bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational characteristics of interictal EEG as objective markers of epileptic spasms
Authors: Smith Rachel J. , Hu Derek K. , Shrey Daniel W. , Rajaraman Rajsekar , Hussain Shaun A. , Lopour Beth A.
Published: November 2020

Objective

Favorable neurodevelopmental outcomes in epileptic spasms (ES) are tied to early diagnosis and prompt treatment, but uncertainty in the identification of the disease can delay this process. Therefore, we investigated five computational electroencephalographic (EEG) measures as markers of ES.

Methods

We measured 1) amplitude, 2) power spectra, 3) entropy, 4) long-range temporal correlations, via detrended fluctuation analysis (DFA) and 5) functional connectivity of EEG data from ES patients (n=40 patients) and healthy controls (n=20 subjects), with multiple blinded measurements during wakefulness and sleep for each patient.

Results

In ES patients, EEG amplitude was significantly higher in all electrodes. Shannon and permutation entropy were lower in ES patients than control subjects, while DFA intercept values in ES patients were significantly higher than control subjects. DFA exponent values were not significantly different between the groups. EEG functional connectivity networks in ES patients were significantly stronger than controls. Using logistic regression, a multi-attribute classifier was derived that accurately distinguished cases from controls (area under curve of 0.96).

Conclusions

Computational EEG features successfully distinguish ES patients from controls in a large, blinded study.

Significance

These objective EEG markers, in combination with other clinical factors, may speed the diagnosis and treatment of the disease, thereby improving long-term outcomes.

Highlights

Objective computational EEG features may aid diagnosis of epileptic spasms (ES)

ES EEG has increased delta and theta power and decreased entropy relative to controls

Stronger functional connectivity networks differentiate ES patients from controls
Predictive attenuation of touch and tactile gating are distinct perceptual phenomena
Authors: Kilteni Konstantina , Ehrsson H. Henrik
Published: November 2020

In recent decades, research on somatosensory perception has led to two important observations. First, self-generated touches that are predicted by voluntary movements become attenuated compared to externally generated touches of the same intensity (attenuation). Second, externally generated touches feel weaker and are more difficult to detect during movement than at rest (gating). Currently, researchers often consider gating and attenuation the same suppression process; however, this assumption is unwarranted because, despite more than forty years of research, no study has combined them in a single paradigm. We quantified how people perceive self-generated and externally generated touches during movement and rest. We show that whereas voluntary movement gates the precision of both self-generated and externally generated touch, the amplitude of self-generated touch is robustly attenuated compared to externally generated touch. Furthermore, attenuation and gating do not interact and are not correlated, and we conclude that they represent distinct perceptual phenomena.
T cells exhibit unexpectedly low discriminatory power and can respond to ultra-low affinity peptide-MHC ligands
Authors: Pettmann Johannes , Abu-Shah Enas , Kutuzov Mikhail , Wilson Daniel B. , Dustin Michael L. , Davis Simon J. , van der Merwe P. Anton , Dushek Omer
Published: November 2020

T cells use their T cell receptors (TCRs) to discriminate between peptide MHC (pMHC) ligands that bind with different affinities but precisely how different remains controversial. This is partly because the affinities of physiologically relevant interactions are often too weak to measure. Here, we introduce a surface plasmon resonance protocol to measure ultra-low TCR/pMHC affinities (KD~ 1000μM). Using naïve, memory, and blasted human CD8+T cells we find that their discrimination power is unexpectedly low, in that they require a large >100-fold decrease in affinity to abolish responses. Interestingly, the discrimination power reduces further when antigen is presented in isolation on artificial surfaces but can be partially restored by adding ligands to CD2 or LFA-1. We were able to fit the kinetic proof-reading model to our data, yielding the first estimates for both the time delay (2.8 s) and number of biochemical steps (2.67). The fractional number of steps suggest that one of the proof-reading steps is not easily reversible.
Exploring new roles for actin upon LTP induction in dendritic spines
Authors: Bonilla-Quintana Mayte , Wörgötter Florentin
Published: November 2020

Dendritic spines, small protrusions of the dendrites, enlarge upon LTP induction, linking morphological and functional properties. Although the role of actin in spine enlargement has been well studied, little is known about its relationship with mechanical membrane properties, such as membrane tension, which is involved in many cell processes, like exocytosis. Here, we use a 3D model of the dendritic spine to investigate how polymerization of actin filaments can effectively elevate the membrane tension to trigger exocytosis in a domain close to the tip of the spine. Moreover, we show that the same pool of actin promotes full membrane fusion after exocytosis and spine stabilization.
Assessing Conservation of Alternative Splicing with Evolutionary Splicing Graphs
Authors: Zea Diego Javier , Laskina Sofya , Baudin Alexis , Richard Hugues , Laine Elodie
Published: November 2020

Understanding how protein function has evolved and diversified is of great importance for human genetics and medicine. Here, we tackle the problem of describing the whole transcript variability observed in several species by generalising the definition of splicing graph. We provide a practical solution to building parsimoniousevolutionarysplicing graphs where each node is a minimal transcript building block defined across species. We show a clear link between the functional relevance, tissue-regulation and conservation of AS events on a set of 50 genes. By scaling up to the whole human protein-coding genome, we identify a few thousands of genes where alternative splicing modulates the number and composition of pseudo-repeats. We have implemented our approach in ThorAxe, an efficient, versatile, and robust computational tool freely available athttps://github.com/PhyloSofS-Team/thoraxe. The results are accessible and can be browsed interactively athttp://www.lcqb.upmc.fr/ThorAxe.
Phenotypic plasticity of ER+ breast cancer in the bone microenvironment
Authors: Bado Igor L. , Wang Hai , Sarkar Poonam , Liu Jun , Wu William , Zhang Weijie , Lo Hin-Ching , Muscallera Aaron , Janghorban Mahnaz , Kim Ik-Sun , Singh Swarnima , Goldstein Amit , Singh Purba , Shixia Huang , Waleed Gaber M. , Ellis Matthew J. , Zhang Xiang H.-F.
Published: November 2020

ER+ breast cancer exhibits a strong bone-tropism in metastasis. How the bone microenvironment impacts the ER signaling and endocrine therapies remains poorly understood. Here, we discover that the osteogenic niche transiently reduces ER expression and activities specifically in bone micrometastases (BMMs), leading to endocrine resistance. This is mediated by gap junctions and paracrine FGF/PDGF signaling, which together generate a stable “memory”: cancer cells extracted from bone remain resistant to endocrine therapies for several generations. Using single cell-derived populations (SCPs), we demonstrated that this process is independent of clonal selection, and represents an EZH2-mediated epigenomic reprogramming. EZH2 drives ER+ BMMs toward a basal and stem-like state. EZH2 inhibition reverses endocrine resistance. Our data demonstrates how epigenomic adaptation to the bone microenvironment drives phenotypic plasticity of metastatic seeds and alters their therapeutic responses together with clonal selection, and provides insights into the clinical enigma of ER+ metastatic recurrences despite endocrine therapies.
Thermal acclimation alters the roles of Na+/K+-ATPase activity in a tissue-specific manner inDrosophila melanogaster
Authors: Cheslock Alexandra , Andersen Mads Kuhlmann , MacMillan Heath A.
Published: November 2020

Insects, like the model speciesDrosophila melanogaster, lose neuromuscular function and enter a state of paralysis (chill coma) at a population- and species-specific low temperature threshold that is decreased by cold acclimation. Entry into this coma is related to a spreading depolarization in the central nervous system, while recovery involves restoration of electrochemical gradients across muscle cell membranes. The Na+/K+-ATPase helps maintain ion balance and membrane potential in both the brain and hemolymph (surrounding muscles), and changes in thermal tolerance traits have therefore been hypothesized to be closely linked to variation in the expression and/or activity of this pump in multiple tissues. Here, we tested this hypothesis by measuring activity and thermal sensitivity of the Na+/K+-ATPase at the tagma-specific level (head, thorax and abdomen) in warm-(25°C) and cold-acclimated (15°C) flies by Na+/K+-ATPase activity at 15, 20, and 25°C. We relate differences in pump activity to differences in chill coma temperature, spreading depolarization temperature, and thermal dependence of muscle cell polarization. Differences in pump activity and thermal sensitivity induced by cold acclimation varied in a tissue-specific manner: While cold-acclimated flies had decreased thermal sensitivity of Na+/K+-ATPase that maintains activity at low temperatures in the thorax (mainly muscle), activity instead decreased in the heads (mainly brain). We argue that these changes may assist in maintenance of K+homeostasis and membrane potential across muscle membranes and discuss how reduced Na+/K+-ATPase activity in the brain may counterintuitively help insects delay coma onset in the cold.
C. elegansprovide milk for their young
Authors: Kern Carina C. , Townsend StJohn , Salzmann Antoine , Rendell Nigel B. , Taylor Graham W. , Comisel Ruxandra M. , Foukas Lazaros C. , Bähler Jürg , Gems David
Published: November 2020

AdultC. eleganshermaphrodites exhibit severe senescent pathology that begins to develop within days of reaching sexual maturity (Ezcurra et al., 2018; Garigan et al., 2002; Herndon et al., 2002; Wang et al., 2018). For example, after depletion of self-sperm, intestinal biomass is converted into yolk leading to intestinal atrophy and yolk steatosis (pseudocoelomic lipoprotein pools, PLPs) (Ezcurra et al., 2018; Garigan et al., 2002; Herndon et al., 2002; Sornda et al., 2019). These senescent pathologies are promoted by insulin/IGF-1 signalling (IIS), which also shortens lifespan (Ezcurra et al., 2018; Kenyon, 2010). This pattern of rapid and severe pathology in organs linked to reproduction is reminiscent of semelparous organisms where massive reproductive effort leads to rapid death (reproductive death) as in Pacific salmon (Finch, 1990; Gems et al., 2020). Moreover, destructive conversion of somatic biomass to support reproduction is a hallmark of reproductive death (Gems et al., 2020). Yet arguing against the occurrence of reproductive death inC. elegansis the apparent futility of post-reproductive yolk production. Here we show that this effort is not futile, since post-reproductive mothers vent yolk through their vulva, which is consumed by progeny and supports their growth; thus vented yolk functions as a milk, andC. elegansmothers exhibit a form of lactation. Moreover, IIS promotes lactation, thereby effecting a costly process of resource transfer from postreproductive mothers to offspring. These results support the view thatC. eleganshermaphrodites exhibit reproductive death involving a self-destructive process of lactation that is promoted by IIS. They also provide new insight into how the strongly life-shortening effects of IIS inC. elegansevolved.
Development of a cricket paralysis virus-based system for inducing RNA interference-mediated gene silencing inDiaphorina citri
Authors: Matsumura Emilyn E. , Nigg Jared C. , Henry Elizabeth M. , Falk Bryce W.
Published: November 2020

Diaphorina citri, the Asian citrus psyllid, is the insect vector of the phloem-limited bacterium ‘CandidatusLiberibacter asiaticus’, which causes the most devastating citrus disease worldwide: Huanglongbing (HLB). An efficient cure for HLB is still not available and the management of the disease is restricted to the use of pesticides, antibiotics and eradication of infected plants. Plant- and insect-infecting viruses have attracted increasing attention for their potential to manipulate traits in insects, especially insect vectors of plant pathogens. However, so far there are no insect virus-based vectors available for use inD. citri. Cricket paralysis virus (CrPV) is a well-studied insect-infecting dicistrovirus with a wide host range and has been used as a model in previous translational studies. In this work, we demonstrate for the first time that CrPV is infectious and pathogenic toD. citri.We show that specific amino acid mutations in the CrPV primary cleavage DvExNPGP motif resulted in a viral mutant that was attenuated compared to wild-type CrPV during infection of eitherDrosophilacells line or adultD. citriinsects. This attenuated CrPV mutant was then used as the backbone for engineering a recombinant CrPV-based vector to specifically alterD. citrigene expression via the RNA interference (RNAi) pathway, a technology called Virus Induced Gene Silencing (VIGS). As proof-of-concept, we engineered recombinant CrPV-based vectors carrying nucleotide sequences derived from a previously reportedD. citritarget gene: the inhibitor of apoptosis gene (IA). RT-qPCR analysis of insects either microinjected or fed with the recombinant CrPV mutants showed decreased IA gene expression as soon as viral replication was detected, indicating that the engineered CrPV-based VIGS system enables functional gene silencing inD. citri. This novel insect virus-based tool is easily amenable to genomic modification and represents a technical advance for understanding interactions between insect virus-based VIGS systems andD. citri.
Role of β-arrestin-2 in short- and long-term opioid tolerance in the dorsal root ganglia
Authors: Muchhala Karan H. , Jacob Joanna C. , Dewey William L. , Akbarali Hamid I.
Published: November 2020

β-arrestin-2 has been implicated in the mechanism of opioid-induced antinociceptive tolerance. G-protein-biased agonists with reduced β-arrestin-2 activation are being investigated as safer alternatives to clinically-used opioids. Opioid-induced analgesic tolerance is classically considered as centrally-mediated, but recent reports implicate nociceptive dorsal root ganglia (DRG) neurons as critical mediators in this process. Here, we investigated the role of β-arrestin-2 in the mechanism of opioid tolerance in DRG nociceptive neurons using β-arrestin-2 knockout mice and the G-protein-biased μ-opioid receptor agonist, TRV130. Whole-cell current-clamp electrophysiology experiments revealed that 15-18-hour overnight exposure to 10 μM morphinein vitroinduced acute tolerance in β-arrestin-2 wild-type but not knockout DRG neurons. Furthermore, in wild-type DRG neurons circumventing β-arrestin-2 activation by overnight treatment with 200 nM TRV130 attenuated tolerance. Similarly, in β-arrestin-2 knockout male mice acute antinociceptive tolerance induced by 100 mg/kg morphine s.c. was prevented in the warm-water tail-withdrawal assay. Treatment with 30 mg/kg TRV130 s.c. also inhibited antinociceptive tolerance in wild-type mice. Alternately, in β-arrestin-2 knockout DRG neurons tolerance induced by 7-dayin vivoexposure to 50 mg morphine pellet was conserved. Likewise, β-arrestin-2 deletion did not mitigatein vivoantinociceptive tolerance induced by 7-day exposure to 25 mg or 50 mg morphine pellet in both female or male mice, respectively. Consequently, these results indicated that β-arrestin-2 mediates acute but not chronic opioid tolerance in DRG neurons and to antinociception. This suggests that opioid-induced antinociceptive tolerance may develop even in the absence of β-arrestin-2 activation, and thus significantly affect the clinical utility of biased agonists.
Image memorability is predicted by discriminability and similarity in different stages of a convolutional neural network
Authors: Koch Griffin E. , Akpan Essang , Coutanche Marc N.
Published: November 2020

The features of an image can be represented at multiple levels—from its low-level visual properties to high-level meaning. What drives some images to be memorable while others are forgettable? We address this question across two behavioral experiments. In the first, different layers of a convolutional neural network (CNN), which represent progressively higher levels of features, were used to select the images that would be shown to 100 participants through a form of prospective assignment. Here, the discriminability/similarity of an image with others, according to different CNN layers dictated the images presented to different groups, who made a simple indoor versus outdoor judgment for each scene. We found that participants remember more scene images that were selected based on their low-level discriminability or high-level similarity. A second experiment replicated these results in an independent sample of 50 participants, with a different order of postencoding tasks. Together, these experiments provide evidence that both discriminability and similarity, at different visual levels, predict image memorability.
The influence of social media usage, self-image congruity and self-esteem on conspicuous online consumption among millennials
Authors: Burnasheva Regina , Suh Yong Gu
Published: November 2020

Purpose

Driven by social comparison and self-congruity theories, this paper's aim was to investigate the associations with Korean millennials' usage of social media, self-image congruity and conspicuous online consumption. The mediating influence of self-image congruity and the moderating effect of self-esteem were also examined.

Design/methodology/approach

These data were gathered through an online research portal from 302 Korean millennials. Structural equation modeling (SEM) analyses and moderated mediation analysis using Hayes PROCESS macro were applied to test proposed hypotheses.

Findings

The result of the structural equation analyses showed strong, positive associations between social media usage, self-image congruity and conspicuous online consumption, while self-image congruity also acted as a mediator between Korean millennials' usage of social media and conspicuous online consumption. Moreover, in moderated mediation analysis, the pathway between self-image congruity and conspicuous online consumption was stronger for millennials with higher self-esteem.

Originality/value

Millennials' social media usage and conspicuous consumption are widely acknowledged in consumer research. However, little is known about how millennials' social media usage could influence their conspicuous online consumption through mediating and moderating mechanisms such as self-image congruity and self-esteem. This research extends previous studies by analyzing these mechanisms.
Automated assessment of architectural spatial layout configurations using fuzzy logic
Authors: Ezzeldin Mohamed , Assem Ayman , Abdelmohsen Sherif
Published: November 2020

Purpose

Conventional approaches of evaluating spatial layout configurations typically involved universal understandings of aspects like connectivity, proximity and visibility, while possibly discarding both partially true solutions and ranges of parameters affecting detailed spatial relations. With the growing need to address spatial uncertainty and ambiguity, the incorporation of methods that embrace soft qualities in design is becoming increasingly significant in spatial layout planning.

Design/methodology/approach

The authors introduce a fuzzy-based approach for the automated assessment of architectural spatial layout configurations while addressing ambiguity in layout design. The authors evaluate soft interdependent design qualities like connectedness, enclosure and spaciousness to satisfy multiple mutually inclusive criteria and account for all logical solutions without discarding likely or less likely solutions. The authors analyze spatial entities, parameters and relations and identify rulesets for logical configurations using linguistic variables, fuzzy sets, membership functions and descriptive rule blocks. As a case study, the authors use grasshopper and fuzzyTECH to represent four pilot layout alternates with varying attributes and a case study focusing on one specific spatial criterion.

Findings

Multiple complex and nuanced spatial relations were inferred by evaluating spatial outputs and their inherent discrepancies and correlations, thus confirming the assumption that fuzzy-based systems could potentially satisfy multiple mutually inclusive criteria and account for exhaustive logical solutions without discarding preferable, likely or less likely solutions.

Originality/value

Most precedent approaches focus on spatial layout design from an occupancy-centered perspective, where occupancy patterns and possibilities are identified in loosely defined spaces or behavioral usage patterns. The added value in this paper involves including a wide array of spatial inputs to describe soft spatial qualities using nuanced rule-based descriptors.
Do level of tourism development and its type make a difference in residents' perceptions? Learning from Turkish cases
Authors: Karamustafa Kurtulus , Ülker Pembe , Çalhan Harun
Published: November 2020

Purpose

This study provides insights on the perceptions of residents in destinations offering different tourism products at different levels of tourism development.

Design/methodology/approach

A total of 1,122 valid responses were gathered through surveys from the residents of three unique destinations, with different levels of tourism development. Non-parametric tests were performed since the data was gathered on an ordinal scale and not distributed normally.

Findings

The tourism perceptions of the residents formed a five-factor structure, namely “socioecological negative”, “socioeconomic positive”, “socioecological development (wellbeing)”, “negative perceptions of tourism” and “tendency to become visitor”. All dimensions except for “socioeconomic positive” differed significantly by destinations in terms of level of tourism development or type of tourism product offered.

Research limitations/implications

Residents' perceptions of tourism differ based on different tourism products and different levels of tourism development of destinations. The residents of the most mature destinations in terms of tourism development have the most negative perceptions of tourism.

Originality/value

Although there are studies investigating how residents' perceptions differ based on the level of tourism development of destinations, this study, with its holistic approach, aims to provide insights on how residents' perceptions of tourism differ based on the tourism products offered by different destinations. The selected destinations differ from each other in both their level of tourism involvement and products they offer, hence the originality of the current study with its unique contribution to the related body of knowledge.
Dynamic capabilities and competitive advantages as mediator variables between market orientation and business performance
Authors: Correia Ricardo Jorge , Dias José G. , Teixeira Mário Sérgio
Published: November 2020

Purpose

This paper aims to explore a new causal link between market orientation and business performance by introducing dynamic capabilities as a mediator of the relationship between market orientation and competitive advantages, which ultimately determine business performance.

Design/methodology/approach

The mediating roles of dynamic capabilities and competitive advantages are tested with a sample of 1,190 Portuguese firms using a structural equation model.

Findings

The results confirm the hypotheses regarding the mediating roles of the competitive advantages (differentiation and cost leadership) in the relationship between dynamic capabilities and business performance. Additionally, dynamic capabilities also mediate the relationship between market orientation and competitive advantages.

Practical implications

This study shows that business performance depends on the capacity of firms to collect the best market information on customers and competitors, to disseminate this information throughout their internal structure and ultimately optimize its use to respond appropriately to market challenges and trends. These will provide firms with a set of capabilities and a competitive advantage.

Originality/value

This study provides empirical evidence on the understanding of the relationship between market orientation and performance, through the mediating effects of both dynamic capabilities and competitive advantages.
On the relationship between sport and financial performances: an empirical investigation
Authors: Di Simone Luca , Zanardi Davide
Published: November 2020

Purpose

Our paper shows an empirical analysis of the European football companies to test the association between sport results, proxied by ranking position and financial performance in panel framework (starting from 59 firms over the 2013–2018 time span).

Design/methodology/approach

We use panel data models for studying the relationship of our interest and we make no a priori assumption about the strict exogeneity of the covariates and estimate equation using both Random Effects GLS (RE-GLS) and Fixed Effects OLS (FE-OLS) estimations.

Findings

Our results suggest there is stable and significant relationship between the two types of performance and that when detectable this is linked in a positive way to the profit maximization of the business model, suggesting that it is more useful for investor remuneration and to increase technical-tactical resources and therefore sports results. Not surprisingly, as for many clubs, concentration effect is relevant while the financial fair play regulation is not. In fact, the current regulation of UEFA authority does not seem to have an impact on sport and financial results.

Originality/value

This work complements literature in several ways. First, we offer new empirical evidence for the association between the sport and financial performance for a panel of the European football companies, listed and not. Second, we show that the persistence of the sport results is strongly correlated with financial performance.
Double-diffusive free convective flow of Casson fluid due to a moving vertical plate with non-linear thermal radiation
Authors: Nandeppanavar Mahantesh M. , M.C. Kemparaju , Raveendra N.
Published: November 2020

Purpose

This paper aims to report the investigation of over heat and mass transfer of convective Casson fluid flow over a moving vertical plate with nonlinear thermal radiation and convective boundary conditions.

Design/methodology/approach

The main partial differential equations of the flow, heat and concentration profiles were rehabilitated to nonlinear ordinary differential equations by using an appropriate similarity transformation. The resultant nonlinear ordinary differential equations (ODEs) are solved numerically applying fourth-order Runge–Kutta shooting technique and functions of ODE45 from MATLAB.

Findings

The effect of convective heat transfer, buoyancy ratio parameter, nonlinear thermal radiation, Prandtl number, Rayleigh number and Schmidt number over velocity, temperature and concentration profiles, equivalent to abundant somatic parameters were graphically scrutinized.

Originality/value

All the results are very promising and further there is got good agreement of results when compared with earlier published results at limiting conditions.
Impact of reducing alcohol consumption through price‐based policies on cancer incidence in Germany 2020–50—a simulation study
Authors: Gredner Thomas , Niedermaier Tobias , Brenner Hermann , Mons Ute
Published: November 2020

Background and Aims

Alcohol is a major cancer risk factor and contributes considerably to the cancer burden in Germany. We aimed to provide projections of preventable cancer cases under different price‐based alcohol policy scenarios.

Design

A macro‐simulation approach was used to estimate numbers and proportions of cancer cases prevented under different price‐based alcohol policy scenarios.

Setting and participants

Published price elasticities for main alcoholic beverages were applied to the mean daily intake of pure alcohol in the German population calculated from the German Health Interview and Examination Survey for Adults 2008–11 (DEGS1) to obtain hypothetical exposure distributions of alcohol consumption under different scenarios of changing price for alcoholic beverages.

Measurements

Age, sex and cancer site‐specific potential impact fractions were calculated for different scenarios of changing the price of alcohol (single price increases, repeated price increases, volumetric price increase) for each year of a 30‐year study period (2020–50).

Findings

Over a 30‐year horizon, an estimated 4.7% (men = 10.1%, women = 1.4%) of alcohol‐related cancer cases could be prevented in Germany, if alcohol intake above risk thresholds were reduced to levels below risk thresholds. Accordingly, the burden of new cancers would be reduced by approximately 244 000 cases (men = 200 000, women = 44 000). Of all price‐based alcohol policy scenarios, a 100% price increase on alcoholic beverages was estimated to be most effective with approximately 213 000 (4.1%; men = 167 000; women = 47 000) preventable alcohol‐related cancer cases, followed by 5‐yearly 25% price increases (2.8%; men = 115 000, women = 29 000) and a volumetric price increase according to the beverage‐specific alcohol content (1.9%; men = 72 000, women = 24 000).

Conclusions

Simulations suggest that a substantial number of alcohol‐related cancer cases could be avoided in Germany by applying price‐based policies to reduce consumption of alcoholic beverages.
Fall of amalgam restoration: a 10‐year analysis of an Australian university dental clinic
Authors: Reher V , Reher P , Peres KG , Peres MA
Published: November 2020

Background

The use of amalgam in Dentistry has decreased since the 1980s. This study aimed to (i) assess the time trend in the usage of amalgam and composite in posterior teeth at Griffith University Dental Clinic from 2010 to 2019; (ii) to test whether this trend varied according to the dental health provider.

Methods

We analysed clinic records from 2010 to 2019. Prais–Winsten analyses were performed, and the average annual percentages change (AAPC) for amalgam and composite was estimated.

Results

There were 397,013 procedures, including 80,995 direct posterior restorations. Amalgam use decreased from 12.9% in 2010 to 0.5% in 2019 among students, while composite use increased from 87.1% to 99.5% of posterior restorations. The annual increase of the composite was 1.4% per year for students, while amalgam decreased by 30.2% per year on average. A similar trend was noted among the dentists.

Conclusions

A significant decrease in the use of amalgam was observed over time for both students and professionals. This trend raises questions about curriculum reviews, focusing on the repair, maintenance and safe removal of amalgam while reinforcing the learning on Minimally Invasive Dentistry and composite restorations based on the patient’s caries risk.
Integrated long‐term multifunctional pediatric mechanical circulatory assist device
Authors: Sarkisyan Harutyun , Stevens Randy , Tchantchaleishvili Vakhtang , Rossano Joseph , Throckmorton Amy
Published: November 2020

There continues to be limited, viable ventricular assist device technology options to support the dysfunctional states of pediatric heart failure. To address this need, we are developing a magnetically suspended, versatile pumping technology that uniquely integrates two blood pumps in a series configuration within a single device housing. This device enables operational switching from the usage of one pump to another as needed for clinical management or to support growth and development of the pediatric patient. Here, we present the initial design where we conducted a virtual fit study, the Taguchi Design Optimization Method, iterative design to develop pump geometries. Computational tools were used to estimate the pressure generation, capacity delivery, hydraulic efficiency, fluid stress levels, exposure time to stresses, blood damage index, and fluid forces on the impellers. Prototypes of the pumps were tested in a flow loop using a water‐glycerin solution. Both designs demonstrated the capability to generate target pressures and flows. Blood damage estimations were below threshold levels and achieved design requirements; however, maximum scalar stress levels were above the target limit. Radial and axial forces were less than 1 N and 10 N, respectively. The performance data trends for physical prototypes correlated with theoretical expectations. The centrifugal prototype was able to generate slightly higher pressure rises than numerical predictions. In contrast, the axial prototype outperformed the computational studies. Experimental data were both repeatable and reproducible. The findings from this research are promising, and development will continue.
Over 10‐year follow‐up outcomes and failure analysis of black diaphragm intraocular lens implantation in traumatic Aniridia
Authors: Li Jun , Li Dongfang , Wu Jie , Dong Xiaoguang
Published: November 2020

Purpose

To determine the over 10‐year follow‐up outcomes and analyse the reason for failure in patients who underwent black diaphragm intraocular lens (IOL) implantation for the management of traumatic aniridia.

Methods

Fifty‐three patients underwent black diaphragm IOL implantation for the treatment of traumatic aniridia from September 1998 to August 2007. 33 eyes of 33 patients were enrolled in our study, and the mean follow‐up period was 185.6 ± 36.2 months (range: 126–247 months). The primary methods employed for assessment of the safety of the IOL and the causes of failure were the ultrasound biomicroscopy (UBM) and observation during reoperation.

Results

In the current study, 13 patients (39.4%) who underwent IOL implantation by means of trans‐scleral fixation were observed to maintain a transparent cornea and normal intraocular pressure. 20 patients (60.6%) developed corneal endothelial decompensation, and 14 patients (42.4%) developed secondary glaucoma. 27 patients were examined by means of UBM or reoperation and the position of black diaphragm IOL in 18 patients was observed to be abnormal; the IOL had shifted forward and directly contacted with the anterior chamber and even the corneal endothelium.

Conclusion

The forward displacement of black diaphragm IOL is a direct cause of treatment failure. Although the implantation of black diaphragm IOL is an effective method of management of traumatic aniridia, the treatment should be guarded and performed in an appropriate manner. Patients should be informed regarding the need for life‐long follow‐up, so that the complications can be identified in a timely manner.
Prevalence and incidence of keratoconus in Norway: a nationwide register study
Authors: Kristianslund Olav , Hagem Anne Marie , Thorsrud Andreas , Drolsum Liv
Published: November 2020

Purpose

To estimate the national prevalence and incidence of keratoconus in Norway.

Methods

In this epidemiologic study, data were obtained from the Norwegian Patient Registry, which provides information from all publicly funded specialist care in Norway. Prevalence of keratoconus was estimated from the total number of patients registered with this diagnosis and incidence from the annual frequency of first‐time registrations of patients up to 40 years of age in the period 2010–2018. Data on age and gender of the keratoconus patients were also gathered.

Results

A total of 9832 keratoconus patients were registered. The estimated prevalence in the general population was 192.1 per 100 000 (95% confidence interval (CI): 188.3–195.9), and the estimated annual incidence was 19.8 per 100 000 (95% CI: 18.1–21.5). There was a predominance of males (73%), and mean age for all patients was 37.5 years at first registration in this period.

Conclusion

This study reports the frequency of keratoconus from a national patient register during a time period with available modern diagnostic tools. The estimated prevalence and incidence were higher than most previous estimates and show that keratoconus is not a rare condition. As screening was not part of the study, the true prevalence in the general population may be even higher.
Initial observation or treatment for diabetic macular oedema with good visual acuity: two‐year outcomes comparison in routine clinical practice: data from the Fight Retinal Blindness! Registry
Authors: Gabrielle Pierre‐Henry , Nguyen Vuong , Bhandari Sanjeeb , Mehta Hemal , Viola Francesco , Arnold Jennifer , Fraser‐Bell Samantha , Barthelmes Daniel , Creuzot‐Garcher Catherine , Gillies Mark
Published: November 2020

Purpose

To compare visual acuity (VA) change at 24 months in eyes with clinically significant DME (CSDME) and good VA initially treated versus initially observed in routine clinical practice.

Methods

Retrospective analysis of treatment‐naïve eyes with CSDME and good VA (baseline VA ≥ 79 letters), with at least 24 months of follow‐up and initially managed with treatment (intravitreal treatment and/or macular laser) or observation with possible treatment after 4 months that were tracked in a prospectively designed observational registry.

Results

We identified 150 eligible eyes (98 initially observed, 52 initially treated) of 130 patients. The proportion of eyes with at least a 5‐letter VA loss at 24 months was not significantly different between the groups: 65% with initial observation and 42% with initial treatment (p = 0.39). However, initially observed eyes were more likely to have a 10‐letter VA loss at 24 months (OR = 4.6, p = 0.022). Most of eyes in the initial observation group received at least one treatment (an intravitreal injection in 66% and macular laser in 20%) during the 24‐month period.

Conclusions

The risk of 5 letters loss was similar between both management groups. However, initially observed eyes were more at risk of developing moderate visual loss and more than 80% of them required treatment over 24 months.
An Approach to Identify and Understand the Main Processes of Weathering that Affect the Pre‐Hispanic STELAE Located in the CALAKMUL Biosphere Reserve in Campeche, Mexico
Authors: Espinosa‐Morales Y. , Alarcón A. L. , Domínguez‐Carrasco M.d. R. , Martínez‐Miranda V. , Arteaga‐Arcos J. C. , Silva‐León I. , Reyes J.
Published: November 2020

Oxpemul is an archaeological site with pre‐Hispanic legacy located in the Calakmul biosphere reserve in Mexico. The stelae in this site have important epigraphic records of the Mayan culture. However, this information can be lost due to weathering processes that these structures undergo. In this work, ion chromatography analysis of ions extracted from samples obtained in situ using cotton poultices was used to discuss the weathering processes involved in four stelae located in Oxpemul. The plots of Ca2+vs SO42−, (Ca2+ + Mg2+) vs HCO3− and Ca2+vs HCO3− and the mineral phases found by x‐ray diffraction (XRD) revealed that the dissolution of carbonates from the limestone and the recrystallization processes of these phases are the main weathering processes that occur in the stelae. Furthermore, it was found that the hydrolysis of silicates by cation exchange reactions to form montmorillonite contributes to the weathering process. The presence of oxalate crystals found by XRD and electron microscopy revealed that biodeterioration reactions also contribute to the weathering of the stelae. This is the first study carried out to identify and understand the weathering processes that occur in these stelae. This information could be useful to establish strategies for preserving, conserving, and restoring these vestiges.
The effects of woody plant encroachment and wildfire on plant species richness and composition: Temporal changes in a forest–steppe mosaic
Authors: Ónodi Gábor , Kertész Miklós , Lengyel Attila , Pándi Ildikó , Somay László , Szitár Katalin , Kröel‐Dulay György
Published: November 2020

Questions

Woody plant encroachment and wildfire may both have major effects on species richness and composition, yet studies that assess these two factors in combination are rare. We asked the following specific questions: (1) how did juniper cover change over a decade in the study area; what are the effects of juniper encroachment and subsequent wildfire on(2) plant species richness; and (3) vegetation composition?

Location

Sand forest–steppe in Kiskunság, Central Hungary.

Methods

We studied a juniper‐encroached grassland hit by a wildfire. We assessed changes in plant species richness and composition in burnt and unburnt grassland and juniper plots for 11 years following the wildfire. Yearly vegetation sampling was performed in permanent quadrats of 1 m2and 25 m2using visual cover estimation. Temporal changes in juniper cover and species richness were evaluated with generalized linear mixed‐effects models. Compositional changes were analysed by non‐metric multidimensional scaling and fidelity analysis.

Results

At the beginning of the study, the presence of individual juniper shrubs increased species richness, and did not alter species composition. However, microsites covered by junipers were extremely species‐poor. Juniper growth during the study period caused a sharp decline in species richness at the edge of juniper shrubs and a shift in species composition compared to grassland plots. Wildfire increased species richness both in grassland and juniper plots. It caused only transient compositional responses in grasslands, but converted juniper habitats back to the grassland state.

Conclusions

We conclude that neither moderate juniper encroachment nor wildfire have negative effects on plant species richness in the studied ecosystem. However, as juniper thickening may cause species loss and devastating fires, conservation management should prevent the development of dense juniper stands.
Emerging chemical scaffolds with potential SHP2 phosphatase inhibitory capabilities – A comprehensive review
Authors: Tripathi Rati Kailash Prasad , Ayyannan Senthil Raja
Published: November 2020

The drug discovery panorama is cluttered with promising therapeutic targets that have been deserted because of inadequate authentication and screening failures. Molecular targets formerly tagged as “undruggable” are nowadays being more cautiously cross‐examined, and whilst they stay intriguing, numerous targets are emerging more accessible. Protein tyrosine phosphatases (PTPs) excellently exemplifies a class of molecular targets that have transpired as druggable, with several small molecules and antibodies recently turned available for further development. In this respect, SHP2, a PTP, has emerged as one of the potential targets in the current pharmacological research, particularly for cancer, due to its critical role in various signalling pathways. Recently, few molecules with excellent potency have entered clinical trials, but none could reach the clinic. Consequently, search for novel, non‐toxic, and specific SHP2 inhibitors are on purview. In this review, general aspects of SHP2 including its structure and mechanistic role in carcinogenesis have been presented. It also sheds light on the development of novel molecular architectures belonging to diverse chemical classes that have been proposed as SHP2‐specific inhibitors along with their structure‐activity relationships (SARs), stemming from chemical, mechanism‐based and computer‐aided studies reported since January 2015 to July 2020 (excluding patents), focusing on their potency and selectivity. The encyclopedic facts and discussions presented herein will hopefully facilitate researchers to design new ligands with better efficacy and selectivity against SHP2.
Subcutaneous white adipose tissue: The deepest layer of the cutaneous immune barrier
Authors: Brüggen Marie‐Charlotte , Stingl Georg
Published: November 2020

Mammalian skin, the outer covering of the body, is composed of three layers, i.e. the epidermis, the dermis and the subcutaneous white adipose tissue (SWAT). While the contribution of epidermis and dermis to the skin's immune function is well established, the role, if any, of SWAT in this regard has yet to be determined. Human SWAT is made up of lobules which consist mainly of adipocytes and are subdivided and separated from each other by vascularized septae of connective tissue. An immunophenotypic analysis of liposuction‐derived SWAT demonstrated that healthy subcutaneous fat tissue, although showing no overt signs of inflammation, harbors an indigenous system of immunocytes. As opposed to epidermis and dermis, they belong mainly to the mononuclear phagocyte lineage and, to a lesser extent, represent T‐lymphocytes. Their phenotype indicates that these two major subsets of SWAT leukocytes are primarily concerned with ant‐inflammatory and/or regulatory functions. It thus appears that SWAT is more than a cushion protecting against mechanical trauma, and may subserve immunomodulatory functions aimed at preventing or, at least, mitigating exaggerated immune and/or inflammatory reactions..
A regulatory element in the 3′‐untranslated region of CEBPA is associated with myeloid/NK/T‐cell leukemia
Authors: Kimura Yukiko , Iwanaga Eisaku , Iwanaga Kouta , Endo Shinya , Inoue Yoshitaka , Tokunaga Kenji , Nagahata Yousuke , Masuda Kyoko , Kawamoto Hiroshi , Matsuoka Masao
Published: November 2020

Objectives

CCAAT/enhancer‐binding protein α (CEBPA) is an essential transcription factor for myeloid differentiation. Not only mutation of the CEBPA gene, but also promoter methylation, which results in silencing of CEBPA, contributes to the pathogenesis of acute myeloid leukemia (AML). We sought for another differentially methylated region (DMR) that associates with the CEBPA silencing and disease phenotype.

Methods

Using databases, we identified a conserved DMR in the CEBPA 3′‐untranslated region (UTR).

Results

Methylation‐specific PCR analysis of 231 AML cases showed that hypermethylation of the 3′‐UTR was associated with AML that had a myeloid/NK/T‐cell phenotype and downregulated CEBPA. Most of these cases were of an immature phenotype with CD7/CD56 positivity. These cases were significantly associated with lower hemoglobin levels than the others. Furthermore, we discovered that the CEBPA 3′‐UTR DMR can enhance transcription from the CEBPA native promoter. In vitro experiments identified IKZF1‐binding sites in the 3′‐UTR that are responsible for this increased transcription of CEBPA.

Conclusions

These results indicate that the CEBPA 3′‐UTR DMR is a novel regulatory element of CEBPA related to myeloid/NK/T‐cell lineage leukemogenesis. Transcriptional regulation of CEBPA by IKZF1 may provide a clue for understanding the fate determination of myeloid vs. NK/T‐lymphoid progenitors.