bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of deacetylase inhibition in metaplastic breast carcinoma using multiple derivations of preclinical models of a new patient-derived tumor
Authors: Chang Tiffany C. , Matossian Margarite D. , Elliott Steven , Burks Hope E. , Sabol Rachel A. , Ucar Deniz A. , Wathieu Henri , Zabaleta Jovanny , De Valle Luis , Gill Sukhmani , Martin Elizabeth , Riker Adam I. , Miele Lucio , Bunnell Bruce A. , Burow Matthew E. , Collins-Burow Bridgette M.
Published: December 2019

Metaplastic breast carcinoma (MBC) is a clinically aggressive and rare subtype of breast cancer, with similar features to basal-like breast cancers. Due rapid growth rates and characteristic heterogeneity, MBC is often unresponsive to standard chemotherapies; and novel targeted therapeutic discovery is urgently needed. Histone deacetylase inhibitors (DACi) suppress tumor growth and metastasis through regulation of the epithelial-to-mesenchymal transition axis in various cancers, including basal-like breast cancers.

We utilized a new MBC patient-derived xenograft (PDX) to examine the effect of DACi therapy on MBC. Cell morphology, cell cycle-associated gene expressions, transwell migration, and metastasis were evaluated in patient-derived cells and tumors after treatment with romidepsin and panobinostat. Derivations of our PDX model, including cells, spheres, organoids, explants, andin vivoimplanted tumors were treated. Finally, we tested the effects of combining DACi with approved chemotherapeutics on relative cell biomass.

DACi significantly suppressed the total number of lung metastasisin vivousing our PDX model, suggesting a role for DACi in preventing circulating tumor cells from seeding distal tissue sites. These data were supported by our findings that DACi reduced cell migration, populations, and expression of mesenchymal-associated genes. While DACi treatment did affect cell cycle-regulating genesin vitro,tumor growth was not affected compared to controls. Importantly, gene expression results varied depending on the cellular or tumor system used, emphasizing the importance of using multiple derivations of cancer models in preclinical therapeutic discovery research. Furthermore, DACi sensitized and produced a synergistic effect with approved oncology therapeutics on inherently resistant MBC.

This study introduced a role for DACi in suppressing the migratory and mesenchymal phenotype of MBC cells through regulation of the epithelial-mesenchymal transition axis and suppression of the CTC population. Preliminary evidence that DACi treatment in combination with MEK1/2 inhibitors exerts a synergistic effect on MBC cells was also demonstrated.
Single cell analysis of the effects of developmental lead (Pb) exposure on the hippocampus
Authors: Bakulski Kelly M. , Dou John F. , Thompson Robert C. , Lee Christopher , Middleton Lauren Y. , Perera Bambarendage P. U. , Ferris Sean P. , Jones Tamara R. , Neier Kari , Zhou Xiang , Sartor Maureen A. , Hammoud Saher S. , Dolinoy Dana C. , Colacino Justin A.
Published: December 2019

Background

Lead (Pb) exposure is ubiquitous and has permanent developmental effects on childhood intelligence and behavior and adulthood risk of dementia. The hippocampus is a key brain region involved in learning and memory, and its cellular composition is highly heterogeneous. Pb acts on the hippocampus by altering gene expression, but the cell type-specific responses are unknown.

Objective

Examine the effects of perinatal Pb treatment on adult hippocampus gene expression, at the level of individual cells, in mice.

Methods

In mice perinatally exposed to control water (n=4) or a human physiologically-relevant level (32 ppm in maternal drinking water) of Pb (n=4), two weeks prior to mating through weaning, we tested for gene expression and cellular differences in the hippocampus at 5-months of age. Analysis was performed using single cell RNA-sequencing of 5,258 cells from the hippocampus by 10x Genomics Chromium to 1) test for gene expression differences averaged across all cells by treatment; 2) compare cell cluster composition by treatment; and 3) test for gene expression and pathway differences within cell clusters by treatment.

Results

Gene expression patterns revealed 12 cell clusters in the hippocampus, mapping to major expected cell types (e.g. microglia, astrocytes, neurons, oligodendrocytes). Perinatal Pb treatment was associated with 12.4% more oligodendrocytes (P=4.4×10−21) in adult mice. Across all cells, differential gene expression analysis by Pb treatment revealed cluster marker genes. Within cell clusters, differential gene expression with Pb treatment (q<0.05) was observed in endothelial, microglial, pericyte, and astrocyte cells. Pathways up-regulated with Pb treatment were protein folding in microglia (P=3.4×10−9) and stress response in oligodendrocytes (P=3.2×10−5).

Conclusion

Bulk tissue analysis may be confounded by changes in cell type composition and may obscure effects within vulnerable cell types. This study serves as a biological reference for future single cell studies of toxicant or neuronal complications, to ultimately characterize the molecular basis by which Pb influences cognition and behavior.
An ALS-associated mutation in human FUS reduces neurotransmission fromC. elegansmotor neurons to muscles
Authors: Markert Sebastian M. , Skoruppa Michael , Yu Bin , Mulcahy Ben , Zhen Mei , Gao Shangbang , Sendtner Michael , Stigloher Christian
Published: December 2019

Amytrophic lateral sclerosis (ALS) is a neurodegenerative disorder that has been associated with multiple genetic lesions, including mutations in the gene FUS (Fused in Sarcoma), an RNA/DNA-binding protein. Expression of the ALS-associated human FUS inC. elegansresults in mislocalization and aggregation of FUS outside the nucleus, and leads to impaired neuromuscular behaviors. However, the mechanisms by which mutant FUS disrupts neuronal health and function remain partially understood. Here we investigated the impact of ALS-associated FUS on motor neuron health using correlative light and electron microscopy, electron tomography, and electrophysiology. Expression of ALS-associated FUS impairs synaptic vesicle docking at neuromuscular junctions, and leads to the emergence of a population of large and electron-dense filament-filled endosomes. Electrophysiological recording of neuromuscular transmission revealed reduced transmission from motor neurons to muscles. Together, these results suggest a potential direct or indirect role of human FUS in the organization of synaptic vesicles, and reduced transmission from motor neurons to muscles.

Summary statement

An ALS-associated mutation in a trafficking protein disrupts the organization of theC. elegansneuromuscular junction.
Advancing motion denoising of multiband resting-state functional connectivity fMRI data
Authors: Williams John C. , Tubiolo Philip N. , Luceno Jacob R. , Van Snellenberg Jared X.
Published: December 2019

Simultaneous multi-slice (multiband) accelerated functional magnetic resonance imaging (fMRI) provides dramatically improved temporal and spatial resolution for resting-state functional connectivity (RSFC) studies of the human brain in health and disease. However, multiband acceleration also poses unique challenges for denoising of subject motion induced data artifacts, the presence of which is a major confound in RSFC research that substantively diminishes reliability and reproducibility. We comprehensively evaluated existing and novel approaches to volume censoring-based motion denoising in the Human Connectome Project (HCP) dataset. We show that assumptions underlying common metrics for evaluating motion denoising pipelines, especially those based on quality control-functional connectivity (QC-FC) correlations and differences between high- and low-motion participants, are problematic, and appear to be inappropriate in their current widespread use as indicators of comparative pipeline performance and as targets for investigators to use when tuning pipelines for their own datasets. We further develop two new quantitative metrics that are instead agnostic to QC-FC correlations and other measures that rely upon the null assumption that no true relationships exist between trait measures of subject motion and functional connectivity, and demonstrate their use as benchmarks for comparing volume censoring methods. Finally, we develop and validate quantitative methods for determining dataset-specific optimal volume censoring parameters prior to the final analysis of a dataset, and provide straightforward recommendations and code for all investigators to apply this optimized approach to their own RSFC datasets.
17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes
Authors: Bowles KR , Pugh DA , Liu Y , Renton AE , Bandres-Ciga S , Gan-Or Z , Heutink P , Siitonen A , Bertelsen S , Cherry JD , Karch CM , Frucht SJ , Kopell BH , Peter I , Park YJ ,   International Parkinson’s Disease Genomics Consortium (IPDGC), Charney A , Raj T , Crary JF , Goate AM
Published: December 2019

Parkinson’s disease (PD) is genetically associated with the H1 haplotype of the MAPT 17q.21.31 locus, although the causal gene and variants underlying this association have not been identified. To better understand the genetic contribution of this region to PD, we fine-mapped the 17q21.31 locus in order to identify novel mechanisms conferring risk for the disease. We identified three novel H1 sub-haplotype blocks across the 17q21.31 locus associated with PD risk. Protective sub-haplotypes were associated with increased LRRC37A/2 copy number and expression in human brain tissue. We found that LRRC37A/2 is a membrane-associated protein that plays a role in cellular migration, chemotaxis and astroglial inflammation. In human substantia nigra, LRRC37A/2 was primarily expressed in astrocytes, interacted directly with soluble α-synuclein, and co-localized with Lewy bodies in PD brain tissue. These data indicate that a novel candidate gene, LRRC37A/2, contributes to the association between the 17q21.31 locus and PD via its interaction with α-synuclein and its effects on astrocytic function and inflammatory response. These data are the first to associate the genetic association at the 17q21.31 locus with PD pathology, and highlight the importance of variation at the 17q21.31 locus in the regulation of multiple genes other than MAPT and KANSL1, as well as its relevance to non-neuronal cell types.
Experimental Evaluation of Methods for Real-Time EEG Phase-Specific Transcranial Magnetic Stimulation
Authors: Shirinpour Sina , Alekseichuk Ivan , Mantell Kathleen , Opitz Alexander
Published: December 2019

Brain oscillations reflect system-level neural dynamics and capture the current brain state. These brain rhythms can be measured noninvasively in humans with electroencephalography (EEG). Up and down states of brain oscillations capture local changes in neuronal excitability. This makes them a promising target for non-invasive brain stimulation methods such as Transcranial Magnetic Stimulation (TMS). Real-time EEG-TMS systems record ongoing brain signals, process the data, and deliver TMS stimuli at a specific brain state. Despite their promise to increase the temporal specificity of stimulation, best practices and technical solutions are still under development. Here, we implement and compare state-of-the-art methods (Fourier based, Autoregressive Prediction) for real-time EEG-TMS and evaluate their performance both in silico and experimentally. We further propose a new robust algorithm for delivering real-time EEG phase-specific stimulation based on short prerecorded EEG training data (Educated Temporal Prediction). We found that Educated Temporal Prediction performs at the same level or better than Fourier-based or Autoregressive methods both in silico and in vivo, while being computationally more efficient. Further, we document a dependency of EEG signal-to-noise ratio (SNR) on algorithm accuracy across all algorithms. In conclusion, our results can give important insights for real-time TMS-EEG technical development as well as experimental design.
Longitudinal cell division is associated with single mutations in the FtsZ-recruiting SsgB inStreptomyces
Authors: Xiao Xiansha , Willemse Joost , Voskamp Patrick , Li Xinmeng , Lamers Meindert , Abrahams Jan Pieter , Pannu Navraj , van Wezel Gilles P.
Published: December 2019

In most bacteria, cell division begins with the polymerization of the GTPase FtsZ at the mid-cell, which recruits the division machinery to initiate cell constriction. In the filamentous bacteriumStreptomyces, cell division is positively controlled by SsgB, which recruits FtsZ to the future septum sites and promotes Z-ring formation. Here we show via site-saturated mutagenesis that various amino acid substitutions in the highly conserved SsgB protein result in the production of ectopically placed septa, that sever spores diagonally or along the long axis, perpendicular to the division plane. Ectopic septa were especially prominent when cells expressed SsgB variants with substitutions in residue E120. Biochemical analysis of SsgB variant E120G revealed that its interaction with - and polymerization of - FtsZ had been maintained. The crystal structure ofS. coelicolorSsgB was resolved and the position of residue E120 suggests its requirement for maintaining the proper angle of helix α3, thus providing a likely explanation for the aberrant septa formed in SsgB E120 substitution mutants. Taken together, our work presents the first example of longitudinal division in a free living bacterium, which is explained entirely by changes in the FtsZ-recruiting protein SsgB.
Live analysis and reconstruction of single-particle cryo-electron microscopy data with CryoFLARE
Authors: Schenk Andreas D. , Cavadini Simone , Thomä Nicolas H. , Genoud Christel
Published: December 2019

Efficient, reproducible and accountable single-particle cryo-electron microscopy structure determination is tedious and often impeded by lack of a standardized procedure for data analysis and processing. To address this issue, we have developed the FMI Live Analysis and Reconstruction Engine (CryoFLARE). CryoFLARE is a modular open-source platform offering easy integration of new processing algorithms developed by the cryo-EM community. It provides a user-friendly interface that allows fast setup of standardized workflows, serving the need of pharmaceutical industry and academia alike who need to optimize throughput of their microscope. To consistently document how data is processed, CryoFLARE contains an integrated reporting facility to create reports.

Live analysis and processing parallel to data acquisition are used to monitor and optimize data quality. Problems at the level of the sample preparation (heterogeneity, ice thickness, sparse particles, areas selected for acquisition, etc.) or misalignments of the microscope optics can quickly be detected and rectified before data collection is continued. Interfacing with automated data collection software for retrieval of acquisition metadata reduces user input needed for analysis, and with it minimizes potential sources of errors and workflow inconsistencies. Local and remote export support in Relion-compatible job and data format allows seamless integration into the refinement process. The support for non-linear workflows and fine-grained scheduling for mixed workflows with separate CPU and GPU based calculation steps ensures optimal use of processing hardware. CryoFLARE’s flexibility allows it to be used for all types of image acquisitions, ranging from sample screening to high-resolution data collection, and offers a new alternative for setting up image processing workflows. It can be used without modifications of the hardware/software delivered by the microscope supplier. As it is running on a server in parallel to the hardware used for acquisition, it can easily be set up for remote display connections and fast control of the acquisition status.
Experimental evaluation of a hybrid electric propulsion system for small UAVs
Authors: Machado Leonardo , Matlock Jay , Suleman Afzal
Published: December 2019

Purpose

This paper aims to experimentally evaluate the performance of a parallel hybrid propulsion system for use in small unmanned aerial vehicles (UAVs).

Design/methodology/approach

The objective is to combine all the individual components of the hybrid electric propulsion system (HEPS) into a modular test bench to characterize the performance of a parallel hybrid propulsion system, and to evaluate a rule-based controller based on the ideal operating line concept for the control of the power plant. Electric motor (EM) designed to supplement the power of the internal combustion engine (ICE) to reduce the overall fuel consumption, with the supervisory controller optimizing ICE torque.

Findings

The EM was able to supplement the power of the ICE to reduce fuel consumption, and proved the capability of acting as a generator to recharge the batteries drawing from ICE power. Furthermore, the controller showed that it is possible to reduce the fuel consumption with a HEPS when compared to its gasoline counterpart by running simulated representative UAV missions. The findings also highlighted the challenges to build and integrate the HEPS in small UAVs.

Originality/value

The modularity of the test bench allows each component to be changed to assess its impact on the performance of the system. This allows for further exploration and improvements of the HEPS in a controlled environment.
(Dis)aggregated earnings forecasts and acquisition financing
Authors: Ordyna Paul
Published: December 2019

Purpose

The purpose of this paper is to examine how a firm’s mergers and acquisitions (M&A) goals influence its voluntary disclosure policy. Specifically, this paper examines how a firm’s M&A financing intentions influence the degree of aggregation in management guidance prior to and after the M&A transaction.

Design/methodology/approach

Using a logistic model, this study tests the relation between M&A financing and the decision to issue disaggregate earnings guidance for 3,929 acquiring firms from 2007 to 2011.

Findings

The logistic regression results show that firms are more likely to provide disaggregate earnings guidance when using mostly stock to finance M&A and that the incentives to disaggregate guidance vary throughout the M&A transactional window. Alternatively, because the value of cash is independent of the true value of the acquirer, the results show that firms offering mostly cash to finance M&A are less likely to issue disaggregate earnings forecasts. Additional analysis reveals that the decision to issue disaggregate earnings guidance also influences post-merger outcomes such as CEO turnover.

Research limitations/implications

The choice to disaggregate earnings guidance and the choice to use stock as a means to finance an acquisition is made by management, thus are endogenous which could introduce bias.

Originality/value

This study provides insights into management’s incentives and attitudes toward the use of management forecasts to effect a potential merger and acquisition. Given the flexibility management has in issuing voluntary forecasts, management can tailor a financial message toward investors and potential targets in attempt to facilitate a merger and acquisition and to further the firm’s goals.
Reasons for food losses during home preparation
Authors: Nonomura Maki
Published: December 2019

Purpose

The purpose of this paper is to explore reasons for household preparation losses.

Design/methodology/approach

Observations of preparation behaviors and semi-structured interviews of nine people were conducted in their kitchens. The data were analyzed through a qualitative data analysis method.

Findings

Three types of preparation losses were identified, i.e. possibly avoidable food waste, excessive removals and unintentional losses. Possibly avoidable food waste and excessive removals were generated owing to people’s perception that is in the gray area between edible and inedible, their preferences, lower quality of food, convenience in preparation, lack of preparation skill and knowledge, and lack of concern about preparation losses. Unintentional losses were tiny pieces of food that were left on cooking tools.

Research limitations/implications

As this study’s participants were nine women living in Japan, further research is needed in order to achieve saturation.

Originality/value

Few studies have discussed reasons for preparation losses, and extant studies were based on a diary method and questionnaires. This present study uncovers several new reasons for preparation losses based on interviews and observations of consumer preparation behaviors. These new details would be helpful for campaigns or programs that aim to reduce food losses.
A breakthrough in business management (Roman private share company as radical novelty)
Authors: Petrosyan Armen E.
Published: December 2019

Purpose

This paper aims to retrace the genesis of private share company in Ancient Rome as one of the greatest innovation in the history of management.

Design/methodology/approach

Relying on a thorough and systematic analysis of the available historical material, and modern research, the author reconstructs the first known form of private share company and the way it came into being under late Republic and early Empire.

Findings

The scope of commercial partnerships and bounds preventing them from concentration of capitals are shown. The popular myth of private corporations allegedly existing in Ancient Rome is debunked. The author reveals how existing business elements (union of co-owners, the module “slave – peculium – free administration” from individual enterprise, and the principle of inseparability of joint ownership) had been combined to form private share company. Are demonstrated its chief differences from corporation, and the untenability of attempts to deny the real existence of private share companies in Ancient Rome. By way of summing up, the pattern of innovations is brought into relief.

Research limitations/implications

The material opens new vistas for historians and allows them to draw an exacter and more comprehensive picture of Roman private entrepreneurship. Experts in management get an opportunity to retrace the background of modern forms of business organizing. A broader circle of researchers may see what the real path of radical novelties – from the need for them to their implementation – is. And altogether, the author’s conclusions provide scholars with a key to understanding breakthrough phenomena of history.

Practical implications

The results obtained may be used in many courses related to the history of economics, business, management, innovations, etc. Besides, they allow practitioners to discern plainly the origins of new business forms and learn how to make for them or facilitate their growth.

Social implications

The author's conception of viable novelties sheds light on the processes of social development and modernization. It may serve as an effective instrument in planning reforms and managing them.

Originality/value

The framework of Roman private share company and many allied issues are investigated for the first time. This type of enterprise is presented as a response to the functional request from private entrepreneurs. That is why the new organizational form, despite its radical nature, proved to be quite efficient, and caught on in business. The author infers from his findings a generalized pattern of innovations able to get integrated into reality.
An analysis of current tax revolt factors in South Africa
Authors: Du Preez Hanneke , Stoman Jacqueline
Published: December 2019

Purpose

The purpose of this study is to determine whether the factors once identified through literature and compared to the current situation in South Africa could predict the possibility of a tax revolt in South Africa. South Africans are experiencing frequent increases in taxes on already overburdened taxpayers, corruption, a lack of service delivery by the government and high unemployment rates. South Africa has seen an increased amount of protests relating to taxes, corruption and a lack of basic services.

Design/methodology/approach

In total, 12,000 Twitter feeds were collected from 14 February 2017 to 1 March 2017, the period before, during and after the South African National Budget Speech on 22 February 2017. The feeds were analysed using a thematic analysis. The emerging themes were identified as factors present in South Africa that may predict a possible tax revolt.

Findings

The factors found to be present in South Africa are: F1-failure of government to address the imminent collapse, F2-significant number of people with substantial debt, F3-onerous tax systems, including many different types of taxes, F4-high number of unemployed people, F5-education frustration, F6-increase in tax rates on citizens already overburdened by current taxes, F7-poor quality of governors, and performance of the country’s leaders and administration, including fraud and F8-wastefulness.

Originality/value

The value of the study is, first to contribute to the existing academic literature examining the factors that are likely to indicate a tax revolts. Second, the study uses an innovative data source, namely, tweets, to examine the climate for a possible tax revolt in South Africa.
Using hybrid SEM – artificial intelligence
Authors: Abubakar A. Mohammed
Published: December 2019

Purpose

Boreout is a psychological state of intense boredom and apathy. Characterized by the absence of mental stimuli (i.e. menial tasks) required to keep employees conscious about their environment, and this incessant decline in mental stimuli may turn employees into “professional zombies.” The diversity in work needs and preferences across generations has become a key organizational factor, generational differences have been studied in Western countries, not much information is available about generational cohorts and satisfaction (i.e. career, life and job satisfaction) in developing countries. The purpose of this paper is to provide more insights on these phenomena.

Design/methodology/approach

Drawing upon conservation of resources theory, this paper examines the potential effects of boreout on important job outcomes (i.e. career, life and job satisfaction) conditioned by generation (Gen-Xers and Gen-Yers) in the service industry. Data analyses with Artificial Intelligence technique (i.e. artificial neural network) and structural equation modeling were conducted with data collated from Nigerian service employees.

Findings

Results revealed that boreout has a negative impact on career, life and job satisfaction. The hypothesized relationships were significantly moderated by generation cohorts as Gen-Xers and Gen-Yers were found to be distinct cohorts.

Originality/value

This paper advocates that non-western organizations should avoid utmost service standardization and rigid stylization of work processes and procedures.
Coping and laughing in the face of broken promises: implications for creative behavior
Authors: De Clercq Dirk , Belausteguigoitia Imanol
Published: December 2019

Purpose

The purpose of this paper is to consider how employees’ perceptions of psychological contract breach, due to their sense that their organization has not kept its promises, might diminish their creative behavior. Yet access to two critical personal resources – emotion regulation and humor skills – might buffer this negative relationship.

Design/methodology/approach

Survey data were collected from employees in a large organization in the automobile sector.

Findings

Employees’ beliefs that their employer has not come through on its promises diminishes their engagement in creative activities. The effect is weaker among employees who can more easily control their emotions and who use humor in difficult situations.

Practical implications

For organizations, the results show that the frustrations that come with a sense of broken promises can be contained more easily to the extent that their employee bases can rely on pertinent personal resources.

Originality/value

This investigation provides a more comprehensive understanding of when perceived contract breach steers employees away from productive work activities, in the form of creativity. This damaging effect is less prominent when employees possess skills that enable them to control negative emotions or can use humor to cope with workplace adversity.
Effect of ultrasonic vibration on interfacial reaction of Ni/Sn/Ni soldered joint
Authors: Liu Yun , Yu Weiyuan , Sun Xuemin , Wang Fengfeng
Published: December 2019

Purpose

This paper aims to investigate the effect of ultrasonic vibration (USV) on the evolution of intermetallic compounds (IMCs), grain morphology and shear strength of soldered Ni/Sn/Ni samples.

Design/methodology/approach

The Ni/Sn/Ni joints were obtained through ultrasonic-assisted soldering. The formation of IMCs, their composition, grain morphology and the fractured-surface microstructures from shear tests were characterized using scanning electron microscopy and energy-dispersive x-ray spectroscopy.

Findings

Without USV, a planar interfacial Ni3Sn4layer was formed at the Ni/Sn interface, and a few Ni3Sn4grains were distributed in the soldered joint. The morphology of these grains was needle-shaped. With USV, several grooves were formed at the interfacial Ni3Sn4layer due to ultrasonic cavitation. Some deepened grooves led to “neck” connections at the roots of the Ni3Sn4grains, which accelerated the strong detachment of Ni3Sn4from the substrate. In addition, two types of Ni3Sn4grains, needle-shaped and granular-shaped, were observed at the interface. Furthermore, the shear strength increased with longer USV time, which was attributed to the thinning of the interfacial IMC layers and dispersion strengthening from the Ni3Sn4particles distributed evenly in the joint.

Originality/value

The novelty of the paper is the detailed study of the effect of USV on the morphology, size changes of interfacial IMC and joint strength. This provides guidance for the application of ultrasonic-assisted soldering in electronics packaging.
An exploratory study of verbal feedback on occupational performance for improving self‐awareness in people with traumatic brain injury
Authors: Fleming Jennifer , Tsi Hui Goh Amelia , Lannin Natasha A. , Ownsworth Tamara , Schmidt Julia
Published: December 2019

Introduction

Impaired self‐awareness negatively impacts on how well persons with traumatic brain injury (TBI) learn and use strategies needed in daily life. Verbal feedback is a component of metacognitive strategy training recommended for addressing impaired self‐awareness in TBI rehabilitation. Yet, it remains unknown how effectively verbal feedback on occupational performance improves self‐awareness for the specific occupation involved. This study investigated the effect of verbal feedback on task‐specific self‐awareness for individuals with TBI.

Methods

A secondary analysis was conducted on selected data extracted from a randomised, assessor‐blinded controlled trial in which 36 participants with impaired self‐awareness post‐TBI were allocated into two feedback intervention groups, verbal feedback and a control condition of experiential feedback only. All participants engaged in four sessions of meal preparation with an occupational therapist using a metacognitive strategy training approach. Participants in the verbal feedback group received feedback on their performance in a discussion with the occupational therapist following each session. Task‐specific self‐awareness was measured using discrepancy scores (therapist ratings minus self‐ratings) on a Meal Independence Rating Scale (MIRS). Data were analysed using a mixed 2 × 2 analysis of variance.

Results

Positive MIRS discrepancy scores at pre‐intervention reflected the propensity of participants to over‐estimate their abilities There was a significant main effect of time, indicating overall gains in task‐specific self‐awareness at post‐intervention (p = .01), but no significant group‐by‐time interaction. Changes in participants’ self‐ratings post‐intervention were minimal. Instead, reduced MIRS discrepancy scores resulted largely from changes in therapists’ ratings, indicating improvement in occupational performance.

Conclusion

Participants in both groups demonstrated improvements in occupational performance, but this did not correspond with changes in task‐specific self‐awareness. In this small sample, there was no statistically significant improvement in self‐awareness associated with the provision of verbal feedback after occupational performance over and above the benefits of experiential feedback.
Clemaichinenoside protects renal tubular epithelial cells from hypoxia/reoxygenation injury in vitro through activating the Nrf2/HO‐1 signalling pathway
Authors: Feng Jie , Kong Ranran , Xie Liyi , Lu Wanhong , Zhang Yali , Dong Hongjuan , Jiang Hongli
Published: December 2019

Renal ischaemia/reperfusion (I/R) is a major cause of acute renal failure with increased morbidity, mortality, and prolonged hospitalizations. Clematichinenoside (AR), a triterpenoid saponin isolated from the roots of Clematis chinensis, was reported to possess a protective effect against I/R injury. However, the effect of AR on renal I/R injury has not been evaluated. This study aims to examine the effect of AR on an in vitro I/R model in human proximal tubular epithelial cells HK‐2. HK‐2 cells were subjected to hypoxia/reoxygenation (H/R) stimulation to mimic I/R in vitro. The results showed that AR improved cell viability of H/R‐stimulated HK‐2 cells. AR pretreatment resulted in decreased production of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as increased in superoxide dismutase (SOD) activity in H/R‐stimulated HK‐2 cells. In addition, AR also presented an anti‐inflammatory activity, as evidenced by decreased secretion of pro‐inflammatory cytokines including IL‐6, IL‐1β, and TNF‐α. Moreover, apoptotic rate was markedly decreased in HK‐2 cells pretreated with AR. The bax expression was decreased, while bcl‐2 expression was increased by AR pretreatment. Furthermore, AR enhanced the H/R‐stimulated activation of the Nrf2/HO‐1 signalling pathway in HK‐2 cells. In conclusion, these findings indicated that AR protected HK‐2 cells from H/R‐induced cell injury via regulating the Nrf2/HO‐1 signalling pathway.
Knockdown of TMEM45A overcomes multidrug resistance and epithelial–mesenchymal transition in human colorectal cancer cells through inhibition of TGF‐β signalling pathway
Authors: Zhu Mo , Jiang Baofei , Yan Dongsheng , Wang Xiaopeng , Ge Hengfa , Sun Yueming
Published: December 2019

Colorectal cancer (CRC), a leading cause of cancer death, has recently been known as the most prevalent malignancy worldwide. Although chemotherapy is an important therapeutic option for CRC patients, multidrug resistance (MDR) still remains a major cause of chemotherapy failure. Transmembrane protein 45A (TMEM45A) has been found highly expressed in various cancers, and is also proposed as an interesting biomarker for chemoresistance. However, the association between TMEM45A and MDR in CRC remains unclear. This study aimed to investigate the key role of TMEM45A in CRC by knockdown of its expression in 5‐FU‐resistant CRC cells (HCT‐8/5‐FU and SW480/5‐FU) and their parental cells (HCT‐8 and SW480). Data showed that TMEM45A was significantly up‐regulated in HCT‐8/5‐FU and SW480/5‐FU cells in comparison with their parental HCT‐8 and SW480 cells. Knockdown of TMEM45A enhanced 5‐FU sensitivity and 5‐FU‐induced apoptosis in HCT‐8/5‐FU and SW480/5‐FU cells. It was also found that inhibition of TMEM45A increased the intracellular accumulation of Rhodamine‐123 and down‐regulated the expression of MDR1 in HCT‐8/5‐FU and SW480/5‐FU cells. In addition, knockdown of TMEM45A suppressed migration and invasion of HCT‐8/5‐FU and SW480/5‐FU cells. Furthermore, knockdown of TMEM45A not only attenuated MDR‐enhanced epithelial–mesenchymal transition (EMT), but also suppressed MDR‐enhanced activation of the TGF‐β signalling pathway in HCT‐8/5‐FU and SW480/5‐FU cells. Taken together, our study suggests that knockdown of TMEM45A can effectively overcome MDR and inhibit EMT via suppression of the TGF‐β signalling pathway in human CRC cells, and that targeting TMEM45A will be a potential strategy in the treatment of MDR in CRC.
The Economics of Ageing—What do you Face?
Authors: McDonald Ian M.
Published: December 2019

The economics of ageing is the study of economic decision‐making by individuals and government aimed at fostering well‐being in old age. These decisions include preparing for old age and dealing with the risks of old age. The risks are substantial. Using the life‐cycle model, this article considers the risks for well‐being that people face in retirement and the role of government and private insurance in meeting those risks. The perspective of the life‐cycle model is also used to consider the gender gap in wealth on retirement.
From Friction to Free Trade Negotiations: Australia's Engagement with the European Union
Authors: Murray Philomena
Published: December 2019

Following decades of skirmishes, Australia's relationship with the European Union (EU) has finally come of age. With the commencement of negotiations for a Free Trade Agreement, the outlook is promising for enhanced cooperation. Yet there are distinctive—and at times diverging—hierarchies of interests. This article argues that, although the EU and Australia regard each other as like‐minded partners, their interests and domestic pressures do not necessarily denote comprehensive convergence. This is due to the burden of memory, divergent concerns and values, some mutual neglect and an element of mutual misunderstanding.
Australian Trade Policy in the Twenty‐First Century
Authors: Pomfret Richard
Published: December 2019

In the 1980s and 1990s, Australia moved from a protectionist trade policy to very open trade policies. This paper analyses the evolution of these policies in the twenty‐first century: first signing bilateral agreements in the 2000s and then participating in negotiation of mega‐regional agreements (TPP/CPTPP and RCEP). To some extent these shifts have reflected stasis in the World Trade Organisation (WTO) and its inability to make agreements on new areas. Underlying drivers of Australia's beyond‐WTO trade agreements have been the fragmentation of trade along global value chains and the emergence of new trade technologies associated with the spread of the internet.
Australia's National Electricity Market after Twenty Years
Authors: Rai Alan , Nelson Tim
Published: December 2019

The Hilmer reforms served electricity consumers well over the first post‐reform decade. However, three key issues emerged from the mid‐2000s: (i) a significant and largely unnecessary rise in network expenditures; (ii) emissions policy discontinuity; and (iii) a large increase in wholesale prices due to rising fuel prices and the sudden exit of generators. The consequence was a doubling in retail prices. Deficiencies in cost‐recovery mechanisms have meant price increases have disproportionately affected low‐income households. We propose three key reforms as rectification: (i) integrating emissions reduction and energy policies; (ii) boosting network capacity utilisation; and (iii) improving cost recovery mechanisms.
Adult obstructive sleep apnoea: Pathogenesis, importance, diagnosis and imaging
Authors: Whyte Andy , Gibson Daren
Published: December 2019

Obstructive sleep apnoea (OSA) is a serious worldwide health problem. Moderate‐to‐severe OSA has been found in up to 50% of men and 25% of women in the middle‐aged population. It results in a fourfold increase in all causes of mortality. The prevalence of OSA is underestimated, partly due to absence of symptoms but also lack of knowledge amongst the population at large as well as sectors of the medical profession. Imaging, performed predominantly by clinicians and research scientists, has been integral to evaluating the anatomical basis of OSA. Increased nasal resistance and a narrowed and elongated oropharynx lead to increased collapsibility of the upper airway, predisposing to airway collapse and apnoea during sleep when there is reduction in tone of the pharyngeal dilator muscles. Unfortunately, a significantly narrowed upper airway is usually ignored by radiologists: it is not part of their reporting ‘check‐list’. The imaging findings in the upper airway that are strongly associated with OSA and its sequelae in various organ systems are discussed. Imaging can strongly suggest OSA; the diagnosis requires a polysomnogram for confirmation. Treatment of moderate‐to‐severe disease is primarily with positive airway pressure applied by a nasal or oral mask which splints the upper airway. Although highly effective, compliance is limited and other treatment modalities are increasingly being utilized.
Is inguinal hernia mesh safe? A prospective study
Authors: Watson Bridget , Roberts Jessica , Dobbs Bruce , Roberts Ross
Published: December 2019

Background

Hernia repair surgery using synthetic mesh is the standard of care in modern surgery. Complications from uro‐gynaecological mesh have been reported in the New Zealand media and there is public concern regarding the use of any mesh for any reason. This study reports long‐term outcomes in inguinal hernia surgery in a large cohort of elective operations using mesh.

Methods

A prospective database of patients having inguinal hernia mesh repairs was maintained in a private two surgeon practice from 2002 to 2016. Patient demographics, method of repair, the pre‐operative and post‐operative pain scores and complications following surgery were recorded.

Results

A total of 1711 hernia in 1366 patients were repaired from 2002 to 2016. One thousand and forty‐seven repairs were laparoscopic total extraperitoneal (LTEP), 333 were open. Post‐operative pain scores were significantly lower than pre‐operative scores in inguinal hernia repair by any method. Only 22% of patients described no pain pre‐operatively and this rose to 76% post‐operatively; conversely 7.9% described severe pain pre‐operatively and this reduced to 1% post‐operatively. The recurrence rate for open inguinal hernia was zero and for LTEP repair was 0.81%.

Conclusion

Inguinal hernia repair using mesh does not appear to produce significant rates of chronic pain long term. Overall, the complications from open or LTEP inguinal hernia repair with mesh are low.
Long‐term radiographic appearance of a bioabsorbable biocomposite tibial tuberosity advancement cage implant
Authors: Ferrell CL , Barnhart MD , Watson AT , Barron‐Chapman ML , Naber SJ
Published: December 2019

Objective

To report the radiographic appearance of a bioabsorbable biocomposite tibial tuberosity advancement cage at least 1 year after implantation.

Design Retrospective case series.

Methods

Medical records (February 2014–March 2015) of dogs receiving a biocomposite tibial tuberosity advancement cage were reviewed. Cases were selected if they had undergone surgery at least 1 year before the selection, no additional surgeries were performed, and no known surgical site infection had occurred. Medical record information assessed included signalment, body weight (kg), affected stifle joint (left or right), date of original surgery and the size of biocomposite cage used (9 or 12 mm). Radiographs were evaluated by two blinded radiologists who calculated percentages of osteolucency present in five zones around the cage and assigned a numerical score based on these calculations. Variables were evaluated statistically for effect on lucency percentage and numerical score.

Results

Fifty dogs were included. Zone 5 (caudoproximal area) was found to have the lowest lucency percentage and score and zone 3 (distal area) had the highest lucency percentage and score. Twelve‐millimetre cages were significantly associated with a higher lucency numerical score than 9 mm cages.

Conclusion

A biocomposite tibial tuberosity advancement cage was found to have variable amounts of radiographically apparent osseous integration at least 1 year after implantation.
hVFL3/CCDC61 is a component of mother centriole subdistal appendages required for centrosome cohesion and positioning
Authors: Pizon Véronique , Gaudin Noémie , Poteau Marion , Cifuentes‐Diaz Carmen , Demdou Roland , Heyer Vincent , Reina San Martin Bernardo , Azimzadeh Juliette
Published: December 2019

Background

The centrosome regulates cell spatial organisation by controlling the architecture of the microtubule (MT) cytoskeleton. Conversely, the position of the centrosome within the cell depends on cytoskeletal networks it helps organizing. In mammalian cells, centrosome positioning involves a population of MT stably anchored at centrioles, the core components of the centrosome. An MT‐anchoring complex containing the proteins ninein and Cep170 is enriched at subdistal appendages (SAP) that decorate the older centriole (called mother centriole) and at centriole proximal ends. Here, we studied the role played at the centrosome by hVFL3/CCDC61, the human ortholog of proteins required for anchoring distinct sets of cytoskeletal fibres to centrioles in unicellular eukaryotes.

Results

We show that hVFL3 co‐localises at SAP and at centriole proximal ends with components of the MT‐anchoring complex, and physically interacts with Cep170. Depletion of hVFL3 increased the distance between mother and daughter centrioles without affecting the assembly of a filamentous linker that tethers the centrioles and contains the proteins rootletin and C‐Nap1. When the linker was disrupted by inactivating C‐Nap1, hVFL3‐depletion exacerbated centriole splitting, a phenotype also observed following depletion of other SAP components. This supported that hVFL3 is required for SAP function, which we further established by showing that centrosome positioning is perturbed in hVFL3‐depleted interphase cells. Finally, we found that hVFL3 is an MT‐binding protein.

Conclusions and significance

Together, our results support that hVFL3 is required for anchoring MT at SAP during interphase and ensuring proper centrosome cohesion and positioning. The role of the VFL3 family of proteins thus appears to have been conserved in evolution despite the great variation in the shape of centriole appendages in different eukaryotic species.