bluuebunny/crossref_metadata_2025 huggingface dataset:
Amelioration of cyclosporine‐induced testicular toxicity by carvedilol and/or alpha‐lipoic acid: Role of TGF‐β1, the proinflammatory cytokines, Nrf2/HO‐1 pathway and apoptosis
Authors: Kabel Ahmed M. , Salama Samir A. , Alghorabi Amal A. , Estfanous Remon S.
Published: February 2020

Cyclosporine is an immunosuppressive agent that is used to prevent organ rejection after organ transplantation. Due to the widespread use of this type of surgery, the effect of cyclosporine on reproduction and fertility should have a specific interest. Our aim was to assess the effect of carvedilol and/or alpha‐lipoic acid on cyclosporine‐induced testicular toxicity in rats. Sixty male Wistar rats were divided into six equal groups: Control; cyclosporine; cyclosporine + carvedilol; cyclosporine + alpha‐lipoic acid; cyclosporine + carboxymethyl cellulose; and cyclosporine + carvedilol +alpha‐lipoic acid. Food intake, testis weight, testicular functions, serum testosterone, luteinizing hormone and follicle‐stimulating hormone were measured. Also, testicular tissue 3 β‐hydroxysteroid dehydrogenase, 17 β‐ hydroxysteroid dehydrogenase, paroxonase‐1, proinflammatory cytokines, transforming growth factor beta‐1, nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2)/Heme oxygenase‐1 (HO‐1) content and sperm characteristics were determined. Parts of the testes were subjected to histopathological and electron microscopic examination. The carvedilol/alpha‐lipoic acid combination restored the food intake, testicular weight and functions, sperm characteristics, hormonal profile and the antioxidant defences compared to the use of each of these drugs alone. Also, this combination significantly ameliorated inflammation (P < .05) and induced significant increase in tissue Nrf2/HO‐1 content (P < .05) and significant improvement of the histopathological and electron microscopic picture (P < .05) compared to the use of each of these drugs alone. So, carvedilol/alpha‐lipoic acid combination might represent a novel therapeutic strategy to ameliorate testicular damage induced by cyclosporine.
What do stress tests test? Experimentation, demonstration, and the sociotechnical performance of regulatory science
Authors: Coombs Nathan
Published: February 2020

After their successful introduction during the 2007–2009 financial crisis, central bank stress tests were adopted as a fixture of international banking supervision. However, in recent years a new normal has emerged where banks are expected to pass the tests, raising questions about the tests’ usefulness and legitimacy. Combining a dramaturgical interpretation of regulatory science with the idea of performativity in the sociology of finance, this article understands stress tests as a sociotechnical Goffmanian performance. With a focus on the Bank of England’s program, the paper argues that the Bank’s decision to make their tests “predictable” is an attempt to shore up central bank legitimacy by constraining regulatory discretion. This is accomplished through the use of calculative and procedural stage management techniques which allow the Bank to control the contingency of the testing process while demonstrating its objectivity. Nevertheless, the conclusion suggests that in the context of low levels of trust in central banks, routine declarations of “all clear” may undermine public confidence in the tests’ credibility and necessity. The study draws on 20 interviews with high‐level regulators, financial practitioners and other stakeholders in the Bank of England’s stress tests.
Antioxidant potential of chrysanthemum morifolium flower extract on lipid and protein oxidation in goat meat patties during refrigerated storage
Authors: Khan Iftikhar Ali , Xu Weimin , Wang Daoying , Yun Ang , Khan Asad , Zongshuai Zhu , Ijaz Muhammad Umair , Yiqun Cheng , Hussain Muzahir , Huang Ming
Published: February 2020

Flavonoid and phenolic acid profile of chrysanthemum morifolium flower extract (CME) was analyzed by using ultra‐performance liquid chromatography (Q‐TOF–MS, Xevo G2‐S; Milford, MA, USA, Waters) system in tandem with a quadruple time‐of‐flight mass spectrometer. The effect of CME on lipid and protein oxidation was investigated in goat patties during 9 days of refrigerated storage (4 ± 1 °C). Patties were prepared from freshly minced meat with the addition of 0.1% and 0.2% CME and compared with the butylated hydroxytoluene (BHT) (0.01%) and control. High level of thiol and lower level of thiobarbituric acid reactive substances and carbonyl content were observed in CME‐treated samples compared to control during storage period. The incorporation of CME in patties reduced the pH and water activity values markedly, but no effect was found on color and sensory analyses. These results show that increased level of CME is more effective against lipid and protein oxidation and therefore can be used as a natural antioxidant in meat products without affecting product acceptability.

Practical Application

Chrysanthemum morifolium flower belongs to the family “Asteraceae” and is a novel natural antioxidant for meat processing industry. It possesses strong antioxidant activities having many phenolic compounds including gallocatechin, apigenin, rosmarinic acid, caffeic acid, rhamnetin, and quercetin, and can be used for development and production of functional food as a natural antioxidant agent.
Diagnostic imaging: Doing the right thing
Authors: Mendelson Richard M
Published: February 2020

Inappropriate diagnostic imaging (DI) is a burgeoning issue and embraces its overuse and its misapplication. The obverse problem is one of underuse – that is when patients who should undergo imaging fail to do so. This article attempts to define these problems, examines the causes and effects and suggests some potential solutions.
Can time‐to‐detection models with fewer survey replicates provide a robust alternative to traditional site‐occupancy models?
Authors: Henry Dominic A. W. , Lee Alan T. K. , Altwegg Res
Published: February 2020

Traditional occupancy models that record detection/non‐detection (DND) of a species typically rely on either spatial or temporal survey replication to estimate model parameters. Recording the time until a species is first encountered after starting a survey is often possible with little extra effort and such time‐to‐detection (TTD) surveys may be more efficient than pure DND surveys. Using continuous time data, TTD occupancy models can in theory estimate occupancy and detection parameters using a single TTD survey. However, the robustness and general applicability of TTD models has not been widely addressed and their effectiveness in different study systems remains unknown.

We use simulations and bird data of 63 species from a field study in the Karoo region of South Africa to explicitly compare estimates of occupancy, detection and species richness between DND and TTD models under various levels of survey replication and for species with different occupancy and detection characteristics.

Simulations revealed that for inconspicuous species single survey TTD models can perform better or equally as well as DND models with a higher number of replicates. This effect was attenuated in widespread species. The benefits of TTD models were more pronounced at low survey replicates and performance of the two methods converged quickly as the number of survey replicates increased. However, results from the field data showed that a single TTD survey was not adequate to reliably estimate occupancy, detection and species richness; especially in rare and inconspicuous species. Increasing the number of TTD surveys to two replicates improved the models substantially.

Our results demonstrate that the general utility of TTD surveys depends on the characteristics of the species considered in the study. A single TTD survey may be sufficient in some study designs but is unlikely to be sufficient in most multi‐species field scenarios where communities are made up of species that have a wide range of detection and occupancy probabilities. TTD surveys do provide benefits, however, in that data can be used to construct detection curves which can be used to guide survey effort in the design of future studies.
Australian not‐for‐profit sector views on the conceptual framework, accounting standards and accounting information
Authors: Kober Ralph , Lee Janet , Ng Juliana
Published: February 2020

In this paper, we examine the conceptual framework, accounting standards and accounting information relevant to the not‐for‐profit (NFP) sector. Based on the responses of 242 Australian NFP managers, we find support for the inclusion of accountability in the conceptual framework, and for a common set of accounting standards across NFP and for‐profit sectors with additional standards or paragraphs to recognise NFP specific issues. Respondents also rated information within general‐purpose financial reports to be useful for decision making within their organisations. We offer suggestions as to what our findings mean for the development of accounting standards for the NFP sector.
Risk‐factors for continuous long‐term use of prescription opioid drugs 3 years after hysterectomy: A nationwide cohort study
Authors: Brunes Malin , Häbel Henrike , Altman Daniel , Ek Marion
Published: February 2020

Introduction

The widespread misuse of prescription pain medication, including opioids, has serious public health implications. Postoperative pain is a risk factor for persistent or chronic pain unless treated effectively. There are only a few studies that have assessed the use of opioid‐containing drugs after gynecological surgery and most of these usually have a short follow‐up period. The aim of this study was to identify risk‐factors for long‐term use of prescription opioid drugs following hysterectomy.

Material and methods

We performed a nationwide cohort study based on prospectively collected data. Information from two population‐based registers, the Swedish National Quality Register of Gynecological Surgery and the Swedish National Drug Register, was linked. The study population consisted of women with benign disease undergoing a total hysterectomy from 1 January 2012 until 31 December 2015. To identify long‐term changes in prescription of opioids, individual data were collected from 1 year prior to to 3 years after surgery between 2011 and 2018. Data analysis was performed using multivariable logistic regression models.

Results

The population included 17 385 women having had hysterectomy for benign disease. Of these women, 4233 (24.4%) were prescribed analgesics continuously for 3 years postoperatively and 1225 (7.1%) used opioids long term. Perioperative predictors of opioid use 3 years after surgery included a diagnosis of adenomyosis (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI] 1.2‐2.7) and preoperative use of opioids (aOR 29.6, 95% CI 19.7‐44.4), psycho‐ (aOR 3.5, 95% CI 2.4‐5.0) and neuroactive drugs (aOR 1.8, 95% CI 1.0‐3.1). For women with no opioid prescription preoperatively (n = 260, 1.5%), mild (aOR 2.8, 95% CI 1.1‐7.3) and severe (3.0% vs 6.2%: aOR 6.4, 95% CI 1.4‐20.0) postoperative complications and preoperative prescription of psychoactive drugs (aOR 4.6, 95% CI 1.9‐10.7) were associated with long‐term use of drugs containing opioids.

Conclusions

Long‐term use of prescription opioids after hysterectomy is common and is, among other risk factors, strongly associated with preoperative use of opioids, as well as psychoactive drugs and adenomyosis. To avoid opioid misuse disorders among women at risk for long‐term opioid drug prescriptions after hysterectomy, further studies and strategies are needed.
Organized labor and corporate philanthropy: Evidence from Korea
Authors: Song Hakjoon , Chun Hongmin , Brodmann Jennifer , Song Youngwook
Published: February 2020

This study examines the impact of organized labor on corporate philanthropy, focusing on Korean firms. We find a positive association between the labor unionization ratio and the corporate philanthropy of firms, especially for non‐Chaebol‐affiliated firms and firms that have positive operating cash flow. The results from the robustness tests, which employ alternative union strength proxies and two‐stage least squares regression analyses, support our major findings. The findings indicate that unionized firms can utilize corporate philanthropy to boost their bargaining power regarding wages and collective bargaining power with unions by reporting lower earnings. This study contributes to the corporate philanthropy and labor union literature by providing evidence that the labor union is a crucial stakeholder that may affect firms' philanthropic behavior. Our findings explain corporate philanthropic decisions in the Korean context.
Morphine‐induced respiratory depression is independent of β‐arrestin2 signalling
Authors: Kliewer Andrea , Gillis Alexander , Hill Rob , Schmiedel Frank , Bailey Chris , Kelly Eamonn , Henderson Graeme , Christie Macdonald J. , Schulz Stefan
Published: February 2020

Background and Purpose

GPCRs can signal through both G proteins and β‐arrestin2. For the μ‐opioid receptor, early experimental evidence from a single study suggested that G protein signalling mediates analgesia, whereas β‐arrestin2 signalling mediates respiratory depression and constipation. Consequently, for more than a decade, much research effort has been focused on developing biased μ‐opioid agonists that preferentially target G protein signalling over β‐arrestin signalling, as it was believed that such drugs would be analgesics devoid of respiratory depressant activity. However, the prototypical compounds that have been developed based on this concept have so far failed in clinical and preclinical development.

Experimental Approach

The present study was set up to re‐examine opioid‐induced respiratory depression in β‐arrestin2 knockout mice. To this end, a consortium was formed consisting of three different laboratories located in different countries to evaluate independently opioid‐induced respiratory depression.

Key Results

Our consensus results unequivocally demonstrate that the prototypical μ‐opioid agonist morphine (3.75–100 mg·kg−1 s.c. or 3–30 mg·kg−1 i.p.) as well as the potent opioid fentanyl (0.05–0.35 mg·kg−1 s.c.) do indeed induce respiratory depression and constipation in β‐arrestin2 knockout mice in a dose‐dependent manner indistinguishable from that observed in wild‐type mice.

Conclusion and Implications

Our findings do not support the original suggestion that β‐arrestin2 signalling plays a key role in opioid‐induced respiratory depression and call into question the concept of developing G protein‐biased μ‐opioid receptor agonists as a strategy for the development of safer opioid analgesic drugs.
Age‐associated changes in chronic rhinosinusitis endotypes
Authors: Ryu Gwanghui , Dhong Hun‐Jong , Park Minsu , Hwang Na Young , Kim Dong‐Kyu , Kim Hyo Yeol , Chung Seung‐Kyu , Rhee Chae‐Seo , Cho Seong‐Ho , Hong Sang Duk , Kim Dae Woo
Published: February 2020

Background

Immunologic function in innate and adaptive immunity changes with the ageing process. Thus, age‐related cytokine profiles in chronic rhinosinusitis (CRS) need to be investigated for precision medicine.

Objective

The objective of this study was to characterize age‐related changes in immunologic profiles according to CRS subtypes.

Methods

Subjects in control (n = 29), CRS without nasal polyps (CRSsNP, n = 86), and CRS with nasal polyps (eosinophilic NP: ENP, n = 81; non‐eosinophilic NP: NENP, n = 113) were enrolled in this study. Twenty markers for type 1/2/3 inflammation and other inflammatory processes were measured in homogenates of sinonasal tissues and statistically analysed.

Results

In control tissues, type 2/3 and proinflammatory mediators showed an inverse correlation with age. CRSsNP and NENP showed an age‐related increase in type 2 cytokines and a decline in type 3 cytokines. Interestingly, the age‐related decrease in type 3 mediators was associated with those of CT scores in NENP. ENP showed an age‐related increase in type 3 cytokines with type 2 mediators sustained at high levels. Smokers with ENP demonstrated age‐associated increases in type 1/2/3 mediators as well as CT scores. These age‐related patterns in each CRS were confirmed by statistically adjusting atopy status, smoking history, and disease duration.

Conclusion

Age‐associated cytokine changes differed among CRS subtypes and control tissues. CRSsNP and NENP demonstrated a decline in type 3 mediators and increase in type 2 mediators, whereas type 3 mediators increased with age in ENP.
d‐dimer is a predictor of clot resolution in patients with pulmonary thromboembolism: A retrospective cohort study
Authors: An Jun , Sun Bo , Ji Yingqun , Zhang Zhonghe , Zhai Zhenguo , Wang Chen
Published: February 2020

Background

This study assessed predictors of pulmonary thromboembolism (PE) resolution and their implications for clinical outcome.

Method

A total of 150 patients with acute PE diagnosed by computed tomography pulmonary angiography (CTPA) were included. All patients received anticoagulant therapy for 3‐6 months and were followed‐up for at least 2 years. d‐dimer levels in plasma were assayed at the first admission and during follow‐up.

Results

The rate of CTPA‐confirmed PE resolution was 48.67% at 6 months, 68% at 12 months, and 78.67% at 24 months. Thirty‐nine patients had recurrent thrombosis after anticoagulation therapy was stopped, whereas 93 patients had complete resolution. The initial d‐dimer level positively correlated with the pulmonary artery obstruction index (PAOI) (r = 0.21; P = 0.015), but did not significantly differ between patients experiencing resolution or recurrence. In contrast, the follow‐up mean d‐dimer level was significantly higher in the recurrent group (P < 0.001), and this level was an independent risk factor for recurrent PE after the termination of anticoagulation treatment (OR 1.003, 95%CI 1.002 to 1.004; P < 0.001). Higher initial thromboembolic burden measured by PAOI was associated with residual thromboemboli (P = 0.004) and recurrence (P = 0.03), but was not an independent risk factor for either.

Conclusions

Elevated d‐dimer is an independent risk factor for PE recurrence. A higher initial thromboembolic burden may be associated with unresolved thromboemboli or recurrence.
Crystalloid structures in lung fine needle aspiration cytology
Authors: Martínez‐Girón Rafael , Pantanowitz Liron
Published: February 2020

An elderly woman was admitted to hospital because of the presence of a necrotizing lung cavity on radiology imaging. A lung FNAC was performed.
Secretory carcinoma: Fine needle aspiration cytology of a rare parotid gland tumour
Authors: Kapatia Gargi , Kithan Lijanthung S. , Rohilla Manish , Gupta Nalini , Srinivasan Radhika , Dey Pranab , Rajwanshi Arvind
Published: February 2020

Mammary analogue secretory carcinoma (MASC) is a rare salivary gland tumor; lack of awareness of this malignancy perhaps, contribute to the tumor being under‐diagnosed.
Endoscopic transpapillary gallbladder drainage for acute cholecystitis is feasible for patients receiving antithrombotic therapy
Authors: Sagami Ryota , Hayasaka Kenji , Ujihara Tetsuro , Nakahara Ryotaro , Murakami Daisuke , Iwaki Tomoyuki , Suehiro Satoshi , Katsuyama Yasushi , Harada Hideaki , Nishikiori Hidefumi , Murakami Kazunari , Amano Yuji
Published: February 2020

Objectives

Patients with acute cholecystitis receiving antithrombotic therapy (ATT) have an increased risk of bleeding complications during surgery and percutaneous drainage. Endoscopic transpapillary gallbladder drainage (ETGBD) is recommended for such cases; however, evidence is limited. To investigate this issue further, we performed a retrospective multicenter study.

Methods

One hundred thirty patients with acute cholecystitis who underwent ETGBD were enrolled. They were divided into an ATT group (continuation of ATT on the day of the procedure and/or heparin substitution) and a Non‐ATT group (discontinuation or no use of ATT). The primary outcome was bleeding complication rate, and the secondary outcomes were technical success rate, clinical success rate and total complication rate.

Results

Eighty‐three patients were enrolled in the ATT group, and 47 were enrolled in the Non‐ATT group. In the ATT group, 42.2% continued multi‐agent ATT. No bleeding complications occurred in either group. There were no significant differences between the ATT and Non‐ATT groups in the technical success rate (84.3% vs 89.4%, P = 0.426 respectively) or the clinical success rate (97.1% vs 100%, P = 0.259, respectively). The overall early complication rate was 3.1% (4/130): mild pancreatitis (n = 3) and cholangitis (n = 1). Stent dysfunction was found in 10.9% of patients (at 196 days on average), and the 12‐month stent patency rate was 69.0%.

Conclusions

No significant difference was found in the bleeding complication rate between ETGBD with and without ATT. ETGBD may be an ideal drainage method for patients with acute cholecystitis receiving ATT.
Corticosteroids and ACTH for infantile spasms: are we closer to equipoise?
Authors: Kelley Sarah Aminoff
Published: February 2020

This commentary is on the systematic review by Li et al. on pages 575–580 of this issue.
Creating Impactful Student Learning in a Business Analytics Program through Leveraging Scholar‐Practitioner Engagement
Authors: Speier‐Pero Cheri , Schoenherr Tobias
Published: February 2020

Industry demand for talented analytics professionals has created a significant increase in degree programs (e.g., MS in Analytics) around the globe. Many of these programs incorporate experiential learning in the curriculum to foster a deeper understanding. This article focuses on the value and challenges in implementing experiential learning in an analytics‐focused degree program by incorporating and scaffolding multiple organizational analytics projects throughout the curriculum. In addition, this article focuses on the manner in which these organizational analytics projects can create value for scholars, beyond student learning. Scholar‐practitioner partnerships have the potential to advance not only the field of academic research but also the rigor of actual practice. We report our experiences and best practices in creating and leveraging scholar‐practitioner partnerships in the context of project‐based experiential learning in a Master of Science in Business Analytics (MSBA) program. We provide motivation for creating such partnerships for teaching analytics, document student and organizational success, offer illustrations of exemplary experiential learning projects, and discuss the challenges that need to be managed.
Ecotone formation through ecological niche construction: the role of biodiversity and species interactions
Authors: Liautaud Kevin , Barbier Matthieu , Loreau Michel
Published: February 2020

Rapid changes in species composition, also known as ecotones, can result from various causes including rapid changes in environmental conditions, or physiological thresholds. The possibility that ecotones arise from ecological niche construction by ecosystem engineers has received little attention. In this study, we investigate how the diversity of ecosystem engineers, and their interactions, can give rise to ecotones. We build a spatially explicit dynamical model that couples a multispecies community and its abiotic environment. We use numerical simulations and analytical techniques to determine the biotic and abiotic conditions under which ecotone emergence is expected to occur, and the role of biodiversity therein. We show that the diversity of ecosystem engineers can lead to indirect interactions through the modification of their shared environment. These interactions, which can be either competitive or mutualistic, can lead to the emergence of discrete communities in space, separated by sharp ecotones where a high species turnover is observed. Considering biodiversity is thus critical when studying the influence of species–environment interactions on the emergence of ecotones. This is especially true for the wide range of species that have small to moderate effects on their environment. Our work highlights new mechanisms by which biodiversity loss could cause significant changes in spatial community patterns in changing environments.
Longitudinal predictors of stigma in first‐episode psychosis: Mediating effects of depression
Authors: Bornheimer Lindsay A. , Tarrier Nicholas , Brinen Aaron P. , Li Juliann , Dwyer Meredith , Himle Joseph A.
Published: February 2020

Aim

Stigma is commonly experienced among individuals with schizophrenia spectrum disorders and has been shown to be a barrier to help‐seeking and behavioural service utilization. Given the established relationships between stigma, barriers to treatment, and poorer psychiatric outcomes including depression and psychotic symptoms, we examined the relationships between symptoms of depression, positive and negative symptoms, and the emergence of stigma longitudinally among a sample of first‐episode of psychosis (FEP) participants in the United States.

Methods

Data were obtained from the Recovery After an Initial Schizophrenia Episode project of National Institute of Mental Health's Early Treatment Program. Participants (n = 404) included adults between ages 15 and 40 with schizophrenia or other psychotic disorders based on the DSM‐IV. Data were analysed using structural equation modelling (SEM).

Results

Findings indicated that increased positive and negative symptoms independently related to greater symptoms of depression at baseline. Furthermore, increased positive symptoms and symptoms of depression at baseline independently related to the emergence of greater stigma being experienced over time.

Conclusions

Considering the role that symptoms of depression played as a factor explaining the relationships between positive and negative symptoms and emergence of stigma over time among individuals in FEP, and symptoms of depression is important predictor of stigma and may furthermore present as a viable and less stigmatizing initial treatment target in the early course of a psychotic disorder.
Participants’ assessments of the continuing educational program with the delivery mode of a periodontal alliance
Authors: Ni Jing , Wu Yifan , Xie Yufeng , Xue Lian , Dai Xing , Shu Rong
Published: February 2020

Objective

To evaluate the effectiveness of the periodontal continuing educational delivery mode via a periodontal alliance.

Methods

An innovative continuing educational delivery mode via a periodontal alliance has been conducted using a periodontal alliance of 30 hospitals in 18 provinces of China. This delivery mode integrates several instructional methods, including lectures, case presentations, and interactive question and answer sessions, all of which were conducted through online platforms. The effectiveness of the mode was evaluated via a questionnaire that was administered to the participants. The questionnaire consisted of 13 closed‐ended questions and 2 open‐ended questions.

Results

Of the 450 participants, 343 (76%) returned the questionnaire. Of the returned surveys, more than 92% provided positive feedback regarding the instructional methods of the program, stating that the techniques helped them study more efficiently and saved them time and money. More than 85% of the participants were satisfied with the instructional content and more than 90% of the participants considered the educational value of the program to be high, as it helped them identify gaps in knowledge, promoted their ability to establish treatment plans, and encouraged them to network with one another and thereby establish a supportive environment. With respect to the responses to the open‐ended questions, the participants claimed that the most useful aspects of the program were related to time and cost savings. The most frequent feedback with respect to improving the program was to include hands‐on courses and to divide the program into different levels.

Conclusions

The participants responded positively to the program. The periodontal alliance delivery mode was determined to be an effective way to improve the quality of continuing dental education.
Cataloguing the dead: breathing new life into pseudokinase research
Authors: Shrestha Safal , Byrne Dominic P. , Harris John A. , Kannan Natarajan , Eyers Patrick A.
Published: February 2020

Pseudoenzymes are present within many, but not all, known enzyme families and lack one or more conserved canonical amino acids that help define their catalytically active counterparts. Recent findings in the pseudokinase field confirm that evolutionary repurposing of the structurally defined bilobal protein kinase fold permits distinct biological functions to emerge, many of which rely on conformational switching, as opposed to canonical catalysis. In this analysis, we evaluate progress in evaluating several members of the ‘dark’ pseudokinome that are pertinent to help drive this expanding field. Initially, we discuss how adaptions in erythropoietin‐producing hepatocellular carcinoma (Eph) receptor tyrosine kinase domains resulted in two vertebrate pseudokinases, EphA10 and EphB6, in which co‐evolving sequences generate new motifs that are likely to be important for both nucleotide binding and catalysis‐independent signalling. Secondly, we discuss how conformationally flexible Tribbles pseudokinases, which have radiated in the complex vertebrates, control fundamental aspects of cell signalling that may be targetable with covalent small molecules. Finally, we show how species‐level adaptions in the duplicated canonical kinase protein serine kinase histone (PSKH)1 sequence have led to the appearance of the pseudokinase PSKH2, whose physiological role remains mysterious. In conclusion, we show how the patterns we discover are selectively conserved within specific pseudokinases, and that when they are modelled alongside closely related canonical kinases, many are found to be located in functionally important regions of the conserved kinase fold. Interrogation of these patterns will be useful for future evaluation of these, and other, members of the unstudied human kinome.
Capital market frictions and human capital investment: Evidence from workplace safety around regulation SHO
Authors: Bai John (Jianqiu) , Lee Eunju , Zhang Chi
Published: February 2020

This paper examines the effect of capital market frictions on firms’ workplace safety. Using Regulation SHO as a natural experiment, we find a significant increase in work‐related injury rates of pilot firms. The effect is stronger for firms in more competitive industries and with high financial constraints, and weaker for firms whose employees have high negotiating power and with good corporate governance. Further tests suggest that managers’ myopia shifts their focus away from investments in workplace safety when workplace safety is not related to firm performance. Overall, the results highlight how capital market frictions affect firms’ investment in human capital.
Can Karst Conduit Models Be Calibrated? A Dual Approach Using Dye Tracing and Temperature
Authors: Berglund James L. , Toran Laura , Herman Ellen K.
Published: February 2020

Modeling flow and transport using both temperature and dye tracing provides constraints that can improve understanding of karst networks. A laminar flow and transport model using the finite element subsurface flow model simulated the conduit connection between a sinking stream and spring in central Pennsylvania to evaluate how conduit morphology might affect dye transport. Single and overly tortuous conduit models resulted in high concentrations as dye flowed back into the conduit from the matrix after dye injections ceased. A forked conduit model diverted flow from the main conduit, reducing falling limb dye concentration. Latin hypercube sampling was performed to evaluate the sensitivity of 52 parameter combinations (conduit hydraulic conductivity, conduit cross‐sectional area, matrix transmissivity, matrix porosity, and dispersivity) for four conduit geometry scenarios. Sensitivity of arrival time for 50% of the dye indicated no parameter combinations which simulate falling limb dye concentrations for tortuous geometries, confirming the importance of the forked geometry regardless of other parameters. Temperature data from high‐resolution loggers were then incorporated into the forked conduit model to reproduce seasonal spring temperature using variable sink inflow. Unlike the dye trace models, the thermal models were sensitive to other model parameters, such as conduit cross‐sectional area and matrix transmissivity. These results showed this dual approach (dye and temperature) to karst network modeling is useful for (1) exploring the role of conduit and matrix interaction for contaminant storage, (2) constraining karst conduit geometries, which are often poorly understood, and (3) quantifying the effect of seasonal trends on karst aquifers.
‘It's Complicated’: Canadian Correctional Officer Recruits’ Interpretations of Issues Relating to the Presence of Transgender Prisoners
Authors: RICCIARDELLI ROSEMARY , PHOENIX JO , GACEK JAMES
Published: February 2020

Drawing upon semi‐structured interviews with correctional officer recruits in training (n = 55), we reflect on recruit interpretations of transgender (trans) prisoner placement within federal prisons in light of recent changes instigated by Canadian Prime Minister Trudeau. Recognising that prison is a carceral and gender binary space, we assert that trans prisoner lives and experiences cannot easily be appropriately recognised or included in prison policy and prisoner management procedures. Our findings reveal that most recruits are supportive and appreciative of the complexities of trans experiences, yet some, especially those with prior experience working in prisons, describe occupational strains tied to accommodating trans prisoners.
Characterization of a mouse model to study the relationship between apical periodontitis and atherosclerosis
Authors: Berlin‐Broner Y. , Alexiou M. , Levin L. , Febbraio M.
Published: February 2020

Aim

First, to determine the feasibility of using the low‐density lipoprotein receptor knockout (LDLR KO) mouse model to study apical periodontitis (AP). Secondly, to investigate the causal relationship between AP and atherosclerosis. It was hypothesized that it would be feasible to induce AP and atherosclerosis in LDLR KO mice and find a difference in atherosclerosis between AP and Sham groups.

Methodology

Using a published methodology, AP was induced in LDLR KO mice by exposing the dental pulp of the four first molars (Tx). Shams received only anaesthesia. Mice were fed a high fat, Western‐type diet (WTD), to induce atherosclerosis. At 16 weeks, mice were euthanized and aortas collected to measure atherosclerosis lesion burden (oil red O staining). Periapical lesions were validated using micro‐CT and histology. Systemic inflammation was measured using a cytokine array.

Results

Both groups developed a similar degree of atherosclerosis (mean lesion area 7.46 ± 0.44% in the Tx group compared with 7.65 ± 0.46%, in the Sham group, P = 0.77), and a similar degree of inflammation. Periapical lesions (PALs) in all four molars were only identified in a small subset of Tx mice.

Conclusions

A novel mouse model, which combines AP and CVD, was created. This model allows investigation of the relationship between the two diseases, whilst avoiding other potential common confounders. Although no difference in the degree of atherosclerosis was found between the groups, more studies in which the number of periapical lesions, changes in systemic inflammation and the degree of atherosclerosis are correlated are necessary to ultimately determine the impact of AP on CVD.
A connectivity mapping approach predicted acetylsalicylic acid (aspirin) to induce osteo/odontogenic differentiation of dental pulp cells
Authors: Rankin R. , Lundy F. T. , Schock B. C. , Zhang S.‐D. , Al‐Natour B. , About I. , Irwin C. , Linden G. J. , El‐Karim I. A.
Published: February 2020

Aim

To use connectivity mapping, a bioinformatics approach, to identify compounds that could induce odontogenic differentiation of dental pulp cells (DPCs) and to experimentally validate this effect. A subsidiary aim was to investigate the anti‐inflammatory effect of any identified compound.

Methodology

The Gene Expression Omnibus (GEO) database was searched for microarray data sets assessing odontogenic differentiation of human DPCs. An odontogenic gene expression signature was generated by differential expression analysis. The statistical significant connectivity map (ssCMap) method was used to identify compounds with a highly correlating gene expression pattern. DPCs were treated with the compound identified, and osteo/odontogenic differentiation was assessed by Alizarin red staining, alkaline phosphatase activity and expression of osteo/odontogenic genes ALPL, RUNX2, COL1A1, DSPP, DMP1 and SPP1 by RT‐PCR. The anti‐inflammatory effect of the compound was assessed using an ex vivo pulpitis model, and cytokine levels were measured with multiplex assay. Means were compared using the t‐test or ANOVA followed by a Bonferroni post hoc test with the level of significance set at P ≤ 0.05.

Results

The GEO database search identified a specific gene expression signature for osteo/odontogenic differentiation. Analysis using ssCMap found that acetylsalicylic acid [(ASA)/aspirin] was the drug with the strongest correlation with that gene signature. The treatment of DPCs with 0.05 mmol L−1 ASA showed increased alkaline phosphatase activity (P < 0.001), mineralization (P < 0.05), and increased the expression of the osteo/odontogenic genes, DMP1 and DSPP (P < 0.05). Low concentration (0.05 mmol L−1) ASA reduced inflammatory cytokines IL‐6 (P < 0.001), CCL21 (P < 0.05) and MMP‐9 (P < 0.05) in an ex vivo pulpitis model.

Conclusions

Connectivity mapping, a web‐based informatics method, was successfully used to identify aspirin as a candidate drug that could modulate the differentiation of DPCs. Aspirin was shown to induce odontogenic differentiation in DPCs in vitro and this, together with its anti‐inflammatory effects, makes it a potential candidate for vital pulp therapies.
Morality, Perspective, and Fantasy: A Comment on Sarah Buss
Authors: Jollimore Troy
Published: February 2020

A response to Sarah Buss's article, ‘Some Musings about the Limits of an Ethics that Can Be Applied,’ focusing on issues connected with Buss’s claims about human insignificance, and the indifference to self that the recognition of insignificance allegedly engenders.
The impact of computer‐mediated immediate feedback on developing oral presentation skills: An exploratory study in virtual reality
Authors: Van Ginkel Stan , Ruiz Dominic , Mononen Asko , Karaman Cendel , de Keijzer Ander , Sitthiworachart Jirarat
Published: February 2020

Feedback plays a central role in learning. Crucial to this is the nature and timing of the feedback. This experimental study explores the efficacy of immediate computer‐mediated feedback within a virtual reality environment designed to facilitate the development of pre‐university students' presentation skills. Two conditions were established to assess the efficacy: immediate computer‐mediated feedback; a control condition of delayed expert‐mediated feedback. Results showed improvement but no statistically relevant difference in performance gains between the two conditions, suggesting both can facilitate learning. Furthermore, students perceived the environment to be an effective and motivating platform in which to practise presentation skills. For educators seeking viable alternatives to face‐to‐face presentation practice and feedback, the finding that immediate computer‐mediated feedback is potentially as effective in aiding presentation performance is crucial for two reasons: first, it expands practice opportunities for students; second, it could result in less pressure on resources, including time and staffing.
A novel tumour suppressor lncRNA F630028O10Rik inhibits lung cancer angiogenesis by regulating miR‐223‐3p
Authors: Qin Limei , Zhong Menglong , Adah Dickson , Qin Li , Chen Xiaoping , Ma Chunquan , Fu Qiang , Zhu Xiaoping , Li Zhili , Wang Nina , Chen Yanfeng
Published: February 2020

Lung cancer is the world's leading cause of cancer‐related morbidity and mortality despite advances in surgery, chemotherapy and immunotherapy; thus, there is an urgent need to find new molecules to develop novel treatment strategies. Although ncRNAs were found to account for 98% transcripts, the number of lncRNAs with distinct function in lung cancer is extremely limited. We previously demonstrated that Plasmodium infection inhibits tumour growth and metastasis, but the exact mechanisms involved have not been fully understood. In this study, we carried out RNA sequencing (RNA‐Seq) of tumour tissues isolated from LLC tumour‐bearing mice treated with either Plasmodium yoelli (Py)‐infected red blood cells or uninfected red blood cells. We found that F630028O10Rik (abbreviated as F63) is a novel lncRNA that was significantly up‐regulated in tumours isolated from mice treated with Py‐infected red blood cells compared to the control. By using gene silencing technique, F63 was found to inhibit both tumour Vascular Endothelial Growth Factor A (VEGFA) secretion and endothelial cells clone formation, migration, invasion and tube formation. Injection of cholesterol‐modified siRNA‐F63 into mice tumour tissues produced a significant increase in tumour volume, blood vessel formation and angiogenesis 17 days after injection. We further showed that inhibiting miR‐223‐3p results in the down‐regulation of VEGFA and VEGFR2 which are vital molecules for angiogenesis. These results reveal that F63 inhibit tumour growth and progression by modulating tumour angiogenesis suggesting F63 can be a novel lncRNA with great potential as a candidate molecule for gene therapy in lung cancer.
Demographic fluctuations lead to rapid and cyclic shifts in genetic structure among populations of an alpine butterfly, Parnassius smintheus
Authors: Jangjoo Maryam , Matter Stephen F. , Roland Jens , Keyghobadi Nusha
Published: February 2020

Many populations, especially in insects, fluctuate in size, and periods of particularly low population size can have strong effects on genetic variation. Effects of demographic bottlenecks on genetic diversity of single populations are widely documented. Effects of bottlenecks on genetic structure among multiple interconnected populations are less studied, as are genetic changes across multiple cycles of demographic collapse and recovery. We take advantage of a long‐term data set comprising demographic, genetic and movement data from a network of populations of the butterfly, Parnassius smintheus, to examine the effects of fluctuating population size on spatial genetic structure. We build on a previous study that documented increased genetic differentiation and loss of spatial genetic patterns (isolation by distance and by intervening forest cover) after a network‐wide bottleneck event. Here, we show that genetic differentiation was reduced again and spatial patterns returned to the system extremely rapidly, within three years (i.e. generations). We also show that a second bottleneck had similar effects to the first, increasing differentiation and erasing spatial patterns. Thus, bottlenecks consistently drive random divergence of allele frequencies among populations in this system, but these effects are rapidly countered by gene flow during demographic recovery. Our results reveal a system in which the relative influence of genetic drift and gene flow continually shift as populations fluctuate in size, leading to cyclic changes in genetic structure. Our results also suggest caution in the interpretation of patterns of spatial genetic structure, and its association with landscape variables, when measured at only a single point in time.
Systematic review of hepatic arterial infusion chemotherapy versus sorafenib in patients with hepatocellular carcinoma with portal vein tumor thrombosis
Authors: Liu Miao , Shi Junyi , Mou Tong , Wang Yang , Wu Zhongjun , Shen Ai
Published: February 2020

Background and Aim

The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is very poor. This study aimed to evaluate hepatic arterial infusion chemotherapy (HAIC) versus sorafenib (SORF) in the treatment of HCC with PVTT.

Methods

Studies were identified online in Embase and MEDLINE before October 31, 2019. The end‐points were overall survival (OS), progression‐free survival (PFS), disease control rate (DCR), and safety.

Results

Six studies with 417 cases were included in this systematic review. Meta‐analyses demonstrated that HAIC is superior to SORF with respect to OS (hazard ratio [HR]: 0.50, 95% confidence interval: 0.38–0.66, P < 0.001) and PFS (HR: 0.47, 95% confidence interval: 0.31–0.73, P = 0.001) irrespective of research territoriality and study quality. Our systematic review also demonstrated that HAIC is superior to SORF with respect to DCR. Subgroup analysis demonstrated that the advantage is more obvious in the treatment of types III–IV PVTT with respect to OS (HR: 0.29, P < 0.001) and PFS(HR: 0.39, P < 0.001). HAIC caused more grades 3–4 neutropenia (HR: 10.71), anemia (HR: 7.55), leukopenia (HR: 10.38), and thrombocytopenia (HR: 13.09) than SORF. However, HAIC caused fewer cases of grades 3–4 aspartate aminotransferase rising (HR: 0.21), diarrhea (HR: 0.14), and hand‐foot syndrome (HR: 0.14) than SORF.

Conclusions

This systematic review demonstrated that HAIC is superior to SORF in HCC with PVTT with respect to OS, PFS, and DCR, especially in HCC with types III–IV PVTT. HAIC caused more myelosuppression, whereas SORF is associated with diarrhea and hand‐foot syndrome. Further randomized controlled trials are warranted.
Dyspnoea Assessment In Adults With End‐Stage Kidney Disease: A Systematic Review
Authors: Chilvers Maria , Johnston Kylie , Ferrar Katia , Williams Marie T.
Published: February 2020

Background

Dyspnoea is a common, disabling symptom of people living with end‐stage kidney disease (ESKD), which may persist despite optimal management. Dyspnoea assessments can be grouped according to the instruments that assess domains related to: sensory‐perception (intensity, sensory quality), affective distress (unpleasantness) and impact/burden (function, quality of life).

Objectives

To describe dyspnoea assessment in adults with ESKD receiving renal replacement therapy (RRT).

Design

Systematic review.

Methods

Five databases were searched. Primary studies reporting an assessment of dyspnoea in adults with ESKD receiving RRT were included. Studies were excluded where participants with ESKD had received palliative/conservative treatment (no dialysis) or renal transplant. Conference abstracts, protocols, commentaries and/or images were excluded. Two independent reviewers screened and extracted the data. Descriptive analysis summarised the (1) number and type of instruments used to assess dyspnoea; (2) which dyspnoea domains to be assessed and (3) rationale and context for dyspnoea assessment.

Results

From 2,234 records screened, 28 studies were eligible for inclusion (observational n = 22 and experimental n = 6). Across studies, 12 different instruments were identified (dyspnoea‐specific n = 3, subscale of a comprehensive instrument n = 9). Most instruments (n = 11, 92%) assessed a single domain (intensity n = 6, unpleasantness n = 6 and impact/burden n = 5). Studies reported a rationale for measuring dyspnoea (n = 26) as either a characteristic of the participant cohort (n = 14) or as an outcome (n = 14).

Conclusions

Surprisingly, a few primary studies reported assessment of dyspnoea in people with ESKD receiving RRT. When assessed, there was a predominance of unidimensional instruments. As dyspnoea is associated with adverse clinical outcomes, routine dyspnoea assessment may improve management and relieve suffering.