bluuebunny/crossref_metadata_2025 huggingface dataset:
What information and resources do carers require pre and post bereavement in the acute hospital setting? A rapid review
Authors: Jackson Brenda , McPeake Joanne , Johnston Bridget
Published: September 2019

Purpose of review:

This mixed-method, rapid review of published research from 2014 to 2019 aims to explore the experiences of pre and postbereaved carers, and the information that they receive in the acute hospital setting. The quality of articles was evaluated using a standardized quality matrix. The techniques of conceptual analysis and idea mapping were used to create a structured synthesis of the findings.

Recent findings:

From the initial search of 432 articles, ten studies met the inclusion criteria for this review. These studies generated data from 42 patients, 1968 family/carers and 139 healthcare staff. Themes that were generated from a synthesis of the included articles were clear and timely communication, workforce provision and environment.

This review has highlighted the need for improvements in information provision for carers as part of end of life care. Furthermore, the need for specific staff education and training to enable staff to confidently communicate with dying patients and their relatives in the acute setting is also warranted. Understanding and addressing gaps in knowledge and practice are essential to develop strategies in this complex area. Simple strategies can be implemented to improve the care of carers both pre and post bereavement in acute care.
CX3CR1 as a Respiratory Syncytial Virus Receptor in Pediatric Human Lung
Authors: Anderson Christopher S. , Chu Chin-Yi , Wang Qian , Mereness Jared A. , Ren Yue , Donlon Kathy , Bhattacharya Soumyaroop , Misra Ravi S. , Walsh Edward E. , Pryhuber Gloria S. , Mariani Thomas J.
Published: September 2019

BACKGROUND

Data on the host factors that contribute to infection of young children by Respiratory Syncytial Virus (RSV) are limited. The human chemokine receptor, CX3CR1, has recently been implicated as an RSV receptor. Here we evaluate a role for CX3CR1 in pediatric lung RSV infections.

METHODS

CX3CR1 transcript levels in the upper and lower pediatric airways were assessed. Tissue localization and cell specific expression was confirmed using in situ hybridization and immunohistochemistry. The role of CX3CR1 in RSV infection was also investigated using a novel physiological model of pediatric epithelial cells.

RESULTS

Low levels of CX3CR1 transcript were often, but not always, expressed in both upper (62%) and lower airways (36%) of pediatric subjects. CX3CR1 transcript and protein expression was detected in epithelial cells of normal human pediatric lung tissues. CX3CR1 expression was readily detected on primary cultures of differentiated pediatric/infant human lung epithelial cells. RSV demonstrated preferential infection of CX3CR1 positive cells, and blocking CX3CR1/RSV interaction significantly decreased viral load.

CONCLUSION

CX3CR1 is present in the airways of pediatric subjects where it may serve as a receptor for RSV infection. Furthermore, CX3CR1 appears to play a mechanistic role in mediating viral infection of pediatric airway epithelial cells in vitro.
Reactions to an Online Demonstration of the Effect of Increased Fruit and Vegetable Consumption on Appearance: Survey
Authors: Cairns Patrick , Ozakinci Gozde , Perrett David Ian
Published: September 2019

Background

Inadequate fruit and vegetable consumption causes a considerable disease burden and premature mortality. Despite considerable public health promotion of a healthy diet the average consumption is still below recommended levels. Fruit and vegetable consumption influences human skin colour, increasing red/yellow/orange pigment in the skin. Given that this colour is deemed attractive and healthy-looking, the appearance benefit may provide motivation to eat more fruit and vegetables. Such appearance motivation could be particularly effective in young individuals who currently eat least fruit and vegetables.

Objectives

To assess how widely the impact of diet on skin colour is known within the UK. To compare the strength of motivation to eat fruit and vegetables based on health and appearance benefits and to compare the effect of different UK demographics on motivation.

Methods

Four groups of UK residents (N = 200 each group) were recruited through the Prolific online platform. Groups comprised younger (aged 18-24) and older adults (aged 40-60) of low and high self-reported socioeconomic status (1-5 and 6-10 on a 10-point rating scale). Facial images simulating the skin colour associated with low and high fruit and vegetable diets were shown to participants. Questionnaires were used to assess (1) background knowledge of the health and skin colour effects of dietary fruit and vegetables; (2) the specific motivational impact of the skin colour illustration and (3) the relative importance of motivation to consume fruit and vegetables arising from health and skin colour appearance benefits.

Results

(1) 61% of all participants were unaware of the dietary–skin colour association. (2) 57% of participants found the simple demonstration of the dietary impact on skin colour positively motivating to eat more fruit and vegetables. The visual demonstration was equally motivating for participants of high and low self-reported socioeconomic status (P= .63) and different ethnic backgrounds (White N = 453, Black N = 182, Asian N = 87,P= .22). Health benefits from a diet high in fruit and vegetables were regarded as more motivating than skin colour appearance benefits. The appearance benefits of a high fruit and vegetable diet (compared to the health benefits) were relatively more important for the younger participants (Mann-Whitney U = 96,263,P< .001) and for women (N = 489) than for men (N = 310, U = 83,763,P= .01).

Conclusions

These findings indicate that promotion of the skin colour effects of diets high in fruit and vegetables could provide additional motivation for a healthier diet. Our study indicates the wide appeal of appearance benefits from dietary fruit and vegetable (across ethnicity and socioeconomic status) and particularly amongst young adults where inadequate diet is most prevalent.
Dose-dependent degeneration of non-cancerous brain tissue in post-radiotherapy patients: A diffusion tensor imaging study
Authors: David Szabolcs , Mesri Hamed Y. , Bodiut Victor A. , Nagtegaal Steven H. J. , Elhalawani Hesham , de Luca Alberto , Philippens Marielle E. P. , Viergever Max A. , Mohamed Abdallah S. R. , Ding Yao , Chung Caroline , Fuller Clifton D. , Verhoeff Joost J. C. , Leemans Alexander
Published: September 2019

Background and purpose

Radiation-induced changes in brain tissue may relate to post-radiotherapy (RT) cognitive decline. Our aim is to investigate changes of the brain microstructural properties after exposure to radiation during clinical protocols of RT using diffusion MRI (dMRI).

Methods and Materials

The susceptibility of tissue changes to radiation was investigated in a clinically heterogenic cohort (age, pathology, tumor location, type of surgery) consisting of 121 scans of 18 patients (10 females). The imaging dataset included 18 planning CTs and 103 dMRI scans (range 2-14, median = 6 per patient) assessing pre-operative, post-operative pre-RT and post-RT states. Diffusion tensor imaging (DTI) metrics were estimated from all scans for a region-of-interest based linear relation analysis between mean dose and change in DTI metrics, while partial volume effects were regressed out.

Results

The largest regional dose dependency with mean diffusivity appear in the white matter of the frontal pole in the left hemisphere by an increase of 2.61 %/(Gy x year). Full brain-wise, pooled results for white matter show fractional anisotropy to decrease by 0.85 %/(30Gy x year); mean diffusivity increase by 9.17 %/(30Gy x year); axial diffusivity increase by 7.30%/(30Gy x year) and radial diffusivity increases by 10.63%/(30Gy x year).

Conclusions

White matter is susceptible to radiation with some regional variability where diffusivity metrics demonstrate the largest relative sensitivity. This suggests that dMRI is a promising tool in assessing microstructural changes after RT, which can help in understanding treatment-induced cognitive decline.
Checklists to Detect Potential Predatory Biomedical Journals: A Systematic Review
Authors: Cukier Samantha , Helal Lucas , Rice Danielle B , Pupkaite Justina , Ahmadzai Nadera , Wilson Mitchell , Skidmore Becky , Lalu Manoj , Moher David
Published: September 2019

Background

We believe there is a large number of checklists to help authors detect predatory journals. It is uncertain whether these checklists contain similar content.

Purpose

Perform a systematic review to identify checklists to detect potential predatory journals and to examine their content and measurement properties.

Data Sources

MEDLINE, Embase, PsycINFO, ERIC, Web of Science and Library, Information Science & Technology Abstracts (January 2012 to November 2018), university library websites (January 2019), YouTube (January 2019).

Study Selection

Original checklists used to detect potential predatory journals published in English, French or Portuguese, with instructions in point form, bullet form, tabular format or listed items, not including lists or guidance on recognizing “legitimate” or “trustworthy” journals.

Data Extraction

Pairs of reviewers independently extracted study data and assessed checklist quality and a third reviewer resolved conflicts.

Data Synthesis

Of 1528 records screened, 93 met our inclusion criteria. The majority of included checklists were in English (n = 90, 97%), could be completed in fewer than five minutes (n = 68, 73%), had an average of 11 items, which were not weighted (n = 91, 98%), did not include qualitative guidance (n = 78, 84%) or quantitative guidance (n = 91, 98%), were not evidence-based (n = 90, 97%) and covered a mean of four (of six) thematic categories. Only three met our criteria for being evidence-based.

Limitations

Limited languages and years of publication, searching other media.

Conclusions

There is a plethora of published checklists that may overwhelm authors looking to efficiently guard against publishing in predatory journals. The similarity in checklists could lead to the creation of evidence-based tools serving authors from all disciplines.

Funding Source

This project received no specific funding. David Moher is supported by a University Research Chair (University of Ottawa). Danielle Rice is supported by a Canadian Institutes of Health Research Health Systems Impact Fellowship; Lucas Helal is supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001, PDSE - 88881.189100/2018 - 01. Manoj Lalu is supported by The Ottawa Hospital Anesthesia Alternate Funds Association.
Deep-learning-based Prediction of Late Age-Related Macular Degeneration Progression
Authors: Yan Qi , Weeks Daniel E. , Xin Hongyi , Swaroop Anand , Chew Emily Y. , Huang Heng , Ding Ying , Chen Wei
Published: September 2019

Both genetic and environmental factors influence the etiology of age-related macular degeneration (AMD), a leading cause of blindness. AMD severity is primarily measured by fundus images and recently developed machine learning methods can successfully predict AMD progression using image data. However, none of these methods have utilized both genetic and image data for predicting AMD progression. Here we jointly used genotypes and fundus images to predict an eye as having progressed to late AMD with a modified deep convolutional neural network (CNN). In total, we used 31,262 fundus images and 52 AMD-associated genetic variants from 1,351 subjects from the Age-Related Eye Disease Study (AREDS) with disease severity phenotypes and fundus images available at baseline and follow-up visits over a period of 12 years. Our results showed that fundus images coupled with genotypes could predict late AMD progression with an averaged area under the curve (AUC) value of 0.85 (95%CI: 0.83-0.86). The results using fundus images alone showed an averaged AUC of 0.81 (95%CI: 0.80-0.83). We implemented our model in a cloud-based application for individual risk assessment.
A Hybrid Machine Learning Framework to Predict Early Risk of Mortality in Paralytic Ileus Patients using Electronic Health Records
Authors: Ahmad Fahad Shabbir , Ali Liaqat , Raza-Ul-Mustafa  , Khattak Hasan Ali , Chan Bukhari Syed Ahmad
Published: September 2019

Background and Objective

Paralytic Ileus (PI) is the pseudo-obstruction of the intestine secondary to intestinal muscle paralysis. PI is caused by several reasons such as overuse of medications, spinal injuries, inflammation, abdominal surgery, etc. We have developed an early mortality prediction framework that can help intensivist, surgeons and other medical professionals to optimize clinical management for PI patients in terms of optimal treatment strategy and resource planning.

Methods

We used publicly available ICU database called MIMIC III v1.4, extracted patients that had paralytic ileus as primary diagnosis over the age of 18 years old. We developed FLAIM Framework a two-phase model (Phase I: Statistical testing and Phase II: Machine Learning application) that was compare to traditional methods of machine learning. We used five different machine learning algorithms to test the validity of our Framework. We evaluated the effectiveness of the proposed framework by comparing accuracy, sensitivity, specificity, Receiver Operating Characteristic (ROC) curves, and area under the curve (AUC) for each model.

Results

The highest improvement in AUC of 7.78% was observed due to application of the proposed FLAIM method. Additionally, almost for all the machine learning models, improvement in accuracy was also observed. With the FLAIM framework, we recorded an accuracy of 81.30% and AUC of 81.38% under support vector machine (with RBF kernel) model in predicting mortality during a hospital stay for the PI patients

Discussion

Our results show promising clinical outcome prediction and application for individual patients admitted to the ICU with paralytic ileus after the first 24 hours of admission.
Intention to learn modulates the impact of reward and punishment on sequence learning
Authors: Steel Adam , Baker Chris I. , Stagg Charlotte J.
Published: September 2019

In real-world settings, learning is often characterised as intentional: learners are aware of the goal during the learning process, and the goal of learning is readily dissociable from the awareness of what is learned. Recent evidence has shown that reward and punishment (collectively referred to as valenced feedback) are important factors that influence performance during learning. Presently, however, studies investigating the impact of valenced feedback on skill learning have only considered unintentional learning, and therefore the interaction between intentionality and valenced feedback has not been systematically examined. The present study investigated how reward and punishment impact behavioural performance when participants are instructed to learn in a goal-directed fashion (i.e. intentionally) rather than unintentionally. In Experiment 1, participants performed the serial response time task with reward, punishment, or control feedback and were instructed to ignore the presence of the sequence, i.e., learn unintentionally. Experiment 2 followed the same design, but participants were instructed to intentionally learn the sequence. We found that punishment was significantly beneficial to performance during learning only when participants learned unintentionally, and we observed no effect of punishment when participants learned intentionally. Thus, the impact of feedback on performance may be influenced by goal of the learner.
Optoretinography: optical measurements of human cone and rod photoreceptor responses to light
Authors: Azimipour Mehdi , Valente Denise , Vienola Kari V. , Werner John S. , Zawadzki Robert J. , Jonnal Ravi S.
Published: September 2019

Rods contribute crucially to human vision and their dysfunction precedes cones’ in several retinal diseases. Here we describe light-evoked, functional responses of human rods and cones, measured noninvasively using adaptive optics optical coherence tomography.
No evidence for an S cone contribution to the human circadian response to light
Authors: Spitschan Manuel , Lazar Rafael , Yetik Ebru , Cajochen Christian
Published: September 2019

Exposure to even moderately bright, short-wavelength light in the evening can strongly suppress the production of melatonin and can delay our circadian rhythm. These effects are mediated by the retinohypothalamic pathway, connecting a subset of retinal ganglion cells to the circadian pacemaker in the suprachiasmatic nucleus (SCN) in the brain. These retinal ganglion cells directly express the photosensitive protein melanopsin, rendering them intrinsically photosensitive (ipRGCs). But ipRGCs also receive input from the classical photoreceptors — the cones and rods. Here, we examined whether the short-wavelength-sensitive (S) cones contribute to circadian photoreception by using lights which differed exclusively in the amount of S cone excitation by almost two orders of magnitude (ratio 1:83), but not in the excitation of long-wavelength-sensitive (L) and medium-wavelength-sensitive (M) cones, rods, and melanopsin. We find no evidence for a role of S cones in the acute alerting and melatonin supressing response to evening light exposure, pointing to an exclusive role of melanopsin in driving circadian responses.
An improved demand curve for analysis of food or drug consumption in animal experiments
Authors: Newman Mark , Ferrario Carrie R.
Published: September 2019

The incorporation of microeconomics concepts into studies using preclinincal self-administration procedures has provided critical insights into the factors that influence consumption of a wide range of food and drug reinforcers. In particular, the fitting of demand curves to consumption data provides a powerful analytic tool for computing objective metrics of behavior that can be compared across a wide range of reward types and experimental settings. The results of these analyses depend crucially on the mathematical form used to fit the data. The most common choice is an exponential form proposed by Hursh and Silberberg, which is widely used and has provided fundamental insights into relationships between cost and consumption, but it also has some disadvantages. In this paper we first briefly review the use of demand curves to quantify the motivating effects of food and drugs, then we describe the current methodology and highlight some potential issues that arise in its application. To address these issues, we propose a new mathematical framework for the analysis of consumption data, including a new functional form for the demand curve. We show that this proposed form gives good fits to data on a range of reinforcers across different animals and different experimental protocols, while allowing for straightforward calculation of key metrics of demand, including preferred consumption level, maximum response, price at maximum response, and price elasticity of demand. We provide software implementing our entire analysis pipeline, including data fits, data visualization, and the calculation of demand metrics.
An integrative assessment of aquatic ecosystem services based on guideline thresholds
Authors: S-Gelais Nicolas F. , Lapierre Jean-François , Siron Robert , Maranger Roxane
Published: September 2019

Ecologists typically associate water quality with trophic status where oligotrophic ecosystems have excellent water quality and presumably provide more aquatic ecosystem services. However water quality is perceived differently among worldviews. Aquatic ecosystem service provisioning to the public health and agriculture sectors is determined using specific guidelines. But are these guidelines related to trophic status? Here, we developed an integrative ecosystem service framework using guideline thresholds for drinking, swimming, irrigation, suitability for livestock and aquatic wildlife in canadian rivers of varying trophic status. Drinkability was the most sensitive ecosystem service, met in 37% of cases, whereas livestock was the least, provided in 99%. Trophic status is a fair proxy for ecosystem services limited by fecal contamination as nutrients are related to human and animal populations, but not to those limited by metals. Using quantitative thresholds to assess the safe provisioning of multiple ecosystem services provides clear guidance for supporting resource management.

In a nutshell

Water quality is a commonly used term in management, but the metrics that determine whether a river can safely provide various aquatic ecosystem services differ among worldviews.

We propose an integrative approach based on guideline thresholds to evaluate the frequency with which rivers are drinkable, swimmable, suitable for irrigation, livestock, and aquatic wildlife and compared this suitability with trophic status.

Trophic status is a fair proxy for ecosystem services limited by fecal contamination, but not for those limited by metals.

Using and developing more guideline thresholds provides a concrete way to assess ecosystem service provisioning that could help serve management.
Hydraulic diversity of El Cien Formation (Baja California Sur, Mexico) and the consequences of functional diversity in paleoclimate estimation using fossil wood
Authors: Martínez-Cabrera Hugo I. , Estrada-Ruiz Emilio
Published: September 2019

Community assembly processes, environmental filtering and limiting similarity, determine functional traits values within communities. Because environment influences the number of viable functional strategies species might take, a strong effect of environmental filter often results in communities having species with similar trait values and narrow functional niches. On the other hand, limiting similarity lead to communities with broader functional spaces. The degree to community assembly processes influence wood trait variation has important implications for paleoclimate estimation using fossil wood since the main tenet of the approach is environmental driven trait convergence, and assumes a central role of environmental filtering. We used functional diversity (FD) to determine how three wood anatomical traits vary in 14 extant communities (272 species) growing under different climate regimes, and inferred the prevalence of environmental filtering/limiting similarity. We also calculated FD metrics for the El Cien Formation fossil woods and discussed the results in light of the current knowledge of the flora. We found lower anatomical diversity in communities growing in dry/cool places (smaller functional spaces and lower abundance of trait combinations), suggesting that strong wood anatomical trait convergence could be the result of stronger habitat filtering in these communities. A lower strength of environmental filter in warm/wet environments, likely results in an amplification of the role of other drivers that promote higher number of hydraulic strategies through niche partition in highly structured communities. More complex ecological structures in mild tropical places likely lead to a higher spread of wood trait values. This asymmetry in the strength of environmental filter along climate gradients, suggest that the imbalances in strength of the trait-climate convergence, should be incorporated in paleoclimate prediction models. FD approach can be used to recognize promising traits with narrow niches along climate gradients, and therefore a constant effect of environmental filter.
Phasic signaling in the bed nucleus of the stria terminalis during fear learning predicts within- and across-session cued fear expression
Authors: Bjorni Max , Rovero Natalie G. , Yang Elissa R. , Holmes Andrew , Halladay Lindsay R.
Published: September 2019

While results from many past studies have implicated the bed nucleus of the stria terminalis (BNST) in mediating the expression of sustained negative affect, recent studies have highlighted a more complex role for BNST that includes aspects of fear learning in addition to defensive responding. As BNST is thought to encode ambiguous or unpredictable threat, it seems plausible that it may be involved in encoding early cued fear learning, especially immediately following a first tone-shock pairing when the CS-US contingency is not fully apparent. To investigate this, we conducted in vivo electrophysiological recording studies to examine neural dynamics of BNST units during cued fear acquisition and recall. We identified two functionally distinct subpopulations of BNST neurons that encode the intertrial interval (ITI) and seem to contribute to within- and across-session fear learning. “Ramping” cell activity during cued fear acquisition parallels the increase in freezing expression as mice learn the CS-US contingency, while “Phasic” cells encode post-shock (USpost) periods (30 s following encounter with footshock) only during early trials. Importantly, the magnitude of Phasic unit responsivity to the first USpostperiod predicted not only freezing expression in response to the subsequent CS during acquisition, but also CS freezing evoked 24 hr later during CS retrieval. These findings suggest for the first time that BNST activity may serve as an instructive signal during cued fear learning.
Disulfide disruption reverses mucus dysfunction in allergic airway disease
Authors: Morgan Leslie E. , Shenoy Siddharth K. , Raclawska Dorota , Emezienna Nkechinyere A. , Richardson Vanessa L. , Hara Naoko , Harder Anna Q. , El-Batal Hassan M. , Magin Chelsea M. , Grove Villalon Diane E. , Duncan Gregg , Hanes Justin S. , Soo Suk Jung , Thornton David J. , Holguin Fernando , Janssen William J. , Thelin William R. , Evans Christopher M.
Published: September 2019

Airway mucus is essential for healthy lung defense1, but excessive mucus in asthma obstructs airflow, leading to severe and potentially fatal outcomes2–5. Current asthma therapies reduce allergic inflammation and relax airway smooth muscle, but treatments are often inadequate due to their minimal effects on mucus obstruction6,7. The lack of efficacious mucus-targeted treatments stems from a poor understanding of healthy mucus function and pathological mucus dysfunction at a molecular level. The chief macromolecules in mucus, polymeric mucins, are massive glycoproteins whose sizes and biophysical properties are dictated in part by covalent disulfide bonds that link mucin molecules into assemblies of 10 or more subunits8. Once secreted, mucin glycopolymers can aggregate to form plugs that block airflow. Here we show that reducing mucin disulfide bonds depolymerizes mucus in human asthma and reverses pathological effects of mucus hypersecretion in a mouse allergic asthma model. In mice challenged with a fungal allergen, inhaled mucolytic treatment acutely loosened mucus mesh, enhanced mucociliary clearance (MCC), and abolished airway hyperreactivity (AHR) to the bronchoprovocative agent methacholine. AHR reversal was directly related to reduced mucus plugging. Furthermore, protection in mucolytic treated mice was identical to prevention observed in mice lacking Muc5ac, the polymeric mucin required for allergic AHR in murine models9. These findings establish grounds for developing novel fast-acting agents to treat mucus hypersecretion in asthma10,11. Efficacious mucolytic therapies could be used to directly improve airflow, help resolve inflammation, and enhance the effects of inhaled treatments for asthma and other respiratory conditions11,12.
Molecular pathway of influenza pan-neuraminidase inhibitors resistance in an immunocompromised patient
Authors: Abed Yacine , Schibler Manuel , Checkmahomed Liva , Carbonneau Julie , Venable Marie-Christine , Giannotti Federica , Goncalves Ana Rita , Kaiser Laurent , Boivin Guy
Published: September 2019

Neuraminidase (NA) inhibitors (NAIs), including oseltamivir and zanamivir, play an important therapeutic role against influenza infections in immunocompromised patients. In such settings, however, NAI therapy may lead to the emergence of resistance involving mutations within the influenza surface genes. The aim of this study was to investigate the evolution of hemagglutinin (HA) and NA genes of influenza A(H1N1)pdm09 virus in an immunocompromised patient receiving oseltamivir then zanamivir therapies. Nasopharyngeal swabs (NPS) samples were collected between 01-27-2018 and 04-20-2018 from a hematopoietic stem cell transplant recipient. These included 11 samples collected either pre-therapy, during oseltamivir and zanamivir as well as after therapy. The A(H1N1)pdm09 HA/NA genes were sequenced. The H275Y NA substitution was quantified by droplet digital RT-PCR assay. A(H1N1)pdm09 recombinant viruses containing HA mutations were tested by HA elution experiments to investigatein vitrobinding properties. Oseltamivir rapidly induced the H275Y NA mutation which constituted 98.33% of the viral population after 15 days of oseltamivir treatment. The related HA gene contained S135A and P183S substitutions within the receptor-binding site. After a switch to zanamivir, 275H/Y and 119E/G/D mixed populations were detected. In the last samples, the double H275Y-E119G NA variant dominated with S135A and P183S HA substitutions. This report confirms that oseltamivir can rapidly induce the emergence of the H275Y substitution in A(H1N1)pdm09 viruses and subsequent switch to zanamivir can lead to additional substitutions at codon E119 resulting in multi-drug resistance. Such data highlight the need for novel antiviral agents.
Epidermal activation of Hedgehog signaling establishes an immunosuppressive microenvironment in basal cell carcinoma by modulating skin immunity
Authors: Grund-Gröschke Sandra , Ortner Daniela , Szenes-Nagy Antal B. , Zaborsky Nadja , Weiss Richard , Neureiter Daniel , Wipplinger Martin , Risch Angela , Hammerl Peter , Greil Richard , Sibilia Maria , Gratz Iris K. , Stoitzner Patrizia , Aberger Fritz
Published: September 2019

Genetic activation of Hedgehog (HH)/GLI signaling causes basal cell carcinoma (BCC), a very frequent non-melanoma skin cancer. Small molecule targeting of the essential HH effector Smoothened (SMO) proved an efficient medical therapy of BCC, although lack of durable responses and frequent development of drug resistance pose major challenges to anti-HH treatments. In light of the recent breakthroughs in cancer immunotherapy, we analyzed in detail the possible immunosuppressive mechanisms in HH/GLI-induced BCC. Using a genetic mouse model of BCC, we identified profound differences in the infiltration of BCC lesions with cells of the adaptive and innate immune system. Epidermal activation of HH/GLI led to an accumulation of immunosuppressive regulatory T cells, and to an increased expression of immune checkpoint molecules including PD-1/PD-L1. Anti-PD1 monotherapy, however, did not reduce tumor growth, presumably due to the lack of immunogenic mutations in common BCC mouse models, as shown by whole-exome sequencing. BCC lesions also displayed a marked infiltration with neutrophils, the depletion of which unexpectedly promoted BCC growth. The results provide a comprehensive survey of the immune status of murine BCC and provide a basis for the design of efficacious rational combination treatments. This study also underlines the need for predictive immunogenic mouse models of BCC to evaluatein vivothe efficacy of immunotherapeutic strategies.
Population coding of reward prediction errors through opponent organization in the fronto parietal network
Authors: Foley Nicholas C. , Cohanpour Michael , Semework Mulugeta , Sheth Sameer A. , Gottlieb Jacqueline
Published: September 2019

Computing expectancy violations is essential for decision making and cognitive functions, but its neural mechanisms are incompletely understood. We describe a novel mechanism by which prefrontal and posterior parietal neurons encode reward prediction errors (RPEs) in their population but not single-neuron activity. Simultaneous recordings of neural populations showed that both areas co-activated information about experienced and expected rewards in a precise opponent organization. Neurons encoding expected rewards with positive (negative) scaling were reactivated simultaneously with those encoding experienced rewards with negative (positive) scaling. This opponent organization was mirrored in polarity-dependent noise correlations. Moreover, it extended to two types of expectancy information – based on task-relevant visual cues and statistically irrelevant reward history - allowing decoding of signed and unsigned RPE in two reference frames. Frontal and parietal areas implement canonical computations that facilitate contextual comparisons and the readout of multiple types of expectancy violations to flexibly serve behavioral goals.
Cross-disorder GWAS meta-analysis for Attention Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Obsessive Compulsive Disorder, and Tourette Syndrome
Authors: Yang Zhiyu , Wu Hanrui , Lee Phil H. , Tsetsos Fotis , Davis Lea K. , Yu Dongmei , Lee Sang Hong , Dalsgaard Søren , Haavik Jan , Barta Csaba , Zayats Tetyana , Eapen Valsamma , Wray Naomi R. , Devlin Bernie , Daly Mark , Neale Benjamin , Børglum Anders D. , Crowley James J. , Scharf Jeremiah , Mathews Carol A. , Faraone Stephen V. , Franke Barbara , Mattheisen Manuel , Smoller Jordan W. , Paschou Peristera
Published: September 2019

Attention Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Obsessive-Compulsive Disorder (OCD), and Tourette Syndrome (TS) are among the most prevalent neurodevelopmental psychiatric disorders of childhood and adolescence. High comorbidity rates across these four disorders point toward a common etiological thread that could be connecting them across the repetitive behaviors-impulsivity-compulsivity continuum. Aiming to uncover the shared genetic basis across ADHD, ASD, OCD, and TS, we undertake a systematic cross-disorder meta-analysis, integrating summary statistics from all currently available genome-wide association studies (GWAS) for these disorders, as made available by the Psychiatric Genomics Consortium (PGC) and the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). We present analysis of a combined dataset of 93,294 individuals, across 6,788,510 markers and investigate associations on the single-nucleotide polymorphism (SNP), gene and pathway levels across all four disorders but also pairwise. In the ADHD-ASD-OCD-TS cross disorder GWAS meta-analysis, we uncover in total 297 genomewide significant variants from six LD (linkage disequilibrium) -independent genomic risk regions. Out of these genomewide significant association results, 199 SNPs, that map onto four genomic regions, show high posterior probability for association with at least three of the studied disorders (m-value>0.9). Gene-based GWAS meta-analysis across ADHD, ASD, OCD, and TS identified 21 genes significantly associated under Bonferroni correction. Out of those, 15 could not be identified as significantly associated based on the individual disorder GWAS dataset, indicating increased power in the cross-disorder comparisons. Cross-disorder tissue-specificity analysis implicates the Hypothalamus-Pituitary-Adrenal axis (stress response) as possibly underlying shared pathophysiology across ADHD, ASD, OCD, and TS. Our work highlights genetic variants and genes that may contribute to overlapping neurobiology across the four studied disorders and highlights the value of re-defining the framework for the study across this spectrum of highly comorbid disorders, by using transdiagnostic approaches.
Site-specific hyperphosphorylation of tau inhibits its fibrillization in vitro, blocks its seeding capacity in cells, and disrupts its microtubule binding; Implications for the native state stabilization of tau
Authors: Haj-Yahya Mahmood , Gopinath Pushparathinam , Rajasekhar Kolla , Mirbaha Hilda , Diamond Marc. I. , Lashuel Hilal A.
Published: September 2019

The consistent observation of aggregated phosopho-tau in the pathology of Alzheimer’s disease and other tauopathies has contributed to the emergence of a model where hyperphosphorylation of tau causes its disassociation from microtubules and subsequent pathological polymerization. However, the large number of possible phosphorylation sites in tau and lack of robust methods that enable the preparation of homogeneously phosphorylated tau species have made it difficult to validate this model. Herein, we applied a total chemical synthetic approach to site-specifically phosphorylate single (pS356) or multiple (pS356/pS262 and pS356/pS262/pS258) residues within the microtubule binding repeat domain (MTBD) of tau and show that hyperphosphorylation within the microtubule MTBD inhibits K18 tau 1) aggregation in vitro; 2) its seeding activity in cells, and 3) its ability to promote microtubule polymerization. The inhibition increased with the number of phosphorylated sites, with phosphorylation at S262 having the strongest effect. On the basis of these findings, we propose that targeting the kinases that regulate phosphorylation at these sites could provide a viable strategy to stabilize the native state of tau and inhibit its aggregation. Taken together, our results argue against the pathogenic hyperphosphorylation hypothesis and underscore the critical importance of revisiting the role of site-specific hyperphosphorylation of tau in regulating its function in health and disease.

Table of content
Transmission of shocks between Chinese financial market and oil market
Authors: Abdelhedi Mouna , Boujelbène-Abbes Mouna
Published: September 2019

Purpose

The purpose of this paper is to empirically investigate the volatility spillover between the Chinese stock market, investor’s sentiment and oil market, specifically during the 2014‒2016 turmoil period.

Design/methodology/approach

This study used the daily and monthly China market price index, oil-price index and composite index of Chinese investor’s sentiment. The authors first use the DCC GARCH model in order to study the correlation between variables. Second, the authors use a continuous wavelet decomposition technique so as to capture both time- and frequency-varying features of co-movement variables. Finally, the authors examine the spillover effects by estimating the BEKK GARCH model.

Findings

The wavelet coherency results indicate a substantial co-movement between oil and Chinese stock markets in the periods of high volatility. BEKK GARCH model outcomes confirm this relation and report the noteworthy bidirectional transmission of volatility between oil market shocks and the Chinese investor’s sentiment, chiefly in the crisis period. These results support the behavioral theory of contagion and highlight that the Chinese investor’s sentiment is a channel through which shocks are transmitted between the oil and Chinese equity markets. Thus, these results are important for Chinese authorities that should monitor the investor’s sentiment to better control the interaction between financial and real markets.

Originality/value

This study makes three major contributions to the existing literature. First, it pays attention to the recent 2015 Chinese stock market bumble. Second, it has gone some way toward enhancing our understanding of the volatility spillover between the investor’s sentiment, investor’s sentiment variation, oil prices and stock market returns (variables of interest) during oil and stock market crises. Third, it uses the continuous wavelet decomposition technique since it reveals the linkage between variables of interest at different time horizons.
The moderating role of organizational environments on the relationship between inventory leanness and venture survival in Chinese manufacturing
Authors: Wang Xinyu , Lin Yu , Shi Yingjie
Published: September 2019

Purpose

The purpose of this paper is to investigate the relationship between inventory leanness and venture survival, and demonstrate the role of organizational environments in moderating this relationship from three dimensions: environmental complexity, dynamism and munificence.

Design/methodology/approach

Using a large panel data of more than 150,000 new Chinese small- and medium-sized enterprises between 2000 and 2007 in the manufacturing sector, the authors employ the method of survival analysis via an accelerated failure time model to explore the non-linear relationship between inventory leanness and the likelihood of survival. Moreover, the moderation model is applied to examine the moderating role of organizational environments.

Findings

At its core, this paper demonstrates the inverted U-shaped relationship between inventory leanness and the likelihood of survival. Furthermore, the authors find that environmental complexity and dynamism can negatively moderate this relationship, whereas environmental munificence acts the exact opposite.

Practical implications

Managers need to realize the trade-off between inventory leanness and venture survival. Collectively, more than 90 percent of new Chinese ventures have great potential to improve the likelihood of survival by implementing inventory leanness management. In addition, firms ought to be fully aware of the internal management and the external environments.

Originality/value

This is the first study to confirm the inverted U-shaped relationship between inventory leanness and the likelihood of survival, and empirically verify the moderating role of environmental complexity, dynamism and munificence on this relationship.
Learning in the ED: chaos, partners and paradoxes
Authors: Hussain Aman , Rossi Tony , Rynne Steven
Published: September 2019

Purpose

Most contemporary research in medical education focuses on the undergraduate component conducted within medical schools. The purpose of this paper, however, is to better understand how medical residents and practicing attending physicians learned to practice within the context of the emergency medicine department (ED) workplace.

Design/methodology/approach

In all, 18 residents and 15 attending physicians were interviewed about their learning in the ED. Interviews were digitally recorded and transcribed verbatim then analysed using an iterative approach. Emergent themes were shared with the participants to ensure they were an accurate representation of their lived experiences.

Findings

The first of the three main findings was that the ED learning environment was characterised as “messy” because of the inherently chaotic nature of the workplace. The second finding was that patients and nurses were informal partners in learning. The third main finding was that learning and working in the ED can be difficult, isolating and often lacks continuity.

Research limitations/implications

The main limitation associated with this research relates to the highly situated and contextually bound nature of this study. Nevertheless, the findings should be generative for others interested in supporting the work and learning of health professionals.

Originality/value

This study shifts the focus in medical education research from formal undergraduate education to learning in high stress and chaotic workplaces. Accordingly, this work provides valuable insights for others interested in the messy realities of learning in professional practice.
Residential property and break-ins
Authors: Badiora Adewumi , Adebara Oyinloluwa B.
Published: September 2019

Purpose

The purpose of this paper is to examine realtors and residents’ perceptions of the effectiveness of Crime Prevention through Environmental Design (CPTED) in reducing night-time and daytime break-ins in residential estate.

Design/methodology/approach

The study adopted case study methods. Two residential estates (one at inner and the other at outer city) were selected as cases of the study. Data were collected from two sets of respondents: realtors and tenants. In the realtors’ cluster, all real estate and property development companies were sampled since the population is very small. Systematic sampling technique was used to select residents. Respondents were asked to answer closed-ended questions on socio-economic and demographic characteristics, perception of property crime, spending on CPTED and effectiveness of CPTED. Data were analyzed using the descriptive and inferential statistics.

Findings

Findings disclose that more than half of the residents of inner and outer city had been victims of housebreaks and these incidences are expected to increase in the nearest future. To reduce break-ins, findings show that realtors and residents have spent on both formal and informal surveillance with emphasis on ensuring visual control over premises. Furthermore, respondents confirm the effectiveness of CPTED in deterring break-ins. The study establishes variation in the realtors and tenants’ perception of break-ins as spending on CPTED strategies vary between them, with locations and types of properties.

Practical implications

Social and human factors remain very important as far as the prevention of break-ins is concerned. These should be taken into considerations when improving CPTED approach in the future. Besides, adequate attentions should be given to daytime break-in. Nonetheless, night-time break-ins should not be neglected. Furthermore, the study emphasizes the importance of visible, clean and well-lit premises as ways of reducing break-ins. It is therefore suggested that residential properties should be well lit at nights, while CCTV and security personnel be positioned in strategic places and within security viewing range so as to send fast alerts to the nearest police stations in the cases of break-in(s).

Originality/value

Very few studies on effectiveness of CPTED have mainly concentrated on how CPTED works in residential estates. No study till date, have explored how realtors perceive CPTED in preventing break-ins. Besides, this study contributes to existing literature having revealed variation in the realtors and tenants’ spending on CPTED on the basis of property location and types of residential properties.
Japanese real‐world study of sequential nivolumab and ipilimumab treament in melanoma
Authors: Tsutsumida Arata , Fukushima Satoshi , Yokota Kenji , Yoshikawa Shusuke , Yamasaki Osamu , Tanemura Atsushi , Okuyama Ryuhei , Uhara Hisashi , Muto Yusuke , Miyashita Azusa , Akiyama Masashi , Kaji Tatsuya , Koga Hiroshi , Kato Junji , Katayama Teruaki , Itakura Eijun , Yamazaki Naoya , Kiyohara Yoshio
Published: September 2019

To describe the treatment patterns of nivolumab and ipilimumab in Japan, a retrospective observational study was conducted in melanoma patients who received nivolumab and ipilimumab sequentially. Patients who received nivolumab and ipilimumab in combination were excluded from this study. Efficacy was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) in terms of the overall response rate (ORR), progression‐free survival (PFS), and disease control rate (DCR). Overall survival (OS) was also evaluated. Safety was assessed by the Common Terminology Criteria for Adverse Events (CTCAE). The treatment for all 68 patients enrolled involved switching from nivolumab to ipilimumab in 61 patients and switching from ipilimumab to nivolumab in seven patients. Switching occurred because of progressive disease in 55 patients and adverse events in eight patients. The median number of ipilimumab doses was three. Ipilimumab treatment achieved an ORR and DCR of 4.9% and 21.3%, respectively, and the median OS from start of ipilimumab was 7.0 months. During the study period, no new safety signals were noted. Independent factors which were indicative of poor prognosis for PFS were high neutrophil‐to‐lymphocyte ratio (NLR) and high C‐reactive protein (CRP) levels before ipilimumab treatment. An evaluation over a washout period indicated that no significant relationship existed with efficacy or safety. For the sequential administration of nivolumab and ipilimumab in Japanese melanoma patients, switch from nivolumab to ipilimumab was common, and the major reason for switching was progressive disease. The major prognostic factors for ipilimumab PFS after nivolumab were NLR and CRP before ipilimumab treatment.