bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased p53 signaling impairs neural differentiation causing HUWE1-promoted intellectual disabilities
Authors: Aprigliano Rossana , Bradamante Stefano , Mihaljevic Boris , Wang Wei , Fordyce Martin Sarah L. , Bordin Diana L. , Bosshard Matthias , Montaldo Nicola P. , Peng Yunhui , Alexov Emil , Skinner Cindy , Liabakk Nina-Beate , Bjørås Magnar , Schwartz Charles E. , van Loon Barbara
Published: May 2020

Essential E3 ubiquitin ligase HUWE1 (HECT, UBA and WWE domain containing 1) regulates key factors, as p53. Mutations inHUWE1have been associated with neurodevelopmental X-linked intellectual disabilities (XLIDs), however the pathomechanism at the onset of heterogenous XLIDs remains unknown. In this work, we identify p53 signaling as the process hyperactivated in lymphoblastoid cells from patients with HUWE1-promoted XLIDs. The hiPSCs-based modeling of the severe HUWE1-promoted XLID, the Juberg Marsidi syndrome (JMS), reviled majorly impaired neural differentiation, accompanied by increased p53 signaling. The impaired differentiation results in loss of cortical patterning and overall undergrowth of XLID JMS patient-specific cerebral organoids, thus closely recapitulating key symptoms, as microcephaly. Importantly, the neurodevelopmental potential of JMS hiPSCs is successfully rescued by restoring p53 signaling, upon reduction of p53 levels. In summary, our findings indicate that increased p53 signaling leads to impaired neural differentiation and is the common cause of neurodevelopmental HUWE1-promoted XLIDs.
Febuxostat ethanol monosolvate
Authors: Gelbrich Thomas , Kahlenberg Volker , Adamer Verena , Nerdinger Sven , Griesser Ulrich J.
Published: May 2020

The title compound, 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-1,3-thiazole-5-carboxylic acid ethanol monosolvate, C16H16N2O3S·C2H6O, (I), displays intermolecular O—H...O and O—H...N bonds in which the carboxyl group of the febuxostat molecule and the hydroxyl group of the ethanol molecule serve as hydrogen-bond donor sites. These interactions result in a helical hydrogen-bonded chain structure. The title structure is isostructural with a previously reported methanol analogue.
Do anti-discrimination laws alleviate labour market duality?
Authors: Choi Hoon
Published: May 2020

Purpose

This paper examines whether and how labour market duality can be alleviated through legislation that prohibits discrimination based on employment type.

Design/methodology/approach

In 2007, the Korean government undertook a labour reform banning discriminatory treatment against fixed-term, part-time and dispatched workers. By exploiting a gradual implementation of the anti-discrimination law by firm size targeting a subset of non-regular workers, the paper identifies the treatment effects of the anti-discrimination law, taking a difference-in-difference-in-differences approach.

Findings

The results suggest that the anti-discrimination law significantly increases hourly wages and the probabilities of being covered by national pension, health insurance, and employment insurance for targeted non-regular workers in small firms relative to other workers. Anticipatory behaviours of employers and selective transitions of employees in response to the implementation of the anti-discrimination law do not underlie the estimated effects. The presence of labour unions contributes to reducing gaps in labour conditions between regular workers and targeted non-regular workers.

Originality/value

The main contribution of this paper is to provide empirical evidence on causal impacts of equal pay legislation on the gaps in labour conditions between different categories of workers, using a difference-in-difference-in-differences estimation.
Public expenditure on education, educational attainment and unemployment nexus in India: an empirical investigation
Authors: Singh Deepti , Shastri Shruti
Published: May 2020

Purpose

The purpose of this paper is to examine the nexus among public expenditure allocated to education, educational attainment at secondary level and unemployment rate in India for the period 1987–2017.

Design/methodology/approach

The study employs autoregressive distributed lags (ARDL) bound testing approach suggested by Pesaranet al.(2001) to find the long-run relationship among the variables. The causal linkages are investigated through block exogeneity test based on vector error correction model.

Findings

The empirical results indicate that educational attainment proxied by gross enrolment ratio at secondary level of education negatively affects unemployment rate in long run as well as in short run. However, public expenditure on education is ineffective in influencing both educational attainment and unemployment rate.

Originality/value

The study is the first empirical effort to identify the causal nexus among public expenditure on education, educational attainment and unemployment in the context of India.

Peer review

The peer review history for this article is available at:https://publons.com/publon/10.1108/IJSE-06-2019-0396
Sensitivity analysis of using solar cells in regional electricity power supply of off-grid power systems in Iran
Authors: Jahangiri Mehdi , Haghani Ahmad , Heidarian Shahram , Mostafaeipour Ali , Raiesi Heidar Ali , Alidadi Shamsabadi Akbar
Published: May 2020

Purpose

Rural areas are one of the effective regions in economy and self-sufficiency field especially in agricultural and livestock section. Planning in the rural section and the effort in solving the problems of farmers lead to increase their interest in farming and manufacturing in the villages and decrease their migration to the cities and metropolitans. Therefore, the present study aimed at feasibility of electricity to a rural household in Iran using off-grid solar-based hybrid system.

Design/methodology/approach

In renewable energy projects, a successful evaluation requires suitable criteria so that one can properly analyze the operational behavior of all feasible scenarios. In the present paper, HOMER software has been used for this purpose for a village with no access to electricity grid (Bar Aftab-e Jalaleh, Iran). Due to drastic fluctuation of fossil fuel prices and varied solar radiations in various years because of climate change, sensitivity analysis has been performed using HOMER.

Findings

In the optimum status economically, 70% of needed energy is provided by solar cells at the price 0.792 $/kWh. The comparison between the optimum condition economically and the condition that only use fossil fuels revealed that the return on investment will occur after less than 2 years and have remained profitable over 23 years.

Social implications

The authors hope that the results of this study can be used in planning of the authorities to realize the interests of people in this village.

Originality/value

According to the surveys, despite Iran being the first country in terms of providing solar power to the villages, so far no socio-economic-environmental assessment has been done for a solar cell-based micro-grid in an off-grid mode for a remote village that is deprived of electricity from a national electricity grid. In addition, for the first time in Iran, the effect of the fuel price and solar radiation parameters variability on the performance of system have been investigated.
The relationship between audit components and audit market adaptability
Authors: Salehi Mahdi , Saravani Mahdi , Rouhi Safoura
Published: May 2020

Purpose

This study aims to study the relationship between audit components and collusion in the audit market.

Design/methodology/approach

The statistical population of the study includes 130 listed firms on the Tehran Stock Exchange from 2012-2017. The data tested using multivariate regression.

Findings

The findings of the study indicate that there is a positive and significant relationship between Rank A audit firms, competition and audit fees and audit market adaptability. The relationship standard fees and audit market adaptability, however, is negative and significant. Moreover, the results of the study show that there is no significant relationship between opinion shopping, type of audit report, audit market concentration, and agency costs with audit market adaptability.

Originality/value

The current study fills the gap in this area, and the results of the study may give direction to researchers and policy makers.
Developing and validating a scale of consumer-based brand equity for SMEs: evidence from Thailand
Authors: Chokpitakkul Nitcha , Anantachart Saravudh
Published: May 2020

Purpose

This study aimed to develop a generalisable small and medium-sized enterprise (SME) brand equity scale and examine its relationship with consumer response factors.

Design/methodology/approach

The study which was done in Thailand included three steps. First, brand communications of 40 successful SMEs and opinions of 56 consumers were collected by document analysis, interview and focus group for generating items and measurement of stimuli. Second, 838 consumers were surveyed to define the dimensions of the brand equity and the top SMEs. Third, surveys with 552 customers of the three most popular SMEs, one from each of the manufacturing, service and trade businesses, were conducted to examine the scale's invariance and its relationships with consumer responses.

Findings

The SME brand equity (SMEBE) scale included 23 items that were grouped into five components named brand awareness, functionality, authenticity, attentiveness and resonance. The scale is applicable across consumers that vary in their product involvement and brand engagement. The SMEBE significantly affected the brand's preference, loyalty and word-of-mouth.

Research limitations/implications

Since the SMEBE scale was tested with three brands, one from each of three business sectors, future studies should measure more than one SME for each business type. To allow for potential cultural characteristics that might affect the study, replications in diverse international settings are required.

Practical implications

SME managers should increase the awareness, functionality, authenticity, attentiveness and resonance of their brands as these components are essential for SMEBE, which, in turn, significantly affects consumer behaviour.

Originality/value

This study develops a ready-to-use SMEBE scale and introduces a practical research design for quantitative research on SME branding.
New member in the boardroom and subsequent strategic change in the product-market scope of the firm
Authors: Süsi Virgo , Lukason Oliver
Published: May 2020

Purpose

The purpose of this paper is to explore the linkages between the appointment of a new management board member and the following strategic change (SC) in the product-market scope of the firm.

Design/methodology/approach

The study is based on the whole population of Estonian firms, in total 16,941 observations and the data are retrieved from Estonian Business Register. First, the authors focus on the association between the appointment of a new board member and the likelihood of different types of SC. Second, the authors focus on the association between the new board member’s previous export experience and export-related SC. Logistic regressions are applied for all models.

Findings

The results indicate that there is a significant association between the appointment of a new board member and the subsequent start of exports and also continuing it, entrance into a new industry and making an SC in more broad terms, though the significance levels vary across the composed models. No significant relationship was found with the entrance into the additional geographic market(s) for already exporting firms. There was also a significant association between the previous export experience of a new board member and the subsequent start of exporting.

Originality/value

The authors look at SC in the product-market domain holistically by applying the same data on both geographic and product portfolio expansion options. The authors also introduce the scale and stability contexts of SCs. These aspects are usually neglected from similar studies.
Ancestral niche separation and evolutionary rate differentiation between sister marine flavobacteria lineages
Authors: Xue Chun‐Xu , Zhang Hao , Lin He‐Yu , Sun Ying , Luo Danli , Huang Yongjie , Zhang Xiao‐Hua , Luo Haiwei
Published: May 2020

Marine flavobacteria are specialists for polysaccharide degradation. They dominate in habitats enriched with polysaccharides, but are also prevalent in pelagic environments where polysaccharides are less available. These niches are likely occupied by distinct lineages, but evolutionary processes underlying their niche differentiation remain elusive. Here, genomic analyses and physiological assays indicate that the sister flavobacteria lineages Leeuwenhoekiella and Nonlabens likely explore polysaccharide‐rich macroalgae and polysaccharide‐poor pelagic niches respectively. Phylogenomic analyses inferred that the niche separation likely occurred anciently and coincided with increased sequence evolutionary rate in Nonlabens compared with Leeuwenhoekiella. Further analyses ruled out the known mechanisms likely driving evolutionary rate acceleration, including reduced selection efficiency, decreased generation time and increased mutation rate. In particular, the mutation rates were determined using an unbiased experimental method, which measures the present‐day populations and may not reflect ancestral populations. These data collectively lead to a new hypothesis that an ancestral and transient mutation rate increase resulted in evolutionary rate increase in Nonlabens. This hypothesis was supported by inferring that gains and losses of genes involved in SOS response, a mechanism known to drive transiently increased mutation rate, coincided with evolutionary rate acceleration. Our analyses highlight the evolutionary mechanisms underlying niche differentiation of flavobacteria lineages.
GATA‐type transcription factor MrNsdD regulates dimorphic transition, conidiation, virulence and microsclerotium formation in the entomopathogenic fungus Metarhizium rileyi
Authors: Xin Caiyan , Yang Jie , Mao Yingyu , Chen Wenbi , Wang Zhongkang , Song Zhangyong
Published: May 2020

The GATA‐type sexual development transcription factor NsdD has been implicated in virulence, secondary metabolism and asexual development in filamentous fungi. However, little is known about its function in the yeast‐to‐hypha transition and in microsclerotium formation. In the current study, the orthologous NsdD gene MrNsdD in the entomopathogenic fungus Metarhizium rileyi was characterized. Transcriptional analysis indicated that MrNsdD was involved in yeast‐to‐hypha transition, conidiation and microsclerotium formation. After targeted deletion of MrNsdD, dimorphic transition, conidiation, fungal virulence and microsclerotium formation were all impaired. Compared with the wild‐type strain, the ΔMrNsdD mutants were hypersensitive to thermal stress. Furthermore, transcriptome sequencing analysis revealed that MrNsdD regulated a distinct signalling pathway in M. rileyi during the yeast‐to‐hypha transition or microsclerotium formation, but exhibited overlapping regulation of genes during the two distinct developmental stages. Taken together, characterization of the MrNsdD targets in this study will aid in the dissection of the molecular mechanisms of dimorphic transition and microsclerotium development.
Mimosa pigra in eastern and southern Africa: Distribution and socio‐ecological impacts
Authors: Witt Arne B.R. , Floyd Kelvin S. , Nunda Winnie , Beale Tim , Shanungu Griffin , Kriticos Darren J.
Published: May 2020

The semiaquatic weed Mimosa pigra has negative impacts on biodiversity, fishing, crop and livestock production, and tourism in most places where it has been introduced, established and proliferated. Many of the ecological impacts are well known, but its impacts on rural livelihoods are less well documented, especially in Africa. We mapped the distribution of M. pigra in eastern and southern Africa, and then compared that with its potential distribution based on an ecoclimatic niche model. Household interviews were conducted to assess the impacts of this weed on local livelihoods. Mimosa pigra was found to be invasive in western Ethiopia, around the shores of Lake Victoria and Lake Tanganyika, and along the Tanzanian coastline, northern Malawi, parts of Mozambique and along the Kafue River and in the Barotse floodplain on the Zambezi River in Zambia. According to respondents living along the Kafue River floodplains in Zambia, it has a negative impact on biodiversity, wildlife, livestock, crop production, fishing and mobility. Dense stands prevented the movement of people and livestock, limiting access to croplands, grazing lands and fishing areas. Fish catches have been reduced and fishing equipment damaged. All respondents agreed that their livelihood options would be considerably enhanced if M. pigra was removed from the landscape. Based on its current and potential impact, we therefore recommend that an integrated management plan be developed and implemented, including the appropriate use of biological control agents to reduce the negative impacts of the weed.
Lack of association between the GNB3 rs5443, HIF1A rs11549465 polymorphisms, physiological and functional characteristics
Authors: Bosnyák Edit , Trájer Emese , Alszászi Gabriella , Móra Ákos , Györe István , Udvardy Anna , Tóth Miklós , Szmodis Márta
Published: May 2020

The aim was to examine the association between the hypoxia‐inducible factor‐1α (HIF1A) gene and the guanine nucleotide binding protein beta polypeptide 3 (GNB3) gene polymorphisms and the endurance/power athlete status and relative aerobic capacity. Another goal of this study was to reveal the connection between GNB3, blood pressure (BP), body composition and body mass index (BMI). Two hundred thirty‐eight people participated in this study: 148 elite athletes (men = 107, women = 41) and 90 controls (men = 51, women = 39). The athletes were divided into two groups: the power and the endurance athletes. BMI and body fat percentage (fat%) were calculated. Fifty of the athletes underwent an incremental treadmill test to exhaustion; BP was monitored before and after the test. There were differences in the genotype frequencies of HIF1A between the endurance and the control group (ProPro: 64% vs.79%, ProSer: 27% vs.19%, SerSer: 9% vs. 2%; p = .0351); in the allele prevalences among the three groups (Pro: 87% vs. 77% vs. 88%; Ser: 13% vs. 23% vs. 12%; p = .0103) and between the endurance and control group (p = .0049) as well. The GNB3 allele proportions differed in the three groups (C: 74% vs. 61% vs. 71%, T: 26% vs. 39% vs. 29%; p = .0436). There were no connections between the genotypes and the relative aerobic capacity and neither between GNB3 genotypes and BP, BMI and fat%. The connection of GNB3 T allele to the endurance performance still remained contradictable.
Ovomucoid epitope‐specific repertoire of IgE, IgG4, IgG1, IgA1, and IgD antibodies in egg‐allergic children
Authors: Suprun Maria , Getts Robert , Grishina Galina , Tsuang Angela , Suárez‐Fariñas Mayte , Sampson Hugh A.
Published: May 2020

Background

Egg‐white ovomucoid, that is, Gal d 1, is associated with IgE‐mediated allergic reactions in most egg‐allergic children. Epitope‐specific IgE levels have been correlated with the severity of egg allergy, while emerging evidence suggests that other antibody isotypes (IgG1, IgG4, IgA, and IgD) may have a protective function; yet, their epitope‐specific repertoires and associations with atopic comorbidities have not been studied.

Methods

Bead‐based epitope assay (BBEA) was used to quantitate the levels of epitope‐specific (es)IgA, esIgE, esIgD, esIgG1, and esIgG4 antibodies directed at 58 (15‐mer) overlapping peptides, covering the entire sequence of ovomucoid, in plasma of 38 egg‐allergic and 6 atopic children. Intraclass correlation (ICC) and coefficient of variation (CV) were used for the reliability assessment. The relationships across esIgs were evaluated using network analysis; linear and logistic regressions were used to compare groups based on egg allergy status and comorbidities.

Results

BBEA had high reliability (ICC >0.75) and low variability (CV <20%) and could detect known IgE‐binding epitopes. Egg‐allergic children had lower esIgA1 (P = .010) and esIgG1 (P = .016) and higher esIgE (P < .001) and esIgD (P = .015) levels compared to the atopic controls. Interestingly, within the allergic group, children with higher esIgD had decreased odds of anaphylactic reactions (OR =0.48, P = .038). Network analysis identified most associations between esIgE with either esIgG4 or esIgD; indicating that IgE‐secreting plasma cells could originate from either sequential isotype switch from antigen‐experienced intermediate isotypes or directly from the IgD+ B cells.

Conclusions

Collectively, these data point toward a contribution of epitope‐specific antibody repertoires to the pathogenesis of egg allergy.
Red‐bellied black snake (Pseudechis porphyriacus) envenomation in 17 dogs: clinical signs, coagulation changes, haematological abnormalities, venom antigen levels and outcomes following treatment with a tiger‐brown snake antivenom
Authors: Finney ER , Padula AM , Leister EM
Published: May 2020

Background

This report describes 17 cases of red‐bellied black snake envenomation (RBBS; Pseudechis porphyriacus) in dogs in south‐eastern Queensland. Patients were prospectively enrolled for the treatment with a new tiger‐brown snake antivenom 8000 units, (TBAV; Padula Serums Pty Ltd, VIC, Australia).

Case Report

Clinical diagnosis of RBBS envenomation was made by either snake venom detection kit, snake identification using scale counting, or owner observed dog‐snake interaction in patients with clinical signs of envenomation. An RBBS venom antigen sandwich ELISA was used to retrospectively quantify venom levels in frozen serum and urine. Mechanical ventilation was required in 11% (2/17) patients, whole blood transfusion in 12% (2/17), tissue swelling at the bite site occurred in 53% (9/17) and facial palsy in 12% (2/17). One dog was euthanised, and overall, 94% (16/17) survived to hospital discharge. Clinicopathological changes pre‐TBAV included variable haemolysis, increased CK, pigmenturia and mildly prolonged active clotting time with a median of 134 s (n = 13, range 91–206 s). Haematological profiles post envenomation revealed anaemia (6/6) and spherocytosis (5/5), which resolved without the use of corticosteroids. Pre‐TBAV, median RBBS venom antigen concentration was 22.6 ng/mL (n = 15, range 2–128) in serum and 58 ng/mL (range 1–452) in urine; RBBS venom antigen was undetectable in serum post‐TBAV in all patients.

Conclusion

Some RBBS envenomed dogs required, critical care including mechanical ventilation, blood transfusion, additional antivenom and prolonged hospitalisation. TBAV was effective with excellent prognosis despite stated specificity for tiger and brown snake.
Combination of a mitogen‐activated protein kinase inhibitor with the tyrosine kinase inhibitor pacritinib combats cell adhesion‐based residual disease and prevents re‐expansion of FLT3‐ITD acute myeloid leukaemia
Authors: Zabkiewicz Joanna , Lazenby Michelle , Edwards Gareth , Bygrave Ceri A. , Omidvar Nader , Zhuang Lihui , Knapper Steve , Guy Carol , Hills Robert K. , Burnett Alan K. , Alvares Caroline L.
Published: May 2020

Minimal residual disease (MRD) in acute myeloid leukaemia (AML) poses a major challenge due to drug insensitivity and high risk of relapse. Intensification of chemotherapy and stem cell transplantation are often pivoted on MRD status. Relapse rates are high even with the integration of first‐generation FMS‐like tyrosine kinase 3 (FLT3) inhibitors in pre‐ and post‐transplant regimes and as maintenance in FLT3‐mutated AML. Pre‐clinical progress is hampered by the lack of suitable modelling of residual disease and post‐therapy relapse. In the present study, we investigated the nature of pro‐survival signalling in primary residual tyrosine kinase inhibitor (TKI)‐treated AML cells adherent to stroma and further determined their drug sensitivity in order to inform rational future therapy combinations. Using a primary human leukaemia‐human stroma model to mimic the cell–cell interactions occurring in patients, the ability of several TKIs in clinical use, to abrogate stroma‐driven leukaemic signalling was determined, and a synergistic combination with a mitogen‐activated protein kinase (MEK) inhibitor identified for potential therapeutic application in the MRD setting. The findings reveal a common mechanism of stroma‐mediated resistance that may be independent of mutational status but can be targeted through rational drug design, to eradicate MRD and reduce treatment‐related toxicity.
Tropical forest loss drives divergent patterns in functional diversity of forest and non‐forest birds
Authors: Matuoka Maísa A. , Benchimol Maíra , Morante‐Filho José Carlos
Published: May 2020

Tropical forests have been facing high rates of deforestation driven by multiple anthropogenic disturbances, with severe consequences for biodiversity. However, the understanding of such effects on functional diversity is still limited in tropical regions, especially considering different ecological groups responses. Here, we evaluated the functional responses of birds to forest loss at the threatened Brazilian Atlantic forest, considering the complete assemblage, and both forest‐dependent and non‐forest‐dependent species. Birds were surveyed in 40 forest sites with a forest cover gradient, located in two regions showing different land use types. We tested different models to assess the responses of functional diversity indices to forest loss in these sites. Although functional diversity did not differ between regions, forest and non‐forest birds showed divergent responses to forest loss. Deforested landscapes presented an increase in functional richness (SESFRic) and evenness for forest species and an increase of functional dispersion for non‐forest birds. Additionally, forested landscapes harbor birds presenting lower body mass and wing length, and non‐forest species with lower tarsus length. The maintenance of some functional metrics through forest loss resulted from a compensatory dynamic between forest and non‐forest birds, indicating that only evaluating the complete assemblage may mask important idiosyncratic patterns of different ecological groups. Although non‐forest species are relatively capable to maintain bird functional diversity in deforested landscapes, forest birds are facing a drastic ongoing collapse in these sites, representing an alarming signal for the maintenance of forest ecosystem function.

Abstract in Portuguese is available with online material.
Modelling and predicting the competitive effects of vertical mergers: The bargaining leverage over rivals effect
Authors: Rogerson William P.
Published: May 2020

A new competitive effect of vertical mergers, based on the Nash bargaining model, has begun to play an important role in antitrust authorities’ evaluations of vertical mergers in the United States, Canada and abroad. The key idea is that a vertical merger will increase the bargaining leverage of the merged firm over its downstream rivals. Its bargaining leverage increases because it now takes into account the additional profit that its own downstream division will earn if it withholds inputs from downstream rivals, which changes its threat point in the bargaining game with downstream rivals. Consequently, the merged firm can increase the price that it charges rival downstream firms for inputs. One strong appeal of this theory is that it provides a simple and very intuitive formula to measure the upward pricing pressure caused by a vertical merger due to changes in bargaining leverage, based on variables whose values can generally be estimated using available data. This article describes this new competitive effect, which will be called the bargaining leverage over rivals (BLR) effect, and derives the upward pricing pressure formula. It also explains why this new competitive effect is distinct from the older raising rivals’ costs (RRC) effect that has been widely discussed in the economics literature, and discusses the relationship between the two different effects.
Glycogen synthase kinase‐3 inhibition overcomes epithelial‐mesenchymal transition‐associated resistance to osimertinib in EGFR‐mutant lung cancer
Authors: Fukuda Koji , Takeuchi Shinji , Arai Sachiko , Kita Kenji , Tanimoto Azusa , Nishiyama Akihiro , Yano Seiji
Published: May 2020

A novel epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitor, osimertinib, has marked efficacy in patients with EGFR‐mutant lung cancer. While epithelial‐mesenchymal transition (EMT) plays a role in the resistance to various targeted drugs, its involvement in EGFR‐inhibitor resistance remains largely unknown. Preclinical experiments with osimertinib‐resistant lung cancer cells showed that EMT was associated with decreased microRNA‐200c and increased ZEB1 expression. In several resistant clone cells, pretreatment with the histone deacetylase inhibitor quisinostat helped overcome the resistance by reverting EMT. Furthermore, drug screening from a library of 100 kinase inhibitors indicated that Glycogen synthase kinase‐3 (GSK‐3) inhibitors, such as LY2090314, markedly inhibited the growth and induced apoptosis of resistant cells, specifically those with a mesenchymal phenotype. These results suggest that GSK‐3 inhibition could be useful to circumvent EMT‐associated resistance to osimertinib in EGFR‐mutant lung cancer.
Three ways to deliver a net positive impact with biodiversity offsets
Authors: Moilanen Atte , Kotiaho Janne S.
Published: May 2020

Biodiversity offsetting is the practice of using conservation actions, such as habitat restoration, management, or protection, to compensate for ecological losses caused by development activity, including construction projects. The typical goal of offsetting is no net loss (NNL), which means that all ecological losses are compensated for by commensurate offset gains. We focused on a conceptual and methodological exploration of net positive impact (NPI), an ambitious goal that implies commitment beyond NNL and that has recently received increasing attention from big business and environmental nongovernmental organizations. We identified 3 main ways NPI could be delivered: use of an additional NPI multiplier; use of slowly developing permanent offsets to deliver additional gains after NNL has first been reached during a shorter offset evaluation time interval; and the combination of permanent offsets with partially temporary losses. An important and novel variant of the last mechanism is the use of an alternate mitigation hierarchy so that gains from the traditional third step of the mitigation hierarchy (i.e., onsite rehabilitation) are no longer be counted toward reduced offset requirements. The outcome from these 3 factors is that for the same ecological damage, larger offsets will be required than previously, thereby improving offset success. As a corollary, we show that offsets are NNL only at 1 ephemeral point in time, before which they are net negative and after which they become either NPI or net negative impact, depending on whether permanent offsets are combined with partially temporary losses or if temporary offset gains are combined with partially permanent losses. To achieve NPI, offsets must be made permanent, and they must achieve NNL during an agreed‐upon offset evaluation period. An additional NPI‐multiplier and use of the modified mitigation hierarchy will deliver additional NPI gains. Achieving NPI is fully conditional on prior achievement of NNL, and NNL offsets have been frequently observed to fail due to inadequate policy requirements, poor planning, or incomplete implementation. Nevertheless, achieving NPI becomes straightforward if NNL can be credibly reached first.
Protecting biodiversity and economic returns in resource‐rich tropical forests
Authors: Ball James G. C. , Burgman Mark A. , Goldman Elizabeth D. , Lessmann Janeth
Published: May 2020

In pursuit of socioeconomic development, many countries are expanding oil and mineral extraction into tropical forests. These activities seed access to remote, biologically rich areas, thereby endangering global biodiversity. We examined how protection of biodiversity and economic revenues can be balanced in biologically valuable regions. Using spatial data on oil profits and predicted species and ecosystem extents, we optimized the protection of 741 terrestrial species and 20 ecosystems of the Ecuadorian Amazon across a range of opportunity costs (i.e., sacrifices of extractive profit). We also applied spatial statistics to remotely sensed, historic deforestation data to focus the optimization on areas most threatened by imminent forest loss. Giving up 5% of a year's oil profits (US$221 million) allowed for a protected area network that retained an average of 65% of the extent of each species and ecosystem. This performance far exceeded that of the network produced by simple optimization for land area (which required a sacrifice of approximately 40% of annual oil profits [US$1.7 billion]) and used only marginally less land to achieve equivalent levels of ecological protection. We identified what we call emergency conservation targets: regions that are essential components of a cost‐effective conservation reserve network but at imminent risk of destruction, thus requiring urgent and effective protection. Governments can use our methods when evaluating extractive‐led development options to responsibly manage the associated ecological and economic trade‐offs and protect natural capital.
Artificial intelligence‐based wind forecasting using variational mode decomposition
Authors: V Vanitha , G Sophia J. , R Resmi , Raphel Delna
Published: May 2020

Intermittency in wind offers the major challenge in accomplishing the wind energy as a dependable sustainable energy resource in power grid. Fluctuations in wind speed occur seasonally over a year and if this seasonality is considered, the prediction of the speed of wind can be made more accurate. In this paper, an attempt is made to apply a signal decomposition technique called Variational Mode Decomposition (VMD), which decomposes series of wind speed data into several intrinsic mode functions (IMFs) to make the data more regular thereby enhancing the accuracy of the wind speed forecast model. Then, artificial intelligence technique, Adaptive neuro fuzzy inference system (ANFIS) is applied for the wind speed prediction by combining the obtained modes from VMD. Here, wind data of two sites in India, Jogimatti and Lamba are taken for the study. Each site data is grouped into high and low wind speed months and later, this series is decomposed into regular modes using VMD. Later, ANFIS is applied for training and predicting the wind speed for different time horizons.
High‐speed and area‐efficient Sobel edge detector on field‐programmable gate array for artificial intelligence and machine learning applications
Authors: Sikka Prateek , Asati Abhijit R , Shekhar Chandra
Published: May 2020

Sobel edge detector is an algorithm commonly used in image processing and computer vision to extract edges from input images using derivative of image pixels in x and y directions against surrounding pixels. Most artificial intelligence and machine learning applications require image processing algorithms running in real time on hardware systems like field‐programmable gate array (FPGAs). They typically require high throughput to match real‐time speeds and since they run alongside other processing algorithms, they are required to be area efficient as well. This article proposes a high‐speed and low‐area implementation of the Sobel edge detection algorithm. We created the design using a novel high‐level synthesis (HLS) design method based on application specific bit widths for intermediate data nodes. Register transfer level code was generated using MATLAB hardware description language (HDL) coder for HLS. The generated HDL code was implemented on Xilinx Kintex 7 field programmable gate array (FPGA) using Xilinx Vivado software. Our implementation results are superior to those obtained for similar implementations using the vendor library block sets as well as those obtained by other researchers using similar implementations in the recent past in terms of area and speed. We tested our algorithm on Kintex 7 using real‐time input video with a frame resolution of 1920 × 1080. We also verified the functional simulation results with a golden MATLAB implementation using FPGA in the loop feature of HDL Verifier. In addition, we propose a generic area, speed, and power improvement methodology for different HLS tools and application designs.
Fam70A binds Wnt5a to regulate meiosis and quality of mouse oocytes
Authors: Zhang Na‐Na , Zhang Teng , Gao Wen‐Yi , Wang Xin , Wang Zi‐Bin , Cai Jin‐Yang , Ma Yang , Li Cong‐Rong , Chen Xi‐Chen , Zeng Wen‐Tao , Hu Fan , Li Jian‐Min , Yang Zhi‐Xia , Zhou Chun‐Xiang , Zhang Dong
Published: May 2020

Objectives

Little is known about the roles of integral membrane proteins beyond channels, carriers or receptors in meiotic oocytes. The transmembrane protein Fam70A was previously identified as a likely “female fertility factor” in Fox3a‐knockout mouse ovaries where almost all follicles underwent synchronous activation and the mice became infertile very early. However, whether Fam70A functions in oocyte meiosis remains unknown. Therefore, the present study aimed to address this question.

Materials and Methods

Co‐immunoprecipitation, immunogold labelling‐electron microscopy, co‐localization and yeast two‐hybrid assays were used to verify the interaction. Antibody or small interfering RNA transfection was used to deplete the proteins. Immunofluorescence, immunohistochemistry and live tracker staining were used to examine the localization or characterize phenotypes. Western blot was used to examine the protein level.

Results

Fam70A was enriched in oocyte membranes important for normal meiosis. Fam70A depletion remarkably disrupted spindle assembly, chromosome congression and first polar body extrusion, which subsequently increased aneuploidy and abnormal fertilization. Moreover, Fam70A directly bound Wnt5a, the most abundant Wnt member within oocytes. Depletion of either Fam70A or Wnt5a remarkably increased adenomatous polyposis coli (APC), which stabilizes active β‐catenin and microtubules. Consequently, depletion of either Fam70A or Wnt5a remarkably increased p‐β‐catenin (inactive form) and acetylated tubulin, while APC knockdown remarkably decreased these two. Furthermore, Fam70A depletion remarkably reduced Akt phosphorylation.

Conclusions

Fam70A regulates meiosis and quality of mouse oocytes through both canonical and non‐canonical Wnt5a signalling pathways.
Exercise interventions in solid organ transplant candidates: A systematic review
Authors: Pesce de Souza Fernanda , Massierer Daniela , Anand Raje Uma , Tansey Catherine M. , Boruff Jill , Janaudis‐Ferreira Tania
Published: May 2020

Introduction

Exercise training may be recommended to solid organ transplant (SOT) candidates to improve fitness and tolerance before surgery. We aimed to determine the acceptance, safety, and effectiveness of exercise interventions in SOT candidates.

Methods

Online databases were searched. Studies of any design were included. Outcomes of interest were acceptance, safety, exercise capacity, and health‐related quality of life.

Results

Twenty‐three articles were included. Acceptance ranged from 16% to 100%. In the fifteen studies that assessed adverse events, none mentioned any adverse events occurring during the study. Five out of seven studies reported an increase in maximal exercise capacity post‐exercise in the intervention group (range of mean change: 0.45 to 2.9 mL/kg). Eight out of fourteen studies reported an increase in 6‐minute walking distance in the intervention group after the training period (range of mean change: 40‐105 m). Two articles showed an improvement in the mental composite scores as well as in the physical composite scores post‐exercise in the intervention group.

Conclusion

There was a lack of significant findings among most randomized controlled trials. Exercise training is acceptable and safe for selective SOT candidates. The effects of exercise training on exercise capacity and quality of life in SOT candidates are unclear.
Potentially inappropriate benzodiazepine use in Australian adults: A population‐based study (2014–2017)
Authors: Zheng Danni , Brett Jonathan , Daniels Benjamin , Buckley Nicholas A. , Pearson Sallie‐Anne , Schaffer Andrea L.
Published: May 2020

Introduction and Aims

Inappropriate benzodiazepine use continues to cause substantial morbidity and mortality globally. We aimed to characterise the initiation of new benzodiazepine treatment episodes in Australia and identify correlates of potentially inappropriate benzodiazepine use.

Design and Methods

We conducted a population‐based cohort study using dispensing claims from a 10% sample of Pharmaceutical Benefit Scheme eligible Australians (2014–2017). Our cohort comprised adults initiating a new benzodiazepine treatment; we defined potentially inappropriate use as ≥3 benzodiazepine dispensing over any continuous 90‐day period in the year following initiation. We examined characteristics associated with potentially inappropriate benzodiazepine use using multivariable logistic regression.

Results

People initiating a new benzodiazepine treatment episode (n = 276 765) were more frequently female (59.1%) and <65 years of age (73.6%). In the 90 days prior to initiating benzodiazepine, people were commonly dispensed antidepressants (26.5%), opioid analgesics (17.6%) and antipsychotics (4.7%). In the first year after initiation, 20 938 (9.5%) people experienced ‘potentially inappropriate use’. Having a greater initial quantity of benzodiazepine dispensed [odds ratio (OR), 1.10; 95% confidence interval (CI) 1.08–1.12 per 10 defined daily doses increase], dispensing of antipsychotics (OR 3.00, 95% CI 2.86–3.15) and >5 unique medicines (OR 2.54, 95% CI 2.44–2.64; vs. ≤5 unique medicines) in the 90 days prior to initiation were associated with potentially inappropriate benzodiazepine use.

Discussion and Conclusions

Approximately, 1 in 10 people who initiated benzodiazepines were using it beyond the guideline recommended period. We identified factors at the time of initiation associated with potentially inappropriate use; clinicians should consider these before prescribing benzodiazepines and initiate conversations about alternative therapy when necessary.
SNPs in PRKCA‐HIF1A‐GLUT1 are associated with diabetic kidney disease in a Chinese Han population with type 2 diabetes
Authors: Huang Yan , Jin Li , Yu Hairong , Jiang Guozhi , Tam Claudia H.T. , Jiang Song , Zheng Chunxia , Jiang Feng , Zhang Rong , Zhang Hong , Chan Juliana C.N. , Ma Ronald C.W. , Jia Weiping , Hu Cheng , Liu Zhihong
Published: May 2020

Objective

To explore the relationship between SNPs in PRKCA‐HIF1A‐GLUT1 and diabetic kidney disease in Chinese Han people.

Materials and methods

A total of 2552 participants from Shanghai Diabetes Institute Inpatient Database of Shanghai Jiao Tong University Affiliated Sixth People's Hospital were involved in the stage 1 cross‐sectional population. A total of 6015 subjects from the Hong Kong Diabetes Register were included for validation. Genotyping of participants was conducted by the MassARRAY Compact Analyzer (Agena Bioscience). The data were analysed by plink, SAS, Haploview.

Results

We identified variants associated with diabetic kidney disease in stage 1. Rs1681851 (P = .0105, OR = 1.331) in GLUT1 as well as rs2301108 (P = .0085, OR = 1.289) and rs79865957 (P = .0204, OR = 1.263) in HIF1A were significantly associated with diabetic kidney disease. Regarding DKD‐related traits, rs1681851 was associated with plasma creatinine levels (P = .0169, β = 4.822) and eGFR (P = .0457, β = −6.956). Moreover, the results showed the interactions between PRKCA‐GLUT1 in the occurrence of DKD. We further sought validation of the 17 SNPs in a prospective cohort and found that rs900836 and rs844501 were associated with the percentage change in eGFR slope. We performed a meta‐analysis of case‐control analysis data from the Hong Kong samples together with the stage 1 data from Shanghai. Rs9894851 showed significant correlation with the serum creatinine level as well as eGFR and no SNP showed association with DKD after meta‐analysis.

Conclusions

Our results suggest potential association between SNPs in PRKCA‐HIF1A‐GLUT1 and diabetic kidney disease in Chinese Han people.
Influence of 38% silver diamine fluoride application on bond stability to enamel and dentin using universal adhesives in self‐etch mode
Authors: Markham Mark D. , Tsujimoto Akimasa , Barkmeier Wayne W. , Jurado Carlos A. , Fischer Nicholas G. , Watanabe Hidehiko , Baruth Andrew G. , Latta Mark A. , Garcia‐Godoy Franklin
Published: May 2020

In order to evaluate the influence of 38% silver diamine fluoride (SDF) application on enamel and dentin bond stability of universal adhesives in self‐etch mode, a 38% SDF and three universal adhesives were used in this study. Initial shear bond strength (ISBS), fatigue bond strength (FBS), and shear bond strength of survivors (SBSS) to enamel and dentin of universal adhesives in self‐etch mode, with and without SDF application, were determined. SDF was applied to the polished enamel or dentin surface for 1 min, water‐rinsed and air‐dried for comparison with controls. The universal adhesives were applied to the prepared samples and composite resin was bonded using a mold‐enclosed method. Enamel bond stability of universal adhesives with SDF (ISBS: 14.7–20.4 MPa; FBS: 5.5–7.4 MPa and SBSS: 14.4–21.5 MPa) was significantly weaker than those without SDF (ISBS: 28.0–29.2 MPa; FBS: 12.1–15.6 MPa and SBSS: 28.4–34.4 MPa). Dentin bond stability with SDF (ISBS: 14.8–20.9 MPa; FBS: 7.1–8.2 MPa and SBSS: 17.3–21.8 MPa) was also significantly weaker than without SDF (ISBS: 19.3–36.1 MPa; FBS: 11.0–13.7 MPa and SBSS: 22.2–34.6 MPa). The results suggest that SDF application on enamel and dentin reduces the bond stability of universal adhesives in self‐etch mode.
A novel method for the classification of Alzheimer's disease from normal controls using magnetic resonance imaging
Authors: Khan Riyaj Uddin , Tanveer Mohammad , Pachori Ram Bilas ,   Alzheimer's Disease Neuroimaging Initiative (ADNI)
Published: May 2020

Alzheimer's disease (AD) is the most prevalent form of dementia. Although fewer people, who suffer from AD are correctly and promptly diagnosed, due to a lack of knowledge of its cause and unavailability of treatment, AD is more manageable if the symptoms of mild cognitive impairment (MCI) are in an early stage. In recent years, computer‐aided diagnosis has been widely used for the diagnosis of AD. The main motive of this paper is to improve the classification and prediction accuracy of AD. In this paper, a novel approach is developed to classify MCI, normal control (NC), and AD using structural magnetic resonance imaging (sMRI) from the Alzheimer's disease Neuroimaging Initiative (ADNI) dataset (50 AD, 50 NC, 50 MCI subjects). FreeSurfer is used to process these MRI data and obtain cortical features such as volume, surface area, thickness, white matter (WM), and intrinsic curvature of the brain regions. These features are modified by normalizing each cortical region's features using the absolute maximum value of that region's features from all subjects in each group of MCI, NC, and AD independently. A total of 420 features are obtained. To address the curse of dimensionality, the obtained features are reduced to 30 features using a sequential feature selection technique. Three classifiers, namely the twin support vector machine (TSVM), least squares TSVM (LSTSVM), and robust energy‐based least squares TSVM (RELS‐TSVM), are used to evaluate the classification accuracy from the obtained features. Five‐fold and 10‐fold cross‐validation are used to validate the proposed method. Experimental results show an accuracy of 100% for the studied database. The proposed approach is innovative due to its higher classification accuracy compared to methods in the existing literature.