bluuebunny/crossref_metadata_2025 huggingface dataset:
Thinly and Thickly Capitalized Projects: Theorizing the Role of the Finance Markets and Capital Supply in Project Management Studies
Authors: Styhre Alexander
Published: June 2020

In the contemporary economy, finance industry interests and finance theory propositions increasingly determine investment behavior. Project management scholars access conceptual frameworks and methods that shed light on day-to-day project management practices, but such practices are themselves shaped by the supply and cost of finance capital. Consequently, project management scholarship would benefit from a closer look at finance industry practices to better understand how, for example, calculations and risk assessments matter for day-to-day project management practices. In order to theorize the project organization form, finance theory and its key concepts of risk and uncertainty need to be recognized and subject to scholarly inquiry. This article presents two cases of project work, wherein the former (life science ventures) is thinly capitalized on the basis of uncertainty in the development activities, whereas the latter case (housing production) is thickly capitalized, which indicates that subsidies, insurances, and exemptions increase investment appetite. In either case, economic and social welfare are not maximized, which calls for project management scholars to recognize the role of finance industry practices when allocating finance capital to various projects.
Impact of primary headache disorder on quality of life among school students in Kuwait
Authors: Al-Hashel Jasem Y. , Alroughani R. , Shuaibi S. , AlAshqar A. , AlHamdan F. , AlThufairi H. , Owayed S. , Ahmed Samar F.
Published: June 2020

Background

Primary headache disorders have being increasingly reported in younger populations. They can have significant effects on their quality of life and academic achievement and may cause significant distress to their families.

Aims and objectives

To assess the burden of primary headache disorder and its impact on the quality of life on school student in Kuwait.

Methods

Across-sectional study was conducted among Kuwaiti primary and middle school students of both genders in randomly selected schools located in two governorates in 2018/2019 academic year. Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire for children and adolescents was used to assess the impact of primary headaches on the quality of life.

Results

One thousand and ninety-one questionnaires were completed by primary and middle school students of both genders; of whom 466 students (girls 321 (68.88%) were diagnosed with primary headache disorders with mean age 11.98 ± 2.03 years. In the month prior to the survey, the effect of the headache was variable. The students lost a mean of 1.99 ± 2.015 days of school while they could not perform their usual activities for a mean of 2.84 ± 4.28 days. Their parents lost a mean of 2 ± 2.03 days of work because of headaches of their children and parents prohibited 5.7% of the students to engage in any activity due to their headaches. Difficulties in concentrations were reported as never sometimes (39.1%), often (24.8%), and always (26%). Majority of the students (51.5%) experienced a feeling of sadness ranging from sometimes to always. Most of the students (67.3%) struggled to cope with the headache and 22.4% were never able to cope. Additionally, 19.4% of students reported they did not want others noticing their headache.

Conclusion

Primary headache disorder can have a significant impact on the quality of life in children. It can affect their engagement in activities and academic achievement. Implementing strategies to properly manage schoolchildren with primary headaches can have profound effects on their quality of life.
Migraine start, course and features over the cycle of combined hormonal contraceptive users with menstrual migraine – temporal relation to bleeding and hormone withdrawal: a prospective diary-based study
Authors: Merki-Feld Gabriele S. , Caveng Nina , Speiermann Gina , MacGregor E. Anne
Published: June 2020

Background

Many studies have described the features of menstrually-related migraines (MRM) in the natural cycle and the efficacy of prevention. MRM in combined hormonal contraceptive (CHC) users has scarcely been researched. Estrogen and progestin withdrawal in CHC users are both more abrupt and from higher hormone levels compared with the natural cycle. An advantage for prevention of MRM in CHC users is that the hormone withdrawal is predictable. It is unknown, whether the attacks during the hormone-free interval are associated with the hormone withdrawal or onset of bleeding. Improved understanding of this relation might contribute to better define and shorten the time interval for prevention.

Methods

For this prospective diary-based trial we collected migraine and bleeding data from CHC users with MRM in at least two of three cycles. We analyzed frequency of migraines over the whole CHC cycle. During the hormone-free phase the relation between onset of migraine and onset of bleeding was studied. We compared pain intensity and identified prolonged-migraine attacks during hormone use and the hormone-free phase.

Results

During the hormone-free interval the number of migraine days and the pain score/migraine day were significantly higher in comparison with the mean during hormone use. The prevalence of migraine attacks was fourfold on hormone-free days 3–6. Migraine typically started on days 1–4. Migraine in relation to bleeding mostly occurred on days − 1 to + 4. In 78% of the cycles the first migraine day occurred during bleeding days 1 ± 2 and 48% started on days − 1 and day 1. The predictability of the first bleeding day was very high.

Conclusion

The day of hormone-withdrawal migraine and the first bleeding day are highly predictable in CHC users. Migraine onset is mostly day − 1 and 1 of the bleeding and on days 1–4 of the hormone-free interval. Migraine attacks of CHC users in the hormone-free interval are severe and long lasting. Further trials are necessary to investigate if this knowledge can be used to optimise prevention.
Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice
Authors: Martin-Kenny Nicole , Bérubé Nathalie G.
Published: June 2020

Background

Alpha-thalassemia/mental retardation, X-linked, or ATRX, is an autism susceptibility gene that encodes a chromatin remodeler. Mutations of ATRX result in the ATR-X intellectual disability syndrome and have been identified in autism spectrum disorder (ASD) patients. The mechanisms by which ATRX mutations lead to autism and autistic-like behaviours are not yet known. To address this question, we generated mice with postnatal Atrx inactivation in excitatory neurons of the forebrain and performed a battery of behavioural assays that assess autistic-like behaviours.

Methods

Male and female mice with a postnatal conditional ablation of ATRX were generated using the Cre/lox system under the control of the αCaMKII gene promoter. These mice were tested in a battery of behavioural tests that assess autistic-like features. We utilized paradigms that measure social behaviour, repetitive, and stereotyped behaviours, as well as sensory gating. Statistics were calculated by two-way repeated measures ANOVA with Sidak’s multiple comparison test or unpaired Student’s t tests as indicated.

Results

The behaviour tests revealed no significant differences between Atrx-cKO and control mice. We identified sexually dimorphic changes in odor habituation and discrimination; however, these changes did not correlate with social deficits.

Conclusion

The postnatal knockout of Atrx in forebrain excitatory neurons does not lead to autism-related behaviours in male or female mice.
The effect of natural materials used as sediment remediation on phosphorus and nitrogen control in a mesocosm
Authors: Tang Mengjuan , Deng Qinghui , Li Xiaowen , Cao Xiuyun , Zhang Zhimin , Zhou Yiyong , Sun Qingye , Song Chunlei
Published: June 2020

Background

Achieving nitrogen (N) and phosphorus (P) control in sediment remediation projects by adding natural materials is receiving increasing attention. In this study, different natural materials, including iron-rich clay minerals, calcite, kaoline, sugarcane bagasse and Phragmites detritus, were applied to test their effects on N and P in a mesocosm experiment.

Results

Iron-rich clay minerals and Phragmites detritus had obvious advantages for P control; they resulted in almost undetectable levels of soluble reactive phosphorus (SRP) in the water column throughout the experiment. This finding can be explained by their strong P adsorption ability. The high level of available organic carbon in the sediment and water column after sugarcane bagasse addition provided enough electron donors for denitrification and dissimilatory nitrate reduction to ammonium (DNRA), which caused nitrate (NO3−-N) deficiency and ammonium (NH4+-N) accumulation in the water column. Additionally, this resulted in anaerobic conditions, further fuelling the release of P from iron-bound P induced by anoxia. Thus, the amount of sugarcane bagasse applied should be considered carefully in order to balance denitrification and DNRA as well as P releases. Calcite and Phragmites detritus are recommended as remediation materials for N removal based on their significant promotion of denitrification and limitation of DNRA, which resulted in low NO3−-N and NH4+-N levels. These results can be explained by the shifts in the functional microbial community composition and abundance after the addition of natural materials.

Conclusions

Iron-rich clay minerals and Phragmites detritus are promising sediment remediation materials for P immobilization due to their strong P adsorption ability. Taken together, the selection of sediment remediation materials should consider the N and P coupling relationship, to prevent NO3−-N removal from causing P leaching or NH4+-N accumulation.
Mercury distribution in the surface soil of China is potentially driven by precipitation, vegetation cover and organic matter
Authors: Zhang Zhao-Yang , Li Gang , Yang Lei , Wang Xin-Jun , Sun Guo-Xin
Published: June 2020

Background

Understanding the mechanism of Hg accumulation in soil, which is a net Hg sink, at a national scale is important for protecting the environment and improving food safety. The mercury (Hg) distribution in surface soil in China is quite uneven, with relatively high concentrations in southeastern China and low concentrations in northwestern China. The reason for this distribution is inconclusive, especially at the continental scale. In this study, the relative contributions of the key impact factors, including dry and wet deposition, soil organic matter (SOM) and solar radiation to soil Hg, were evaluated.

Results

Wet and dry deposition associated with precipitation and vegetation cover and emissions influenced by SOM are key factors controlling Hg distribution in surface soil. In southeastern China, high levels of wet deposition associated with the South Asia monsoon and dry deposition, enhanced by vegetation canopies, together with low levels of emissions caused by highly vegetated surfaces and solar radiation, are responsible for the high Hg levels in soil (> 0.08 mg/kg). In northeastern China, moderate levels of wet Hg deposition, high levels of dry deposition via throughfall and litterfall, low emissions due to weak solar radiation and high levels of SOM are responsible for high Hg accumulation in soil. In northwestern China, low levels of wet deposition, together with high emissions levels, low vegetation cover (bare soil) and SOM and strong solar radiation, contributed to the low Hg level in the surface soil (< 0.03 mg/kg).

Conclusions

We suggest that wet deposition derived from the Asian monsoon, dry deposition linked to vegetated surfaces and Hg emissions associated with vegetation cover, SOM and solar radiation play key roles in the soil Hg level in China. In other terrestrial environments worldwide, especially in regions with significantly high levels of wet deposition and high amounts of vegetation cover and soil SOM, high Hg concentrations may exist in the surface soil.
FSBC: fast string-based clustering for HT-SELEX data
Authors: Kato Shintaro , Ono Takayoshi , Minagawa Hirotaka , Horii Katsunori , Shiratori Ikuo , Waga Iwao , Ito Koichi , Aoki Takafumi
Published: June 2020

Background

The combination of systematic evolution of ligands by exponential enrichment (SELEX) and deep sequencing is termed high-throughput (HT)-SELEX, which enables searching aptamer candidates from a massive amount of oligonucleotide sequences. A clustering method is an important procedure to identify sequence groups including aptamer candidates for evaluation with experimental analysis. In general, aptamer includes a specific target binding region, which is necessary for binding to the target molecules. The length of the target binding region varies depending on the target molecules and/or binding styles. Currently available clustering methods for HT-SELEX only estimate clusters based on the similarity of full-length sequences or limited length of motifs as target binding regions. Hence, a clustering method considering the target binding region with different lengths is required. Moreover, to handle such huge data and to save sequencing cost, a clustering method with fast calculation from a single round of HT-SELEX data, not multiple rounds, is also preferred.

Results

We developed fast string-based clustering (FSBC) for HT-SELEX data. FSBC was designed to estimate clusters by searching various lengths of over-represented strings as target binding regions. FSBC was also designed for fast calculation with search space reduction from a single round, typically the final round, of HT-SELEX data considering imbalanced nucleobases of the aptamer selection process. The calculation time and clustering accuracy of FSBC were compared with those of four conventional clustering methods, FASTAptamer, AptaCluster, APTANI, and AptaTRACE, using HT-SELEX data (>15 million oligonucleotide sequences). FSBC, AptaCluster, and AptaTRACE could complete the clustering for all sequence data, and FSBC and AptaTRACE performed higher clustering accuracy. FSBC showed the highest clustering accuracy and had the second fastest calculation speed among all methods compared.

Conclusion

FSBC is applicable to a large HT-SELEX dataset, which can facilitate the accurate identification of groups including aptamer candidates.

Availability of data and materials

FSBC is available athttp://www.aoki.ecei.tohoku.ac.jp/fsbc/.
CoreSimul: a forward-in-time simulator of genome evolution for prokaryotes modeling homologous recombination
Authors: Bobay Louis-Marie
Published: June 2020

Background

Prokaryotes are asexual, but these organisms frequently engage in homologous recombination, a process that differs from meiotic recombination in sexual organisms. Most tools developed to simulate genome evolution either assume sexual reproduction or the complete absence of DNA flux in the population. As a result, very few simulators are adapted to model prokaryotic genome evolution while accounting for recombination. Moreover, many simulators are based on the coalescent, which assumes a neutral model of genomic evolution, and those are best suited for organisms evolving under weak selective pressures, such as animals and plants. In contrast, prokaryotes are thought to be evolving under much stronger selective pressures, suggesting that forward-in-time simulators are better suited for these organisms.

Results

Here, I present CoreSimul, a forward-in-time simulator of core genome evolution for prokaryotes modeling homologous recombination. Simulations are guided by a phylogenetic tree and incorporate different substitution models, including models of codon selection.

Conclusions

CoreSimul is a flexible forward-in-time simulator that constitutes a significant addition to the limited list of available simulators applicable to prokaryote genome evolution.
Genomic and transcriptomic survey of an endophytic fungus Calcarisporium arbuscula NRRL 3705 and potential overview of its secondary metabolites
Authors: Cheng Jin-Tao , Cao Fei , Chen Xin-Ai , Li Yong-Quan , Mao Xu-Ming
Published: June 2020

Background

Secondary metabolites as natural products from endophytic fungi are important sources of pharmaceuticals. However, there is currently little understanding of endophytic fungi at the omics levels about their potential in secondary metabolites. Calcarisporium arbuscula, an endophytic fungus from the fruit bodies of Russulaceae, produces a variety of secondary metabolites with anti-cancer, anti-nematode and antibiotic activities. A comprehensive survey of the genome and transcriptome of this endophytic fungus will help to understand its capacity to biosynthesize secondary metabolites and will lay the foundation for the development of this precious resource.

Results

In this study, we reported the high-quality genome sequence of C. arbuscula NRRL 3705 based on Single Molecule Real-Time sequencing technology. The genome of this fungus is over 45 Mb in size, larger than other typical filamentous fungi, and comprises 10,001 predicted genes, encoding at least 762 secretory-proteins, 386 carbohydrate-active enzymes and 177 P450 enzymes. 398 virulence factors and 228 genes related to pathogen-host interactions were also predicted in this fungus. Moreover, 65 secondary metabolite biosynthetic gene clusters were revealed, including the gene cluster for the mycotoxin aurovertins. In addition, several gene clusters were predicted to produce mycotoxins, including aflatoxin, alternariol, destruxin, citrinin and isoflavipucine. Notably, two independent gene clusters were shown that are potentially involved in the biosynthesis of alternariol. Furthermore, RNA-Seq assays showed that only expression of the aurovertin gene cluster is much stronger than expression of the housekeeping genes under laboratory conditions, consistent with the observation that aurovertins are the predominant metabolites. Gene expression of the remaining 64 gene clusters for compound backbone biosynthesis was all lower than expression of the housekeeping genes, which partially explained poor production of other secondary metabolites in this fungus.

Conclusions

Our omics data, along with bioinformatics analysis, indicated that C. arbuscula NRRL 3705 contains a large number of biosynthetic gene clusters and has a huge potential to produce a profound number of secondary metabolites. This work also provides the basis for development of endophytic fungi as a new resource of natural products with promising biological activities.
Understanding the early cold response mechanism in IR64 indica rice variety through comparative transcriptome analysis
Authors: Dasgupta Pratiti , Das Abhishek , Datta Sambit , Banerjee Ishani , Tripathy Sucheta , Chaudhuri Shubho
Published: June 2020

Background

Cellular reprogramming in response to environmental stress involves alteration of gene expression, changes in the protein and metabolite profile for ensuring better stress management in plants. Similar to other plant species originating in tropical and sub-tropical areas,indicarice is highly sensitive to low temperature that adversely affects its growth and grain productivity. Substantial work has been done to understand cold induced changes in gene expression in rice plants. However, adequate information is not available for early gene expression, especially inindicavariety. Therefore, a transcriptome profile was generated for cold shock treated seedlings of IR64 variety to identify early responsive genes.

Results

The functional annotation of early DEGs shows enrichment of genes involved in altered membrane rigidity and electrolytic leakage, the onset of calcium signaling, ROS generation and activation of stress responsive transcription factors in IR64. Gene regulatory network suggests that cold shock induced Ca2+ signaling activates DREB/CBF pathway and other groups of transcription factors such as MYB, NAC and ZFP; for activating various cold-responsive genes. The analysis also indicates that cold induced signaling proteins like RLKs, RLCKs, CDPKs and MAPKK and ROS signaling proteins. Further, several late-embryogenesis-abundant (LEA), dehydrins and low temperature-induced-genes were upregulated under early cold shock condition, indicating the onset of water-deficit conditions. Expression profiling in different high yielding cultivars shows high expression of cold-responsive genes in Heera and CB1indicavarieties. These varieties show low levels of cold induced ROS production, electrolytic leakage and high germination rate post-cold stress, compared to IR36 and IR64. Collectively, these results suggest that these varieties may have improved adaptability to cold stress.

Conclusions

The results of this study provide insights about early responsive events inOryza sativa l.ssp. indicacv IR64 in response to cold stress. Our data shows the onset of cold response is associated with upregulation of stress responsive TFs, hydrophilic proteins and signaling molecules, whereas, the genes coding for cellular biosynthetic enzymes, cell cycle control and growth-related TFs are downregulated. This study reports that the generation of ROS is integral to the early response to trigger the ROS mediated signaling events during later stages.
Transcriptome profiling of venom gland from wasp species: de novo assembly, functional annotation, and discovery of molecular markers
Authors: Tan Junjie , Wang Wenbo , Wu Fan , Li Yunming , Fan Quanshui
Published: June 2020

Background

Vespa velutina, one of the most aggressive and fearful wasps in China, can cause grievous allergies and toxic reactions, leading to organ failure and even death. However, there is little evidence on molecular data regarding wasps. Therefore, we aimed to provide an insight into the transcripts expressed in the venom gland of wasps.

Results

In our study, high-throughput RNA sequencing was performed using the venom glands of four wasp species. First, the mitochondrial cytochrome C oxidase submit I (COI) barcoding and the neighbor joining (NJ) tree were used to validate the unique identity and lineage of each individual species. After sequencing, a total of 127,630 contigs were generated and 98,716 coding domain sequences (CDS) were predicted from the four species. The Gene ontology (GO) enrichment analysis of unigenes revealed their functional role in important biological processes (BP), molecular functions (MF) and cellular components (CC). In addition, c-type, p1 type, p2 type and p3 type were the most commonly found simple sequence repeat (SSR) types in the four species of wasp transcriptome. There were differences in the distribution of SSRs and single nucleotide polymorphisms (SNPs) among the four wasp species.

Conclusions

The transcriptome data generated in this study will improve our understanding on bioactive proteins and venom-related genes in wasp venom gland and provide a basis for pests control and other applications. To our knowledge, this is the first study on the identification of large-scale genomic data and the discovery of microsatellite markers from V. tropica ducalis and V. analis fabricius.
NeuroConstruct-based implementation of structured-light stimulated retinal circuitry
Authors: Elbaz Miriam , Buterman Rachel , Ezra Tsur Elishai
Published: June 2020

Background

Retinal circuitry provides a fundamental window to neural networks, featuring widely investigated visual phenomena ranging from direction selectivity to fast detection of approaching motion. As the divide between experimental and theoretical visual neuroscience is fading, neuronal modeling has proven to be important for retinal research. In neuronal modeling a delicate balance is maintained between bio-plausibility and model tractability, giving rise to myriad modeling frameworks. One biologically detailed framework for neuro modeling is NeuroConstruct, which facilitates the creation, visualization and analysis of neural networks in 3D.

Results

Here, we extended NeuroConstruct to support the generation of structured visual stimuli, to feature different synaptic dynamics, to allow for heterogeneous synapse distribution and to enable rule-based synaptic connectivity between cell populations. We utilized this framework to demonstrate a simulation of a dense plexus of biologically realistic and morphologically detailed starburst amacrine cells. The amacrine cells were connected to a ganglion cell and stimulated with expanding and collapsing rings of light.

Conclusions

This framework provides a powerful toolset for the investigation of the yet elusive underlying mechanisms of retinal computations such as direction selectivity. Particularly, we showcased the way NeuroConstruct can be extended to support advanced field-specific neuro-modeling.
The challenges in data integration – heterogeneity and complexity in clinical trials and patient registries of Systemic Lupus Erythematosus
Authors: Le Sueur Helen , Bruce Ian N. , Geifman Nophar ,   on behalf of the MASTERPLANS Consortium
Published: June 2020

Background

Individual clinical trials and cohort studies are a useful source of data, often under-utilised once a study has ended. Pooling data from multiple sources could increase sample sizes and allow for further investigation of treatment effects; even if the original trial did not meet its primary goals. Through the MASTERPLANS (MAximizing Sle ThERapeutic PotentiaL by Application of Novel and Stratified approaches) national consortium, focused on Systemic Lupus Erythematosus (SLE), we have gained valuable real-world experiences in aligning, harmonising and combining data from multiple studies and trials, specifically where standards for data capture, representation and documentation, were not used or were unavailable. This was not without challenges arising both from the inherent complexity of the disease and from differences in the way data were captured and represented across different studies.

Main body

Data were, unavoidably, aligned by hand, matching up equivalent or similar patient variables across the different studies. Heterogeneity-related issues were tackled and data were cleaned, organised and combined, resulting in a single large dataset ready for analysis. Overcoming these hurdles, often seen in large-scale data harmonization and integration endeavours of legacy datasets, was made possible within a realistic timescale and limited resource by focusing on specific research questions driven by the aims of MASTERPLANS. Here we describe our experiences tackling the complexities in the integration of large, diverse datasets, and the lessons learned.

Conclusions

Harmonising data across studies can be complex, and time and resource consuming. The work carried out here highlights the importance of using standards for data capture, recording, and representation, to facilitate both the integration of large datasets and comparison between studies. Where standards are not implemented at the source harmonisation is still possible by taking a flexible approach, with systematic preparation, and a focus on specific research questions.
Organised and opportunistic prevention in primary health care: estimation of missed opportunities by population based health interview surveys in Hungary
Authors: Sándor János , Tokaji Ildikó , Harsha Nouh , Papp Magor , Ádány Róza , Czifra Árpád
Published: June 2020

Background

Improvement of preventive services for adults can be achieved by opportunistic or organised methods in primary care. The unexploited opportunities of these approaches were estimated by our investigation.

Methods

Data from the Hungarian implementation of European Health Interview Surveys in 2009 (N = 4709) and 2014 (N = 5352) were analysed. Proportion of subjects used interventions in target group (screening for hypertension and diabetes mellitus, and influenza vaccination) within a year were calculated. Taking into consideration recommendations for the frequency of intervention, numbers of missed interventions among patients visited a general practitioner in a year and among patients did not visit a general practitioner in a year were calculated in order to describe missed opportunities that could be utilised by opportunistic or organised approaches. Numbers of missed interventions were estimated for the entire population of the country and for an average-sized general medical practice.

Results

Implementation ratio were 66.8% for blood pressure measurement among subjects above 40 years and free of diagnosed hypertension; 63.5% for checking blood glucose among adults above 45 and overweighed and free of diagnosed diabetes mellitus; and 19.1% for vaccination against seasonal influenza. There were 4.1 million interventions implemented a year in Hungary, most of the (3.8 million) among adults visited general practitioner in a year. The number of missed interventions was 4.5 million a year; mostly (3.4 million) among persons visited general practitioner in a year. For Hungary, the opportunistic and organised missed opportunities were estimated to be 561,098, and 1,150,321 for hypertension screening; 363,270, and 227,543 for diabetes mellitus screening; 2,784,072, and 380,033 for influenza vaccination among the < 60 years old high risk subjects, and 3,029,700 and 494,150 for influenza vaccination among more than 60 years old adults, respectively. By implementing all missed services, the workload in an average-sized general medical practice would be increased by 12–13 opportunistic and 4–5 organised interventions a week.

Conclusions

The studied interventions are much less used than recommended. The opportunistic missed opportunities is prevailing for influenza vaccination, and the organised one is for hypertension screening. The two approaches have similar significance for diabetes mellitus screening.
Self-reported generalised pruritus among community-dwelling older adults in Malaysia
Authors: Yong Shin Shen , Kwan Zhenli , Ch’ng Chin Chwen , Yong Adrian Sze Wai , Tan Leng Leng , Han Winn Hui , Kamaruzzaman Shahrul Bahyah , Chin Ai-Vyrn , Tan Maw Pin
Published: June 2020

Background

The ageing skin is more susceptible to pruritic dermatoses, which are associated with adverse psychosocial effects and reduced quality of life among older adults. This cross-sectional study aimed to identify the burden of pruritus and factors associated with its presence and severity among older adults recruited to the Malaysian Elders Longitudinal Research study.

Methods

Seven hundred seventy individuals aged 55 years (lower age limit) and above were interviewed as to whether they experienced pruritus during the preceding week and the locations involved if present. The association between generalised pruritus, sleep quality, and major systemic risk factors were explored.

Results

5.97% of respondents reported generalised pruritus. Generalised pruritus was associated with poorer sleep quality, with Pittsburgh Sleep Quality Index score above 6. Mean haemoglobin level was lower in subjects with generalised pruritus (13.14 g/dL) but there was no significant difference in the frequency of generalised pruritus and severe generalized pruritus between subjects with clinically defined anaemia. Also, there were no significant associations between other major systemic risk factors and generalised pruritus in this population-based study. There was no association between generalised pruritus with depression, anxiety or stress.

Conclusion

The negative effect of pruritus on sleep quality suggests a possible deleterious effect of pruritus on health and quality of life. Further prospective research on the longer-term effects of pruritus on health status is now warranted.

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Ancestry effects on type 2 diabetes genetic risk inference in Hispanic/Latino populations
Authors: Chande Aroon T. , Rishishwar Lavanya , Conley Andrew B. , Valderrama-Aguirre Augusto , Medina-Rivas Miguel A. , Jordan I. King
Published: June 2020

Background

Hispanic/Latino (HL) populations bear a disproportionately high burden of type 2 diabetes (T2D). The ability to predict T2D genetic risk using polygenic risk scores (PRS) offers great promise for improved screening and prevention. However, there are a number of complications related to the accurate inference of genetic risk across HL populations with distinct ancestry profiles. We investigated how ancestry affects the inference of T2D genetic risk using PRS in diverse HL populations from Colombia and the United States (US). In Colombia, we compared T2D genetic risk for the Mestizo population of Antioquia to the Afro-Colombian population of Chocó, and in the US, we compared European-American versus Mexican-American populations.

Methods

Whole genome sequences and genotypes from the 1000 Genomes Project and the ChocoGen Research Project were used for genetic ancestry inference and for T2D polygenic risk score (PRS) calculation. Continental ancestry fractions for HL genomes were inferred via comparison with African, European, and Native American reference genomes, and PRS were calculated using T2D risk variants taken from multiple genome-wide association studies (GWAS) conducted on cohorts with diverse ancestries. A correction for ancestry bias in T2D risk inference based on the frequencies of ancestral versus derived alleles was developed and applied to PRS calculations in the HL populations studied here.

Results

T2D genetic risk in Colombian and US HL populations is positively correlated with African and Native American ancestry and negatively correlated with European ancestry. The Afro-Colombian population of Chocó has higher predicted T2D risk than Antioquia, and the Mexican-American population has higher predicted risk than the European-American population. The inferred relative risk of T2D is robust to differences in the ancestry of the GWAS cohorts used for variant discovery. For trans-ethnic GWAS, population-specific variants and variants with same direction effects across populations yield consistent results. Nevertheless, the control for bias in T2D risk prediction confirms that explicit consideration of genetic ancestry can yield more reliable cross-population genetic risk inferences.

Conclusions

T2D associations that replicate across populations provide for more reliable risk inference, and modeling population-specific frequencies of ancestral and derived risk alleles can help control for biases in PRS estimation.
Oxytocin receptor gene, childhood maltreatment and borderline personality disorder features among male inmates in China
Authors: Zhang Min , Liu Na , Chen Haocheng , Zhang Ning
Published: June 2020

Background

Borderline personality disorder (BPD) is caused by a variety of biological and environmental factors. Accumulating evidence suggests that childhood maltreatment is a risk environmental factor in the development of BPD, but research on the genetic pathology of BPD is still in its early stages, and very little is known about the oxytocin receptor (OXTR) gene. The purpose of this study is to further explore the interactive effects between OXTR gene polymorphisms and childhood maltreatment on BPD risk.

Methods

Among the 1804 Chinese Han male inmates, 765 inmates who had BPD or antisocial personality disorder (ASPD) or highly impulsive or violent crime were considered as high-risk inmates and included in this study. Childhood maltreatment, BPD, antisocial personality disorder (ASPD) and impulsivity were measured by self-reported questionnaires. Peripheral venous blood was collected for the genotype test.

Results

Analyses revealed that the BP group (inmates with BPD features) had higher rs53576 AA genotype frequency and rs237987 AA genotype frequency than the non-BP group, while the statistical significances were lost after Bonferroni correction. Total childhood maltreatment score, emotional abuse and neglect could positively predict BPD risk. Among the high-risk samples, rs53576 GG genotype carriers had higher BPD scores at higher levels of physical abuse and sexual abuse and had lower BPD scores at lower levels of physical abuse and sexual abuse.

Conclusions

The findings suggest that the interaction between OXTR gene variations and childhood maltreatment is an important mechanism for the development of BPD. The moderating role of the OXTR gene provides evidence for gene plasticity.
Evaluation of serum amino acids and non-enzymatic antioxidants in drug-naïve first-episode major depressive disorder
Authors: Islam Md. Rabiul , Ali Samia , Karmoker James Regun , Kadir Mohammad Fahim , Ahmed Maizbha Uddin , Nahar Zabun , Islam Sardar Mohammad Ashraful , Islam Mohammad Safiqul , Hasnat Abul , Islam Md. Saiful
Published: June 2020

Background

The alterations of biological markers are thought to be effective tools to understand the pathophysiology and management of major depressive disorder (MDD). A lot of researches has implied many markers for depression, but any of them fully discovered the association between the markers and depression. The present study investigated the serum levels of amino acids and non-enzymatic antioxidants in major depression, and also explained their association with depression.

Methods

This study examined 247 MDD patients and 248 healthy controls (HCs) matched by age and sex. The Hamilton Depression Rating Scale (Ham-D) was used to all the participants to measure the severity of depression. Quantification of serum amino acids, vitamin A and E were carried out using the HPLC system whereas vitamin C levels were measured by UV-spectrophotometer. All the statistical analysis was performed by SPSS statistical software (version 23.0). The independent sample t-test, the Mann-Whitney U test, and the Fisher’s exact test were applied to detect the group differences where a Bonferroni correction applied to thepvalue.

Results

It was observed that serum levels of four amino acids (methionine, phenylalanine, tryptophan, and tyrosine) along with three non-enzymatic antioxidants (vitamin A, E, and C) were significantly dropped in MDD patients compared to HCs (Cohen’s d (d): − 0.45, − 0.50, − 0.68, − 0.21, − 0.27, − 0.65, and − 0.24, respectively). Furthermore, Ham-D scores of cases were negatively correlated with serum levels of methionine (r = − 0.155,p = 0.015) and tyrosine (r = − 0.172,p = 0.007).

Conclusion

The present study suggests that lowered serum methionine, phenylalanine, tryptophan, tyrosine, and non-enzymatic antioxidants are associated with depression. The reduction of these parameters in MDD patients may be the consequence, and not the cause, of major depression.
GUIP1: a R package for dose escalation strategies in phase I cancer clinical trials
Authors: Dinart D. , Fraisse J. , Tosi D. , Mauguen A. , Touraine C. , Gourgou S. , Le Deley M. C. , Bellera C. , Mollevi C.
Published: June 2020

Background

The main objective of phase I cancer clinical trials is to identify the maximum tolerated dose, usually defined as the highest dose associated with an acceptable level of severe toxicity during the first cycle of treatment. Several dose-escalation designs based on mathematical modeling of the dose-toxicity relationship have been developed. The main ones are: the continual reassessment method (CRM), the escalation with overdose control (EWOC) method and, for late-onset and cumulative toxicities, the time-to-event continual reassessment method (TITE-CRM) and the time-to-event escalation with overdose control (TITE-EWOC) methods. The objective of this work was to perform a user-friendly R package that combines the latter model-guided adaptive designs.

Results

GUIP1 is an R Graphical User Interface for dose escalation strategies in Phase 1 cancer clinical trials. It implements the CRM (based on Bayesian or maximum likelihood estimation), EWOC and TITE-CRM methods using the dfcrm and bcrm R packages, while the TITE-EWOC method has been specifically developed. The program is built using the TCL/TK programming language, which can be compiled via R software libraries (tcltk, tkrplot, tcltk2). GUIP1 offers the possibility of simulating and/or conducting and managing phase I clinical trials in real-time using file management options with automatic backup of study and/or simulation results.

Conclusions

GUIP1 is implemented using the software R, which is widely used by statisticians in oncology. This package simplifies the use of the main model-based dose escalation methods and is designed to be fairly simple for beginners in R. Furthermore, it offers multiple possibilities such as a full traceability of the study. By including multiple innovative adaptive methods in a free and user-friendly program, we hope that GUIP1 will promote and facilitate their use in designing future phase I cancer clinical trials.
Use of the theoretical domains framework and behaviour change wheel to develop a novel intervention to improve the quality of multidisciplinary cancer conference decision-making
Authors: Fahim Christine , Acai Anita , McConnell Meghan M. , Wright Frances C. , Sonnadara Ranil R. , Simunovic Marko
Published: June 2020

Background

Multidisciplinary Cancer Conferences (MCCs) are prospective meetings involving cancer specialists to discuss treatment plans for patients with cancer. Despite reported gaps in MCC quality, there have been few efforts to improve its functioning. The purpose of this study was to use theoretically-rooted knowledge translation (KT) theories and frameworks to inform the development of a strategy to improve MCC decision-making quality.

Methods

A multi-phased approach was used to design an intervention titled the KT-MCC Strategy. First, key informant interviews framed using the Theoretical Domains Framework (TDF) were conducted with MCC participants to identify barriers and facilitators to optimal MCC decision-making. Second, identified TDF domains were mapped to corresponding strategies using the COM-B Behavior Change Wheel to develop the KT-MCC Strategy. Finally, focus groups with MCC participants were held to confirm acceptability of the proposed KT-MCC Strategy.

Results

Data saturation was reached at n = 21 interviews. Twenty-seven barrier themes and 13 facilitator themes were ascribed to 11 and 10 TDF domains, respectively. Differences in reported barriers by physician specialty were observed. The resulting KT-MCC Strategy included workshops, chair training, team training, standardized intake forms and a synoptic discussion checklist, and, audit and feedback. Focus groups (n = 3, participants 18) confirmed the acceptability of the identified interventions.

Conclusion

Myriad factors were found to influence MCC decision making. We present a novel application of the TDF and COM-B to the context of MCCs. We comprehensively describe the barriers and facilitators that impact MCC decision making and propose strategies that may positively impact the quality of MCC decision making.
New targeted approaches for epigenetic age predictions
Authors: Han Yang , Franzen Julia , Stiehl Thomas , Gobs Michael , Kuo Chao-Chung , Nikolić Miloš , Hapala Jan , Koop Barbara Elisabeth , Strathmann Klaus , Ritz-Timme Stefanie , Wagner Wolfgang
Published: June 2020

Background

Age-associated DNA methylation changes provide a promising biomarker for the aging process. While genome-wide DNA methylation profiles enable robust age-predictors by integration of many age-associated CG dinucleotides (CpGs), there are various alternative approaches for targeted measurements at specific CpGs that better support standardized and cost-effective high-throughput analysis.

Results

In this study, we utilized 4647 Illumina BeadChip profiles of blood to select CpG sites that facilitate reliable age-predictions based on pyrosequencing. We demonstrate that the precision of DNA methylation measurements can be further increased with droplet digital PCR (ddPCR). In comparison, bisulfite barcoded amplicon sequencing (BBA-seq) gave slightly lower correlation between chronological age and DNA methylation at individual CpGs, while the age-predictions were overall relatively accurate. Furthermore, BBA-seq data revealed that the correlation of methylation levels with age at neighboring CpG sites follows a bell-shaped curve, often associated with a CTCF binding site. We demonstrate that within individual BBA-seq reads the DNA methylation at neighboring CpGs is not coherently modified, but reveals a stochastic pattern. Based on this, we have developed a new approach for epigenetic age predictions based on the binary sequel of methylated and non-methylated sites in individual reads, which reflects heterogeneity in epigenetic aging within a sample.

Conclusion

Targeted DNA methylation analysis at few age-associated CpGs by pyrosequencing, BBA-seq, and particularly ddPCR enables high precision of epigenetic age-predictions. Furthermore, we demonstrate that the stochastic evolution of age-associated DNA methylation patterns in BBA-seq data enables epigenetic clocks for individual DNA strands.
Knockdown of ALPK2 inhibits the development and progression of Ovarian Cancer
Authors: Zhu Xiaogang , Yan Siqi , Xiao Songshu , Xue Min
Published: June 2020

Background

Alpha protein kinase 2 (ALPK2) was known to play a vital role in cancer by regulating cell cycle and DNA repair. Ovarian cancer (OC) is one of the most lethal malignancies in the female reproductive system. The emphasis of this study is to explore the role of ALPK2 in OC.

Methods

Firstly, tumor and normal tissues were collected for detecting expression of ALPK2 in OC. Lentivirus-mediated shRNA knockdown of ALPK2 was used to construct OC cell model, which was verified by qRT-PCR and Western blot. The cell proliferation was detected by MTT, cell cycle and apoptosis were measured through flow cytometry. Wound-healing assay was conducted to detect the migration of OC cells.

Results

It was proved that the expression of ALPK2 in OC tissues was significantly higher than that in normal ovarian tissues. Moreover, knockdown of ALPK2 could inhibit proliferation, migration and promote apoptosis, arrested cell cycle of OC cells. It was also found that ALPK2 knockdown inhibited tumor growth in xenograft mice in vivo. Furthermore, ALPK2 was involved in OC cells via regulating EMT-related proteins (N-cadherin, Vimentin and Snail), inhibiting apoptosis-related proteins (Bcl-2, Bcl-w, HSP27, HSP60, IGF-I, IGF-1sR, Survivin and XIAP), as well as the regulation of downstream pathways (Akt, p-Akt, Cyclin D1, CDK6 and PIK3CA).

Conclusions

In conclusion, ALPK2 might serve as an optional target for prognosis and therapeutic of OC patients.
Untargeted LC–MS/MS analysis reveals metabolomics feature of osteosarcoma stem cell response to methotrexate
Authors: Wang Feng , Zhang Zhiyu , Li Qin , Yu Tao , Ma Chengbin
Published: June 2020

Background

Cancer stem cell (CSC) is identified in osteosarcoma (OS) and considered resistant to chemotherapeutic agents. However, the mechanism of osteosarcoma stem cell (OSC) resistant to chemotherapy remains debatable and vague, and the metabolomics feature of OSC is not clarified.

Materials and methods

OSC was isolated by using sphere forming assay and identified. Untargeted LC–MS/MS analysis was performed to reveal the metabolomics feature of OSC and underlying mechanisms of OSC resistant to methotrexate (MTX).

Results

OSC was efficiently isolated and identified from human OS 143B and MG63 cell lines with enhanced chemo-resistance to MTX. The untargeted LC–MS analysis revealed that OSC showed differential metabolites and perturbed signaling pathways, mainly involved in metabolisms of fatty acid, amino acid, carbohydrate metabolism and nucleic acid. After treated with MTX, metabolomics feature of OSC was mainly involved metabolisms of amino acid, fatty acid, energy and nucleic acid. Moreover, compared with their parental OS cells response to MTX, the differential metabolites and perturbed signaling pathways were mainly involved in metabolism of amino acid, fatty acid and nucleic acid. What’s more, Rap1 signaling pathway and Ras signaling pathway were involved in OS cells and their SCs response to MTX.

Conclusion

Sphere-forming assay was able to efficiently isolate OSC from human OS cell lines and the untargeted LC–MS/MS analysis was suggested a sufficient methodology to investigate metabolomics features of OS cells and OSCs. Moreover, the metabolomics features of OSCs response to MTX might reveal a further understanding of chemotherapeutic resistance in OS.