoscopy in pregnancy”.

Discussion

There are no national or international guidelines on the management of GSPP. However a number surgical societies, e.g. SAGES, have published advice to support clinical decision‐making. Gestational age is a main factor that determines diagnostic studies or intervention, such as endoscopic or surgical therapy. Management should ideally be deferred to the second trimester. Therapeutic endoscopic retrograde cholangiopancreatography (ERCP) can be carried out successfully, by limiting fluoroscopy time, shielding the pelvis and foetus, and reduced radiation dose. A critical part not to be overlooked is the consent, portraying the risks to the mother and foetus with continuous counselling.

Conclusion

Our review highlights the challenges that persist in the management of gall stone pancreatitis in pregnancy. A multidisciplinary approach is crucial to achieve the best outcomes. Timely action as clinically appropriate is recommended; and this has to be tailored to the needs of both lives.
Anterior segment imaging in minimally invasive glaucoma surgery – A systematic review
Authors: Kan John Tsia‐Chuen , Betzler Bjorn Kaijun , Lim Sheng Yang , Ang Bryan Chin Hou
Published: July 2021

Minimally invasive glaucoma surgery (MIGS) has grown in popularity over the past decade. This systematic review explores the peri‐operative and intraoperative application of anterior segment imaging to maximize the efficacy and safety of MIGS. A review of the PubMed, EMBASE and CINAHL databases was conducted, with inclusion criteria restricted to MIGS that had received United States Food and Drug Administration (FDA) premarket approval, FDA 510(K) premarket notification, or were listed as a class 1 device exempt from FDA approval or notification. 21 manuscripts from 21 unique studies were identified pertaining to MIGS devices including the XEN Gel Stent, Trabectome, iStent Inject, 1st‐generation iStent and the Kahook Dual Blade (KDB). Anterior segment imaging modalities included anterior segment optical coherence tomography (AS‐OCT), ultrasound biomicroscopy (UBM), aqueous angiography, OCT volumetric scans and in vivo confocal microscopy. Identification and evaluation of aqueous outflow pathways before and after MIGS have potential for improving patient preoperative patient selection and postoperative outcomes. Intraoperative imaging potentially provides the resolution needed for good visualization of angle anatomy and accurate evaluation of surgical endpoints in angle‐based MIGS. Anterior segment imaging has been used to identify procedural complications, provide objective information on implant location in relation to surrounding anatomy, assess the post‐implantation structural impact of MIGS devices and manage bleb failure and scarring. Technical difficulties in incorporating imaging modalities into the surgical microscope, variable quality of images and optical interference from ocular structures or surgical instruments are remaining barriers, which discourage the widespread clinical use of this technology.
Multiparametric magnetic resonance imaging to characterize cabotegravir long‐acting formulation depot kinetics in healthy adult volunteers
Authors: Jucker Beat M. , Fuchs Edward J. , Lee Sarah , Damian Valeriu , Galette Paul , Janiczek Robert , Macura Katarzyna J. , Jacobs Michael A. , Weld Ethel D. , Solaiyappan Meiyappan , D'Amico Ronald , Shaik Jafar Sadik , Bakshi Kalpana , Han Kelong , Ford Susan , Margolis David , Spreen William , Gupta Manish K. , Hendrix Craig W. , Patel Parul
Published: July 2021

Aim

Cabotegravir long‐acting (LA) intramuscular (IM) injection is being investigated for HIV preexposure prophylaxis due to its potent antiretroviral activity and infrequent dosing requirement. A subset of healthy adult volunteers participating in a Phase I study assessing cabotegravir tissue pharmacokinetics underwent serial magnetic resonance imaging (MRI) to assess drug depot localization and kinetics following a single cabotegravir LA IM targeted injection.

Methods

Eight participants (four men, four women) were administered cabotegravir LA 600 mg under ultrasonographic‐guided injection targeting the gluteal muscles. MRI was performed to determine injection‐site location in gluteal muscle (IM), subcutaneous (SC) adipose tissue and combined IM/SC compartments, and to quantify drug depot characteristics, including volume and surface area, on Days 1 (≤2 hours postinjection), 3 and 8. Linear regression analysis examined correlations between MRI‐derived parameters and plasma cabotegravir exposure metrics, including maximum observed concentration (Cmax) and partial area under the concentration–time curve (AUC) through Weeks 4 and 8.

Results

Cabotegravir LA depot locations varied by participant and were identified in the IM compartment (n = 2), combined IM/SC compartments (n = 4), SC compartment (n = 1) and retroperitoneal cavity (n = 1). Although several MRI parameter and exposure metric correlations were determined, total depot surface area on Day 1 strongly correlated with plasma cabotegravir concentration at Days 3 and 8, Cmax and partial AUC through Weeks 4 and 8.

Conclusion

MRI clearly delineated cabotegravir LA injection‐site location and depot kinetics in healthy adults. Although injection‐site variability was observed, drug depot surface area correlated with both plasma Cmax and partial AUC independently of anatomical distribution.
Multicompartmental pharmacokinetic evaluation of long‐acting cabotegravir in healthy adults for HIV preexposure prophylaxis
Authors: Shaik Jafar Sadik , Weld Ethel D. , Edick Stacey , Fuchs Edward , Riddler Sharon , Marzinke Mark A. , D'Amico Ronald , Bakshi Kalpana , Lou Yu , Hendrix Craig , Han Kelong , Ford Susan L. , Margolis David , Spreen William , Patel Parul
Published: July 2021

Aims

Cabotegravir is an integrase strand transfer inhibitor in clinical development as long‐acting (LA) injectable HIV preexposure prophylaxis.

Methods

This phase I study assessed pharmacokinetics of cabotegravir in plasma and anatomical sites associated with sexual HIV‐1 transmission after repeated oral and single intramuscular (IM) LA dosing in healthy adults. Following a 28‐day oral lead‐in period of cabotegravir 30 mg and a washout period of 14–42 days, participants were administered a single ultrasound‐guided gluteal IM cabotegravir LA 600‐mg injection. The study objective was to characterize cabotegravir concentrations in plasma, cervical, vaginal and rectal tissues, and cervicovaginal and rectal fluids and up to Week 12 after IM injection.

Results

Nineteen participants enrolled and 16 completed the study through Week 52. Cabotegravir was detected in plasma and all tissues and fluids. Median plasma cabotegravir concentrations exceeded the in vitro protein‐adjusted 90% maximal inhibitory concentration through Week 12. Median tissue‐ and fluid‐to‐plasma cabotegravir concentration ratios across all visits were 0.32 for rectal fluid and 0.08–0.16 for other tissues and fluids. Adjusted R2 coefficients between cabotegravir concentrations in plasma and cervical, vaginal and rectal tissues were 0.78, 0.79 and 0.90, respectively. Injection‐site reactions were common (88% of participants) and were mostly grade 1 in intensity (82%). Two participants reported 11 non–drug‐related serious adverse events.

Conclusion

Concentrations of cabotegravir in tissues and fluids were proportional to plasma over time, with strong correlations between tissue and plasma concentrations. Cabotegravir LA tissue‐to‐plasma ratios may be important for understanding its use as preexposure prophylaxis.
Decomposing changes in establishment‐level emissions with entry and exit
Authors: Holladay J. Scott , LaPlue Lawrence D.
Published: July 2021

This paper decomposes pollution releases by US manufacturing establishments to show the relative importance of four establishment‐level channels: entry, exit, reallocation between survivors and within‐establishment adjustment of emissions intensity. Using a panel of establishment‐level output and pollution emissions to air and water for US manufacturers, we decompose changes in pollution emissions into the three channels typically presented in the literature: changes in scale (output), composition (industry market share) and industry‐level technique (emissions intensity). We then decompose changes due to industry‐level emissions intensity into four establishment‐level channels for three criteria air pollutants and water pollution. For volatile organic compound emissions, nearly two thirds of the reduction in sector‐level emissions intensity is due to within‐establishment reductions in emissions intensity. The other third is driven by reallocation to cleaner establishments. Though the magnitudes differ, results are broadly similar for particulate matter and sulfur dioxide. On‐site releases of effluents to water exhibit a similar pattern, though the relative importance of reallocation is greater. We also find that within‐establishment reductions in water emissions are associated with increased transfers to off‐site publicly owned treatment facilities. The heterogeneous contributions across channels suggests that the cleanup in the US manufacturing sector likely has multiple sources.
Comparison of the effect of metal mordants and bio‐mordants on the colorimetric and antibacterial properties of natural dyes on cotton fabric
Authors: Shahmoradi Ghaheh Fatemeh , Moghaddam Meghdad Kamali , Tehrani Majid
Published: July 2021

The main objective of this study was to evaluate the effect of bio‐mordants versus metal mordants in terms of colour measurement, colour fastness, and antibacterial properties of a natural dye extract (Hibiscus sabdariffaL.) on the cotton fabric. Accordingly, some bio‐mordants including tannic acid, pine cone, lemon peel, and sodium alginate, as well as some metal mordants such as iron(II) sulphate, copper sulphate, zinc sulphate, and aluminium potassium sulphate were investigated based on three conventional mordanting procedures (pre‐, meta‐ and after‐mordanting). The method appropriate forH. sabdariffadyeing on the cotton fabric, according to the colour fastness factor, was found to be the after‐mordanting method. The bio‐mordants used in this study, the same as metal salts, increased the colour fastness on the dyed cotton fabrics and produced excellent light fastness (rating of 5 to 6), wash fastness (rating of 4 to 5), and dry/wet rub fastness (rating of 4 to 5). The higher antibacterial activities (> 90% bacterial reduction) againstEscherichia coli,Staphylococcus aureus, andPseudomonasaeruginosawere observed when tannic acid, pine cone, and lemon peel were applied to the dyed cotton fabric. The use of bio‐mordants in the natural dyeing of the cotton fabric could be, therefore, recommended due to the biocompatibility and non‐toxicity of natural mordants, along with excellent colour fastness and appropriate antibacterial properties.
An unusual case of malignant peritoneal effusion
Authors: Panigrahi Chinmayee , Sethy Madhusmita , Adhya Amit Kumar
Published: July 2021

Diagnosis of a high grade neuroendocrine carcinoma may be difficult in fluid cytology. Although, based on
its nuclear atypia, it is easy to identify the cells as malignant, it is difficult to classify them beyond malignancy. Immunohistochemistry on cell blocks can help in making the proper diagnosis.
Unpacking the effect of autonomous motivation on workplace performance: Engagement and distributive justice matter!
Authors: Roussillon Soyer Claude , Balkin David B. , Fall Amar
Published: July 2021

Self‐determination theory explains the effects of autonomous motivation on work engagement and job performance. We use a self‐determination theory framework to examine the interaction between distributive justice and autonomous motivation in the context of the allocation of pay to employees. We performed an empirical study in France that took place over three time periods to examine this relationship. Our findings show that when autonomous motivation is high employee perceptions of distributive justice are viewed as a source of control and results in decreased levels of autonomous motivation, work engagement and performance. As such, practical implications for human resource management are proposed to manage the prominence of attention given to employee perceptions of distributive justice of their rewards so that it should not be too high. In a context of high autonomous motivation in the workplace, managers could use ex post rewards.
Cortical low‐frequency power correlates with behavioral impairment in animal model of focal limbic seizures
Authors: Gummadavelli Abhijeet , Martin Reese , Goshay Derek , Sieu Lim‐Anna , Xu Jingwen , Gruenbaum Benjamin F. , McCafferty Cian , Gerrard Jason L. , Blumenfeld Hal
Published: July 2021

Objective

Impairment in consciousness is a debilitating symptom during and after seizures; however, its mechanism remains unclear. Limbic seizures have been shown to spread to arousal circuitry to result in a "network inhibition" phenomenon. However, prior animal model studies did not relate physiological network changes to behavioral responses during or following seizures.

Methods

Focal onset limbic seizures were induced while rats were performing an operant conditioned behavioral task requiring response to an auditory stimulus to quantify how and when impairment of behavioral response occurs. Correct responses were rewarded with sucrose. Cortical and hippocampal electrophysiology measured by local field potential recordings was analyzed for changes in low‐ and high‐frequency power in relation to behavioral responsiveness during seizures.

Results

As seen in patients with seizures, ictal (p < .0001) and postictal (p = .0015) responsiveness was variably impaired. Analysis of cortical and hippocampal electrophysiology revealed that ictal (p = .002) and postictal (p = .009) frontal cortical low‐frequency 3–6‐Hz power was associated with poor behavioral performance. In contrast, the hippocampus showed increased power over a wide frequency range during seizures, and suppression postictally, neither of which were related to behavioral impairment.

Significance

These findings support prior human studies of temporal lobe epilepsy as well as anesthetized animal models suggesting that focal limbic seizures depress consciousness through remote network effects on the cortex, rather than through local hippocampal involvement. By identifying the cortical physiological changes associated with impaired arousal and responsiveness in focal seizures, these results may help guide future therapies to restore ictal and postictal consciousness, improving quality of life for people with epilepsy.
Fatigue crack growth analysis of biaxially loaded hole‐edge cracks using boundary cracklet method (BCM)
Authors: Ahmed Talal , Yavuz Abdulkadir , Turkmen Halit S.
Published: July 2021

Fatigue crack growth (FCG) behavior of two symmetric cracks originating at different orientations from the outer periphery of a hole in an infinite plate under biaxial tension‐tension loading is presented using two‐dimensional boundary cracklet method. Symmetric precracks of known length and orientation are modelled as initial cracks, and biaxial traction is applied as a far‐field loading. The rate of FCG is computed using Walker's equation, whereas the direction of propagation of crack tip is predicted using the minimum strain energy density criterion. The parametric study is performed with various orientations of initial precracks, biaxiality stress ratios (λ), and stress ratios (R) to show their effects on FCG behavior. Results suggest that for equiaxial loading, the crack propagation direction depends upon the position and initial angle of the crack. Cracks tend to grow perpendicular to that stress which is dominant of the two applied stresses when the biaxiality ratio is not unity.
Systematic review of interventions targeting fundamental care to reduce hospital‐associated decline in older patients
Authors: de Foubert Marguerite , Cummins Helen , McCullagh Ruth , Brueton Valerie , Naughton Corina
Published: July 2021

Aims

To examine the effectiveness of targeted nursing interventions on mobilization, nutrition and cognitive engagement to reduce functional and hospital‐associated decline (HAD) in older patients.

Design

Systematic review of experimental studies using randomized and quasi‐experimental designs.

Data sources

We searched electronic databases CINAHL, MEDLINE, EMBASE, Cochrane library, google scholar and BMJ quality reports from January 2009 to February 2020.

Review methods

We reviewed intervention studies that targeted ward nursing teams to increase mobilization, nutrition or cognitive engagement of older adults. Inclusion criteria included older patients, acute care (medical, surgical and older adult wards) and reporting patient level outcomes. Quality appraisal included the Joanna Briggs Critical Appraisal Checklist for Quasi‐Experimental Studies.

Results

From 1729 papers, 18 studies using quasi‐experimental and pre‐post designs were selected. Study heterogeneity necessitated a narrative synthesis. The quality of evidence was low to moderate. All studies used multicomponent strategies, and 10 studies used evidence translation frameworks to align interventions to local barriers. Overall, 74% (n = 14) of studies reported a significant improvement in the stated primary outcome. Eight studies reported a significant increase in mobilization (e.g., sitting in a chair or walking), and four reported improved functional outcomes. Five studies improved nutrition outcomes (e.g., protein or energy intake), and three studies reported a significant reduction in delirium.

Conclusion

Acknowledging methodological limitations, the evidence indicates that nursing teams using evidence‐translation frameworks can improve mobilization, nutrition and cognitive engagement in acute care settings. Future research requires higher‐quality pragmatic trial designs, standardized outcomes, staff co‐designed interventions, evidence‐translation frameworks and patient engagement to make more confident inference about effectiveness.

Impact

Nursing teams with the support of hospital management have to address ward and system barriers to prioritize fundamental care to improve patient outcomes. There is sufficient evidence on multicomponent interventions and implementation strategies to inform nurse‐led quality improvement.
Polymeric biomaterials maintained the esthetic efficacy and reduced the cytotoxicity of in‐office dental bleaching
Authors: Ortecho‐Zuta Uxua , de Oliveira Duque Carla Caroline , de Oliveira Ribeiro Rafael Antonio , Leite Maria Luísa , Soares Diana Gabriela , Hebling Josimeri , Briso André Luiz Fraga , de Souza Costa Carlos Alberto
Published: July 2021

Evaluate the kinetics of hydrogen peroxide (H2O2) degradation, esthetic efficacy and cytotoxicity of a bleaching gel with 35%H2O2 applied on enamel previously covered or not with polymeric nanofibrillar scaffold (SNan), polymeric primer catalyst (PPol), and both. Standardized enamel/dentin discs (n = 128) obtained from bovine teeth were adapted to pulp chambers. After covering enamel with the polymeric products, the bleaching gel was applied for 45 min, establishing the following groups: G1: no treatment (negative control); G2: 35%H2O2 (positive control); G3: SNan; G4: PPol; G5: SNan + PPol; G6: SNan + 35%H2O2; G7: PPol + 35%H2O2; G8: SNan + PPol + 35%H2O2. The kinetics of H2O2 degradation (n = 8), bleaching efficacy (ΔE/ΔWI; n = 8), trans‐amelodentinal cytotoxicity (n = 8), and cell morphology (n = 4) were assessed (ANOVA/Tukey test; p < 0.05). Greater H2O2 degradation occurred in G7 and G8. Bleaching efficacy (ΔE) was higher in G6, G7, and G8 in comparison with G2 (p < 0.05). However, no difference was observed for ΔWI (p > 0.05). G8 presented the lower level of trans‐amelodentinal diffusion of H2O2, oxidative stress, and toxicity to the MDPC‐23 cells (p < 0.05). Polymeric biomaterials increased the kinetics of H2O2 decomposition, as well as maintained the esthetic efficacy and minimized the cytotoxicity caused by a bleaching gel with 35%H2O2.

Clinical Significance

Application of a bleaching gel with 35%H2O2 on enamel previously covered by polymeric biomaterials maintains the esthetic efficacy and reduces the cytotoxicity caused by a single session of in‐office dental bleaching.