bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and cellular transcriptome foundations of human brain disease
Authors: Zeighami Yashar , Bakken Trygve E. , Nickl-Jockschat Thomas , Peterson Zeru , Jegga Anil G. , Miller Jeremy A. , Evans Alan C. , Lein Ed S. , Hawrylycz Michael
Published: May 2021

Genes associated with risk for brain disease exhibit characteristic expression patterns that reflect both anatomical and cell type relationships. Brain-wide transcriptomic patterns of disease risk genes provide a molecular based signature for identifying disease association, often differing from common phenotypic classification. Analysis of adult brain-wide transcriptomic patterns associated with 40 human brain diseases identified five major transcriptional patterns, represented by tumor-related, neurodegenerative, psychiatric and substance abuse, and two mixed groups of diseases. Brain disease risk genes exhibit unique anatomic transcriptomic signatures, based on differential co-expression, that often uniquely identify the disease. For cortical expressing diseases, single nucleus data in the middle temporal gyrus reveals cell type expression gradients separating neurodegenerative, psychiatric, and substance abuse diseases. By homology mapping of cell types across mouse and human, transcriptomic disease signatures are found largely conserved, but with psychiatric and substance abuse related diseases showing important specific species differences. These results describe the structural and cellular transcriptomic landscape of disease in the adult brain, highlighting significant homology with the mouse yet indicating where human data is needed to further refine our understanding of disease-associated genes.
Multiple brace root phenotypes promote anchorage and limit root lodging in maize
Authors: Hostetler Ashley N. , Erndwein Lindsay , Reneau Jonathan W. , Stager Adam , Tanner Herbert G. , Cook Douglas , Sparks Erin E.
Published: May 2021

Plant mechanical failure (lodging) causes global yield losses of 7-66% in cereal crops. We have previously shown that the above-ground nodal roots (brace roots) in maize are critical for anchorage. However, it is unknown how brace root phenotypes vary across genotypes and the functional consequence of this variation. This study quantifies the contribution of brace roots to anchorage, brace root traits, plant height, and root lodging susceptibility in 52 maize inbred lines. We show that the contribution of brace roots to anchorage and root lodging susceptibility varies among genotypes and this contribution can be explained by plant architectural variation. Additionally, supervised machine learning models were developed and show that multiple plant architectural phenotypes can predict the contribution of brace roots to anchorage and root lodging susceptibility. Together these data define the plant architectures that are important in lodging resistance and show that the contribution of brace roots to anchorage is a good proxy for root lodging susceptibility.
A Trio of Ubiquitin Ligases Sequentially Drive Ubiquitylation and Autophagic Degradation of Dysfunctional Yeast Proteasomes
Authors: Marshall Richard S. , Vierstra Richard D.
Published: May 2021

As central effectors of ubiquitin (Ub)-mediated proteolysis, proteasomes are regulated at multiple levels, including degradation of unwanted or dysfunctional particles via autophagy (termed proteaphagy). In yeast, inactive proteasomes are exported from the nucleus, sequestered into cytoplasmic aggresomes via the Hsp42 chaperone, extensively ubiquitylated, and then tethered to the expanding phagophore by the autophagy receptor Cue5. Here, we demonstrate the need for ubiquitylation driven by the trio of Ub ligases (E3s) San1, Rsp5 and Hul5, which, together with their corresponding E2s, work sequentially to promote nuclear export and Cue5 recognition. Whereas San1 functions prior to nuclear export, Rsp5 and Hul5 likely decorate aggresome-localized proteasomes in concert. Ultimately, topologically complex Ub chain(s) containing both K48 and K63 Ub-Ub linkages are assembled, mainly on the regulatory particle, to generate autophagy-competent substrates. As San1, Rsp5, Hul5, Hsp42, and Cue5 also participate in general proteostasis, proteaphagy likely engages an essential mechanism for eliminating inactive/misfolded proteins.

HIGHLIGHTS

Ubiquitylation is essential for the autophagic turnover of dysfunctional proteasomes.

The San1, Rsp5 and Hul5 E3s act sequentially to drive proteaphagy.

The E2s Ubc1, Ubc4 and Ubc5 are collectively required.

Both K48- and K63-mediated Ub-Ub linkages are assembled for efficient proteaphagy.
MHD and nonlinear thermal radiation effects on hybrid nanofluid past a wedge with heat source and entropy generation
Authors: Mabood Fazle , Shafiq Anum , Khan Waqar Ahmed , Badruddin Irfan Anjum
Published: May 2021

Purpose

This study aims to investigate the irreversibility associated with the Fe3O4–Co/kerosene hybrid-nanofluid past a wedge with nonlinear radiation and heat source.

Design/methodology/approach

This study reports the numerical analysis of the hybrid nanofluid model under the implications of the heat source and magnetic field over a static and moving wedge with slips. The second law of thermodynamics is applied with nonlinear thermal radiation. The system that comprises differential equations of partial derivatives is remodeled into the system of differential equations via similarity transformations and then solved through the Runge–Kutta–Fehlberg with shooting technique. The physical parameters, which emerges from the derived system, are discussed in graphical formats. Excellent proficiency in the numerical process is analyzed by comparing the results with available literature in limiting scenarios.

Findings

The significant outcomes of the current investigation are that the velocity field uplifts for higher velocity slip and magnetic strength. Further, the heat transfer rate is reduced with the incremental values of the Eckert number, while it uplifts with thermal slip and radiation parameters. An increase in Brinkmann’s number uplifts the entropy generation rate, while that peters out the Bejan number. The results of this study are of importance involving in the assessment of the effect of some important design parameters on heat transfer and, consequently, on the optimization of industrial processes.

Originality/value

This study is original work that reports the hybrid nanofluid model of Fe3O4–Co/kerosene.
Strategic supply chains: a configurational perspective
Authors: Feizabadi Javad , Gligor David , Alibakhshi Somayeh
Published: May 2021

Purpose

Drawing on configuration theory and adopting a holistic perspective, the authors aim to explore strategic supply chain elements' interaction with internal and external contextual conditions. Specifically, they evaluate multivariate co-alignment of supply chain's capabilities (agility, adaptability, alignment), adhocracy organizational structure and environmental uncertainty (dynamism, munificence and complexity) that lead to superior performance outcomes (supply chain cycle time, financial performance, market performance).

Design/methodology/approach

A survey research design is adopted to collect primary and secondary data from 182 international firms. Cluster analysis and profile deviation techniques are employed first to derive a taxonomy of strategic supply chains and then examine multivariate co-alignment.

Findings

The analysis reveals that four groups of triple-A supply chains could emerge. It is found that strategic supply chains exhibit a flexible/organic/fluid organizational structure and a high level of triple-As in their processes. These supply chains perform superior to a higher level of environmental complexity, munificence and dynamism.

Practical implications

This study's results provide insights for practitioners by informing their investment decisions for developing strategic supply chains. Specifically, this research highlights the contextuality of triple-A supply chains and offers best practices to capitalize on strategic supply chains.

Originality/value

Executives in organizations require a holistic understanding of various elements to ensure that the organizational system as a whole performs effectively. This research offers insights into the interdependencies of triple-A supply chains with other organizational and external environmental elements. Noteworthy implications for scholarship in operations/supply chain management and supply chain practitioners are presented.
Service quality benchmarking of amusement parks using a hybrid approach
Authors: James Ajith Tom
Published: May 2021

Purpose

The purpose of this paper is to develop a framework for benchmarking the service quality of amusement parks.

Design/methodology/approach

A hybrid approach, which is a combination of AHP (analytic hierarchy process) and TOPSIS (Technique for Order Preference by Similarity to Ideal Solution), is applied for service quality benchmarking.

Findings

Amusement parks are centers of attraction at various tourist destinations across the world. Their service quality is constituted by the attainment of certain quality attributes that varies with different parks. For sustaining in the industry, the managers of the parks need to have a good overview of the practices followed by them and their competitors that necessitate benchmarking of the service quality.

Practical implications

The developed framework using the hybrid methodology of AHP and TOPSIS can be applied for comparing different amusement parks based on quality attributes, which will help the organizers in improving their service quality.

Originality/value

The paper identifies various service quality attributes of amusement parks and an evaluation scheme for those attributes had been developed. Based on these, a framework had been developed for benchmarking of service quality of different amusement parks.
A pursuit to reliability – Toward a structural based reliability framework (FSR)
Authors: Ghaith Ahmad , Ma Huimin , Labib Ashraf W.
Published: May 2021

Purpose

High-reliability performance and high-hazard are intertwined in High-Reliability Organizations (HROs) operations; these organizations are highly safe, highly hazardous and highly significant for the modern society, not only for the valuable resources they have, but also the indispensable services they provide. This research intend to understand how HROs could produce high quality performance despite their challenging and demanding contexts. The research followed an emic approach to develop an organizational framework that reflects the contribution of the seeming traits of the organizations to the operations safety based on the workers point of views about the safety of workstations.

Design/methodology/approach

This research adopted mixed methods of in-depth interviews and literature review to identify the structural characteristics of high-reliability organizations (HROs) embedded in the organizations studies and developed a theoretical based structural framework for HROs. Furthermore, a systemic literature review was adopted to find the evidence from the organizations literature for the identified characteristics from the interviews from the first stage. The setting for this study is six Chinese power stations, four stations in Hubei province central China and two stations in the southern China Guangdong province.

Findings

The organizational framework is a key determinant to achieve high-reliability performance; however, solely it cannot explain how HROs manage the risks of hazard events and operate safely in high-hazard environments. High-reliability performance is attributed to the interaction between two sets of determinants of safety and hazard. The findings of this research indicate that HROs systems would be described as reliable or hazardous depending on the tightly coupled setting, complexity, bureaucracy involvement and dynamicity within the systems from one hand, and safety orientation, failure intolerance, systemwide processing, the institutional setting and the employment of redundant systems on other hand.

Originality/value

The authors developed an organizational framework of organizing the safety work in HROs. The applied method of interviewing and literature review was not adopted in any other researches.
The role of absorptive capacity and organizational unlearning in the link between social media and service dominant orientation
Authors: Ortega-Gutiérrez Jaime , Cepeda-Carrión Ignacio , Alves Helena
Published: May 2021

Purpose

This paper aims to study the relationship between the knowledge obtained in social networks by firms together with the firms’ knowledge absorptive capacity and organizational unlearning as influencers of service-dominant (S-D) orientation, as well as the mediating role of absorption capacity and organizational unlearning in this process.

Design/methodology/approach

The sample amounts to 101 responding companies, obtained from the SABI database. The companies belong to the service sector in Spain and have at least 50 employees and 5 years or more of existence in the market. The model was estimated through partial least squares structural equation modeling with smartPLS software 3.2.6.

Findings

The results show that the use of social media is very important for firms to acquire knowledge and capabilities that help them to become S-D oriented. In addition, absorptive capacity and unlearning processes are dynamic capabilities necessary to transform the knowledge acquired in social media and to become S-D oriented.

Research limitations/implications

Companies’ managers draw conclusions that can generate great value, while better meeting the needs and desires of the market, the more knowledge is obtained. In addition, the use of the knowledge generated in this process will reduce the risk of sudden changes in the market.

Practical implications

The more knowledge is gained using social networks, the better the companies’ managers will be able to draw conclusions that can generate great value, while at the same time better satisfying the needs and desires of the market, and thus create capacities that allow the company to be service-oriented. In addition, the use of these knowledge platforms strengthens the strategic advantage of companies through the promotion of innovation and by relating dynamic capabilities with the orientation toward sustainable development. As mentioned above, a process will be generated that will reduce the risk of sudden changes in the market.

Originality/value

This is one of the few studies trying to study the antecedents of S-D orientation and the first to study the direct effect of social media use, and the direct and indirect effect of absorptive capacity and organizational unlearning on S-D orientation as dynamic capabilities.
Attended home delivery in Indian public distribution system: an iterated local search approach
Authors: Chakraborty Sayan , Darbhe Kalpit , Sarmah Sarada
Published: May 2021

Purpose

In the modern era of e-grocery, attended home delivery (AHD) has been identified as a crucial part of the last-mile delivery problem. This paper aims to deal with a real-life last-mile-delivery problem in the context of the Indian public distribution system (PDS). The authors identified two different environments for the said AHD problem and proposed two different approaches to address the issue under these problem settings.

Design/methodology/approach

In this study, the authors first consider the problem in a static environment and propose an iterated local search (ILS) integrated with an adaptive large neighborhood search (ALNS) meta-heuristic algorithm to obtain a routing solution. Thereafter, they extend the study in a dynamic environment where new delivery requests occur dynamically and propose a heuristic algorithm to solve the problem. For the dynamic case, multiple scenarios for the occurrence of delivery requests are considered to determine decisions regarding the opportunity to include a new request into the current solution.

Findings

By computational experiments, the authors show that the proposed approach performs significantly well for large size problem instances. They demonstrate the differences and advantages of the dynamic problem setting through a set of different scenarios. Also, they present a comparative analysis to show the benefits of adopting the algorithm in dynamic routing scenarios.

Research limitations/implications

Future research may extend the scope of this study by incorporating stochastic delivery failure probabilities and customer behavior affecting the delivery response. Also, the present study does not take inventory policies at the depot into consideration. It will be of interest to see how the system performs under the uncertainty of supply from the depot. Despite the limitations, the authors believe that this study provides food for thought and encouragements for practitioners.

Practical implications

This study shows the benefits of adopting an AHD problem in a dynamic setting in terms of customer service as compared to a traditional static environment. The authors clearly demonstrate the differences and advantages of the dynamic problem setting through a set of different scenario analysis.

Social implications

This paper investigates a real-life AHD problem faced by the Department of Food, Supply and Consumer Affairs, India. The findings of this study will be of particular interest to the policy-makers to build a more robust PDS in India.

Originality/value

The study is unique and highly relevant for real-world applications and can help build a more robust AHD system. Also, the proposed solution approaches to aid the problem in both static and dynamic routing scenarios will be of particular interest to practitioners.
Factors related to suicide among students: a narrative review of psychological literature
Authors: Javed Saba , Munawar Khadeeja
Published: May 2021

Purpose

The purpose of this paper is to provide an educational overview of suicidal behavior and the factors related to suicidality among students between the ages of 18 and 30 years.

Design/methodology/approach

The literature related to suicide among students were identified through various electronic database searches. The databases searched included: PsycINFO, PubMed, MEDLINE, ERIC/ProQuest, Embase, Scopus, Google Scholar and PMC using the following search terms and their derivatives: suicide/self-harm, suicide risk and students, mental health issues and suicide, substance use and suicide, childhood adversities and suicide, recent life stressors, help-seeking attitude and elevated suicidal risk, help-seeking behavior and suicide and subjective factors and suicide.

Findings

Suicide is an important public health problem. Several factors influence suicide (including suicidal ideation and taking life or dying by suicide) such as genetics, family functions, socioeconomic status, personality and psychiatric comorbidity. The main themes that were investigated included: mental health issues, childhood adversity and recent life stressors, barriers toward seeking professional help and subjective factors (psychache risk of suicidal behavior, impulsivity, aggression).

Originality/value

This review focuses on several modifiable psychological factors that have been shown to contribute toward suicidal ideation in youth, especially among university students.
Five strategy shifts for innovation
Authors: Dobni C. Brooke , Klassen Mark , Wilson Grant Alexander
Published: May 2021

Purpose

In an era where competitive landscapes are changing dynamically, traditional strategic approaches are no longer delivering the value required to support growth in many organizations. In response, many organizations have pursued an innovation agenda, but with mixed results. This paper offers five implementation “shifts” for more effective strategy execution.

Design/methodology/approach

Based on two recent global innovation studies, five strategy shifts were identified, permitting organizations to amplify their strategy without having to completely abandon current methods. These shifts were derived by analyzing the most polarizing differences between high innovative organizations and low innovative organizations in the global innovation studies.

Findings

The five strategy shifts include the engagement in innovation culture management, strategic external collaborations, advanced technologies, innovation methodologies, and measurement of innovation.

Originality/value

Examples of how organizations can operationalize strategy shifts are provided so executives can increase innovativeness and see how traditional strategic approaches fall short.
Local adaptation to contrasting climatic conditions in Sakhalin fir (Abies sachalinensis) revealed by long‐term provenance trials
Authors: Ishizuka Wataru , Kon Hirokazu , Kita Kazuhito , Kuromaru Makoto , Goto Susumu
Published: May 2021

Conifer populations across wide geographical ranges often demonstrate adaptation to local environments related to heterogeneous climatic conditions. Long‐term provenance experiments are powerful tools for evaluating transfer effect and detecting a home‐site advantage in transplant performance. The transplant responses of Sakhalin fir (Abies sachalinensis), which is widely distributed in the boreal forests of Hokkaido, northern Japan, were evaluated by >30‐year‐old provenance trials using seed sources throughout Hokkaido and conducted at two sites, namely Akkeshi (AKS) and Bibai (BBI), with contrasting conditions in climates of snowfall in winter and sun exposure in summer. Intraspecific variations among seed sources were observed in survival rate, tree height, diameter, and volume (V) at the both sites. To test the home‐site advantage, we used the transplant performance (survival rate × V) and two transfer distances; the geographic horizontal distance (GDIST) between seed sources and the sites; as well as the environmental distance (EDIST) that was calculated from principal components of candidate climatic factors. In general, the decrease of the transplant performance with increasing transfer distance was detected at the both sites, thus indicating the remarkable home‐site advantage of this species. The best models using EDIST at site AKS and using GDIST at site BBI were selected, and larger transfer effect was predicted at site AKS. Distinct adaptive divergence among seed sources at site AKS was consistent with already known intraspecific variations in juvenile‐growth and some tolerances to snowfall‐related stresses. The climatic gradient associated with winter conditions in Hokkaido might involve asymmetric local adaptation in A. sachalinensis.
Review article: Paramedic pain management of femur fractures in the prehospital setting: A systematic review
Authors: Davis Samantha , Olaussen Alexander , Bowles Kelly‐Ann , Shannon Brendan
Published: May 2021

Femur shaft and neck of femur (NOF) fractures are often undertreated in the prehospital setting. These injuries can present unique clinical and logistical concerns in the prehospital setting. This systematic review aimed to investigate paramedic prehospital pain management of patients who had suffered NOF or femur fractures, and to investigate which interventions are effective. A systematic review was conducted in line with Preferred Reporting Item for Systematic Reviews and Meta‐Analyses guidelines. Four databases were searched from inception date 23 March 2020. Articles were independently reviewed by two authors and conflicts resolved by a third author, followed by a hand search of the included reference lists. References were included if they addressed paramedic interventions for NOF or femur shaft fractures. Outcomes of interest were the effectiveness and complications of different modalities administered by paramedics. The search yielded 6868 articles, of which 19 met the final inclusion criteria. Studies investigated a variety of interventions including traction splints, intravenous (IV) analgesia and alternative analgesic options. Traction splinting and IV analgesia were consistently reported as underutilised. Alternative analgesics such as auricular acupressure, transcutaneous electrical nerve stimulation (TENS) and fascia iliaca compartment block were found to be effective techniques that could be safely and competently employed by paramedics, reducing pain for patients with limited adverse events. NOF and femur shaft fractures are an undertreated injury in the prehospital setting. Traction splinting and IV analgesia remain the traditional methodologies of treatment for these injuries; however, there are alternatives such as TENS, auricular acupressure and fascia iliaca compartment block that appear to be emerging as safe and effective options for the prehospital setting.
Impact of a Persistent Pelvic Pain Clinic: Emergency attendances following multidisciplinary management of persistent pelvic pain
Authors: Wilkinson Rachel , Wynn‐Williams Michael , Jung Albert , Berryman Jayne , Wilson Erin
Published: May 2021

Persistent pelvic pain (PPP) is an important cause of psychological distress and productivity loss in women. In 2017, a multidisciplinary clinic was established to care for Queensland women with PPP. By analysing clinic and emergency department data, we found 19% fewer patients required any presentation to the emergency department for exacerbations of pelvic pain (P = 0.003) within 12 months of clinic attendance. There was also a reduction in number of presentations, short stay admissions and daily opiate use in regular users. The Persistent Pelvic Pain Clinic (PPPC) made a difference to these women and reduced resource burden on a busy emergency department.
Pregnant women report being denied medications to treat severe nausea and vomiting of pregnancy or hyperemesis gravidarum – findings from an Australian online survey
Authors: Hsiao Han‐Fang , Thomas Alicia , Kay‐Smith Caitlin , Grzeskowiak Luke E.
Published: May 2021

We conducted an online survey of 249 Australian women who currently or previously experienced severe nausea and vomiting of pregnancy (NVP) or hyperemesis gravidarum (HG) and examined their experiences in being denied medications during pregnancy. One in four women reported being denied medications for NVP/HG, which most commonly involved doxylamine and encounters with community pharmacists. Women’s experiences reflected that lack of awareness of guidelines and unfavourable risk‐benefit assessments appeared to be key barriers to facilitating medication access. Approaches towards identifying and effectively addressing barriers to the provision of effective treatments for severe NVP and HG are urgently needed.
Increasing use of intraoperative cholangiogram in Australia: is it evidence‐based?
Authors: Mui Jasmine , Mayne Darren J. , Davis Kimberley J. , Cuenca Jose , Craig Steven J.
Published: May 2021

Background

The role of routine intraoperative cholangiograms (IOCs) for prevention of bile duct injury (BDI) is contentious. There are recent reports of limited utility of IOC in preventing BDI. In Australia, IOCs are used more frequently than internationally. This study aimed to evaluate the rate of IOC use in Australia and explore potential changes in practice in light of evolving evidence for the utility of IOC.

Methods

Data were collated using service item numbers in Medicare Benefits Scheme records on the Australian Government Medicare website, for services claimed between 1 January 2001 and 31 December 2019. These data were used to analyse trends in rates of IOC, cholecystectomy and BDI repair. Data were age‐standardized to account for changes in the population over time.

Results

The number of IOCs claimed increased by 31.8% and cholecystectomies by 7.0% over the study period. Age‐standardized service rates per 100 000 persons increased by 5.5 and 32.6, respectively. Rates of IOC per 100 000 cholecystectomies steadily increased across the study period, while BDI repair rates remained low and erratic.

Conclusion

Increasing use of IOC over the last 20 years reflects a trend towards routine rather than selective IOC; however, there is little discernible change in the number of BDIs requiring repair procedures. This suggests that routine IOC use to prevent or minimize BDI is unwarranted. Further investigation is required into the selective IOC use in high‐risk patients rather than mandatory use in all patients.
Has the reporting of patient‐important outcomes improved in surgical trials? A meta‐epidemiological study
Authors: Menon Rahul , Wang Andy , Chamberlain Kira , Harris Laura , Li Tom , Harris Ian A , Naylor Justine , Pinheiro Marina B , Adie Sam
Published: May 2021

Background

Clinical trials should ideally use patient‐important outcomes to ensure their results are clinically relevant. We aimed to determine if the proportion of patient‐important outcomes in surgical trials has changed over the last decade, and to determine whether patient‐important outcomes are more likely to be specified as primary outcomes.

Methods

The 350 most recent randomized controlled trials examining surgical interventions on humans and published in English were included. Outcomes were classified as patient‐important, surrogate or laboratory using standardized definitions, along with either primary, secondary or unspecified. Mean proportions were calculated across all trials and a chi‐squared test was used to detect the difference between time periods. Contingency tables were populated with each trial's outcomes, characterizing whether each outcome was patient‐important or not, and whether it was specified as primary or secondary. Odds ratios were then combined in a random‐effects meta‐analysis to calculate a pooled odds ratio.

Results

A total of 64% of all outcomes were patient‐important. The mean (standard deviation) proportion of patient‐important outcomes per trial was 66% (31.4), which significantly increased over the last decade, from 60% (31.6) in 2009. The mean proportion of primary outcomes which were patient‐important increased from 64% (46.0) in 2009 to 77% (40.6) in 2019. Patient‐important outcomes were not significantly associated with being a primary outcome and this did not change significantly over the decade.

Conclusion

Patient‐important outcomes are still poorly represented as primary outcomes. The ongoing impact of updated reporting guidelines may improve the reporting of patient‐important outcomes in surgical trials.
The origins of imperial yellow glazed porcelain in the Ming Dynasty (1,368 to 1,644) China: Technical comparison to low‐fired tile with yellow glaze
Authors: Hou Jia Yu , Li He , Kang Bao Qiang , Wood Nigel , Wang Guang Yao , Jiang Jian Xin , Wang Zhe Yu , Zou Fu An
Published: May 2021

The imperial yellow‐glazed porcelain of the Ming Dynasty originated in the early15th century AD. Its high status and fine material quality make its beginnings, glaze characteristics and technological development worthy of further study. In this research, EDXRF, optical microscope and spectrophotometer were used to investigate both yellow‐glazed tiles and imperial porcelains of the early Ming Dynasty. It was found that the imperial yellow glaze is essentially similar to that used on glazed tile, both of which are high‐lead, low‐temperature compositions. However, there is a clear high‐temperature glaze between the coloured glaze and the body paste of imperial yellow‐glazed porcelain, which makes the glaze brighter and provides a warm jade‐like texture. In addition, the slightly bluish tones of the clear glaze and body paste of imperial yellow‐glazed porcelain correct the colour of the iron‐based, low‐temperature lead glaze, which has a reddish component. Therefore, compared with the early Ming Dynasty glazed tiles, imperial yellow‐glazed porcelain achieves a higher glaze brightness and a purer yellow hue. In summary, imperial yellow‐glazed porcelain can be seen as a combination of lead‐glazed tile and Jingdezhen porcelain technology in the early Ming Dynasty.
Testicular structure and development of the male germinal epithelium in the freshwater drum Aplodinotus grunniens (Perciformes: Sciaenidae) from the Usumacinta River, Southern Mexico
Authors: Hernández‐Gómez Raúl Enrique , Contreras‐Sánchez Wilfrido Miguel , Hernández‐Franyutti Arlette , Perera‐García Martha Alicia , Torres‐Martínez Aarón
Published: May 2021

The present study describes the morphological changes in the male germinal epithelium of the freshwater drum Aplodinotus grunniens inhabiting southern Mexico. To our knowledge, this is the first study to provide a detailed description of the testicular structure and morphological changes of the germinal epithelium of this species. Based on the histological characteristics of the germinal epithelium, four main reproductive phases were described in A. grunniens males: Developing, Spawning Capable, Regressing and Regenerating. The germinal epithelium varied from a proliferative continuous germinal epithelium during the regenerating and development phases to a sperm storing discontinuous germinal epithelium during the Spawning Capable and Regressing phases. The seminiferous lobules ranged from a simple unrestricted lobular organization to an anastomosing‐like testis that transformed the testis of A. grunniens into a sperm storage organ. Our study provides valuable information about the morphophysiological aspects of the testis of A. grunniens that may be used for further investigations on the testicular physiology of this species or for comparative studies on gonad morphology. The description of the testicular cycle of the freshwater drum provided here will allow the reproductive staging of male individuals for a variety of purposes either for fisheries management or for the incipient aquaculture of this species.
Dietary nitrate prevents progression of carotid subclinical atherosclerosis through blood pressure‐independent mechanisms in patients with or at risk of type 2 diabetes mellitus
Authors: Morselli Franca , Faconti Luca , Mills Charlotte E. , Morant Steven , Chowienczyk Philip J. , Yeung Joshua Au , Cavarape Alessandro , Cruickshank J. Kennedy , Webb Andrew J.
Published: May 2021

Aims

To test if 6 months' intervention with dietary nitrate and spironolactone could affect carotid subclinical atherosclerosis and stiffness, respectively, vs. placebo/doxazosin, to control for blood pressure (BP).

Methods

A subgroup of participants in our double‐blind, randomized‐controlled, factorial VaSera trial had carotid imaging. Patients with hypertension and with/at risk of type 2 diabetes were randomized to active nitrate‐containing beetroot juice or placebo nitrate‐depleted juice, and spironolactone or doxazosin. Vascular ultrasound for carotid diameter (CD, mm) and intima–media thickness (CIMT, mm) was performed at baseline, 3‐ and 6‐months. Carotid local stiffness (CS, m/s) was estimated from aortic pulse pressure (Arteriograph) and carotid lumen area. Data were analysed by modified intention to treat and using mixed‐model effect, adjusted for confounders.

Results

In total, 93 subjects had a baseline evaluation and 86% had follow‐up data. No statistical interactions occurred between the juice and drug arms and BP was similar between the juices and between the drugs. Nitrate‐containing vs. placebo juice significantly lowered CIMT (−0.06 [95% confidence interval −0.12, −0.01], P = .034), an overall difference of ~8% relative to baseline; but had no effect on CD or CS. Doxazosin appeared to reduce CS from baseline (−0.34 [−0.62, −0.06]) however, no difference was detected vs. spironolactone (−0.15 [−0.46, 0.16]). No differences were detected between spironolactone or doxazosin on CIMT and CD.

Conclusions

Our results show that 6 months' intervention with dietary nitrate influences vascular remodelling, but not carotid stiffness or diameter. Neither spironolactone nor doxazosin had a BP‐independent effect on carotid structure and function.
Implementation of oral anticoagulation treatment guidelines in patients with newly diagnosed atrial fibrillation
Authors: Arbel Anat , Abu‐Ful Zomoroda , Preis Meir , Cohen Shai , Saliba Walid
Published: May 2021

Aims

Oral anticoagulants (OACs) are considered the mainstay in preventing stroke in atrial fibrillation (AF). OAC treatment remains suboptimal among AF patients, even after the introduction of direct oral anticoagulants (DOACs). We aimed to assess trends overtime and current implementation of OAC treatment guidelines in AF, using a large dataset of real world data from Israel.

Methods

This is a retrospective cohort study that includes all adult members of Clalit Health Services, the largest healthcare provider in Israel, with newly diagnosed nonvalvular AF between January 2014 and December 2019 with CHA2DS2‐VASc score ≥2. OAC treatment rates were calculated and multivariate regression models were used to identify predictors of OACs initiation.

Results

Overall, 46 531 patients were included in the study. The 3‐months cumulative OAC treatment rates increased consistently over the years: 46.9% (95% confidence interval, 46.1–47.7%), 54.9% (54.1–55.6%) and 61.7% (60.9–62.4%) during 2014–2015, 2016–2017 and 2018–2019, respectively. DOACs constituted 51.3% of prescribed OACs in 2014–2015 and increased to 95.1% during 2018–2019. On multivariate analyses, the likelihood of OACs initiation among AF patients increased across the years and across higher socioeconomic classes, and was more likely among females, Jews, statins users and patients previously screened for colorectal cancer, but less likely among smokers and patients with impaired renal function. The likelihood of treatment increased with higher CHA2DS2‐VASc score and decreased with higher HAS‐BLED score.

Conclusion

Despite the increasing OAC treatment rates among high‐risk AF patients, mainly attributed to the expanding DOAC use, OAC treatment scope is still far from optimal.
Negative interpretations of ambiguous ‘psychosis‐like’ and ‘anxiety‐like’ experiences in recovery from psychosis or anxiety
Authors: Sired Rebecca , Griffith Emma , Jamalamadaka Taruna , Salkovskis Paul
Published: May 2021

Objectives

Fear of relapse (FOR) after experiencing psychosis has been found to predict actual relapse; however, potential mechanisms underlying this relationship have not been investigated. Negative appraisals of ‘prodromal symptoms’ are believed to play an important role in both psychosis and mental health anxiety (MHA). This study aimed to explore whether people in recovery from psychosis or anxiety disorders show an enduring tendency to negatively interpret ambiguous experiences both related and less related to their previous mental health difficulty relative to controls.

Design

Cross‐sectional between‐groups questionnaire design.

Methods

Participants self‐reported as in recovery from psychosis (n = 33) or anxiety (n = 77) or without previous experience of mental health problems (n = 61) were recruited online or via NHS services. Interpretations of psychosis‐like, anxiety‐like, and external‐control experiences were measured using the newly developed Experiences Interpretation Questionnaire (EIQ). MHA and FOR were measured using self‐report questionnaires.

Results

People in recovery from psychosis interpreted psychosis‐like experiences significantly more negatively than the other groups. Negative interpretations of anxiety‐like experiences were greater than controls but comparable between mental health groups. Contrary to predictions, FOR was not significantly different between the mental health groups. MHA and FOR did not significantly predict negative interpretations of psychosis‐like items in the psychosis group, however, MHA predicted negative interpretations of anxiety‐like items in the anxiety group. The EIQ subscales demonstrated good test–retest reliability.

Conclusions

People in self‐defined recovery from psychosis or anxiety are more likely to negatively interpret ambiguous experiences relating to their previous mental health difficulties. Clinical and future research implications are outlined.

Practitioner points

People in recovery from psychosis or anxiety appraise possible symptoms of their previous difficulties negatively/catastrophically (as indicating relapse) relative to those without prior MH problems.

Clinicians should consider attending to how people in recovery appraise possible symptoms when encouraging early signs monitoring as part of relapse prevention. This may be important to ensure that self‐monitoring leads to helpful responses rather than being counterproductive, with catastrophic interpretations leading to anxiety and thus increasing the risk of relapse.

Interventions drawing on CBT principles to address catastrophic interpretations of possible symptoms may potentially be a useful addition to relapse prevention work; in psychosis this may also include symptoms of anxiety.
The timing of 30‐month stay expirations and generic entry: A cohort study of first generics, 2013–2020
Authors: Kannappan Sunand , Darrow Jonathan J. , Kesselheim Aaron S. , Beall Reed F.
Published: May 2021

Before the first generic version of a drug is marketed, patent litigation often occurs. The process begins when generic manufacturers notify the US Food and Drug Administration (FDA) of their intent to market a generic copy of a brand‐name drug protected by patents, which they allege to be invalid or not infringed (called a Paragraph IV certification). Assuming the brand‐name manufacturer responds with litigation within 45 days, a 30‐month stay period is triggered, which bars the FDA from authorizing generic entry until the stay period expires or litigation is resolved in favor of the generic manufacturer. To understand whether 30‐month stays delay generic entry, we examined the timing of major legal events leading to generic entry for a cohort of 46 generic drugs, including the timing of Paragraph IV certification filings, stay period expirations, the FDA approvals of generics, and generic product launches. We found Paragraph IV certifications were filed a median of 5.2 years after the brand drug’s FDA approval. There was a median of 3.2 years between the stay period expiration and subsequent generic launch. Because stay periods generally expire well in advance of when generic entry typically occurs, 30‐month stays are unlikely to delay the timing of generic entry. Patent litigation could begin even earlier, however, if litigation was allowed to start immediately following a brand‐name drug’s FDA approval; but by law currently, the soonest this can begin is 4 years after the brand drug’s FDA approval.

Study Highlights

WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Before generic versions of new drugs reach the market, patent litigation often occurs. Once litigation has been initiated, a 30‐month regulatory stay period is triggered that bars the US Food and Drug Administration (FDA) from approving the generic application until litigation resolves or the stay period expires.

WHAT QUESTION DID THIS STUDY ADDRESS?

What is the timing of key legal events in the regulatory approval process for generic drugs in relation to the eventual launch of the generic product?

WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

We identified the typical timing of the initiation of patent litigation and expiration of the 30‐month stay period prior to the eventual launch of generic products. Litigation is often initiated as soon as legally possible (i.e., 4 years after the launch of the brand product), and stay periods typically expire well before generic entry occurs.

HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Stay periods are unlikely to delay generic entry directly because stay expirations often occur well before the time of generic launch. Allowing the submission of generic drug applications immediately following a brand drug’s FDA approval would facilitate earlier patent dispute resolution and prevent unnecessary delays in the anticipated generic product launch date.
Sweet syndrome with perifollicular involvement because of koebnerization from facial hair plucking
Authors: Flanagan Kelly E. , Krueger Steven , Amano Shinya , Auerbach Amanda , St. John Jessica , Deng April
Published: May 2021

Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is an uncommon skin eruption characterized by fever, leukocytosis, and tender erythematous papules, nodules, and plaques. Histopathologically, SS lesions are characterized by marked superficial papillary edema with a dense neutrophilic infiltrate. SS is known to demonstrate both the Koebner phenomenon and pathergy. The majority of reported cases of these phenomena occur following significant cutaneous injury (e.g., biopsies, burns) rather than minor trauma such as pressure and friction. Here, we present the first known reported case of SS koebnerization secondary to minor grooming‐related hair plucking. In addition, this is also the first reported case to our knowledge of SS with perifollicular involvement on histopathology.
The level of agreement between rapid‐on‐site evaluation of endoscopic ultrasound fine needle aspirate and surgical histological diagnosis in gastrointestinal lesions
Authors: Khoury Tawfik , Sbeit Wisam
Published: May 2021

Objective

Endoscopic ultrasound (EUS) is the main tool for biopsy via fine needle aspiration (FNA) from gastrointestinal (GI) lesions including pancreatic, upper gastrointestinal, and adjacent lesions. The variable diagnostic yield and delay until the final pathological results can affect treatment planning and cause patient anxiety. We aimed to assess the agreement of rapid on‐site evaluation (ROSE) of EUS‐FNA with the surgical histological diagnosis of patients who underwent resection.

Method

A retrospective study was performed including all patients 18 years or older who underwent EUS‐FNA with ROSE for GI lesions. For patients who underwent surgical resection, the correlation between ROSE and the surgical histological diagnosis was evaluated with the kappa coefficient.

Results

Overall, 73 patients who underwent EUS‐FNA with ROSE were included, of whom 22 (30.1%) had curative resection. The final pathological diagnosis from surgery showed 17 malignant and 5 benign lesions. Among the benign lesions, ROSE correctly identified 2 (diagnostic accuracy of 40%), while among the malignant lesions, ROSE correctly identified 14 (diagnostic accuracy of 82.4%), yielding a fair kappa coefficient of 0.366 (95% CI 0.035‐0.697). When classifying the lesions as either malignant vs benign or suspicious of malignancy, the kappa coefficient increased to 0.58 (95% CI 0.180‐0.975) for the subgroup of pancreatic lesions, with diagnostic accuracy of 81.2% for the malignant category.

Conclusions

A high level of agreement for malignancy was found between FNA‐EUS with ROSE and the final surgical histological diagnosis. ROSE can be used as an adjuvant diagnostic tool to optimise patient management and decrease delay‐related anxiety.
Problems in using Beals' index to detect species trends in incomplete floristic monitoring data (Reply to Bruelheide et al. (2020))
Authors: Christensen Erik , Christensen Björn , Christensen Sören
Published: May 2021

Bruelheide et al. (Diversity and Distributions, 26, 2020, 782) explored repeated habitat mapping data to identify floristic changes over time on the basis of two surveys. Because of the incompleteness of the data, they utilized the Beals' index based on the aggregated data from both surveys as a statistical tool for the analysis. The aim of this note is to illustrate problems of this approach, which in particular is shown to produce a systematic underestimation of species decrease (and—potentially less relevant in practice—increase). A specific set of model cases will be introduced to show the effects of unjustified usage of the Beals' index in this specific form.