bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Fixation Location in Intraoral Reduction Malarplasty Using an L-Shaped Osteotomy
Authors: Kim Jin Woo , Hwang Woosuk
Published: August 2019

Background:

Reduction malarplasty, popular among Asians, is currently performed preferably via the intraoral approach. However, to prevent complications such as malunion and cheek drooping, a rigid fixation is essential to compensate for the action of the masseter. Accordingly, the authors aimed to perform an experimental study on the optimal fixation location during intraoral reduction malarplasty using an L-shaped osteotomy.

Methods:

Fixation points that are not difficult to access during an L-shaped osteotomy were selected as 1 point in the freed zygomaticomaxillary complex and 3 points in the medial part of the malar complex (low, middle, and high levels).

After setting the fixation points in the medial malar complex and lateral segment of skull replicates, resistance to traction was measured at each level, and maxillary bone thickness was also measured at each level at the fixation points of the medial malar complex in a cadaveric head.

Results:

In the medial malar complex, resistance to traction increased at higher levels, while the maxillary bone was much thicker at the high level than at the low-middle level.

Conclusion:

This study demonstrated that it is better to locate the fixation point at a higher level in the medial part of the malar complex, closer to the lateral orbital rim.
Adjuvant Chemotherapy Versus Observation Following Resection for Patients With Nonmetastatic Poorly Differentiated Colorectal Neuroendocrine Carcinomas
Authors: Mao Rui , Li Kan , Cai Jian-Qiang , Luo Sheng , Turner Megan , Blazer Dan , Zhao Hong
Published: August 2019

Objective:

The aim of this study was to determine whether adjuvant chemotherapy (AC) provides a survival benefit in patients with nonmetastatic poorly differentiated colorectal neuroendocrine carcinomas (CRNECs) following resection.

Background:

There is little evidence to support the association between use of AC and improved overall survival (OS) in patients with CRNECs.

Methods:

Patients with resected non-metastatic CRNECs were identified in the National Cancer Database (2004–2014). Inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. IPTW-adjusted Kaplan-Meier curves and Cox proportional hazards models were used to compare OS of patients in different treatment groups.

Results:

A total of 806 patients diagnosed between 2004 and 2014 met the study entry criteria. Of these, 394 patients (48.9%) received AC. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer for AC versus observation [57.4 (interquartile range, IQR, 14.8–153.8) vs 38.2 (IQR, 10.4–125.4) months; P = 0.007]. In IPTW-adjusted Cox proportional hazards regression analysis, AC was associated with a significant OS benefit [hazard ratio (HR) = 0.73, 95% confidence interval (CI) 0.64–0.84; P < 0.001]. The results were consistent across subgroups stratified by pathologic T stage, pathologic N stage, and surgical margin status. Subgroup analysis according to tumor location demonstrated improved OS in the adjuvant therapy cohort among patients with left-sided neuroendocrine carcinomas (HR, 0.55; 95% CI, 0.44–0.68), but not in those with right-sided disease (HR, 0.89; 95% CI, 0.74–1.07).

Conclusions:

Patients with nonmetastatic CRNECs may derive survival benefit from AC. These findings support current guidelines recommending AC in patients with poorly differentiated neuroendocrine carcinomas in the colon and rectum. Efforts in education and adherence to national guidelines for NECs are needed.
Cell motion as a stochastic process controlled by focal contacts dynamics
Authors: Lo Vecchio Simon , Thiagarajan Raghavan , Caballero David , Vigon Vincent , Navoret Laurent , Voituriez Raphaël , Riveline Daniel
Published: August 2019

Directed cell motion is essential in physiological and pathological processes such as morphogenesis, wound healing and cancer spreading. Chemotaxis has often been proposed as the driving mechanism, even though evidence of long-range gradients is often lacking in vivo. By patterning adhesive regions in space, we control cell shape and the associated potential to move along one direction in another mode of migration coined ratchetaxis. We report that focal contacts distributions collectively dictate cell directionality, and bias is non-linearly increased by gap distance between adhesive regions. Focal contact dynamics on micro-patterns allow to integrate these phenomena in a consistent model where each focal contact can be translated into a force with known amplitude and direction, leading to quantitative predictions for cell motion in every condition. Altogether, our study shows how local and minutes timescale dynamics of focal adhesions and their distribution lead to long term cellular motion with simple geometric rules.
Rampant loss of social traits during domestication of aBacillus subtilisnatural isolate
Authors: Barreto Hugo C. , Cordeiro Tiago N. , Henriques Adriano O. , Gordo Isabel
Published: August 2019

Most well-studied bacteria have been domesticated to some extent. How fast can a natural isolate diverge from its ancestral phenotypes under domestication to a novel laboratory environment is poorly known. Yet such information is key to understand rates of evolution, the time scale at which a natural isolate can be propagated without loss of its natural adaptive traits and the reliability of experimental results across labs. Using experimental evolution, phenotypic assays and whole-genome sequencing, we show that within a week of propagation in a common laboratory environment, a natural isolate ofBacillus subtilisacquires mutations that cause changes in a multitude of traits. A single adaptive mutational step, in the gene coding for the transcriptional regulator DegU, impairs a DegU-dependent positive autoregulatory loop and leads to loss of robust biofilm architecture, impaired swarming motility, reduced secretion of exoproteases and changes in the dynamics of sporulation across environments. Importantly, domestication also resulted in improved survival when the bacteria face pressure from cells of the innate immune system. These results show thatdegUis a key target for mutations during domestication and also underscore the importance of performing careful and extremely short-term propagations of natural isolates to conserve the traits encoded in their original genomes.

Domestication is the process by which organisms are selected to live in specific conditions and an important phenomenon that shapes the evolution and variation in many animals and plants. In microbes, domestication is also a key driver of adaptation. It can be beneficial, when improving microbes abilities that are important for biotechnology, but also problematic, especially when studying microbe-host interactions and the microbe’s natural behavior. Using a natural isolate ofBacillus subtilis, we determined the speed and genetic basis of microbial domestication using experimental evolution. Within one week of growth in the common laboratory media, mutations in the pleiotropic transcriptional regulator, DegU, emerge and spread in the populations. These lead to loss of social traits, increased resistance to bacteriophages and increased survival in the presence of macrophages. The data highlights the extreme caution that is needed when culturing natural microbial isolates and may help explain why some key microbial social traits and behaviors may differ between different laboratories, even when studying the same strains.
Characterization and Sap Transmission of Citrus Bent Leaf Viroid in Malaysia
Authors: Iftikhar Yasir , Khoo Ying Wei , Murugan Taneswari , Roslin Nur Athirah , Adawiyah Rabiatul , Kong Lih Ling , Vadamalai Ganesan
Published: August 2019

A 328 nucleotide (nt) variant of Citrus bent leaf viroid (CBLVd) was characterized from citrus varieties in Malaysia showing leaf bending, stunting and midvein necrosis. CBLVd was detected by RT-PCR assay using CBLVd specific primers in 12 out of 90 samples, collected from six different areas in Malaysia. The viroid was present in five species of citrus namely Citrofortunella microcarpa, Citrus aurantifolia, C. hystrix, C. maxima and C. sinensis. Sequence analysis of the isolates obtained from this study showed 99-100% sequence identity to CBLVd Jp isolate (AB006734). Inoculation of sap obtained from a CBLVd positive C. aurantifolia, inoculated into six months old C. microcarpa seedlings showed the symptoms leaf bending, reduced leaf size of matured leaves and mild mosaic between 4 to 6 months after inoculation. The presence of CBLVd in the inoculated seedlings were confirmed by RT-PCR assay and sequencing.

Author Summary

The authors during a limited survey collected the citrus samples from citrus growing areas of Malaysia to detect the citrus viroids. Citrus viroids are associated with decline in citrus production. Thus, the presence of the citrus viroids and their spread needs to be investigated to facilitate the management of this pathogen in citrus orchards. The authors detected and characterized Citrus bent leaf viroid in Malaysian citrus.
Structure of GTP cyclohydrolase I fromListeria monocytogenes, a potential anti-infective drug target
Authors: Schüssler Sonja , Haase Ilka , Perbandt Markus , Illarionov Boris , Siemens Alexandra , Richter Klaus , Bacher Adelbert , Fischer Markus , Gräwert Tobias
Published: August 2019

A putative open reading frame encoding GTP cyclohydrolase I fromListeria monocytogeneswas expressed in a recombinantEscherichia colistrain. The recombinant protein was purified and was confirmed to convert GTP to dihydroneopterin triphosphate (Km= 53 µM;vmax= 180 nmol mg−1 min−1). The protein was crystallized from 1.3 Msodium citrate pH 7.3 and the crystal structure was solved at a resolution of 2.4 Å (Rfree= 0.226) by molecular replacement using human GTP cyclohydrolase I as a template. The protein is aD5-symmetric decamer with ten topologically equivalent active sites. Screening a small library of about 9000 compounds afforded several inhibitors with IC50values in the low-micromolar range. Several inhibitors had significant selectivity with regard to human GTP cyclohydrolase I. Hence, GTP cyclohydrolase I may be a potential target for novel drugs directed at microbial infections, including listeriosis, a rare disease with high mortality.
5,10-Dihydroindeno[2,1-a]indene
Authors: Detert Heiner , Schollmeyer Dieter
Published: August 2019

The title compound, C16H12, crystallizes with four half molecules in the asymmetric unit, each of which is located on a crystallographic centre of inversion. The molecules are essentially planar. The crystal studied was a non-merohedral twin.
Relationships between conflicts and employee perceived job performance
Authors: Ye Zhongjun , Liu Hefu , Gu Jibao
Published: August 2019

Purpose

Over 83.72 million Chinese firms employing more than 775 million employees. It is essential to explore employee relationships and conflict management practices in China. Although collectivism can influence employee cognition and emotions, the psychological mechanism that links collectivism and job satisfaction is still unclear. Researchers have found existing empirical findings on conflict–performance relationships to be mixed and inconsistent, and have identified the need to pinpoint the explanatory mechanisms and boundary conditions that underlie the effect of conflict on job performance. This study aims to provide some clarification to this important yet relatively unclear issue.

Design/methodology/approach

A questionnaire survey was conducted in China to collect data. The authors received completed questionnaires from 466 employees.

Findings

Analysis of questionnaire results reveals that job satisfaction mediates the relationships between conflicts and perceived job performance, and that collectivism moderates the relationships between conflicts and job satisfaction. Specifically, the positive relationship between task conflict and job satisfaction is amplified by high levels of horizontal collectivism (HC) and vertical collectivism (VC), while the negative relationship between relationship conflict and job satisfaction is strengthened by HC.

Research limitations/implications

The main limitation is that this study used a cross-sectional design, meaning that causality in relationships cannot be established from results. Despite this limitation, the present findings provide insights into conflict management, job satisfaction and culture value literature.

Originality/value

This paper examines the moderating role of employees’ collectivist orientation (not national culture) on the relationships between conflicts and employee job satisfaction at the individual level. It also explores HC and VC and identifies their differential effects on the relationships between conflicts and job satisfaction.
How to use lean Six Sigma methodology to improve service process in higher education
Authors: Li Na , Laux Chad Matthew , Antony Jiju
Published: August 2019

Purpose

The purpose of this paper is to use a practical case study approach to demonstrate the power to use lean Six Sigma (LSS) to improve service process in a higher education institution (HEI). The paper also illustrated the barriers and challenges met and lessons learnt for the LSS adoption in this HEI.

Design/methodology/approach

Prior to the study, extensive literature review was conducted to understand various aspects of LSS in HE industry. The authors use a single descriptive case study as methodology to explain how DMAIC was applied within a HEI environment.

Findings

In this LSS case study, the team found HEI service process contains a large human behavior component, which dramatically increases the unpredictability of the entire service delivery process and increases the complexity of the process and the ability of the improvement team to identify the root cause. This case study demonstrates the numerous challenges will occur in working with the intangible factors that are both hard to recognize, quantify and rarely tracked by organization.

Practical implications

During the research, the pre-award service process was studied, data were recorded and various statistical tool and techniques were used to discover and resolve the root cause. The lessons learnt of the LSS adoption in this service process in HEI and the problems encountered were all recorded in this study, which will be helpful for future research in HEI industry.

Originality/value

From the literature review, LSS has been widely adopted in manufacturing industry, increased adoption in service, but there has been limited academic research about the implementation in nonprofit, service sectors, particular to higher education industry. The major benefit of implementation LSS in both manufacturing and service is considerable improvement to the bottom line. However, in this HEI case study, it has opened up the direction to implement LSS to better serve your customer as ultimate mission instead of financial gains.
Understanding speculative investment behavior in the Bitcoin context from a dual-systems perspective
Authors: Ryu Hyun-Sun , Ko Kwang Sun
Published: August 2019

Purpose

The purpose of this paper is to examine users’ decision-making mechanism of speculative investment behavior and its sequential consequences in the Bitcoin context from a dual-systems perspective.

Design/methodology/approach

Original data were collected via a survey of 334 participants with experience in Bitcoin speculative investment. The partial least squares method was used to test the proposed model.

Findings

Speculative investment behavior in the Bitcoin context is driven by strong impulse and weak self-control, leading to negative consequences. The extent of the imbalance between the two cognitive systems is greater with the subjective norm than without it, thus facilitating speculative investment behavior. Noteworthy differences in the impulse and self-control effects on Bitcoin speculative investment are found with differences in Bitcoin objective and subjective knowledge.

Originality/value

This study is the first attempt to empirically investigate users’ decision-making mechanism used when speculating in Bitcoin.
Fuzzy sliding mode control of a wearable rehabilitation robot for wrist and finger
Authors: Abbasi Moshaii Alireza , Mohammadi Moghaddam Majid , Dehghan Niestanak Vahid
Published: August 2019

Purpose

The purpose of this paper is to introduce a new design for a finger and wrist rehabilitation robot. Furthermore, a fuzzy sliding mode controller has been designed to control the system.

Design/methodology/approach

Following an introduction regarding the hand rehabilitation, this paper discusses the conceptual and detailed design of a novel wrist and finger rehabilitation robot. The robot provides the possibility of rehabilitating each phalanx individually which is very important in the finger rehabilitation process. Moreover, due to the model uncertainties, disturbances and chattering in the system, a fuzzy sliding mode controller design method is proposed for the robot.

Findings

With the novel design for moving the DOFs of the system, the rehabilitation for the wrist and all phalanges of fingers is done with only two actuators which are combined in one device. These features make the system a good choice for home rehabilitation. To control the robot, a fuzzy sliding mode controller has been designed for the system. The fuzzy controller does not affect the coefficient of the sliding mode controller and uses the overall error of the system to make a control signal. Thus, the dependence of the controller to the model decreases and the system is more robust. The stability of the system is proved by the Lyapunov theorem.

Originality/value

The paper provides a novel design of a hand rehabilitation robot and a controller which is used to compensate the effects of the uncertain parameters and chattering phenomenon.
The entrepreneur-salaried employee-associate
Authors: Ballon Justine
Published: August 2019

Purpose

The increasing number of self-employed workers in France transforms the historical work relationship. In this perspective, the case of entrepreneurs who works in Business and Employment Cooperatives (BECs) with the status of entrepreneur–employee–associate is studied. They combine two legal status of self-employed and employee which were previously legally and institutionally separated. BECs question the forms of relationships governing production and labor. This paper aims to determine to what degree this combination of relationships improves the autonomy of entrepreneurs and reduces the risks of autonomous activity.

Design/methodology/approach

This qualitative action research combined with a pragmatic approach using abductive reasoning was carried out in three BECs. It is based on participant observations and interviews.

Findings

The results show that three types of relationships are embedded in the labor relations of cooperative activity: the entrepreneurial relationship, the employment relationship and the associate member relationship. This configuration contributes to achieving autonomy in the organization of labor and the reduction of risks linked to entrepreneurial activity. However, the complexity of the embedded relations, the persistence of asymmetry and the contrast between the rules of cooperatives and companies limit the ambition of BECs.

Practical implications

They determine the ability of BECs to invent appropriate mechanisms to empower their entrepreneur members.

Originality/value

This study combines an action research stance with a pluridisciplinary approach. It offers new perspectives for understanding the mutations that modes of production and labor mobilization are going through in a period of change toward a post-Fordist paradigm.
Six strategies that define digital winners
Authors: Butner Karen
Published: August 2019

Purpose

IBM research sought to identify the characteristics and strategies of the world’s most prosperous digital companies. The goal was to learn, “What is the secret to successfully leveraging platforms, AI and other digital technologies in today’s digital race? What strategies and operating models are winning?”

Design/methodology/approach

The IBM Institute for Business Value (IBV) conducted a comprehensive worldwide study of 1,500 mostly C-level executives to learn about their investments, leading practices and cultures.

Findings

The capabilities that differentiate Leaders from others–learning, speed and ongoing exploration–enable their strategies. Leaders are passionate about developing customer experience-based connections, integrating workflows with artificial intelligence (AI) and automated technologies and personalizing their brands and employee experiences.

Practical implications

The six top strategies Leaders employ to perpetuate success are: 10; 10;1.9; Orchestrate digital ecosystems and platforms. 10;2.9; Build trust to build your brand. 10;3.9; Reimagine customer behavior. 10;4.9; Curate data that “thinks” and “acts.” 10;5.9; Create an exponential learning environment. 10;6.9; Foster a culture of inclusion. 10;

Originality/value

The study has significant value because it identifies the strategies of the Leader group and explains the processes and culture changes that empower them. The study also reveals numerous surprises such as the eagerness of the leading companies to step outside the norm and disrupt their markets, and then prepare to do it again..
Spatio‐temporal variation of biotic and abiotic stress agents determines seedling survival in assisted oak regeneration
Authors: López‐Sánchez Aida , Peláez Marta , Dirzo Rodolfo , Fernandes G. Wilson , Seminatore Mizael , Perea Ramón
Published: August 2019

Mediterranean oak woodlands are currently undergoing considerable anthropogenic changes that globally threaten their long‐term persistence. Restoration efforts via assisted regeneration depend on species traits and type of stress. However, how different sources of stress vary across space (microsites) and time (intra‐ and inter‐annual variation) for co‐occurring oak species remains largely unknown.

We examined spatio‐temporal variation of biotic (herbivory, seed predation) and abiotic (drought) stress agents to evaluate seedling survival across different regeneration microsites, and considering two climatically contrasting years. We used two co‐occurring species of contrasting ecology and leaf traits in California oak woodlands: the deciduous Quercus lobata (valley oak) and the evergreen Q. agrifolia (coast live oak).

Most oak seedlings (98.8%) suffered from some type of stress. For both species, summer drought was the main cause of mortality, followed by rodent damage, ungulate browsing and insect damage. Rodents represented the predominant biotic stress, as all rodent‐affected seedlings eventually died. Interactions among stress factors were nuanced: insect and ungulate‐browsing stresses were greater during dry year, whereas rodent damage was similar in dry and average years. Intra‐annually, rodent damage was the main stress agent in early spring, whereas water stress and ungulate‐browsing were greater from late spring to early fall. Plant species traits were also determinant: overall, the evergreen species had greater survival probability than the deciduous one.

Across microsites, water stress showed higher occurrence in open grassland habitats, while rodent damage was prevalent under palatable shrubs and ungulate browsing under conspecific trees. Shrub and tree cover reduced damage attributed to water stress but increased rodent and ungulate damage, respectively. Interestingly, lower water stress but higher rodent damage was found further inside the shrub cover.

Synthesis and applications. Intra‐ and inter‐annual variation are critical determinants of stress type and intensity on oak recruitment. Spatial variation (microsite identity) is highly useful to manipulate stress agent impact. We conclude that assisted regeneration should consider not only the predominance and lethality of each stress type and microsite, but also the interactions thereof and thus manipulate protective microsites accordingly.
Nutrient Concentration Targets to Achieve Periphyton Biomass Objectives Incorporating Uncertainties
Authors: Snelder T.H. , Moore C. , Kilroy C.
Published: August 2019

Nutrient concentration targets are an important component of managing river eutrophication. Relationships between periphyton biomass and site characteristics for 78 gravel‐bed rivers in New Zealand were represented by regression models. The regression models had large uncertainties but identified broad‐scale drivers of periphyton biomass. The models were used to derive concentration targets for the nutrients, total nitrogen (TN) and dissolved reactive phosphorous (DRP), for 21 river classes to achieve periphyton biomass thresholds of 50, 120, and 200 mg chlorophyll a m−2. The targets incorporated a temporal exceedance criterion requiring the specified biomass threshold not be exceeded by more than 8% of samples. The targets also incorporated a spatial exceedance criterion requiring the biomass thresholds will not be exceeded at more than a fixed proportion (10%, 20%, or 50%) of locations. The spatial exceedance criterion implies, rather than requiring specific conditions at individual sites, the objective is to restrict biomass to acceptable levels at a majority of locations within a domain of interest. A Monte Carlo analysis was used to derive the uncertainty of the derived nutrient concentration targets for TN and DRP. The uncertainties reduce with increasing size of the spatial domain. Tests indicated the nutrient concentration targets were reasonably consistent with independent periphyton biomass data despite differences in the protocols used to measure biomass at the training and test sites.
Temporal Dynamics of Transdermal Alcohol Concentration Measured via New‐Generation Wrist‐Worn Biosensor
Authors: Fairbairn Catharine E. , Kang Dahyeon
Published: August 2019

Background

The development of a transdermal alcohol biosensor could represent a tremendous advance toward curbing problematic drinking. But several factors limit the usefulness of extant transdermal technology, including relatively lengthy delays between blood alcohol concentration (BAC) and transdermal alcohol concentration (TAC), as well as the large/bulky designs of currently available transdermal sensors (e.g., ankle monitors). The current research examined the lag time between BAC and TAC using a prototype of BACtrack Skyn—a new‐generation wrist‐worn transdermal sensor featuring a compact design and smartphone integration.

Methods

Participants (N = 30) received either a dose of alcohol (target BAC 0.08%) or a nonalcoholic beverage in the laboratory while wearing both the AMS SCRAM ankle monitor and a Skyn prototype. Participants were monitored in the laboratory until breath alcohol concentration (BrAC) dropped below 0.025%.

Results

Device failure rates for Skyn prototypes were relatively high (18 to 38%) compared with nonprototype SCRAM devices (2%). Among participants with usable data, both Skyn‐ and SCRAM‐measured TAC showed strong correlations with BrAC, and both Skyn and SCRAM devices detected alcohol within 30 minutes of first alcohol administration. Skyn‐measured TAC peaked over 1 hour earlier than SCRAM‐measured TAC (54 versus 120 minutes after peak BrAC, respectively), and time‐series models suggested that, on average across all measured portions of the BrAC curve, Skyn TAC lagged behind BrAC by 24 minutes, whereas SCRAM TAC lagged behind BrAC by 69 minutes—all differences statistically significant at p < 0.001.

Conclusions

Results provide preliminary evidence for the validity of a new‐generation wrist‐worn transdermal sensor under controlled laboratory conditions and further suggest favorable properties of this sensor as they pertain to the latency of transdermal alcohol detection. The prototype version of Skyn employed here displayed a higher failure rate compared with SCRAM, and, in future, more reliable and robust Skyn prototypes will be required suitable to field testing across diverse environmental conditions.
Disrupted topological properties of brain networks in erectile dysfunction patients owing predominantly to psychological factors: a structural and functional neuroimaging study
Authors: Chen J. , Huang X. , Liu S. , Lu C. , Dai Y. , Yao Z. , Chen Y.
Published: August 2019

Introduction

Human brain was a complex network of interconnected regions. Recent neuroimaging studies had showed that the disruption of brain connectivity was associated with psychological disorders. Abnormal rich club and robustness of brain networks might have a key role in the pathophysiology of psychogenic erectile dysfunction (pED).

Methods

Both diffusion and functional magnetic resonance imaging were performed in pED patients and healthy controls (HC). Measures of rich club organization and robustness under targeted attack were explored.

Results

Both pED and HC showed structural and functional rich club organization. However, reduced rich club coefficient was found in pED and different regions in the rich club of structural brain network were less than that of functional brain network. Moreover, decreased connectivity density and strength were only found in feeder connections of functional brain network in pED. In addition, pED showed remarkably reduced resilient to targeted attack and the stability of the functional brain network organization showed more vulnerable to targeted attack in pED.

Conclusion

Together, our results provided evidence that pED was characterized by a selective disruption of rich club organization and reduced robustness to attack. The abnormal hub regions and connections of functional brain network, less stable organization of structural brain network, and the abnormal psychological factors might lead to the development of erectile dysfunction in pED.
Effects of ultrasound energy on the porcine corneal endothelium – Establishment of a phacoemulsification damage model
Authors: Kunzmann Berenike C. , Wenzel Daniel A. , Bartz‐Schmidt Karl U. , Spitzer Martin S. , Schultheiss Maximilian
Published: August 2019

Purpose

The purpose of this study was to establish a standardized in vitro phacoemulsification damage model for future investigations of the effects of phacoemulsification, surgical devices, protective ophthalmic viscoelastic devices (OVDs), irrigation solutions and other aspects related to cataract phacoemulsification surgery on the corneal endothelium using porcine eyes.

Methods

Thirty‐four porcine eyes were randomly assigned to three groups (phacoemulsification (n = 13), irrigation (n = 9), control (n = 12)). A total of 5 min of ultrasound energy with intermittent irrigation/aspiration was applied in the eyes of the phacoemulsification group. The eyes of the irrigation group received the identical treatment, but without the application of ultrasound energy. The control group was left untreated. All eyes were then prepared to split corneal buttons followed by 15 days of cultivation. Endothelial cell density (ECD) was assessed blinded on day 15.

Results

Endothelial cell density declined significantly more until day 15 in the phacoemulsification group (2567 ± 317/267 cells/mm² (median ± 25%/75%‐quartiles), −32.5 ± 7.0/6.4%) compared to the irrigation (3450 ± 350/383 cells/mm², −11.8 ± 5.3/2.6%; p < 0.001) and the control group (3650 ± 288/258 cells/mm², −10.2 ± 3.2/4.6%; p < 0.001).

Conclusion

The phacoemulsification damage model presented in this study is sensitive to phacoemulsification energy and may reliably be used to investigate various factors involved in phacoemulsification with regard to their influence on corneal endothelial cells. This method is able to replace animal experiments or in vitro cell culture experiments that often do not translate well to the in vivo situation in humans.
Oxidative homeostasis in oocyte competence for in vitro embryo development
Authors: Barros Fabiana Dakkach de Almeida , Adona Paulo Roberto , Guemra Samuel , Damião Bruno Cesar Michelette
Published: August 2019

The objective of this study was to evaluate the levels of reactive oxygen species (ROS) and glutathione (GSH) in oocytes from follicles of different diameters and their relevance in the in vitro production of embryos (IVPE). Bovine ovaries were aspirated according to the diameter of the follicle [2–8 (general), 4–8 (large), and 2 < 4 mm (small)]. The oocytes were evaluated for levels of ROS, GSH, in vitro maturation, and IVPE. Higher levels of ROS and GSH were observed (p < 0.05) in oocytes of the large group (85.6 ± 7.2 and 140.0 ± 9.6) followed by those in the general (81.1 ± 10.5 and 134.3 ± 7.8) and small (73.5 ± 10.1 and 125.0 ± 10.6) groups. However, the proportion of ROS/GSH did not differ (p > 0.05) between the general, large, and small groups. The maturation was higher (p < 0.05) in the large group (87.8 ± 3.0%) than in the small group (72.2 ± 5.8%), but both were similar (p > 0.05) to that in the general group (82.2 ± 2.5%), whereas the IVPE of the large group (57.3 ± 3.0%) was higher (p < 0.05) than those in the general (44.7 ± 4.4%) and small (34.0 ± 4.0%) groups. We report that oocytes from large follicles are more competent for IVPE, whereas higher levels of ROS and GSH appear to be correlated with oocyte competence, as long as oxidative homeostasis is retained.
CYP2E1 and miRNA‐378a‐3p contribute to acetaminophen‐ or tripterygium glycosides‐induced hepatotoxicity
Authors: Chen Keguang , Guo Nan , Zhang Rui , Wei Chunmin , Guo Ruichen
Published: August 2019

Increased expression of CYP2E1 may represent the main factor contributing to oxidative stress‐mediated liver damage in drug‐induced liver injury (DILI). However, the regulation mechanism of CYP2E1 expression is poorly described. The present study was aimed to investigate the role of CYP2E1 in acetaminophen (APAP)‐ or tripterygium glycosides (TG)‐induced hepatotoxicity as well as the regulation of CYP2E1 and miR‐378a‐3p expression by APAP or TG. Rats were randomly divided and treated with APAP, TG, chlormethiazole (CMZ), APAP + CMZ and TG + CMZ, respectively, for 4 weeks. Then, blood and liver samples were collected. Serum and hepatic biochemical parameters were measured using commercial kits. Liver histopathology was tested by H&E staining. Expression levels of CYP2E1 mRNA and miR‐378a‐3p were detected by qRT‐PCR. CYP2E1 protein expression was determined by Western blot. Our results showed that CMZ effectively restored the hepatic histopathological changes, oxidative stress biomarkers and TNF‐α levels induced by APAP or TG. CYP2E1 mRNA and/or protein expression levels were dramatically increased after chronic APAP or TG treatment, while this induction was significantly reversed by CMZ co‐treatment. Of note, miR‐378a‐3p expression levels were significantly suppressed after APAP, TG and/or CMZ treatment. These results suggested that CYP2E1 were highly induced after chronic APAP or TG treatment, which in turn play an important role in APAP‐ or TG‐induced hepatotoxicity. These inductions of CYP2E1 expression were probably carried out by inhibition of miR‐378a‐3p. Our findings might provide a new molecular basis for DILI.
A journey through infectious risk associated with ruxolitinib
Authors: Sant’Antonio Emanuela , Bonifacio Massimiliano , Breccia Massimo , Rumi Elisa
Published: August 2019

Ruxolitinib has proved to be effective for the treatment of patients with myelofibrosis (either primary or secondary) and polycythaemia vera, and its approval led to a significant change in the current treatment algorithm. Despite its efficacy and beyond its well described haematological toxicity, a peculiar immunosuppressive effect emerged as our clinical experience grew, both within and outside of a clinical trial setting. Definite and negative interactions with multiple pathways of the immune system of patients have been reported so far, involving both adaptive and innate immune responses. These pathophysiological mechanisms may contribute to the increased risk of reactivation of silent infections (e.g., tuberculosis, hepatitis B virus and varicella zoster virus) that have been associated with the drug. Even though such infectious events may be fatal or may lead to significant impairment of organ function, compromising the eligibility of patients for an allotransplant procedure, there are no dedicated guidelines that may help us in assessing and managing the risk of developing serious infections. On this basis, our aim for the present work was to review the current knowledge on the pathophysiological mechanisms through which ruxolitinib may exert its immunosuppressive effect, and to illustrate our personal approach to the management of three peculiar clinical scenarios, for which a risk‐based algorithm is suggested.
Screening protocol for the identification of modulators by immunofluorescent cell‐based assay
Authors: Klett Javier , Gómez‐Casero Elena , Méndez‐Pertuz Marinela , Urbano‐Cuadrado Manuel , Megias Diego , Blasco María A. , Martínez Sonia , Pastor Joaquín , Blanco‐Aparicio Carmen
Published: August 2019

High‐throughput assays are a common strategy for the identification of compounds able to modulate a certain cellular activity. Here, we show an automatized analysis platform for the quantification of nuclear foci as inhibitory effect of compounds on a target protein labeled by fluorescent antibodies. Our experience led us to a fast analysis platform that combines cell‐based assays, high‐content screening, and confocal microscopy, with an automatic and user‐friendly statistical analysis of plate‐based assays including positive and negative controls, able to identify inhibitory effect of compounds tested together with the Z‐prime and Window of individual plate‐based assays to assess the reliability of the results. The platform integrates a web‐based tool implemented in Pipeline Pilot and R, and allows computing the inhibition values of different parameters obtained from the high‐content screening and confocal microscopy analysis. This facilitates the exploration of the results using the different parameters, providing information at different levels as the number of foci observed, the sum of intensity of foci, area of foci, etc, the detection and filtering of outliers over the assay plate, and finally providing a set of statistics of the parameters studied together with a set of plots that we believe significantly helps to the interpretation of the assay results.
Adopting a utilitarian approach to culling wild animals for conservation in National Parks
Authors: Gordon Iain J.
Published: August 2019

As human populations increase and become wealthier, the demand for red meat will increase. Much of this increased demand will be supplied through the traditional livestock supply chains; however, there are alternative commodities that can be used to meet some of the demand. Game meat harvested from wildlife is a growing commodity in the developed world, valued for its nutritional qualities and taste. However, there are some perverse management actions whereby wildlife, culled for conservation purposes (usually because they are deemed to be overabundant within National Parks and Protected Areas), are often not utilized as either human or pet food. In this Perspective, I highlight how the products from these culled animals in NPs are used, or not, and discuss some innovative ways in which the products are, or could be, brought into the economic and livelihood system (i.e., utilitarian conservation). These include bringing products from culled animals into the human and pet food supply chains.
Complex and subtle structural changes in prefrontal cortex induced by inhibitory control training from childhood to adolescence
Authors: Delalande Lisa , Moyon Marine , Tissier Cloélia , Dorriere Valérie , Guillois Bernard , Mevell Katel , Charron Sylvain , Salvia Emilie , Poirel Nicolas , Vidal Julie , Lion Stéphanie , Oppenheim Catherine , Houdé Olivier , Cachia Arnaud , Borst Grégoire
Published: August 2019

A number of training interventions have been designed to improve executive functions and inhibitory control (IC) across the lifespan. Surprisingly, no study has investigated the structural neuroplasticity induced by IC training from childhood to late adolescence, a developmental period characterized by IC efficiency improvement and protracted maturation of prefrontal cortex (PFC) subregions involved in IC. The aim of the present study was to investigate the behavioral and structural changes induced by a 5‐week computerized and adaptive IC training in school‐aged children (10‐year‐olds) and in adolescents (16‐year‐olds). Sixty‐four children and 59 adolescents were randomly assigned to an IC (i.e. Color‐Word Stroop and Stop‐Signal tasks) or an active control (AC) (knowledge‐ and vocabulary‐based tasks) training group. In the pre‐ and posttraining sessions, participants performed the Color‐Word Stroop and Stop‐signal tasks, and an anatomical resonance imaging (MRI) was acquired for each of them. Children's IC efficiency improved from the pre‐ to the posttraining session in boys but not in girls. In adolescents, IC efficiency did not improve after IC training. Similar to the neuroplastic mechanisms observed during brain maturation, we observed IC training‐related changes in cortical thickness and cortical surface area in several PFC subregions (e.g. the pars opercularis, triangularis, and orbitalis of the inferior frontal gyri) that were age‐ and gender‐specific. Because no correction for multiple comparisons was applied, the results of our study provide only preliminary evidence of the complex structural neuroplastic mechanisms at the root of behavioral changes in IC efficiency from pre‐ to posttraining in school‐aged children and adolescents.
Physical activity and sedentary behaviour in children with spina bifida
Authors: Claridge Everett A , Bloemen Manon A T , Rook Rosanne A , Obeid Joyce , Timmons Brian W , Takken Tim , Van Den Berg‐Emons Rita J G , De Groot Janke F , Gorter Jan Willem
Published: August 2019

Aim

To describe active and sedentary time in children with spina bifida and to compare their physical activity on weekdays versus weekends.

Method

In this exploratory cross‐sectional study, data from 13 Canadian and 22 Dutch children with spina bifida (14 females, 21 males; mean age 10y 11mo, standard deviation [SD] 3y 6mo, range 5y 6mo–18y; Hoffer classification distribution: community [n=28], household [n=3], non‐functional [n=3], and non‐ambulator [n=1]) were analysed. Objective measures of physical activity and sedentary behaviour were obtained by using ActiGraph or Actiheart activity monitors. Data for the participants wearing the ActiGraph were compared with age‐ and sex‐matched controls that were developing typically using independent‐samples t‐tests. Activity data collected on weekdays was compared to those on weekends.

Results

ActiGraph data demonstrated children with spina bifida spent more time sedentary (mean [SD] 49.5min/h [5.78]) and less time in moderate to vigorous physical activity (mean [SD] 2.33min/h [1.61]) compared with the typically developing group (mean [SD] 41.0min/h [5.76] and 5.46min/h [2.13], p=0.001 and p<0.001 respectively). For both ActiGraph‐ and Actiheart‐derived data, physical activity and sedentary time were not significantly different between weekdays and weekends.

Interpretation

Children with spina bifida have reduced levels of physical activity and increased sedentary behaviour, with no statistical differences seen between weekdays and weekends. Several methodological issues related to activity monitoring warrant consideration when choosing the appropriate method to quantify physical activity and sedentary behaviour.

What this paper adds

Reduced levels of physical activity and sedentary time were quantified in children with spina bifida.

Objective quantification of physical behaviour in ambulatory and non‐ambulatory school‐aged children with spina bifida is possible.
Systematic literature review and network meta‐analysis of sodium‐glucose co‐transporter inhibitors vs metformin as add‐on to insulin in type 1 diabetes
Authors: Langford Bryony E. , Evans Marc , Haskins‐Coulter Tao , O'Connor Molly , Cant Harriet E. O. , Eddowes Lucy A. , Edmonds Christopher , Tank Amarjeet
Published: August 2019

Aims

To identify and synthesize phase 3 and phase 4 randomized controlled trials (RCTs) of sodium‐glucose co‐transporter (SGLT) inhibitors and metformin as adjuncts to insulin in type 1 diabetes (T1DM) using network meta‐analysis (NMA).

Materials and methods

A systematic literature review (SLR) identified relevant RCTs of ≥12 Weeks duration. MEDLINE, Embase, the Cochrane Library and grey literature were searched through October 2018. NMAs indirectly compared SGLT inhibitors and metformin for change from baseline in HbA1c, weight, total daily insulin dose and systolic blood pressure at Week 24 to 26 and Week 52. Safety outcomes were also explored.

Results

Nine trials (N = 6780) were included in the SLR. NMAs indicated that all therapies performed better than placebo for the efficacy outcomes at both time points. Compared with metformin at Week 24 to 26, the SGLT inhibitors dapagliflozin (5 mg), sotagliflozin (200 mg) and empagliflozin (10 mg) had larger reductions in HbA1c (mean difference [MD] = −0.24, 95% credible interval [CrI], −0.41 to −0.07, MD = −0.23, 95% CrI, −0.39 to −0.08 and MD = −0.35, 95% CrI, −0.51 to −0.19, respectively) and in weight, which were sustained in sensitivity analyses. There were few differences observed in the results of safety outcomes, such as risk of diabetic ketoacidosis (DKA), which should be interpreted cautiously because of wide CrIs.

Conclusions

Adjunctive use of SGLT inhibitors in T1DM can improve glycaemic control compared with metformin while enabling weight loss, with consistent efficacy across the class. However, these results are based on indirect evidence so confirmation in a head‐to‐head study would be valuable.
Identifying routine clinical predictors of non‐adherence to second‐line therapies in type 2 diabetes: A retrospective cohort analysis in a large primary care database
Authors: Shields Beverley M. , Hattersley Andrew T. , Farmer Andrew J.
Published: August 2019

Aims

To investigate whether combinations of routinely available clinical features can predict which patients are likely to be non‐adherent to diabetes medication.

Materials and Methods

A total of 67 882 patients with prescription records for their first and second oral glucose‐lowering therapies were identified from electronic healthcare records (Clinical Practice Research Datalink). Non‐adherence was defined as a medical possession ratio (MPR) ≤80%. Potential predictors were examined, including age at diagnosis, sex, body mass index, duration of diabetes, glycated haemoglobin, Charlson index and other recent prescriptions.

Results

Routine clinical features were poor at predicting non‐adherence to the first diabetes therapy (c‐statistic = 0.601 for all in combined model). Non‐adherence to the second drug was better predicted for all combined factors (c‐statistic =0.715) but this improvement was predominantly a result of including adherence to the first drug (c‐statistic =0.695 for this alone). Patients with an MPR ≤80% for their first drug were 3.6 times (95% confidence interval 3.3,3.8) more likely to be non‐adherent to their second drug (32% vs. 9%).

Conclusions

Although certain clinical features were associated with poor adherence, their performance for predicting who is likely to be non‐adherent, even when combined, was weak. The strongest predictor of adherence to second‐line therapy was adherence to the first therapy. Examining previous prescription records could offer a practical way for clinicians to identify potentially non‐adherent patients and is an area warranting further research.