bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nasal delivery of single-domain antibodies improves symptoms of SARS-CoV-2 infection in an animal model
Authors: Haga Kei , Takai-Todaka Reiko , Matsumura Yuta , Takano Tomomi , Tojo Takuto , Nagami Atsushi , Ishida Yuki , Masaki Hidekazu , Tsuchiya Masayuki , Ebisudani Toshiki , Sugimoto Shinya , Sato Toshiro , Yasuda Hiroyuki , Fukunaga Koichi , Sawada Akihito , Nemoto Naoto , Song Chihong , Murata Kazuyoshi , Morimoto Takuya , Katayama Kazuhiko 
Published: April 2021

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the disease COVID-19 can lead to serious symptoms, such as severe pneumonia, in the elderly and those with underlying medical conditions. While vaccines are now available, they do not work for everyone and therapeutic drugs are still needed particularly for treating life-threatening conditions. Here, we showed nasal delivery of a new, unmodified camelid single-domain antibody (VHH), termed K-874A, effectively inhibited SARS-CoV-2 titers in infected lungs of Syrian hamsters without causing weight loss and cytokine induction.In vitrostudies demonstrated that K-874A neutralized SARS-CoV-2 in both VeroE6/TMPRSS2 and human lung-derived alveolar organoid cells. Unlike other drug candidates, K-874A blocks viral membrane fusion rather than viral attachment. Cryo-electron microscopy revealed K-874A bound between the receptor binding domain and N-terminal domain of the virus S protein. Further, infected cells treated with K-874A produced fewer virus progeny that were less infective. We propose that direct administration of K-874A to the lung via a nebulizer could be a new treatment for preventing the reinfection of amplified virus in COVID-19 patients.Author summaryVaccines for COVID-19 are now available but therapeutic drugs are still needed to treat life-threatening cases and those who cannot be vaccinated. We discovered a new heavy-chain single-domain antibody that can effectively neutralize the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19. Unlike other drug candidates, which prevent the virus from attaching to the receptor on the host cell, this new antibody acts by blocking the virus membrane from fusing with the host cell membrane. We studied the behavior of the new antibodyin vitrousing VeroE6/TMPRSS2 cells and human lung organoids. When delivered through the nose to infected Syrian hamsters, we found that this antibody could prevent the typical symptoms caused by SARS-CoV-2. Our results are significant because delivering simple drugs directly to infected lungs using a nebulizer could increase the potency of the drugs while reducing the risk of immune reaction that could occur if the drugs escape or are delivered through the blood stream.
Regulation of the Dimerization and Activity of SARS-CoV-2 Main Protease through Reversible Glutathionylation of Cysteine 300
Authors: Davis David A. , Bulut Haydar , Shrestha Prabha , Yaparla Amulya , Jaeger Hannah K. , Hattori Shin-ichiro , Wingfield Paul T. , Mitsuya Hiroaki , Yarchoan Robert 
Published: April 2021

AbstractSARS-CoV-2 encodes main protease (Mpro), an attractive target for therapeutic interventions. We show Mprois susceptible to glutathionylation leading to inhibition of dimerization and activity. Activity of glutathionylated Mprocould be restored with reducing agents or glutaredoxin. Analytical studies demonstrated that glutathionylated Mproprimarily exists as a monomer and that a single modification with glutathione is sufficient to block dimerization and loss of activity. Proteolytic digestions of Mprorevealed Cys300 as a primary target of glutathionylation, and experiments using a C300S Mpromutant revealed that Cys300 is required for inhibition of activity upon Mproglutathionylation. These findings indicate that Mprodimerization and activity can be regulated through reversible glutathionylation of Cys300 and provides a novel target for the development of agents to block Mpro dimerization and activity. This feature of Mpromay have relevance to human disease and the pathophysiology of SARS-CoV-2 in bats, which develop oxidative stress during flight.
Rad53 checkpoint kinase regulation of DNA replication fork rate via Mrc1 phosphorylation
Authors: McClure Allison W. , Diffley John F.X. 
Published: April 2021

SummaryThe Rad53 DNA checkpoint protein kinase plays multiple roles in the budding yeast cell response to DNA replication stress. Key amongst these is its enigmatic role in safeguarding DNA replication forks. Using DNA replication reactions reconstituted with purified proteins, we show Rad53 phosphorylation of Sld3/7 or Dbf4-dependent kinase blocks replication initiation whilst phosphorylation of Mrc1 or Mcm10 slows elongation. Mrc1 phosphorylation is necessary and sufficient to slow replication forks in complete reactions; Mcm10 phosphorylation can also slow replication forks, but only in the absence of unphosphorylated Mrc1. Mrc1 stimulates the unwinding rate of the replicative helicase, CMG, and Rad53 phosphorylation of Mrc1 prevents this. We show that a phosphorylation-mimicking Mrc1 mutant cannot stimulate replicationin vitroand partially rescues the sensitivity of arad53null mutant to genotoxic stressin vivo. Our results show that Rad53 protects replication forks in part by antagonising Mrc1 stimulation of CMG unwinding.
A sensory intervention to improve sleep behaviours and sensory processing behaviours of children with sensory processing disorders
Authors: Spira Geela 
Published: April 2021

Purpose
This paper aims to investigate if a sensory intervention of moderate pressure touch of children with sensory processing disorder (SPD) affects sleep behaviours and sensory processing behaviours.

Design/methodology/approach
A total of 50 children, aged 5–11 years with both SPD and sleep difficulties in Israel, were randomly divided into an experimental and a control group, nonblinded. Participants in the experimental group received three weeks of nightly massage by their parents, with a baseline week on both ends. Parents filled out questionnaires reporting on sensory and sleep behaviours and filled out a nightly sleep log. Parents determined outcome goals using goal attainment scoring. The assessment tools used were the short sensory profile and the child sleep habits questionnaire (Dunn, 1999; Owens et al., 2000).

Findings
Significant improvement was found in the total and subgroup scores of sleep participation measures including sleep onset, sleep anxiety, parasomnias, sleep duration, daytime sleepiness, as well as the total sleep score (F (1,48) = 24.71, p < 0.001).

Originality/value
Results of this study suggest that consistent application of moderate pressure touch as advised or trained by an occupational therapist may be used in clinical practice to improve sleep participation in children with SPD.
Novel fractional hybrid impedance control of series elastic muscle-tendon actuator
Authors: Fotuhi Mohammad Javad , Bingul Zafer 
Published: April 2021

Purpose
This paper aims to develope a novel fractional hybrid impedance control (FHIC) approach for high-sensitive contact stress force tracking control of the series elastic muscle-tendon actuator (SEM-TA) in uncertain environments.

Design/methodology/approach
In three different cases, the fractional parameters of the FHIC were optimized with the particle swarm optimization algorithm. Its adaptability to the pressure of the sole of the foot on real environments such as grass (soft), carpet (medium) and solid floors (hard) is far superior to traditional impedance control. The main aim of this paper is to derive the dynamic simulation models of the SEM-TA, to develop a control architecture allowing for high-sensitive contact stress force control in three cases and to verify the simulation models and the proposed controller with experimental results. The performance of the optimized controllers was evaluated according to these parameters, namely, maximum overshoot, steady-state error, settling time and root mean squared errors of the positions. Moreover, the frequency robustness analysis of the controllers was made in three cases.

Findings
Different simulations and experimental results were conducted to verify the control performance of the controllers. According to the comparative results of the performance, the responses of the proposed controller in simulation and experimental works are very similar.

Originality/value
Origin approach and origin experiment.
Reputation and financial reporting in Finnish public organizations
Authors: Rautiainen Antti , Luoma-aho Vilma 
Published: April 2021

PurposeThis article analyzes the links between financial reports and reputation in the context of Finnish public sector organizations. In general, the paper discusses the accounting treatment of intangible and tangible assets and the quality and relevance of public sector financial reporting.Design/methodology/approachFor data, we combine three data sets: financial statement information of eight anonymous Finnish public organizations, the results of a reputation survey among their key stakeholders (N = 914) and a sample of the social media sentiment around the organizations.FindingsOur findings suggest that a decrease in spending and, surprisingly in the nonprofit sector, an increase in the surplus, indicate better perceived financial performance. An increase in surplus is positively linked with the reputational factors, for example, trust. However, disclosing excessive amounts of information, for example, in financial reporting seems to contribute to negative discussions on social media.Practical implicationsWe highlight the importance of managing intangibles, including those not recognized in the balance sheet, such as reputation. We present three propositions with potential managerial relevance.Originality/valueDespite the considerable amount of financial information disclosed by public sector organizations, few studies have analyzed its relevance or connection to reputation. This first-of-a-kind paper combines intangible and tangible assets by analyzing how financial data and intangible reputation are linked in the public sector accounting context. Six reputational factors were discovered, and financial performance was found to correlate with trust in the public sector.
“Can I go or should I stay?” A theoretical framework of social lock-in during unsatisfactory service encounters
Authors: Volkers Maarten 
Published: April 2021

PurposeThis article demonstrates that the type of service setting and the first interaction with an employee influences the customers' intention to stay or leave during an unsatisfactory service encounter, and that these effects are mediated by social lock-in, which describes the perception of a customer that exiting a service encounter early violates social norms.Design/methodology/approachThe hypotheses are tested with two scenario-based experiments using a collective (theater) and high-contact service (restaurant) (N = 1143; 1485).FindingsThe results suggest that social lock-in and the intention to stay are higher in a closed as opposed to an open setting and that the type of setting is, in fact, more important for the decision to stay than sunk costs. Moreover, customers are more likely to stay after an interaction with an employee.Research limitations/implicationsThis article contributes to the research aimed at explaining customers' decisions to stay or leave during an unsatisfactory service encounter. In doing so, the study highlights the constraining power of social norms in service encounters, which contributes to the research on the relationship between the social context and customers' behavior.Practical implicationsThis study suggests that service providers can manage servicescape cues and employee behavior to influence customers' social lock-in perceptions and their decision to stay on or to leave early.Originality/valueThis is the first study to provide quantitative evidence for social lock-in and its determinants in service encounters.
How over-the-top (OTT) platforms engage young consumers over traditional pay television service? An analysis of changing consumer preferences and gamification
Authors: Sadana Mayank , Sharma Dipasha 
Published: April 2021

Purpose
This paper aims to analyse how the top over-the-top (OTT) platform is becoming a preferred source of entertainment amongst young consumers over traditional Pay TV service (Cable TV/DTH) in India and what factors play a vital role in such preferences along with gamification of content. The study follows the theoretical framework of use and gratifications theory and Niche analysis.

Design/methodology/approach
The study establishes a conceptual framework of understanding the preference of consumers, which triggers the shift from old media to new. This research develops an approach to understanding the relevant implications in responses of consumers through a structured online survey conducted amongst different age groups by applying exploratory and confirmatory factor analysis. To further comprehend the relations between measured variables and constructs, the statistical technique is incorporated, i.e. logistic regression.

Findings
Empirical results and discussion insinuated the five factors which affect consumers’ choices concerning entertainment i.e. content and viewing behaviour, expenses incurred on services, shifts influenced by offerings/incentives, convenience and telecom. Logistic regression validated the strength of these factors which made content and viewing behaviour, expenses incurred on services and convenience the three most important factors.

Research limitations/implications
This study analyses the driving factors that are revolutionising the entertainment industry and can be applied in designing a comfortable and engaging experience for a consumer in the future.

Originality/value
This research is original in nature and the findings of this study are valuable for online streaming services, video-on-demand services, Cable TV operators and entertainment content producers.
Comparing the clinicopathological characteristics of combined hepatocellular–cholangiocarcinoma with those of other primary liver cancers by use of the updated World Health Organization classification
Authors: Yen Chih‐Chieh , Yen Chia‐Jui , Shan Yan‐Shen , Lin Yih‐Jyh , Liu I‐Ting , Huang Hsuan‐Yi , Yeh Matthew M , Chan Shih‐Huang , Tsai Hung‐Wen 
Published: April 2021

AimsCombined hepatocellular–cholangiocarcinoma (cHCC‐CCA) is an uncommon hepatic malignancy with a poor outcome. The 2019 World Health Organization (WHO) classification modified the definition and discarded the subtypes with stem cell features. However, the differences among cHCC‐CCA, hepatocellular carcinoma (HCC), HCC with stem cell/progenitor features (HCCscf) and intrahepatic cholangiocarcinoma (iCCA) remain undetermined. The aim of this study was to investigate the characteristics of cHCC‐CCA in comparison with those of other primary liver cancers by utilising the updated WHO classification.Methods and resultsWe retrospectively analysed 64 cHCC‐CCA patients and 55 HCCscf patients from December 2007 to May 2018. Propensity score matching was conducted to compare these with HCC and iCCA patients. Clinicopathological characteristics, event‐free survival and overall survival were evaluated with multivariate Cox proportional hazard regression. During a median follow‐up of 55.9 months, cHCC‐CCA patients had significantly poorer survival than HCCscf patients, and survival intermediate between that of HCC patients and that of iCCA patients. Hepatitis B virus (HBV) infection and high levels of tumour‐infiltrating lymphocytes (TILs) were associated with favourable survival in cHCC‐CCA patients. In the multivariate analysis, poor hepatic reserve, absence of HBV infection, stage IV disease and low levels of TILs were significant negative prognostic factors in cHCC‐CCA patients. After being pooled with other primary liver cancers, cHCC‐CCA and iCCA resulted in the worse survival.ConclusionscHCC‐CCA patients have survival intermediate between that of HCC patients and iCCA patients, and HBV infection and high levels of TILs predict favourable survival. Our study provides clinical correlations for the new 2019 WHO classification.
FABP5 enhances malignancies of lower‐grade gliomas via canonical activation of NF‐κB signaling
Authors: Wang Yichang , Wahafu Alafate , Wu Wei , Xiang Jianyang , Huo Longwei , Ma Xudong , Wang Ning , Liu Hao , Bai Xiaobin , Xu Dongze , Xie Wanfu , Wang Maode , Wang Jia 
Published: April 2021

AbstractLow‐grade gliomas (LGGs) are grade III gliomas based on the WHO classification with significant genetic heterogeneity and clinical properties. Traditional histological classification of gliomas has been challenged by the improvement of molecular stratification; however, the reproducibility and diagnostic accuracy of LGGs classification still remain poor. Herein, we identified fatty acid binding protein 5 (FABP5) as one of the most enriched genes in malignant LGGs and elevated FABP5 revealed severe outcomes in LGGs. Functionally, lentiviral suppression of FABP5 reduced malignant characters including proliferation, cloning formation, immigration, invasion and TMZ resistance, contrarily, the malignancies of LGGs were enhanced by exogenous overexpression of FABP5. Mechanistically, epithelial‐mesenchymal transition (EMT) was correlated to FABP5 expression in LGGs and tumour necrosis factor α (TNFα)‐dependent NF‐κB signalling was involved in this process. Furthermore, FABP5 induced phosphorylation of inhibitor of nuclear factor kappa‐B kinase α (IKKα) thus activated nuclear factor kappa‐B (NF‐κB) signalling. Taken together, our study indicated that FABP5 enhances malignancies of LGGs through canonical activation of NF‐κB signalling, which could be used as individualized prognostic biomarker and potential therapeutic target of LGGs.
Comparison of patients’ and staff’s perspectives on the causes of violence and aggression in psychiatric inpatient settings: An integrative review
Authors: Fletcher Alice , Crowe Marie , Manuel Jenni , Foulds James 
Published: April 2021

Accessible summaryWhat is known on the subject?

Aggression and violence are persistent problems in psychiatric inpatient units.

Violence preventive factors have been identified from both staff's and patients’ perspectives.

Violent and aggressive inpatient incidents have not been adequately explained in research and reviews to date.

What this paper adds to existing knowledge?

This review is novel in that it provides a comparison of patients’ and staff's perspectives and identified that these differ and were influenced by factors attributable to the inpatient culture.

The one contributory factor both agreed upon was the role of staff's interpersonal skills in either exacerbating or de‐escalating aggression and violence.

The inpatient culture was found to engender differing perceptions of most contributory factors to violence and aggression.

What are the implications for practice?

While staff's interpersonal skills were identified as a primary influence on whether their interaction with patients contributed to aggression and violence, this was shaped by the inpatient environment's culture.

Patient‐centred interactional skills need to focus on the patients’ needs for respect and active participation rather than engendering feelings of disrespect or coercion.

Patient‐centred communication skills that demonstrate an understanding of the patient's experience in the inpatient environment need to be core skills for mental health nurses.

AbstractIntroductionHigh rates of aggression and violence are a persistent problem in inpatient mental health environments. A comparison of staff's and patients’ perceptions of the causes may provide novel insights.AimThis review aimed to compare patients’ and staff's perspectives on the causes of aggression and violence in inpatient environments.MethodAn integrative review of the literature was conducted with a search of Ovid (Medline, Embase, PsycINFO) databases and manual searching.ResultsThirty articles met criteria for inclusion. Interactions prior to aggressive or violent incidents were characterized by patients as disrespectful and coercive, and by staff as indicative of the patient's mental state or personality. Both groups identified the importance of patient‐centred communication skills.DiscussionThe review identified that patients and staff have differing perspectives on the causes of violence and aggression. There was an interactional dynamic between staff and patients that was shaped by the culture of the inpatient setting.Implications for PracticeUnderstanding how the inpatient culture plays a role in shaping a dynamic between patients and staff and developing communication skills that acknowledge this may help reduce violence and aggression in inpatient settings.
SLI1 confers broad‐spectrum resistance to phloem‐feeding insects
Authors: Kloth Karen J. , Shah Parth , Broekgaarden Colette , Ström Cecilia , Albrectsen Benedicte R. , Dicke Marcel 
Published: April 2021

AbstractResistance (R) genes usually compete in a coevolutionary arms race with reciprocal effectors to confer strain‐specific resistance to pathogens or herbivorous insects. Here, we investigate the specificity of SLI1, a recently identified R gene in Arabidopsis that encodes a small heat shock‐like protein involved in resistance to Myzus persicae aphids. In a panel with several aphid and whitefly species, SLI1 compromised reproductive rates of three species: the tobacco aphid M. persicae nicotianae, the cabbage aphid Brevicoryne brassicae and the cabbage whitefly Aleyrodes proletella. Electrical penetration graph recording of aphid behaviour, revealed shorter salivations and a 3‐to‐5‐fold increase in phloem feeding on sli1 loss‐of‐function plants. The mustard aphid Lipaphis erysimi and Bemisia tabaci whitefly were not affected by SLI1. Unlike the other two aphid species, L. erysimi exhibited repetitive salivations preceding successful phloem feeding, indicating a role of salivary effectors in overcoming SLI1‐mediated resistance. Microscopic characterization showed that SLI1 proteins localize in the sieve tubes of virtually all above‐ and below‐ground tissues and co‐localize with the aphid stylet tip after penetration of the sieve element plasma membrane. These observations reveal an unconventional R gene that escapes the paradigm of strain specificity and confers broad‐spectrum quantitative resistance to phloem‐feeding insects.