bluuebunny/crossref_metadata_2025 huggingface dataset:
UnityMol prototype for FAIR sharing of molecular-visualization experiences: from pictures in the cloud to collaborative virtual reality exploration in immersive 3D environments
Authors: Martinez Xavier , Baaden Marc
Published: May 2021

Motivated by the current COVID-19 pandemic, which has spurred a substantial flow of structural data, the use of molecular-visualization experiences to make these data sets accessible to a broad audience is described. Using a variety of technology vectors related to the cloud, 3D and virtual reality gear, how to share curated visualizations of structural biology, modeling and/or bioinformatics data sets for interactive and collaborative exploration is examined. FAIR is discussed as an overarching principle for sharing such visualizations. Four initial example scenes related to recent COVID-19 structural data are provided, together with a ready-to-use (and share) implementation in the UnityMol software.
Identification and fermentative properties of an indigenous strain ofWickerhamomyces anomalusisolated fromRosa roxburghiiTratt
Authors: Liu Xiaozhu , Li Yinfeng , Zhao Hubing , Yu Zhihai , Hardie William James , Huang Mingzheng
Published: May 2021

Purpose

The purpose of this paper is to identify and analyse the fermentative properties of a strain of indigenousWickerhamomyces anomalus(W. anomalus) fromRosa roxburghiiTratt (R. roxburghii).

Design/methodology/approach

Morphological and molecular methods were used to determine the species of the selected strainW. anomalusC11. The physiological tolerances to glucose, ethanol, citric acid and sulphur dioxide (SO2) were further assessed by checking the growth of cells, and the oenological performances were proved to measure the related fermentative properties ofR. roxburghiiwines.

Findings

TheW. anomalusC11 strain could be grown faster than commercialS. cerevisiaeX16 in its logarithmic growth period and had preferable tolerances to glucose, ethanol, citric acid and SO2. Moreover, this strain of nativeR. roxburghiiyeastW. anomalusC11 produced less sulphuretted hydrogen and had a higherβ-glucosidase activity. Furthermore,W. anomalusC11 could reduce the volatile acids, reduce the sourness and enhance volatile aroma richness and complexity ofR. roxburghiiwines including types of aroma and content thereof. Taken together, theR. roxburghiinative yeastW. anomalusC11 may have potential for use inR. roxburghiiwinemaking.

Originality/value

(1) The fermentative properties of a strain of indigenousW. anomalus(named as C11) fromR. roxburghiiwas evaluated. (2) The strain ofW. anomalusC11 had preferable tolerances to glucose, ethanol, citric acid and SO2. (3) This strain of nativeR. roxburghiiyeastW. anomalusC11 produced less sulphuretted hydrogen and had a higherß-glucosidase activity. (4)W. anomalusC11 could reduce the volatile acids, reduce the sourness and enhance volatile aroma richness and complexity ofR. roxburghiiwines including types of aroma and content thereof.
How to increase job satisfaction: the role of participative decisions and feeling trusted
Authors: Guinot Jacob , Monfort Adrián , Chiva Ricardo
Published: May 2021

Purpose

In the last few years a new management style and paradigm has emerged with the aim of improving employee motivation, commitment and satisfaction through participatory management practices and more democratic organizational structures. Based on this new paradigm, this study examines the consequences of participative decision making for job satisfaction and trust.

Design/methodology/approach

To examine the proposed relationships structural equation modelling was used on a sample of 3,364 employees conducted by the European Foundation for the Improvement of Living and Working Conditions (Eurofound).

Findings

Results confirm that participative decisions positively influence job satisfaction both directly and indirectly by means of employees' perception of trust.

Originality/value

Based on democratic management style, this study shows how participative decisions and trust can increase job satisfaction.
Season ticket holder segmentation in professional sports: an application of the sports relationship marketing model
Authors: Finch David J. , Abeza Gashaw , O'Reilly Norm , Nadeau John , Levallet Nadège , Legg David , Foster Bill
Published: May 2021

Purpose

The segmentation of customers into homogeneous groups is well researched, reflecting its importance to marketers. Specific to professional sports, published research on customer segmentation first occurred in the early 2000s, but no studies exist based on internal data from season ticket holders, an attractive and loyal customer group which is the most important customer for professional sports teams. Thus, the purpose of this research was to fill this gap in the literature through a sequential study of season ticket holders of a professional sports club.

Design/methodology/approach

Study 1 employed six focus groups (n = 56) to determine the constructs, understand the issues, and sequentially inform the survey instrument for the second study. Study 2 used an online survey (n = 1,007) to collect data on factors including socio-demographics, consumption, media engagement, fan satisfaction, future intentions and sports fan motivation.

Findings

The results identified the engagement factors and selection variables which drive season ticket holder purchase and allowed for the segmentation analysis, which identified fourteen unique fan segments for a professional sports club, generalizable to other clubs.

Originality/value

The identification of 14 segments of season ticket holders based on a sequential study framed by the sports relationship marketing model is a needed contribution for practice (i.e. a specific direction on how to efficiently allocate resources when marketing to season ticket holders) and advances our conceptual knowledge by applying the model to the context of the most loyal customers in professional sports season ticket holders.
Metacognition as a core skill for wise decision-making in higher education: investigating gender differences
Authors: Abedini Yasamin
Published: May 2021

Purpose

The present study aimed to predict department heads' wisdom in Tehran universities based on their metacognitive beliefs and gender.

Design/methodology/approach

The study employed a nonexperimental design. The statistical population consisted of all male and female heads of departments in Tehran universities, among whom 150 participants were selected using Morgan's table and via the random sampling method. The research instruments were the Meta-Cognitive Beliefs Questionnaire (Wells, 1997) and the Wisdom Scale (Schmitet al., 2012). The data were analyzed using multiple regression analysis and independent-samplest-test.

Findings

The total scores of male and female principals were significantly different in the two scales and some of their subscales. The metacognitive beliefs scale and its components were good and significant predictors of the principals' wisdom. Cognitive self-awareness was the best positive predictor, and positive beliefs about worries were the best negative predictor for their wisdom.

Practical implications

Wise department heads are usually more empathetic, and this makes their decisions for the well-being and satisfaction of their colleagues as well as the students. Therefore, when faculty members are more satisfied and relaxed, they can do their teaching better and establish more effective relationships with their students. They should also be more motivated to do scientific research studies. Because wise managers are happier and more relaxed, they can focus more on solving educational problems in their department, and this, in turn, improves the educational quality of their department. The higher the quality of the university educational system, the less stress and the more mental health the students will have. Students in such educational environments are more focused on learning courses and gain better expertise. These students will provide more specialized services to the community in the future.

Social implications

Wisdom is associated with better contributing to a happy life, and as a result, we have a healthier and more productive society.

Originality/value

It can be concluded that positive metacognitive knowledge, such as cognitive self-awareness via affecting the principals' mental awareness and regulating thoughts, and negative metacognitive experiences, such as worrying about the future, low meta memory and sensitive-obsessive control negatively affecting their affective and cognitive states, affect the principals' decisions and behaviors in educational settings. According to the results of this research, university presidents can hold workshops to increases metacognitive skills to their administrators and teachers. Also, the results of the present study can help the heads of university departments to establish more constructive and effective relationships with the faculty members and students by strengthening their metacognitive skills.
The lost generation of entrepreneurs? The impact of COVID-19 on the availability of risk capital in Canada
Authors: Croteau Martin , Grant Kenneth A. , Rojas Claudio , Abdelhamid Hadeer
Published: May 2021

Purpose

Canada has lagged in access to capital for high-potential, growth-oriented new ventures, but has made considerable strides in the past decade. This study aims to examine the evolving state of the market for risk capital in Canada during the COVID-19 pandemic, providing a critical assessment of government policy from the perspective of angel investors and diverse communities of entrepreneurs.

Design/methodology/approach

A thematic analysis was conducted of seven COVID-19 roundtable discussions hosted by the National Angel Capital Organization that included 51 global and national-level business and political leaders. The analysis extracted the most salient details from the discussions, distilling them into timely and actionable insights for policymakers.

Findings

The analysis suggests that the government’s economic policy response to the COVID-19 crisis fails to address the sudden liquidity problems faced by new ventures. Entrepreneurs and angel investors have remained resilient, rallied as a community and demonstrated an extraordinary level of trust. Traditionally under-represented communities of entrepreneurs are more affected by the crisis than others.

Practical implications

The findings and recommendations are of relevance to policymakers interested in post-COVID-19 economic policies to address the unique challenges faced by start-ups and ensure their full contribution to economic recovery.

Originality/value

The paper presents several policy recommendations and proposes a novel framework to describe the impacts of the pandemic on different categories of start-ups.
How top management's environmental awareness affect corporate green competitive advantage: evidence from China
Authors: Cao Cuizhen , Tong Xiujun , Chen Yunqi , Zhang Yue
Published: May 2021

Purpose

Green ambidexterity innovation and green competitive advantage are of great significance to enterprises' sustainable development. From the perspective of upper echelons theory, This paper aims to investigate the role of top managers in gaining green competitive advantage and the intermediary effect of the green ambidexterity innovation between them.

Design/methodology/approach

This paper uses empirical data from heavily polluting enterprises in China for constructing a model to infer how enterprises achieve the green competitive advantage.

Findings

The paper shows that (a) top managers' environmental awareness and the green ambidexterity innovation are both positively related to the green competitive advantage of enterprises, while there is a difference between the exploitative green innovation and the exploratory green innovation regarding the heterogeneity; the positive effect of the exploratory green innovation on enterprises' green competitive advantage is greater than that of the exploitative green innovation; (b) the green ambidexterity innovation plays a partial intermediary effect between top managers' environmental awareness and enterprises' green competitive advantage and (c) strategic flexibility positively moderates the relation between the green ambidexterity innovation and the green competitive advantage. The study concludes that top managers' environmental awareness has a significantly positive impact on reinforcing green competitive advantages and adopting the green ambidexterity innovation for heavily polluting enterprises in China.

Originality/value

This paper contributes to the green innovation management literature by offering a theoretical framework for examining how top managers' environmental awareness influences enterprises' green competitive advantage.
Bridging the learning divide: the role of institutional WOM in stimulating emerging countries’ SMEs internationalization
Authors: Aliedan Meqbel
Published: May 2021

Purpose

The purpose of this study is to explore the relationship between experiential knowledge of foreign markets, institutional word of mouth (WOM) and small and medium enterprises’ (SMEs’) internationalization. Specifically, it aims to provide explanations of what and how cross-border experiential knowledge can be institutionally transmitted for SMEs’ internationalization purposes via WOM.

Design/methodology/approach

An exploratory approach was adopted within the phenomenological/qualitative research tradition. The data collection process was conducted through 23 semi-structured interviews with founders and chief executive officers of Saudi international SMEs.

Findings

The study’s findings confirm that SMEs seeking productive opportunities in the international market could improve their internationalization experience if they made proper use of institutional WOM as a catalyst for inter-firm learning. This concerns SMEs from emerging countries in particular as they are usually in a bid to legitimatize their presence in foreign markets.

Originality/value

The triadic relationship between experiential knowledge, institutional WOM and internationalization has not been previously researched. The current study, therefore, clearly adds value to the concept of WOM from three dimensions: institutionalization, cross-borderity and SMEs’ internationalization.
Tourism in the post COVID-19 era: evidence from hotels in the North East of England
Authors: Spanaki Maria Zoi , Papatheodorou Andreas , Pappas Nikolaos
Published: May 2021

Purpose

This paper aims to examine developments in tourism during the COVID-19 pandemic using the hotel sector in the North-East of England as the area of study. The country has attracted a lot of attention not only because of its importance as a tourism destination but also due to its rather controversial management of the pandemic at least in its early stages.

Design/methodology/approach

Fifteen semi-structured interviews based on ten open-ended questions were conducted with North East of England-based hotel managers of international brands on the level of their hotels’ preparedness to effectively deal with pandemic cases. The interviews took place in August and September 2020 with participants kept anonymous.

Findings

Meeting new operational and bureaucratic requirements added to the cost structure and proved a major challenge for managers who saw their hotel occupancy rates and revenue collapsing within a short period of time. Innovative and aggressive pricing strategies were introduced to lure especially younger travelers in the absence of business clientele. Staff were made redundant and/or asked to work overtime making effective human resource management very difficult.

Originality/value

This is one of the first research attempts to highlight the importance of the COVID-19 pandemic for the hotel sector in a major region of the UK. The paper also attempts some generalization by discussing managerial implications and suggesting a possible way forward for the hotel sector. Developing resilience by building on previously used successful business practices proves of essence.
Disaster management in Indonesian tourist destinations: how institutional roles and community resilience are mediated
Authors: Rahmafitria Fitri , Sukmayadi Vidi , Suryadi Karim , Rosyidie Arief
Published: May 2021

Purpose

This paper attempts to evaluate the current collaborative model of disaster management initiated by the Indonesian Government at the regional level. The paper aims at providing recommendations for a more functional model of local communities' resilience by promoting the synergy of roles among the community, industry and local government.

Design/methodology/approach

To achieve the study objective, the authors conducted the qualitative approach. The study used The Hyogo Framework to Action (HFA) 2000–2015 disaster management approach. The HFA approach contains substances of disaster management guidelines on social, economic and environmental aspects, as well as the strategies for implementing the guidelines.

Findings

The study's findings have indicated that substandard institutions can hamper collaborative processes and lower the level of community resilience. A collaborative model can appropriately operate when the formal institution plays its role as the central coordinator and ensures that transparency, decision-making and representation are met. Furthermore, the community and formal educational institutions are essentials as the foundation of building community resilience.

Practical implications

This study was limited to a case study in an Indonesian popular tourist destination. Hence, it could be extended by conducting comparative studies with other destinations in developing countries to explore their disaster management and the government involvement in each respective countries.

Social implications

This study was limited to a case study in an Indonesian popular tourist destination. Hence, it could be extended by conducting comparative studies with other destinations in developing countries to explore their disaster management and government involvement in each respective country.

Originality/value

In this paper, the authors propose a novel approach to improve the current disaster management model. The proposed approach focuses on designing an institutional model for tourism destinations' disaster management, where the stakeholders are less-functional in working collaboratively. The study findings suggest that educational institutions and disaster communities must take the mediator role in bridging knowledge transfer among the government, the community and the tourism industry.
The Israeli travel and tourism industry faces COVID-19: developing guidelines for facilitating and maintaining a nuanced response and recovery to the pandemic
Authors: Schmidt Joshua , Altshuler Alex
Published: May 2021

Purpose

This paper aims to discuss how the tourism industry is contending with the economic and interorganizational challenges wrought by the COVID-19 outbreak and heightened by a lack of communication between the government and local businesses in the state of Israel. The researchers examine the dependency of the tourism industry on the general preparation programs that were developed and are currently being deployed by the relevant national stakeholders and question whether instead, it should use the pandemic as a catalyst for formulating its own nuanced tourism-travel-and-hospitality-oriented strategies and procedures.

Design/methodology/approach

Applying an ethnographic-based mix-methods research approach, this paper draws on insights from data compiled by fusing existing theoretical and emerging practical knowledge with empirical research (qualitative and quantitative) conducted among numerous relevant macro (governmental/centralized industry) and micro (hotels, travel and tourism operators and service providers) stakeholders as well as potential consumers.

Findings

It is essential that national and local government bodies form collaborative interorganizational relationships with local stakeholders to jointly activate case-specific hospitality and travel-specific risk mitigation management strategies. Moreover, the pandemic laid bare the tentative and fragile nature of the globalized tourism industry supply and demand chains, a condition that may be remedied via a pivot toward using national or even regional supply chains and goods and service providers. Within Israel, such changes could lead to increased economic benefits that extend beyond the tourism industry to provide certain security-related benefits.

Originality/value

Relating to idiosyncratic factors relevant to an Israeli cultural context, this paper uses the ethnographic field-borne familiarity of the researchers with the tourism and travel industries in Eilat and the Dead Sea to offer applicable suggestions for leveraging certain industry resources to both meet the demands of the present-day circumstances and cultivate a multifaceted organizational web of macro and micro social, economic and environmental networks so as to foster a more diversified and therefore resilient local tourism and travel economy.
Symptomatic improvement after mesh removal: a prospective longitudinal study of women with urogynaecological mesh complications
Authors: Pace N , Artsen A , Baranski L , Palcsey S , Durst R , Meyn L , Moalli PA
Published: May 2021

Objective

To compare clinical characteristics and outcomes in patients undergoing excision of polypropylene urogynaecological mesh for pain, mesh exposure or both.

Design

Prospective, longitudinal cohort.

Setting

Academic tertiary referral centre.

Population

Women undergoing complete vaginal mesh excision for mesh exposure and/or pain.

Methods

Clinical and patient‐reported outcomes assessing pain (visual analog scale, VAS), bother (Pelvic Floor Distress Inventory, PFDI) and functional impact (Pelvic Functional Impact Questionnaire, PFIQ) were collected at baseline, 6, 12 and 24 months after complete mesh excision. Outcomes were compared by mesh type (sling, prolapse [transvaginal or sacrocolpopexy mesh], both) and complication (pain, exposure, both).

Main outcome measures

‘Much better’ or ‘Very much better’ on Patient Global Impression of Improvement (PGI‐I) up to 2 years after removal.

Results

Of 173 women, 48 underwent removal for pain, 27 for exposure and 98 for exposure plus pain. ‘Moderate to severe’ baseline symptoms were reported by 75%; the most prevalent and severe symptom was dyspareunia. Patients with pain alone were most bothered (PFDI median 234.2, interquartile range 83, P = 0.02) and had the highest functional impact (PFIQ median 181, interquartile range 138, P < 0.001). After excision, only 33.3% of women with pain alone reported ‘improved’ symptoms (PGI‐I), versus 73.9% with exposure, 58.3% with exposure plus pain (P = 0.03) with no differences in PGI‐I by mesh type. VAS scores decreased in all groups, but PFDI and PFIQ did not improve in pain patients.

Conclusions

In women experiencing a pain complication after urogynaecological mesh insertion, mesh removal often does not improve symptoms.

Tweetable abstract

Only 33% of women with pain complications have improved symptoms after urogynaecological mesh removal.
Important research outcomes for treatment studies of perinatal depression: systematic overview and development of a core outcome set
Authors: Hellberg C , Österberg M , Jonsson AK , Fundell S , Trönnberg F , Jonsson M , Skalkidou A
Published: May 2021

Objective

To develop a Core Outcome Set (COS) for treatment of perinatal depression.

Design

Systematic overview of outcomes reported in the literature and consensus development study.

Setting

International.

Population

Two hundred and twenty‐two participants, mainly patients, healthcare professionals and researchers, representing 13 countries.

Methods

A systematic overview of outcomes reported in recently published research, a two‐round Delphi survey and a consensus meeting at which the final COS was decided using modified nominal group technique.

Main results

In the literature search, 1772 abstracts were identified and evaluated, and 165 studies were finally included in the review. In all, 106 outcomes were identified and included in the Delphi survey. In all, 222 participants registered for the first round of the Delphi survey and 151 (68%) responded. In the second round, 123 (55%) participants responded. Thirteen participants attended the consensus meeting, where the following nine outcomes were agreed upon for inclusion in the final COS: self‐assessed symptoms of depression, diagnosis of depression by a clinician, parent to infant bonding, self‐assessed symptoms of anxiety, quality of life, satisfaction with intervention, suicidal thoughts, attempted or committed suicide, thoughts of harming the baby, and adverse events.

Conclusions

The relevant stakeholders prioritised outcomes and reached consensus on a COS comprising nine outcomes. We expect that this COS will contribute to the consistency and uniformity of outcome selection and reporting in future clinical trials involving treatment of perinatal depression.

Tweetable abstract

Development of a core outcome set regarding treatment for perinatal depression by @SBU_en.
Quantifying the rate of recurrence of postoperative Crohn's disease with biological therapy. A meta‐analysis
Authors: Jain Sneha R. , Ow Zachariah G. W. , Chin Yip H. , Lim Wen H. , Kong Gwyneth , Tham Hui Y. , Wong Neng W. , Chong Choon S. , Foo Fung J. , Chan Webber P. W.
Published: May 2021

Objective

Preventing the postoperative recurrence (POR) of Crohn's disease (CD) poses a significant challenge to clinicians. With the advent of biologics, various studies have observed a reduction of recurrence after surgery. Hence, we performed a systematic review and meta‐analysis to identify the rate of POR at different time points in the era of biologic use.

Methods

We performed a literature search using Medline and Embase databases for studies investigating biologics in preventing the POR of CD. Data were extracted, and a single‐arm meta‐analysis with generalized linear mixed model and Clopper‐Pearson method for confidence interval (CI) was performed to identify endoscopic, clinical and surgical recurrence rates at 6 months and 1, 2 and 5 years postoperatively.

Results

Altogether 24 studies were included in the meta‐analysis. The endoscopic, clinical and surgical POR rate with the use of anti‐tumor necrosis factor (TNF)‐α agents at 1 year was 21.72% (95% CI 16.28%‐28.37%), 13.06% (95% CI 8.18%‐18.92%) and 3.76% (95% CI 1.37%‐9.91%), respectively. The 5‐year recurrence rate was 84.21% (95% CI 72.35%‐91.57%) and 17.49% (95% CI 9.17%‐30.80%) for endoscopic and surgical recurrence, respectively. Subgroup analyses at 1 year for the type of anti‐TNF‐α agent or the timing of initiation after surgery showed no significant difference in endoscopic, clinical and surgical recurrence rates.

Conclusions

Anti‐TNF‐α agents are effective at preventing clinical, endoscopic and surgical POR of CD. The timing of initiating biological therapy after surgery has no significant effect on the rate of POR. The efficacy of infliximab and adalimumab for postoperative recurrence prevention is similar.
Durable virological response and functional cure of chronic hepatitis D after long‐term peginterferon therapy
Authors: Hercun Julian , Kim Grace E. , Da Ben L. , Rotman Yaron , Kleiner David E. , Chang Richard , Glenn Jeffrey S. , Hoofnagle Jay H. , Koh Christopher , Heller Theo
Published: May 2021

Background

Hepatitis delta virus (HDV) infection is the most aggressive form of chronic viral hepatitis. Response rates to therapy with 1‐ to 2‐year courses of pegylated interferon alpha (peginterferon) treatment are suboptimal.

Aims

To evaluate the long‐term outcomes of patients with chronic hepatitis D after an extended course of peginterferon.

Methods

Patients were followed after completion of trial NCT00023322 and classified based on virological response defined as loss of detectable serum HDV RNA at last follow‐up. During extended follow‐up, survival and liver‐related events were recorded.

Results

All 12 patients who received more than 6 months of peginterferon in the original study were included in this analysis. The cohort was mostly white (83%) and male (92%) and ranged in age from 18 to 58 years (mean = 42.6). Most patients had advanced but compensated liver disease at baseline, a median HBV DNA level of 536 IU per mL and median HDV RNA level of 6.86 log10 genome equivalents per mL. The treatment duration averaged 6.1 years (range 0.8‐14.3) with a total follow‐up of 8.8 years (range 1.7‐17.6). At last follow‐up, seven (58%) patients had durable undetectable HDV RNA in serum, and four (33%) cleared HBsAg. Overall, one of seven (14%) responders died or had a liver‐related event vs four of five (80%) non‐responders.

Conclusions

With further follow‐up, an extended course of peginterferon therapy was found to result in sustained clearance of HDV RNA and favourable clinical outcomes in more than half of patients and loss of HBsAg in a third.
Feeling the refugee camp: Affectual research, bodies, and suspicion
Authors: Brankamp Hanno
Published: May 2021

This paper advances debates in camp geographies and forced migration studies by centring the methodological import of emotions and affect in research on refugee camps. Camps are often spatial expressions of compassion, fear, care, suspicion, but also incubate hope, solidarity, and feelings of belonging among encamped communities. Researchers are never insulated from these complex emotions and affects. While qualitative, ethnographic, experiential, or otherwise sensory methods continue to be widely used in this field of study, the emotional entanglements that arise from the embodied encounters between researchers, residents, and camp spaces are not yet well understood. The paper argues that it is methodologically pertinent to not simply incorporate such affectual intensities into existing readings of the camp as an exceptional space, but to understand people's differentially experienced feelings as actively shaping the camp's geography. It illustrates this argument by engaging with feelings of suspicion that pervaded my long‐term ethnographic fieldwork in Kakuma refugee camp in Kenya. Ultimately, the paper urges scholars to explore camps beyond their known capacities for controlling mobility and motion as spaces that are also imbued with feelings and sensibilities.
Pharmacokinetics of capmatinib in participants with hepatic impairment: A phase 1, open‐label, single‐dose, parallel‐group study
Authors: Chen Xinhui , Cui Xiaoming , Pognan Nathalie , Quinlan Michelle , Kapoor Shruti , Rahmanzadeh Gholamreza , Giovannini Monica , Marbury Thomas C.
Published: May 2021

Aims

Capmatinib, a mesenchymal–epithelial transition factor tyrosine kinase inhibitor, is metabolized by cytochrome P450 (CYP) 3A4 and aldehyde oxidase. In individuals with hepatic impairment, alterations in hepatobiliary excretion and metabolism could lead to higher capmatinib exposure. We compared the pharmacokinetics of a single oral dose of capmatinib 200 mg administered to participants with varying degrees of hepatic impairment vs. matched controls with normal hepatic function.

Methods

This phase 1, multicentre, open‐label, parallel‐group study enrolled adult participants with normal hepatic function and mild, moderate and severe hepatic impairments. Eligible participants received a single oral dose of 200 mg capmatinib. The pharmacokinetic parameters of capmatinib were analysed and compared across participants with impaired and normal hepatic function.

Results

Of 31 enrolled participants, 29 had an evaluable pharmacokinetic profile: normal (n = 9); mild (n = 6); moderate (n = 8); severe (n = 6). Compared with the normal group, geometric mean (GM) maximum (peak) observed plasma drug concentration after single‐dose administration decreased by 27.6% in the mild group (GM ratio [GMR] = 0.724; 90% confidence interval [CI]: 0.476–1.10), by 17.2% in the moderate group (GMR = 0.828; 90% CI: 0.563–1.22) and remained unchanged in the severe group (GMR = 1.02; 90% CI: 0.669–1.55). Compared with the normal group, GM area under the plasma concentration–time curve from time zero to infinity decreased by 23.3% in the mild group (GMR = 0.767; 90% CI: 0.532–1.11), by 8.6% in the moderate group (GMR = 0.914; 90% CI: 0.652–1.28) and increased by 24% in the severe group (GMR = 1.24; 90% CI: 0.858–1.78).

Conclusion

Mild, moderate and severe hepatic impairment did not have a clinically relevant impact on capmatinib pharmacokinetics. No new safety findings are reported in this study.
DNA and modified vaccinia Ankara prime–boost vaccination generates strong CD8+ T cell responses against minor histocompatibility antigen HA‐1
Authors: Eldershaw Suzy A. , Pearce Hayden , Inman Charlotte F. , Piper Karen P. , Abbotts Ben , Stephens Christine , Nicol Samantha , Croft Wayne , Powell Richard , Begum Jusnara , Taylor Graham , Nunnick Jane , Walsh Donna , Sirovica Mirjana , Saddique Shamyla , Nagra Sandeep , Ferguson Paul , Moss Paul , Malladi Ram
Published: May 2021

Allogeneic immune responses underlie the graft‐versus‐leukaemia effect of stem cell transplantation, but disease relapse occurs in many patients. Minor histocompatibility antigen (mHAg) peptides mediate alloreactive T cell responses and induce graft‐versus‐leukaemia responses when expressed on patient haematopoietic tissue. We vaccinated nine HA‐1‐negative donors against HA‐1 with a ‘prime–boost’ protocol of either two or three DNA ‘priming’ vaccinations prior to ‘boost’ with modified vaccinia Ankara (MVA). HA‐1‐specific CD8+ T cell responses were observed in seven donors with magnitude up to 1·5% of total CD8+ T cell repertoire. HA‐1‐specific responses peaked two weeks post‐MVA challenge and were measurable in most donors after 12 months. HA‐1‐specific T cells demonstrated strong cytotoxic activity and lysed target cells with endogenous HA‐1 protein expression. The pattern of T cell receptor (TCR) usage by HA‐1‐specific T cells revealed strong conservation of T cell receptor beta variable 7‐9 (TRBV7‐9) usage between donors. These findings describe one of the strongest primary peptide‐specific CD8+ T cell responses yet recorded to a DNA–MVA prime–boost regimen and this may reflect the strong immunogenicity of mHAg peptides. Prime–boost vaccination in donors or patients may prove of substantial benefit in boosting graft‐versus‐leukaemia responses.
Discovery of novel antibacterial agents: Recent developments in D‐alanyl‐D‐alanine ligase inhibitors
Authors: Qin Yinhui , Xu Linlin , Teng Yuetai , Wang Yinhu , Ma Peizhi
Published: May 2021

Bacterial infections can cause serious problems that threaten public health over a long period of time. Moreover, the continuous emergence of drug‐resistant bacteria necessitates the development of novel antibacterial agents. D‐alanyl‐D‐alanine ligase (Ddl) is an indispensable adenosine triphosphate‐dependent bacterial enzyme involved in the biosynthesis of peptidoglycan precursor, which catalyzes the ligation of two D‐alanine molecules into one D‐alanyl‐D‐alanine dipeptide. This dipeptide is an essential component of the intracellular peptidoglycan precursor, uridine diphospho‐N‐acetylmuramic acid (UDP‐MurNAc)‐pentapeptide, that maintains the integrity of the bacterial cell wall by cross‐linking the peptidoglycan chain, and is crucial for the survival of pathogens. Consequently, Ddl is expected to be a promising target for the development of antibacterial agents. In this review, we present a brief introduction regarding the structure and function of Ddl, as well as an overview of the various Ddl inhibitors currently being used as antibacterial agents, specifically highlighting their inhibitory activities, structure–activity relationships and mechanisms of action.
Trends in the clinical features of amyotrophic lateral sclerosis: A 14‐year Chinese cohort study
Authors: Chen Lu , Xu Lu , Tang Lu , Xia Kailin , Tian Danyang , Zhang Gan , Wang Yajun , Yu Zhou , Ma Jingyue , Zhang Yixuan , Wang Fan , Sun Can , Zhang Gaoqi , Fu Jiayu , Jiao Lin , Yilihamu Mubalake , Wang Shengfeng , Zhan Siyan , Fan Dongsheng
Published: May 2021

Background and purpose

The aim was to determine the transitional patterns in the clinical characteristics, treatments and comorbidities in amyotrophic lateral sclerosis (ALS) patients over the past 14 years using data from a large clinical cohort in mainland China.

Methods

Sporadic ALS patients who visited the Peking University Third Hospital from January 2005 to December 2018 were included in this study. The 14 years were divided into three periods, and changes in the baseline characteristics of the participants were analyzed at 5‐year intervals.

Results

In total, 3410 patients with sporadic ALS were recruited: 2181 were men and 1229 were women. The proportion of patients with bulbar‐onset ALS increased from 13.0% in 2005–2009 to 19.5% in 2015–2018 (p < 0.001). The mean (standard deviation) age at onset increased from 49.5 (11.4) years in 2005–2009 to 53.0 (11.0) years in 2015–2018 (p < 0.001). ALS patients with diabetes or hypertension showed a delay in ALS onset, and the delay was even more apparent when the patients had both comorbidities. The proportion of riluzole users in 2015–2018 was approximately 2.5‐fold of that in 2005–2009 (p < 0.001).

Conclusions

In the context of a lack of clinical data on ALS in mainland China, this study evaluated a large cohort of patients diagnosed over a 14‐year period. The age at onset and percentage of patients who used riluzole both increased over the study period. Additionally, it was found that patients with comorbidities such as diabetes and hypertension had a delayed age of ALS onset.
Evaluation of 3D design lower limb exoskeleton on human musculoskeletal with various loads
Authors: Sohane Anurag , Agarwal Ravinder
Published: May 2021

The surface electromyography (SEMG) based exoskeleton presents a new opportunity for human augmentation and rehabilitation. Developing an efficient exoskeleton in real‐time is challenging as each individual's muscles and joint forces are unique. The aim of this research article is to analyze and evaluate the design of the lower limb exoskeleton during the squatting movement in a simulated environment to address problems concerning the development of a functional exoskeleton for an individual. An exoskeleton was designed in SolidWorks CAD software and imported into AnyBody Modelling Software (AMS). Thereafter, the performance of 3D designed exoskeleton was evaluated by placing various loads (0:5:25 kg) on both the shoulders of the human musculoskeletal. The results show the force in the knee muscles with the assistance of the exoskeleton were reduced significantly by 65.18–97.20% in the biceps femoris, 50.01–33.16% in the rectus femoris, 41.87–28.31% in the vastus lateralis, 42.25–28.78% in the vastus medialis, 7.28–22.91% in gluteus medius, and 22.54–13.13% in semitendinosus. The force in the knee joint was reduced by 44.04–31.43% as the load increases. Individual muscle force estimated from the SEMG signal and AMS during squatting was also compared for validation. The developed model helps in understanding the load effects on different muscles and provides useful information for the construction of an individual's optimized exoskeleton.
Number of teeth, denture wearing and cognitive function in relation to nutritional status in residents of nursing homes
Authors: Suma Shino , Furuta Michiko , Takeuchi Kenji , Tomioka Mikiko , Iwasa Yasuyuki , Yamashita Yoshihisa
Published: May 2021

Background

Although statistical associations between tooth loss and cognitive decline have been reported, there are few previous studies on denture wearing. Additionally, it remains unclear whether nutritional status mediates this association.

Objective

Our purpose was to test for the hypothesis that the association between the number of teeth and denture wearing with cognitive function is mediated by nutritional status in residents of nursing homes.

Materials and Methods

We enrolled 162 participants who required long‐term care (mean age: 87.7 ± 7.5 years, 26 men and 136 women) and were admitted to eight nursing homes in Fukuoka city, from September 2013 to March 2014. A trained dentist conducted dental and swallowing examinations, and the care‐staff assessed nutritional status, comorbid conditions and cognitive function using the Clinical Dementia Rating (CDR).

Results

Poisson regression analysis showed that 0‐19 teeth without dentures were associated with severe cognitive impairment (CDR 3) (prevalence ratio = 2.00; 95% confidence interval: 1.13‐3.55) after adjustment for sex, age, suspected swallowing dysfunction and comorbid conditions. Mediation analysis confirmed that the nutritional status as a mediator of this association (the percentage mediated effect through nutritional status was 23.1%).

Conclusion

There is an association between dental status and cognitive impairment in elder individuals, and dentures and poor nutrition are involved in this association. However, due to the cross‐sectional design of this study, there is a possibility that this association is bidirectional.
Integrase strand transfer inhibitor treatment does not increase the incidence of immune reconstitution inflammatory syndrome in HIV‐infected Koreans
Authors: Kim J , Nam H‐J , Kang S‐J , Jung S‐I , Hwang CH , Kim Y‐S , Chang H‐H , Kim S‐W , Park K‐Hwa
Published: May 2021

Objectives

Immune reconstitution inflammatory syndrome (IRIS) is a major concern when starting antiretroviral therapy (ART) in patients with advanced HIV infection. The aim of this study was to determine the incidence and risk factors of IRIS in HIV‐infected Koreans initiating ART, and whether integrase strand transfer inhibitor (INSTI) treatment increases the risk of IRIS.

Methods

This retrospective analysis included adults living with HIV, seen at four university‐affiliated hospitals in South Korea, who were naïve to ART and had a CD4 T‐cell count < 200 cells/μL between January 2004 and May 2019. IRIS was determined through a medical record review within 6 months of ART initiation. Propensity score‐matched case–control study between the non‐INSTI and INSTI groups was performed.

Results

The study included 501 patients; 192 were assigned to the INSTI group, who started ART based on INSTIs as the initial treatment. There were opportunistic infections (OIs) in 253 (50.5%) cases before ART initiation. The three most common OIs were Pneumocystis jirovecii pneumonia, candidiasis and tuberculosis (TB). We identified 47 cases of IRIS; TB‐IRIS was the most common type. The incidence of IRIS within 6 months of ART initiation was 9.4%, and there were no significant differences in baseline characteristics and incidence of IRIS between the matched groups. The risk factors for IRIS were pre‐ART CD4 T‐cell count (< 30 cells/μL), higher pre‐ART viral load (≥ 75 000 copies/mL), and TB‐OI.

Conclusions

The incidence of IRIS was 9.4% in Korean HIV patients. The INSTI regimen was not related to IRIS occurrence.
Online engagement during COVID‐19: Role of agency on collaborative learning orientation and learning expectations
Authors: Almusharraf Norah Mansour , Bailey Daniel
Published: May 2021

During the COVID‐19 outbreak, students had to cope with succeeding in video‐conferencing classes susceptible to technical problems like choppy audio, frozen screens and poor Internet connection, leading to interrupted delivery of facial expressions and eye‐contact. For these reasons, agentic engagement during video‐conferencing became critical for successful learning outcomes. This study explores the mediating effect agentic engagement has on collaborative language learning orientations (CLLO) within an EFL video‐conferencing course to understand better how interactions influence academic learning expectations. A total of 329 (Male = 132, Female = 197) students were recruited from four South Korean universities to participate in this questionnaire study. Data analysis was carried out using the statistical software packages SPSS, and a series of data screening procedures were carried out. Findings revealed that collaborative language learning orientations were a statistically significant predictor of academic learning expectations, but this relationship was fully mediated when agentic engagement was added to the model. Students with a propensity for social language learning strategies believe they will succeed; however, this relationship is explained by their propensity to interact with the instructor when video‐conferencing. An assortment of learning activities should be provided to support both collaborative and individual learning orientations for academic success. Students with collaborative learning tendencies and a propensity to actively engage the instructor during video conference classes are active participants in the eLearning context, possibly leading to positive course expectations.
Social efficiency of entry: Implications of network externalities
Authors: Basak Debasmita , Petrakis Emmanuel
Published: May 2021

We examine the welfare effects of entry in the presence of network externalities. We show that if network goods are fully incompatible, entry is socially insufficient as long as the entry cost is high, the goods are sufficiently differentiated, and the degree of network externality is low. Further, we show that as the degree of compatibility between the network goods increases, insufficient entry becomes more likely. Our findings provide policy guidelines for anticompetitive and procompetitive entry regulations.
Association of frailty with outcomes in individuals with COVID‐19: A living review and meta‐analysis
Authors: Dumitrascu Flavia , Branje Karina E. , Hladkowicz Emily S. , Lalu Manoj , McIsaac Daniel I.
Published: May 2021

Background and Objectives

Frailty leaves older adults vulnerable to adverse health outcomes. Frailty assessment is recommended by multiple COVID‐19 guidelines to inform care and resource allocation. We aimed to identify, describe, and synthesize studies reporting the association of frailty with outcomes (informed by the Institute for Healthcare Improvement's Triple Aim [health, resource use, and experience]) in individuals with COVID‐19.

Design

Systematic review and meta‐analysis.

Setting

Studies reporting associations between frailty and outcomes in the setting of COVID‐19 diagnosis.

Participants

Adults with COVID‐19.

Measurements

Following review of titles, abstracts and full text, we included 52 studies that contained 118,373 participants with COVID‐19. Risk of bias was assessed using the Quality in Prognostic studies tool. Our primary outcome was mortality, secondary outcomes included delirium, intensive care unit admission, need for ventilation and discharge location. Where appropriate, random‐effects meta‐analysis was used to pool adjusted and unadjusted effect measures by frailty instrument.

Results

The Clinical Frailty Scale (CFS) was the most used frailty instrument. Mortality was reported in 37 studies. After confounder adjustment, frailty identified using the CFS was significantly associated with mortality in COVID‐19 positive patients (odds ratio 1.79, 95% confidence interval [CI] 1.49–2.14; hazard ratio 1.87, 95% CI 1.33–2.61). On an unadjusted basis, frailty identified using the CFS was significantly associated with increased odds of delirium and reduced odds of intensive care unit admission. Results were generally consistent using other frailty instruments. Patient‐reported, cost and experience outcomes were rarely reported.

Conclusion

Frailty is associated with a substantial increase in mortality risk in COVID‐19 patients, even after adjustment. Delirium risk is also increased. Frailty assessment may help to guide prognosis and individualized care planning, but data relating frailty status to patient‐reported outcomes are urgently needed to provide a more comprehensive overview of outcomes relevant to older adults.