bluuebunny/crossref_metadata_2025 huggingface dataset:
Parkinson’s disease-related phosphorylation at Tyr39 rearranges α-synuclein amyloid fibril structure revealed by cryo-EM
Authors: Zhao Kun , Lim Yeh-Jun , Liu Zhenying , Long Houfang , Sun Yunpeng , Hu Jin-Jian , Zhao Chunyu , Tao Youqi , Zhang Xing , Li Dan , Li Yan-Mei , Liu Cong
Published: April 2020

Post-translational modifications (PTMs) of α-synuclein (α-syn), e.g. phosphorylation, play an important role in modulating α-syn pathology in Parkinson’s disease (PD) and α-synucleinopathies. Accumulation of phosphorylated α-syn fibrils in Lewy bodies and Lewy neurites is the histological hallmark of these diseases. However, it is unclear how phosphorylation relates to α-syn pathology. Here, by combining chemical synthesis and bacterial expression, we obtained homogeneous α-syn fibrils with site-specific phosphorylation at Y39, which exhibits enhanced neuronal pathology in rat primary cortical neurons. We determined the cryo-EM structure of pY39 α-syn fibril, which reveals a new fold of α-syn with pY39 in the center of the fibril core forming electrostatic interaction network with eight charged residues in the N-terminal region of α-syn. This structure composed of residues 1-100 represents the largest α-syn fibril core determined so far. This work provides structural understanding on the pathology of pY39 α-syn fibril, and highlights the importance of PTMs in defining the polymorphism and pathology of amyloid fibrils in neurodegenerative diseases.
Sub-millisecond time-resolved small-angle neutron scattering measurements at NIST
Authors: Glinka Charles , Bleuel Markus , Tsai Peter , Zákutná Dominika , Honecker Dirk , Dresen Dominique , Mees Flore , Disch Sabrina
Published: April 2020

Instrumentation for time-resolved small-angle neutron scattering measurements with sub-millisecond time resolution, based on Gähler's TISANE (time-involved small-angle neutron experiments) concept, is in operation at NIST's Center for Neutron Research. This implementation of the technique includes novel electronics for synchronizing the neutron pulses from high-speed counter-rotating choppers with a periodic stimulus applied to a sample. Instrumentation details are described along with measurements demonstrating the utility of the technique for elucidating the reorientation dynamics of anisometric magnetic particles.
XTIP – the world's first beamline dedicated to the synchrotron X-ray scanning tunneling microscopy technique
Authors: Rose Volker , Shirato Nozomi , Bartlein Michael , Deriy Alex , Ajayi Tolulope , Rosenmann Daniel , Hla Saw-Wai , Fisher Mike , Reininger Ruben
Published: April 2020

In recent years, there have been numerous efforts worldwide to develop the synchrotron X-ray scanning tunneling microscopy (SX-STM) technique. Here, the inauguration of XTIP, the world's first beamline fully dedicated to SX-STM, is reported. The XTIP beamline is located at Sector 4 of the Advanced Photon Source at Argonne National Laboratory. It features an insertion device that can provide left- or right-circular as well as horizontal- and vertical-linear polarization. XTIP delivers monochromatic soft X-rays of between 400 and 1900 eV focused into an environmental enclosure that houses the endstation instrument. This article discusses the beamline system design and its performance.
Creative Design Ltd.: the path to youth entrepreneurship
Authors: Chuang Ya-Hsueh , Kang Tsan-Ching , Chang Wen-Ching , Chen Po-Ju
Published: April 2020

Learning outcomes

By the end of this session, students should be able to: explain what a business model is; summarize the case firm’s business strategy using the elements of business model canvas proposed by Alexander Osterwalder and practice how to apply the business model canvas to analyze the business model of a firm; understand how a firm can seize an opportunity for innovation; and discuss how the case firm navigated through problems that came up as it grew.

Case overview/synopsis

Creative Design was a start-up company in Taiwan. To fulfill a course requirement while she was still in school, the founder had formed a team and entered an entrepreneurship competition. They won the second runner up award in that competition and impressed some firms who enquired if they would be interested in doing corporate identity system (CIS) design. They discovered that without establishing a corporate structure their prospective clients would be unable to pay an invoice. As a consequence, the founder and one of the team members established Creative Design Ltd. This case discusses the challenge Creative Design faced at the end of 2012. Wonderland farmers’ association (WFA) wanted to market locally grown jasmine but did not know how to go about it. They reached out to the founder and her company for assistance. The case of WFA was uncharted territory. Creative Design already had extensive experience in CIS design, but it did not have any experience in handling agriculture products. In this case, they had to deal with the full supply chain from production to exhibition. The risk for this project was high but Creative Design accepted the case and became the first design firm offering a “total solution.” Currently, Creative Design works with all kinds of cases, from simple CIS designs to more complicated total solutions of various scales. The founder now has to contemplate if the design house should develop more total solution cases. Doing so would require recruiting more staff and the dilemma of balancing revenue and costs.

Complexity academic level

The case study is designed for the undergraduate and graduate students of the College of Management; the case can be adopted for the courses of management, innovation and entrepreneurship, etc.

Supplementary materials

Teaching Notes are available for educators only.

Subject code

CSS: 3 Entrepreneurship.
Sustainability funding in higher education: a literature-based review
Authors: Montenegro de Lima Carlos Rogério , Coelho Soares Thiago , Andrade de Lima Maurício , Oliveira Veras Manoela , Andrade Guerra José Baltazar Salgueirinho Osório de Andrade
Published: April 2020

Purpose

The purpose of this paper is to report a literature review on sustainability funding in higher education and an analysis of the theoretical influence on academic research. The theoretical contribution and the most influential authors were examined to better understand the intellectual structure that links the theories and authors that have researched this topic. This study not only allows comprehension of the current research scenario but also, based on the gaps identified, provides guidelines for future studies on sustainability in higher education.

Design/methodology/approach

Citations and co-citations were analyzed in a sample of 745 papers, published between 1994 and 2018 in international journals, found in the Web of Science database on the topic of sustainability in higher education. Using the co-citations map, multidimensional scaling (MDS) and exploratory factor analysis (EFA), the conceptual and theoretical relations in these studies were identified.

Findings

It was possible to identify five clusters of the topics investigated, namely, sustainability competences; campus greening; co-creation and transfer of knowledge; sustainability science; and sustainability in university courses and curricula. A considerable number of studies were found in the areas of sustainability competencies and campus greening that focus on sustainability aspects. The clusters co-creation and transfer of knowledge, and sustainability science are related to the management of sustainability in higher education. The sustainability in university courses and curricula cluster focuses on actions within the scope of the courses and academic training.

Research limitations/implications

Although there are limitations related to the choice of a single database (Web of Science), as the study was limited to 745 papers, the analysis of the citations and co-citations provides important information on the study of sustainability in high education. The results are also limited to the presentation of the data grouped according to the factors extracted in the period analyzed, as it is not the objective of this study to examine in depth the characteristics of each of the 745 papers and their relationship with the theoretical dimensions identified.

Originality/value

This paper is original, as it identifies by applying MDS and EFA to scientific papers, the topic of sustainability in higher education and the clusters that constitute this field of study. The main contribution of this research is the finding that, although there are five different theoretical dimensions of sustainable financing, they are not treated separately. This study also contributes to increasing the knowledge on the main topics, concepts and relations, which can guide future research.
A new love–hate scale for sports fans
Authors: Shuv-Ami Avichai , Toder Alon Anat , Loureiro Sandra Maria Correia , Kaufmann Hans Ruediger
Published: April 2020

Purpose

This study, an empirical research, aims to construct and validate a new love-hate scale for sports fans and tested its antecedents and consequences.

Design/methodology/approach

The scale was designed and validated in three separate empirical survey studies in the context of Israeli professional basketball. In Phase 1, the authors verified the factorial validity of the proposed scale using exploratory factor analysis. In Phase 2, the authors conducted a confirmatory factor analysis using structural equation modeling. In Phase 3, the authors tested the nomological network validity of the scale.

Findings

The findings show that fans' involvement, loyalty and fandom significantly predicted their love–hate, which in turn significantly predicted self-reported fan aggression, fans' acceptance of fan aggression, price premium and frequency of watching games.

Research limitations/implications

The model was tested on a relatively small sample of fans within a single country. This lack of generalizability should be addressed in future studies by examining the model in other sports contexts and countries.

Practical implications

This study suggests that understanding the properties of the love–hate measure may assist team sports clubs in identifying, preventing and controlling potential fan aggression.

Originality/value

The study provides three incremental contributions above and beyond existing research: it develops and validates a scale for measuring the phenomenon of sports fans' love and hate as mixed emotions; it makes it possible to capture the variations in the magnitude of fans' love–hate; and it relates fans' love–hate to important attitudinal and behavioral outcomes.
Exploring differences in competitive performance based on Miles and Snow's strategy typology for the semiconductor industry
Authors: Lin Chinho , Chiu Yu-Wen , Chen Wen-Chieh , Ting Shu-Fang
Published: April 2020

Purpose

The aim of this article is to construct a performance evaluation framework that can be employed in companies to enhance their business operations and strengthen their financial advantage in the current environment. To validate the approach, a case example has been included to assess the practicality and validity of this approach when applied in a real environment.

Design/methodology/approach

This study focuses on an important part of the strategic planning process: internal scrutiny and environmental (external) scanning, in which an evaluation of company performance is divided into two stages by using network DEA and the cross-efficiency approach. In addition, this article employs Miles and Snow's typology for classifying the strategies used by companies.

Findings

The analytical results show that the proposed framework can be useful for companies seeking to evaluate which strategies may be the most appropriate, based on Miles and Snow's typology, to effectively reallocate limited resources.

Research limitations/implications

The evaluation in this study only uses financial data and does not take other nonfinancial indicators into consideration.

Originality/value

This research provides value by classifying each company included in the study in terms of its capability and financial efficiency according to Miles and Snow's system of strategy classification. Second, an internal and external performance measuring framework is constructed. Finally, some propositions for top management are provided by analyzing the financial advantages of using a performance evaluation framework that can help top management make decisions more objectively.
Analysis of two financing modes in green supply chains when considering the role of data collection
Authors: Zhao Nenggui , Wang Qiang
Published: April 2020

Purpose

More and more attention has been paid to the financing of small- and medium-sized enterprises (SMEs) and environmental protection. Many literatures have done detailed research on them; yet, few of them studied the interaction between corporate financing behaviors and environmental concerns. This study aims to incorporate the impact of the role of data collection into the mathematical model to explore the optimal financial and ordering strategies when considering environmental protection.

Design/methodology/approach

A Stackelberg game modeling and backward induction methods are used to derive the optimal equilibrium solutions, using numerical experiments to further explore the influences of various financing strategies on the green degree of product and ordering policies.

Findings

No matter which financing modes the capital-constrained retailer chooses, both the loan interest rate and order quantity considering environmental protection are larger than that without environmental protection concerns. As the retailer's initial capital increases, the optimal loan interest rates under various financing modes are all decreasing. The application of big data technology would promote the environmental protection of enterprises and increase the accuracy of financing decisions.

Originality/value

This paper studies financing activities of a supply chain considering data collection and environmental protection behaviors, which provides meaningful guidance for the financing and environmental decision-making of enterprises.
What drives total factor productivity and its growth in post-communist countries? The case of the Czech food industry
Authors: Blažková Ivana , Dvouletý Ondřej , Machek Ondřej
Published: April 2020

Purpose

The paper aims to investigate factors that drive the total factor productivity (TFP) and its growth in the Czech food industry over 2003–2017. The authors’ analysis focuses on firm-level characteristics such as location choice, sub-sector affiliation, use of debt, liquidity, asset turnover, firm size and firm age.

Design/methodology/approach

The determinants of productivity were tested econometrically by estimation of multivariate regression models. The firm-level panel data set consisted of 14,488 observations (data of 980 firms spanning 15 years). TFP was estimated by three regression-based techniques – ordinary least squares (OLS) regression, instrumental variables (IV) approach and two-way generalized method of moments (GMM) regression. All three measures of TFP were used as outcome variables to estimate the impact of firm-level determinants on both TFP level and growth.

Findings

The results have shown statistically significant and reversed U-shaped relationship between the firm age and the TFP level (with a turning point in the age of 12.5 years). However, the dynamic models investigating the TFP growth have found that younger firms achieve higher productivity growth in comparison with older ones. Higher market share and assets turnover were positively associated with both TFP level and its growth.

Research limitations/implications

This study brings several relevant propositions for future research. First, the authors recommend future researchers to study not only differences in the levels of productivity but also determinants of its growth. Second, the authors believe that adding a non-linear component to age as a factor explaining changes in the levels of productivity might be a very relevant contribution to the literature.

Originality/value

Although it is generally accepted that successful and sustainable growth of firms, regions and economies can be achieved particularly through viable companies with high productivity, there is still a limited number of firm-level studies explaining the determinants of productivity levels and growth in agribusiness sectors in transition economies. Therefore, this study is expected to contribute to a better understanding of this important topic.
Spiritual leadership and intention to stay: examining the mediating role of employee voice behaviour
Authors: KA Zakkariya , Aboobaker Nimitha
Published: April 2020

Purpose

Spiritual leadership focuses on intrinsically motivating the workforce though shared values, attitudes and behaviours and is about achieving organizational excellence through shared aspirations. In the context of tough competition among organizations and relentless disruptions of existing business processes, leaders look forward to devise strategies that will help keep their employees stay alongside, offering constructive criticisms as well. This study aims to examine the influence of spiritual leadership style on employees' intention to stay with the organization, mediated through their voice behaviour.

Design/methodology/approach

This cross-sectional study followed a descriptive research design, and data were collected from 357 employees working in the information technology sector in India. Validated instruments in the existing literature were used among the sample respondents, and structural equation modelling was done to test the proposed hypotheses.

Findings

The findings of the study suggest that employees' experience of dimensions of spiritual leadership style had varying influences on their voice behaviour and intention to stay with the organization. Also, employee voice behaviour mediated the relationships between two dimensions of spiritual leadership (hope and altruistic love) and intention to stay, but not the relationship between vision and intention to stay.

Originality/value

This study is pioneering in conceptualizing and testing a theoretical model linking spiritual leadership style, employee voice behaviour and their intention to stay with the organization. The results of the study emphasis the need for cultivating a leadership style of shared vision, value congruence and facilitating standards of excellence grounded on values of integrity, humility, compassion and perseverance. Implications for management development on how to promote employee voice behaviour are also discussed.
Migration intentions: a sign of a weak nation brand? A multi-group analysis between China and Pakistan
Authors: Yousaf Salman , Tauni Mohammad Zubair , Xiucheng Fan
Published: April 2020

Purpose

This study aims to focus on the internal audiences of a nation brand, i.e. the citizens of a country and is built on the theoretical premise that migration intentions (MIs) prevalent among the skilled and educated elite of a home country signifies a weak nation brand.

Design/methodology/approach

Through the theoretical support of the migration motive theory of push and pull (Richmond, 1993), nation branding theory (Anholt, 2006) and the two-construct country image model (Roth and Diamantopoulos, 2009), the authors constructed a framework that incorporates the relationship between affective and cognitive country images of both home and migrant country and migration motives and intentions to migrate.

Findings

The findings reveal that push and pull factors are strongly affected by the images of the home country and the migrant country, respectively and strong home country images are associated with weak MIs, while the opposite is true if a strong migrant country image is possessed. Further, evidence of the dominance effect of cognitive images in complex decision-making environments such as migration was also provided. Moreover, the results also suggest significant differences between Chinese and Pakistani respondents.

Practical implications

This study guides nation branding researchers by opening up a debate on self-images and conceptually independent attitudinal constructs of country image. For policymakers in developing countries, the results reveal that they should primarily strengthen their internal brands and focus on cognitive images to stem the flow of brain drain.

Originality/value

This study takes the traditional country image debate to migration discourse, moves it forward, contextualizes it as a function of a nation’s brand strength and provides evidence that confluence of migration studies with the theoretical stream of nation branding can provide significant explanations for migrant behavior.
The logics of enclosure: deep‐time trajectories in the spread of land tenure boundaries in late prehistoric northern Europe
Authors: Løvschal Mette
Published: April 2020

Invasive schemes involving the erection of land tenure boundaries are currently spreading quickly across vast areas throughout the globe, turning former unfenced forests and grasslands into closed‐off parcels. These processes pose intriguing questions about the deep history of colonizing assemblages consisting of particular tenure practices, temporalities, and technologies, as well as their potential long‐term repercussions. This article expands the temporal horizon applied to human‐nonhuman configurations, endeavouring to focus beyond the ethnographic present or the event on trajectories as a particular spatial and temporal logic of fencing and the virtuality that ensues. It explores the earliest large‐scale spread of land tenure boundaries across northern Europe, a process which occurred between the seventeenth and fifth centuries BCE, several millennia after Neolithization. Significant ebbs and flows in this process demonstrate how fencing exerts pressure on the future, a conspiring of forces and potentialities regarding what may or may not turn into long‐term paths towards ever‐increasing or enduring boundaries. By applying a 2,000‐year timespan to the study of material ontologies, this article explores new interfaces between archaeology and new materialism which reveal the presence of formative yet dynamic processes and quasi‐paths.
Comparison of high‐intensity focused ultrasound ablation and secondary myomectomy for recurrent symptomatic uterine fibroids following myomectomy: a retrospective study
Authors: Liu X , Tang J , Luo Y , Wang Y , Song L , Wang W
Published: April 2020

Objective

To compare the long‐term symptom alleviation and re‐intervention of high‐intensity focused ultrasound (HIFU) ablation and secondary myomectomy for women with recurrent symptomatic uterine fibroids following myomectomy.

Design

A retrospective analysis.

Setting

A general hospital in China.

Population

One hundred and eighty‐eight women with recurrent symptomatic uterine fibroids following myomectomy.

Methods

Women who underwent HIFU ablation (n = 101) and secondary myomectomy (n = 87) at Chinese PLA General Hospital from January 2008 to December 2016 were analysed. Symptom relief and recurrence were evaluated using the transformed symptom severity scale (tSSS). The additional intervention and treatment‐related complications were also recorded and compared.

Main outcome measures

Difference in symptom alleviation, recurrence, re‐intervention and complications.

Results

Follow‐up time was comparable for the two groups (56 versus 60 months; P = 0.88). Regarding tSSS, at 3 months there was improvement in all tSSS for both treatment groups. The time to re‐intervention was shorter in the myomectomy group. The cumulative risk for re‐intervention after HIFU ablation at 1 and 3 years was lower than that after secondary myomectomy (0% versus 4.8%, 3.2% versus 11.9%, respectively); however, no significant difference was observed at 5 and 8 years. There were fewer adverse events in the HIFU ablation group than the myomectomy group (59.4% versus 77%, P = 0.01).

Conclusions

High‐intensity focused ultrasound ablation of recurrent symptomatic uterine fibroids offers comparable long‐term alleviation of symptoms with longer time interval to re‐intervention and fewer adverse events compared with secondary myomectomy.

Tweetable abstract

High‐intensity focused ultrasound ablation of recurrent uterine fibroids offered a longer time interval to re‐intervention and fewer adverse events compared with myomectomy.
Valuing Initial Public Offerings Using Article 11 Pro Forma Financial Information in the Prospectus*
Authors: Chen Jerry W. , Zhou Jing
Published: April 2020

We investigate whether Article 11 pro forma financial information assists investors in valuing IPOs. While the SEC expects it to be helpful in assisting investment decisions, Article 11 pro forma financial information is based on registrants' understanding and assumptions, and registrants can exercise their own judgment when preparing pro forma financial statements. It is therefore an empirical question whether the information contained in pro forma financial statements is useful to investors. We examine the association between pro forma adjustments of earnings and book value of equity and the IPO offer value and find asymmetric results. While positive pro forma adjustments of earnings and book value of equity are positively associated with the IPO offer value, negative pro forma adjustments of earnings and book value of equity are negatively associated with the IPO offer value, suggesting that negative pro forma adjustments are priced as growth opportunities. Additional analyses reveal that the association between pro forma adjustments of book value of equity and the IPO offer value varies across different time periods and industries and that pro forma adjustments of book value of equity are initially mispriced by investors. In contrast, we do not find similar results for pro forma adjustments of earnings. Further empirical tests show that the asymmetric results of mispricing of pro forma adjustments of earnings and book value of equity may be explained by the requirements of Article 11 of Regulation S‐X for pro forma adjustments dictating that adjustments to earnings reflect only recurring items while adjustments to book value reflect both recurring and nonrecurring items.
Trading Prior to the Disclosure of Material Information: Evidence from Regulation Fair Disclosure Form 8‐Ks*
Authors: Campbell John L. , Twedt Brady J. , Whipple Benjamin C.
Published: April 2020

Regulation Fair Disclosure (Reg FD) Form 8‐K filings provide a venue where managers release information to the market as a whole that they designate as being material. Using this setting, we study trading patterns immediately prior to the public disclosure of material information. We offer three main results. First, using both intraday and daily trading data, we find abnormal trading volume of 21 percent (13 percent) in the hour (day) prior to the public disclosure, respectively. Second, we find that this pre‐disclosure abnormal trading volume is concentrated in firms that are smaller, have more growth opportunities, issue fewer voluntary disclosures, and have weaker external monitoring. Finally, we find that this pre‐disclosure volume is concentrated in subsamples in which the information relates to a firm's material contracts, a firm holds investor/analyst conferences, and there is insider trading activity in a firm's shares. Our results do not concentrate in a small number of firms or industries, and do not appear to be explained by the form through which managers first release the material information (e.g., Form 8‐K, press release, website posting, or social media). Our results are also robust to controlling for the firm's other filings and peer filings that occur around the disclosure. Overall, the trading patterns we document may show that, inconsistent with the spirit of Reg FD, a subset of investors trade on information managers deem material prior to its broad, public release.
Cannabis use disorder and the lungs
Authors: Gracie Kathryn , Hancox Robert J.
Published: April 2020

Cannabis is one of the world's most widely used recreational drugs and the second most commonly smoked substance. Research on cannabis and the lungs has been limited by its illegal status, the variability in strength and size of cannabis cigarettes (joints), and the fact that most cannabis users also smoke tobacco, making the effects difficult to separate. Despite these difficulties, the available evidence indicates that smoking cannabis causes bronchitis and is associated with changes in lung function. The pattern of effects is surprisingly different from that of tobacco. Whereas smoking cannabis appears to increase the risk of severe bronchitis at quite low exposure, there is no convincing evidence that this leads to chronic obstructive pulmonary disease. Instead, cannabis use is associated with increased central airway resistance, lung hyperinflation and higher vital capacity with little evidence of airflow obstruction or impairment of gas transfer. There are numerous reports of severe bullous lung disease and pneumothorax among heavy cannabis users, but convincing epidemiological data of an increased risk of emphysema or alveolar destruction are lacking. An association between cannabis and lung cancer remains unproven, with studies providing conflicting findings.
Global opioid agonist treatment: a review of clinical practices by country
Authors: Jin Harry , Marshall Brandon D. L. , Degenhardt Louisa , Strang John , Hickman Matt , Fiellin David A. , Ali Robert , Bruneau Julie , Larney Sarah
Published: April 2020

Aims

We assessed how opioid agonist treatment (OAT) for opioid use disorder (OUD), specifically methadone and buprenorphine, including buprenorphine‐naloxone, is delivered in routine clinical practice, with a focus on factors that affect access to and delivery of these services. The aims of this review were to summarize eligibility criteria for entry to OAT, doses in routine clinical practice, access to and eligibility for unsupervised dosing and urine drug screening practices in OAT programs globally.

Methods

We completed searches of PubMed, Embase, and grey literature databases for cross‐sectional or observational cohort studies of OAT using either methadone or buprenorphine. Dose data extracted from eligible studies were compared with guidelines provided by WHO.

Results

We found 140 reports from 41 countries that contained data for at least one of the relevant indicators. A diagnosis of opioid dependence or opioid use disorder was the most common eligibility requirement for OAT (13 or 17 countries). Reported mean or median doses for methadone ranged from 16–131 mg whereas range for buprenorphine was 2.5–19 mg. Access to unsupervised dosing under some conditions was reported in 18 of 27 countries. Frequency of regular urine drug screenings (UDS) ranged from several times a week to eight times per year (methadone) or as clinically indicated.

Conclusions

Opioid agonist treatment practices, including doses prescribed, vary greatly both within and across countries. Of particular concern is the persistence of lower dose prescribing practices, in which patients may be prescribed doses below those proven to yield significant clinical benefits.
Mortality and morbidity of locally acquired hepatitis E in the national Scottish cohort: a multicentre retrospective study
Authors: Wallace Sebastian J. , Swann Rachael , Donnelly Mhairi , Kemp Linda , Guaci Julia , Murray Aimee , Spoor Johannes , Lin Nan , Miller Michael , Dalton Harry R. , Hussaini S. Hyder , Gunson Rory , Simpson Kenneth , Stanley Adrian , Fraser Andrew
Published: April 2020

Background

Hepatitis E virus (HEV) is the most common acute viral hepatitis in Scotland. Little is known about the burden of morbidity and mortality, which can be high in chronic liver disease or immunocompromised states.

Aims

To record the morbidity and mortality of HEV in Scotland.

Methods

Demographic, clinical and laboratory data were collected retrospectively from all cases of HEV reported to virology departments across nine NHS health boards, between January 2013 and January 2018.

Results

Five hundred and eleven cases were included (Mean age 62, 64% male). 58 (11%) cases had pre‐existing cirrhosis and 110 (21%) had diabetes. Three hundred and three patients required admission (59%), totalling 2747 inpatient bed days. Seventeen (3.3%) HEV‐related deaths were recorded. Factors that predicted mortality included haematological malignancy (OR 51.56, 95% CI 3.40‐782.83, P = 0.005), cirrhosis (OR 41.85, 95% CI 2.85‐594.16, P = 0.006), higher serum bilirubin (OR 1.01, 95% CI 1.01‐1.02, P = 0.011) and chronic HEV infection (OR 0.02, 95% CI 0.02‐0.28, P < 0.001). HEV infection affected 35 transplant patients of 106 total immunosuppressed patients (21%). Of these, 25 patients received Ribavirin therapy with a sustained virological remission of 76%. Thirty‐five (6.7%) patients developed acute or acute‐on‐chronic liver failure with two requiring transplant. Thirty‐seven (7.2%) patients reported neurological complications with 10 developing neuralgic amyotrophy, 6 Guillain‐Barré and 2 encephalitis. Forty‐four (8.6%) patients developed acute kidney injury.

Conclusion

In Scotland, HEV causes a significant burden of inpatient admissions, organ failure and death. Cirrhosis and haematological malignancy are significant predictors of mortality. Neurological and renal complications occur in a significant minority.
Novel use of cathodoluminescence to identify differences in source rocks for Late Paleoindian quartzite tools
Authors: Legg R. , Neilson J. , Demel S.
Published: April 2020

Heterogeneous quartzite artefact finds from North America's Late Paleoindian period occur in several areas throughout the Northern Great Lakes region. Standard petrographic analysis, back‐scatter scanning electron microscopy and cathodoluminescence are used to identify the properties of a regionally abundant, high‐quality orthoquartzite stone as compared with high‐quality Hixton silicified sandstone from the Silver Mound Archeological District in Jackson, Wisconsin. The results demonstrate the potential for reducing misidentification among material sources, and also exhibit the acutely discerning tendencies of pre‐contact peoples. Lithological interpretations of thin sections identify the different properties of the Hixton material. Conversely, Mesnard quartzite, while it functions adequately as a tool stone, is fundamentally compromised of a tightly packed microstructure. This microstructure produces a hard, less tractable material with erratic breakage, possibly explaining Mesnard quartzite's limited distribution prehistorically.
Comparison of the fecal microbiota of two monogastric herbivorous and five omnivorous mammals
Authors: Kobayashi Rana , Nagaoka Kentaro , Nishimura Naomichi , Koike Satoshi , Takahashi Eiki , Niimi Kimie , Murase Harutaka , Kinjo Teruo , Tsukahara Takamitsu , Inoue Ryo
Published: April 2020

Fecal microbiota in seven different monogastric animal species, elephant, horse, human, marmoset, mouse, pig and, rat were compared using the same analytical protocol of 16S rRNA metagenome. Fecal microbiota in herbivores showed higher alpha diversity than omnivores except for pigs. Additionally, principal coordinate analysis based on weighted UniFrac distance demonstrated that herbivores and pigs clustered together, whereas other animal species were separately aggregated. In view of butyrate‐ and lactate‐producing bacteria, predominant genera were different depending on animal species. For example, the abundance of Faecalibacterium, a known butyrate producer, was 8.02% ± 3.22% in human while it was less than 1% in other animal species. Additionally, Bifidobacterium was a predominant lactate producer in human and marmoset, while it was rarely detected in other omnivores. The abundance of lactate‐producing bacteria in herbivores was notably lower than omnivores. On the other hand, herbivores as well as pig possess Fibrobacter, a cellulolytic bacterium. This study demonstrated that fecal microbiota in herbivorous animals is similar, sharing some common features such as higher alpha diversity and higher abundance of cellulolytic bacterium. On the other hand, omnivorous animals seem to possess unique fecal microbiota. It is of interest that pigs, although omnivore, have fecal microbiota showing some common features with herbivores.
Development of a method for clinical pharmacokinetic testing to allow for targeted Melphalan dosing in multiple myeloma patients undergoing autologous transplant
Authors: Sweiss Karen , Vemu Bhaskar , Hofmeister Craig C. , Wenzler Eric , Calip Gregory Sampang , Galvin John P. , Mahmud Nadim , Rondelli Damiano , Johnson Jeremy James , Patel Pritesh
Published: April 2020

Aims

High dose melphalan (HDM) and autologous stem cell transplant (ASCT) is standard of care for multiple myeloma (MM), but there is significant variability in melphalan exposure (area under the plasma drug concentration–time curve, AUC) when using body surface area‐based dosing. Our aim was to establish a method of pharmacokinetic (PK) testing for real‐time melphalan dose adjustments.

Methods

We performed a prospective PK study of melphalan 140 or 200 mg/m2 in MM patients undergoing ASCT. Twenty MM patients were administered HDM on days −2 and − 1, with PK sampling at 8–10 time points. PK testing was performed on day −2 in all patients, and on day −1 in 5 patients.

Results

Less than 20% interpatient variation in the day −2 and − 1 AUC was observed. The day −2 range in AUC (4.95–11.28 mg h/L) confirmed significant interpatient variability. The hypothetical total dose ranged from 133–302 mg/m2 to achieve the total median AUC. A 4‐time point AUC (0, 30, 150 and 240 min) highly correlated with the AUC from the 8‐time point schedule. A higher AUC correlated with increased risk of febrile neutropenia (P = .05).

Conclusion

Here we outline the methods to establish novel melphalan dosing using PK testing in MM patients undergoing ASCT to target a desired melphalan AUC.
Long-term efficacy and safety of brodalumab in psoriasis through 120 weeks and after withdrawal and retreatment: subgroup analysis of a randomized phase III trial (AMAGINE-1)
Authors: Papp K. , Menter A. , Leonardi C. , Soung J. , Weiss S. , Pillai R. , Jacobson A.
Published: April 2020

Background

Brodalumab is efficacious for the treatment of moderate-to-severe plaque psoriasis through 52 weeks.

Objectives

To evaluate the efficacy and safety of brodalumab through 120 weeks, including following withdrawal and retreatment.

Methods

At baseline, patients were randomized to brodalumab (n = 222) or placebo (n = 220). At week 12, patients achieving a static Physician's Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1) with brodalumab were rerandomized to brodalumab (n = 83) or placebo (n = 84; later re-treated with brodalumab if sPGA ≥ 3 occurred), and patients receiving placebo switched to brodalumab (n = 208). Safety was assessed by exposure-adjusted rates of treatment-emergent adverse events.

Results

Among those who achieved sPGA 0/1 at week 12 and were rerandomized to brodalumab, 96% and 80% using observed data, respectively, and 74% and 61% using nonresponder imputation, respectively, achieved 75% improvement in Psoriasis Area and Severity Index (PASI 75) and PASI 100 at week 120. Following withdrawal from brodalumab, return of disease occurred after a mean ± SD duration of 74·7 ± 50·5 days. Among those who switched from brodalumab to placebo at week 12, PASI 75 rates using observed data and nonresponder imputation were 55% and 51% at week 20, respectively and 94% and 75% at week 120, respectively; PASI 100 rates at week 120 were 75% and 60%, respectively. Efficacy was maintained through week 120 in those receiving brodalumab after placebo. No new safety signals were observed.

Conclusions

These findings indicate that brodalumab is efficacious and safe for continuous long-term treatment of psoriasis, and support the potential for response after discontinuation and retreatment.
“StoryWeb”: A storytelling‐based knowledge‐sharing application among multiple stakeholders
Authors: Park Jaehyun , Mostafa Noha A. , Han Hyo‐Joo
Published: April 2020

The research objective of this paper is to develop a storytelling‐based knowledge‐sharing application that enables users to co‐create their own stories for both individuals and groups. To address this, a design science research methodology was applied for elucidating users' requirements. As empirical evidence, a case study was conducted on the children's book industry to synthesize a knowledge‐sharing design application named “StoryWeb”. Usability tests were conducted to reconfigure users' feedback and suggestions after two StoryWeb prototypes were developed. This study makes three main contributions. First, it empirically tests individual's or group's creativity and co‐creation by a view of knowledge sharing. Second, it methodologically applies a design thinking approach into a knowledge‐sharing study. Third, it also practically suggests feasible guidelines for the creativity and innovation research community on which features of storytelling‐based applications can be configured.
Genetic characterization of a large cohort of Argentine 21‐hydroxylase Deficiency
Authors: Fernández Cecilia S. , Taboas Melisa , Bruque Carlos D. , Benavides‐Mori Belén , Belli Susana , Stivel Mirta , Oneto Adriana , Pasqualini Titania , Delea Marisol , Espeche Lucía D. , Kolomenski Jorge E. , Alba Liliana , Buzzalino Noemí , Dain Liliana
Published: April 2020

Context

21‐hydroxylase deficiency is the most common cause of Congenital Adrenal Hyperplasia. It presents as severe or classical forms—salt wasting and simple virilizing—and a mild or nonclassical (NC). Several studies have reported the frequency of pathogenic variants in different populations, although few of them included a large number of NC patients.

Objective

To analyse the CYP21A2 gene defects in a large cohort of Argentine patients.

Design

Molecular characterization of 628 patients (168 classical, 460 nonclassical, representing 1203 nonrelated alleles), 398 relatives, 126 partners.

Methods

Genetic variants were assessed by allele‐specific PCR, PCR‐RFLP or direct sequencing. Deletions, duplications and large gene conversions (LGC) were studied by Southern blot/MLPA or long‐range PCR. Biological implications of novel variants were analysed by structure‐based in silico studies.

Results

The most frequent pathogenic variants were p.V282L (58%) in NC alleles and c.293‐13C>G (31.8%) and p.I173N (21.1%) in classical. Deletions and LGC were found at low frequency (6.2%), 57 alleles had rare pathogenic variants, and 3 had novel variants: p.(S166F); p.(P189R), p.(R436L). Genotype‐phenotype correlation was observed in 98.6% of the cases, 11 asymptomatic first‐degree relatives had pathogenic variants in both alleles, and 21/126 partners were carriers.

Conclusions

We conducted a comprehensive genetic characterization of the largest cohort of 21‐hydroxylase patients from the region. In particular, we add to the molecular characterization of a large number of NC patients and to the estimation of the disease carrier's frequency in our population.
Diagnostic significance of DNA methylation of PTEN and DAPK in thyroid tumors
Authors: Wei Feng , Wu Yun , Wang Zhaoxia , Li Yongchao , Wang Jing , Shao Guo , Yang Ying , Shi Bingyin
Published: April 2020

Objective

DNA Methylation of the tumour suppressor gene leading to gene silencing plays an important role in thyroid tumour development. The purpose was to determine the DNA methylation status of phosphatase and tensin homolog (PTEN) and death‐associated protein kinase (DAPK) in patients with thyroid nodules and to explore whether they can be used as molecular diagnostic tools to differentiate benign and malignant thyroid nodules.

Design, patients and measurements

Thyroid tissue and blood samples were obtained from normal healthy individuals (controls) and patients suffering from clinically diagnosed thyroid nodular disease [papillary thyroid carcinoma (PTC), adenoma and nodular goitre]. DNA methylation level, mRNA expression and protein expression of PTEN and DAPK in the thyroid tissues and peripheral blood were detected using methylation‐specific PCR, semi‐quantitative reverse transcription PCR and Western blot, respectively. Diagnostic sensitivity, specific and accuracy of detection were evaluated between blood and thyroid tissue.

Results

There was a significant increase in the level of DNA methylation of PTEN and DAPK in PTC (P < .05) compared with controls and other types of thyroid nodules. Levels of the mRNA of both PTEN and DAPK were lower in PTC in both peripheral blood and tissue samples compared with controls, while there was concomitant decrease of both PTEN and DAPK protein expression in PTC tissues (P < .05). There was no significant difference in diagnostic specificity, sensitivity and accuracy between blood sample and thyroid tissues.

Conclusions

Hypermethylated status of both PTEN and DAPK in peripheral blood and tissue samples can be useful biomarkers for clinical diagnosis and, distinguishing of benign and malignant thyroid nodules.
Primary stability of narrow‐diameter dental implants with a multiple condensing thread design placed in bone with and without osteotomes: An in vitro study
Authors: Romanos Georgios E. , Lau Jessica , Delgado‐Ruiz Rafael , Javed Fawad
Published: April 2020

Background

The authors hypothesized that there is no difference in the primary stability (PS) of multiple condensing thread design (MCTD) implants placed in simulated type‐IV bone with and without using osteotomes.

Purpose

This in vitro study assessed the PS of narrow‐diameter dental implants with MCTD placed in simulated soft (type‐IV) bone with and without using osteotomes.

Materials and Methods

Sixty MCT‐designed implants (diameter: 3.0 mm; length: 11.5 mm) were placed using 800 rpm drilling speed in cellular rigid polyurethane foam bone‐blocks that simulated type‐IV bone. Prior to placement, the implants were divided into three groups (20 implants per group) depending upon the protocol used for osteotomy preparation—Group‐1: Conventional drilling (CD); Group‐2: CD followed by osseous condensation using a chisel‐shaped tapered osteotome with maximum diameter of 3 mm; and Group‐3: CD followed by osseous condensation using a cylindrical osteotome with maximum diameter of 3 mm. Abutments were connected to all implants and PS was recorded using resonance frequency analysis (RFA) and the periotest (PTV). Group comparisons were performed using analysis and Bonferroni post‐hoc adjustment tests. Level of significance was set at P < .05.

Results

There was no statistically significant difference in the RFA values for the MCT‐designed implants placed in groups 1, 2, and 3 (59.85 ± 0.72, 59.67 ± 0.76 and 59.42 ± 0.92, respectively). There was no statistically significant difference in the PTV values for MCT‐designed implants in groups 1, 2, and 3 (1.655 ± 0.82, 1.405 ± 0.57, and 1.078 ± 0.63, respectively).

Conclusion

The MCTD implants with narrow diameters have a high PS in artificial soft bone in vitro. Due to the condensation effect of the thread design, there is no need for additional condensation of the peri‐osteotomy bone in order to improve implant stability.