bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of the histone demethylase, KDM5B, directly induces re-expression of tumor suppressor protein HEXIM1 in cancer cells
Authors: Montano Monica M. , Yeh I-Ju , Chen Yinghua , Hernandez Chris , Kiselar Janna G. , de la Fuente Maria , Lawes Adriane M. , Nieman Marvin T. , Kiser Philip D. , Jacobberger James , Exner Agata A. , Lawes Matthew C. 
Published: December 2019

Abstract
Background
The tumor suppressor actions of hexamethylene bis-acetamide (HMBA)-inducible protein 1 (HEXIM1) in the breast, prostate, melanomas, and AML have been reported by our group and others. Increased HEXIM1 expression caused differentiation and inhibited proliferation and metastasis of cancer cells. Historically, HEXIM1 has been experimentally induced with the hybrid polar compound HMBA, but HMBA is a poor clinical candidate due to lack of a known target, poor pharmacological properties, and unfavorable ADMETox characteristics. Thus, HEXIM1 induction is an intriguing therapeutic approach to cancer treatment, but requires better chemical tools than HMBA.

Methods
We identified and verified KDM5B as a target of HEXIM1 inducers using a chemical proteomics approach, biotin–NeutrAvidin pull-down assays, surface plasmon resonance, and molecular docking. The regulation of HEXIM1 by KDM5B and KDM5B inhibitors was assessed using chromatin immunoprecipitation assays, RT-PCR, western blotting, and depletion of KDM5B with shRNAs. The regulation of breast cancer cell phenotype by KDM5B inhibitors was assessed using western blots, differentiation assays, proliferation assays, and a mouse model of breast cancer metastasis. The relative role of HEXIM1 in the action of KDM5B inhibitors was determined by depleting HEXIM1 using shRNAs followed by western blots, differentiation assays, and proliferation assays.

Results
We have identified a highly druggable target, KDM5B, which is inhibited by small molecule inducers of HEXIM1. RNAi knockdown of KDM5B induced HEXIM1 expression, thus validating the specific negative regulation of tumor suppressor HEXIM1 by the H3K4me3/2 demethylase KDM5B. Known inhibitors of KDM5B were also able to induce HEXIM1 expression, inhibit cell proliferation, induce differentiation, potentiate sensitivity to cancer chemotherapy, and inhibit breast tumor metastasis.

Conclusion
HMBA and 4a1 induce HEXIM1 expression by inhibiting KDM5B. Upregulation of HEXIM1 expression levels plays a critical role in the inhibition of proliferation of breast cancer cells using KDM5B inhibitors. Based on the novel molecular scaffolds that we identified which more potently induced HEXIM1 expression and data in support that KDM5B is a target of these compounds, we have opened up new lead discovery and optimization directions.
The distributions of protein coding genes within chromatin domains in relation to human disease
Authors: Muro Enrique M. , Ibn-Salem Jonas , Andrade-Navarro Miguel A. 
Published: December 2019

AbstractBackgroundOur understanding of the nuclear chromatin structure has increased hugely during the last years mainly as a consequence of the advances in chromatin conformation capture methods like Hi-C. The unprecedented resolution of genome-wide interaction maps shows functional consequences that extend the initial thought of an efficient DNA packaging mechanism: gene regulation, DNA repair, chromosomal translocations and evolutionary rearrangements seem to be only the peak of the iceberg. One key concept emerging from this research is the topologically associating domains (TADs) whose functional role in gene regulation and their association with disease is not fully untangled.ResultsWe report that the lower the number of protein coding genes inside TADs, the higher the tendency of those genes to be associated with disease (p-value = 4 × $$10^{-54}$$10-54). Moreover, housekeeping genes are less associated with disease than other genes. Accordingly, they are depleted in TADs containing less than three protein coding genes (p-value = 3.9 × $$10^{-34}$$10-34). We observed that TADs with higher ratios of enhancers versus genes contained higher numbers of disease-associated genes. We interpret these results as an indication that sharing enhancers among genes reduces their involvement in disease. Larger TADs would have more chances to accommodate many genes and select for enhancer sharing along evolution.ConclusionsGenes associated with human disease do not distribute randomly over the TADs. Our observations suggest general rules that confer functional stability to TADs, adding more evidence to the role of TADs as regulatory units.
A pediatric cancer patient with suspected chemical coping following high-dose opioid therapy: a case report
Authors: Miura Mototsugu , Tsuruga Kenkichi , Morimoto Yuji 
Published: November 2019

Abstract
Background
Chemical coping is an inappropriate method for dealing with stress through the use of opioids; it is considered the stage prior to abuse and dependence. In patients with cancer, it is important to evaluate the risk of chemical coping when using opioids. There are some pediatric opioid use-related tolerances and addictions; however, no mention of chemical coping has been found.

Case presentation
We present a case of an 11-year-old Japanese boy with acute lymphocytic leukemia. After transplantation, he complained of abdominal and articular pain, which are considered as symptoms of graft-versus-host disease; thus, opioid therapy was initiated, and the dose was gradually increased for pain management, resulting in a high dose of 2700 μg/day of fentanyl (4200–4700 μg/day including the rescue dose). After switching from fentanyl to oxycodone injections, he continued to experience pain, and there was no change in the frequency of oxycodone rescue doses. Physically, his pain was considered to have alleviated; thus, there was the possibility of mental anxiety resulting in the lowering of pain threshold and the possibility of chemical coping. Mental anxiety and stress with progress through schooling was believed to have resulted in chemical coping; thus, efforts were made to reduce the boy’s anxiety, and opioid education was provided. However, dose reduction was challenging. Ultimately, with guidance from medical care providers, the opioid dose was reduced, and the patient was successfully weaned off opioids.

Conclusions
When chemical coping is suspected in pediatric patients, after differentiating from pseudo-addiction, it might be necessary to restrict the prescription for appropriate use and to provide opioid education while taking into consideration the emotional background of the patient that led to chemical coping.
Detection of severe hypertension in a patient with neurofibromatosis type 1 during anesthesia induction: a case report
Authors: Wang Juan , Wei Guohua , Wang Zhongyun , Huang He 
Published: November 2019

Abstract
Background
Neurofibromatosis type 1 has a higher prevalence of pheochromocytoma and paraganglioma than the general population: 1.0–5.7% versus 0.2–0.6%. Currently, there are no generally accepted guidelines for screening for pheochromocytoma and paragangliomas in asymptomatic patients with neurofibromatosis type 1.

Case presentation
Severe hypertension developed during anesthesia induction in our patient, a 44-year-old Chinese man with neurofibromatosis type 1. We screened for catecholamine level after glioma resection, and the patient was diagnosed with combined pheochromocytoma and paraganglioma.

Conclusions
A delay in diagnosis or lack of a diagnosis in pheochromocytoma and paraganglioma may increase the perioperative morbidity and mortality risk due to excess catecholamine secretion. Therefore, routine pheochromocytoma and paraganglioma screening preoperatively in patients with neurofibromatosis type 1 is very important.
Clitoral sizes and anogenital distances in term newborns in Nigeria
Authors: Adekoya Adesola Olubunmi , Fetuga Musili Bolanle , Jarrett Olumide Olatokunbo , Ogunlesi Tinuade Adetutu , Chanoine Jean-Pierre , Adekoya Abiola Omobonike 
Published: December 2019

Abstract
Background
Previous studies suggest significant ethnic and racial differences in clitoral sizes and anogenital distances in the newborn. This study aimed to document normative data on clitoral sizes and anogenital distances of apparently normal term female infants in Sagamu.

Methods
The study was a multi-center, cross-sectional descriptive research carried out among 317 female term infants within the first 72 h of life. Interviewer-based questionnaire was applied to obtain sociodemographic data, pregnancy and birth history. A sliding digital caliper was used for measurement. Data analysis was with SPSS version 20.0.

Results
The mean clitoral length was 6.7 ± 1.6 mm while the mean clitoral width was 5.6 ± 0.8 mm. The mean fourchette-clitoris distance, anus-clitoris distance and anus-fourchette distance were 21.9 ± 2.1 mm, 35.5 ± 2.5 mm and 17.0 ± 2.6 mm respectively. The anus-clitoris and anus-fourchette distances significantly correlated with the anthropometric parameters while the clitoral measurements did not.

Conclusion
The mean values recorded in this study were higher than observed in most previous studies. This simple, affordable and non-invasive evaluation could aid early diagnosis and treatment of female infants with potentially harmful conditions such as congenital adrenal hyperplasia.
What are the impacts of within-field farmland management practices on the flux of greenhouse gases from arable cropland in temperate regions? A systematic map protocol
Authors: Collins Alexandra M. , Haddaway Neal R. , Macura Biljana , Thomas James , Randall Nicola , Taylor Jessica J. , Cooke Steve , Gilbert Alyssa 
Published: December 2019

Abstract
Background
Reducing greenhouse gas emissions is a vital step in limiting climate change and meeting the goals outlined in the COP 21 Paris Agreement of 2015. Studies have suggested that agriculture accounts for around 11% of total greenhouse gas emissions and the industry has a significant role in meeting international and national climate change reduction objectives. However, there is currently little consensus on the mechanisms that regulate the production and assimilation of greenhouse gases in arable land and the practical factors that affect the process. Practical advice for farmers is often overly general, and models based on the amount of nitrogen fertiliser applied, for example, are used despite a lack of knowledge of how local conditions affect the process, such as the importance of humus content and soil types. Here, we propose a systematic map of the evidence relating to the impact on greenhouse gas flux from the agricultural management of arable land in temperate regions.

Methods
Using established methods for systematic mapping in environmental sciences we will search for, collate and catalogue research studies relating to the impacts of farming in temperate systems on greenhouse gas emissions. We will search 6 bibliographic databases using a tested search string, and will hand search a web-based search engine and a list of organisational web sites. Furthermore, evidence will be sought from key stakeholders. Search results will then be screened for relevance at title, abstract and full text levels according to a predefined set of eligibility criteria. Consistency checking will be employed to ensure the criteria are being applied accurately and consistently. Relevant studies will then be subjected to coding and meta-data extraction, which will be used to populate a systematic map database describing each relevant study’s settings, methods and measured outcomes. The mapping process will help to identify knowledge gaps (subjects lacking in evidence warranting further primary research) and knowledge clusters (subjects with sufficient studies to allow a useful full systematic review), and will highlight best and suboptimal research methods.
Evidence of colistin resistance genes (mcr-1 and mcr-2) in wild birds and its public health implication in Egypt
Authors: Ahmed Zeinab S. , Elshafiee Esraa A. , Khalefa Hanan S. , Kadry Mona , Hamza Dalia A. 
Published: December 2019

Abstract
Background
Antimicrobial resistance has become one of the most severe global threats to human and veterinary Medicine. colistin is an effective therapeutic agent against multi-drug-resistant pathogens. However, the discovery of transferable plasmids that confer resistance to colistin (mcr-1) has led to challenges in medical science. This study describes the role of wild birds in the harbouring and environmental spread of colistin-resistant bacteria, which could pose a potential hazard to human and animal health.

Methods
In total, 140 faecal samples from wild birds (migratory and resident birds) were tested. Twenty surface water samples were collected from the area in which wild bird trapping was conducted, and 50 human stool samples were collected from individuals residing near the surface water sources and farm buildings. Isolation and identification of Enterobacteriaceae and Pseudomonas aeruginosa from the different samples were performed using conventional culture techniques and biochemical identification. PCR amplification of the mcr genes was performed in all positive isolates. Sequencing of mcr-1 genes from three randomly selected E. coli carrying mcr-1 isolates; wild birds, water and humans was performed.

Result
The bacteriological examination of the samples showing isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca and P. aeruginosa. The results of multiplex PCR of the mcr genes revealed that E. coli was the most prevalent gram-negative bacterium harbouring the mcr genes, whereas a low prevalence was observed for K. pneumoniae. The prevalence of mcr-1 in resident birds, migratory birds, water sources and humans were 10.4, 20,16.6 and 9.6% while the prevalence of mcr-2 were 1.4, 3.6, 11.1 and 9.6%, respectively. Sequencing of the mcr-1 gene from the three E. coli carrying mcr-1 isolates indicated a possible correlation between the wild bird and surface water isolates.

Conclusion
The detection of mcr-1-positive bacteria in wild birds in Egypt indicates the possible environmental dissemination of this gene through bird activity. The impact of the interaction between domestic and wild animals on public health cannot be overlooked.
Genetics and functions of the retinoic acid pathway, with special emphasis on the eye
Authors: Thompson Brian , Katsanis Nicholas , Apostolopoulos Nicholas , Thompson David C. , Nebert Daniel W. , Vasiliou Vasilis 
Published: December 2019

AbstractRetinoic acid (RA) is a potent morphogen required for embryonic development. RA is formed in a multistep process from vitamin A (retinol); RA acts in a paracrine fashion to shape the developing eye and is essential for normal optic vesicle and anterior segment formation. Perturbation in RA-signaling can result in severe ocular developmental diseases—including microphthalmia, anophthalmia, and coloboma. RA-signaling is also essential for embryonic development and life, as indicated by the significant consequences of mutations in genes involved in RA-signaling. The requirement of RA-signaling for normal development is further supported by the manifestation of severe pathologies in animal models of RA deficiency—such as ventral lens rotation, failure of optic cup formation, and embryonic and postnatal lethality. In this review, we summarize RA-signaling, recent advances in our understanding of this pathway in eye development, and the requirement of RA-signaling for embryonic development (e.g., organogenesis and limb bud development) and life.
On using MapReduce to scale algorithms for Big Data analytics: a case study
Authors: Kijsanayothin Phongphun , Chalumporn Gantaphon , Hewett Rattikorn 
Published: November 2019

AbstractIntroductionMany data analytics algorithms are originally designed for in-memory data. Parallel and distributed computing is a natural first remedy to scale these algorithms to “Big algorithms” for large-scale data. Advances in many Big Data analytics algorithms are contributed by MapReduce, a programming paradigm that enables parallel and distributed execution of massive data processing on large clusters of machines. Much research has focused on building efficient naive MapReduce-based algorithms or extending MapReduce mechanisms to enhance performance. However, we argue that these should not be the only research directions to pursue. We conjecture that when naive MapReduce-based solutions do not perform well, it could be because certain classes of algorithms are not amendable to MapReduce model and one should find a fundamentally different approach to a new MapReduce-based solution.Case descriptionThis paper investigates a case study of a scaling problem of “Big algorithms” for a popular association rule-mining algorithm, particularly the development of Apriori algorithm in MapReduce model.Discussion and evaluationFormal and empirical illustrations are explored to compare our proposed MapReduce-based Apriori algorithm with previous solutions. The findings support our conjecture and our study shows promising results compared to the state-of-the-art performer with 7% increase in performance on the average of transactions ranging from 10,000 to 120,000.ConclusionsThe results confirm that effective MapReduce implementation should avoid dependent iterations, such as that of the original sequential Apriori algorithm. These findings could lead to many more alternative non-naive MapReduce-based “Big algorithms”.
Association between coat colour and the behaviour of Australian Labrador retrievers
Authors: van Rooy Diane , Wade Claire M. 
Published: November 2019

Abstract
Background
Making assumptions regarding temperament and intelligence based on the physical appearance of dogs can be a conscious or unconscious human act. Labrador retrievers with chocolate-coloured coats are anecdotally considered to be less trainable and more hyperactive and aggressive than their black or yellow peers. To test these assertions, we analysed the owner-reported behavioural traits of Labradors in relation to both their observable coat colour, and their TYRP1 and MC1R genotypes.

Results
We used the results of an owner-based questionnaire to determine scores for 21 behavioural traits and test whether these scores varied with coat colour (n = 225). Familiar dog aggression was the only trait that was found to vary significantly with coat colour (P = 0.013). Yellow Labradors had a higher score than chocolate Labradors, even when corrected for multiple testing (P = 0.021).
We repeated the analyses for a subset of 63 Labradors with available genotyping data for the genes (MC1R and TYRP1) that are known to determine the primary coat colours in Labradors. Familiar dog aggression scores varied with both the observed coat colour and MC1R genotype. Dogs homozygous for MC1R recessive allele (with yellow coat colour) scored higher for familiar dog aggression than either black or chocolate Labradors. However, no association maintained significance when incorporating Bonferroni correction. Dog trainability scores decreased additively as the number of recessive brown alleles for TYRP1 increased. This allelic association was independent of the observable coat colour. Dogs homozygous for the brown allele were considered less trainable than dogs with no brown alleles (P = 0.030).

Conclusions
Our results do not support that chocolate-coloured Labradors are more hyperactive or aggressive than either black or yellow Labradors. Trainability scores varied with TYRP1 genotype but not the observable coat colour. Further validation is required.
Fully dynamic earthquake sequence simulation of a fault in a viscoelastic medium using a spectral boundary integral equation method: does interseismic stress relaxation promote aseismic transients?
Authors: Miyake Yuki , Noda Hiroyuki 
Published: December 2019

AbstractAlong subduction interfaces or some major faults, a seismogenic layer in the upper crust is underlain by a zone of slow-slip events (SSEs) and tremors, and seismicity disappears at greater depths. The transition between seismogenic and aseismic behavior may be caused by changes in the frictional properties of the fault or changes in viscoelastic properties of the surrounding medium. Although aseismic transients have been numerically generated in previous studies by changing the frictional properties and compared to SSEs, the effect of viscoelasticity on the transition remains to be studied. In this study, we implemented interseismic viscoelastic stress relaxation in a simulation code for two-dimensional antiplane fully dynamic earthquake sequences in a uniform elastic material based on a spectral boundary integral equation method. In the implementation, we developed a suitable algorithm in which the viscoelastic relaxation is calculated by evolution of an “effective slip,” which gives viscoelastic stress change on the fault if convolved with a static Green’s function. We conducted parametric studies for a fault with a rate-weakening patch on two parameters: viscoelastic relaxation time $$t_{c}$$tc and characteristic length of the state evolution in the rate- and state-dependent friction law L. The behavior of the simulated fault can be classified into four classes, earthquakes (EQ), aseismic transients (AT), stable sliding (SS), and stuck (ST), in which the central part of the rate-weakening patch has a diminishingly small slip rate and is permanently locked. A phase diagram of the fault behavior shows that there are two different types of seismogenic–aseismic transition. As L increases, an EQ patch changes to an AT patch before becoming an SS patch, as has been reported in previous studies in an elastic limit. The boundary between AT and SS can be explained via linear stability analysis of a system composed of a spring, a dashpot, and sliders. As $$t_{c}$$tc decreases, the recurrence interval of the earthquakes diverges, and an EQ patch changes to an ST patch unless L is within a narrow range. Therefore, the transition associated with SSEs and tremors is dominated by changes in frictional properties rather than changes in viscoelastic properties.
Development and validity evidence of the multidimensional scale of sexual self-concept in a Spanish-speaking context
Authors: Ferrer-Urbina Rodrigo , Sepúlveda-Páez Geraldy Lorena , Henríquez Diego-Tomás , Acevedo-Castillo Daniel Ignacio , Llewellyn-Alvarado Débora Alejandra 
Published: December 2019

AbstractBackground/objectiveSTIs and HIV/AIDS are an important public health problem, transmitted by risky sex behaviours. In this context, it is necessary to identify protective factors, of those behaviours, as sexual self-concept. Sexual self-concept is a multidimensional trait (i.e. sexual self-esteem; sexual self-efficacy; and sexual assertiveness), but, in an extensive review, we did not find any measure to assess this multidimensional construct in a Spanish-speaking context. The objective of this research is development a scale to assess sexual self-concept in young people and adults.MethodTime-space sampling with a total size of 792 participants, coming from the two Chilean cities (i.e. Arica and Iquique) with the highest HIV rates, aged between 17 and 53 years old (ME = 23.42; SD = 6.33), with 66.2% women (N= 500), 33.6% men (N= 258).ResultsFinal scale has 16 items and 4 dimensions: sexual self-esteem, sexual self-efficacy, assertive sexual communication, and assertive sexual behaviour. The identified structure provides satisfactory levels of reliability (ω > .8) and presents robust evidence of validity, based on the internal structure of the test, using ESEM (RMSEA = .060; CFI = .99; TLI = .98), evidence of validity based on relationship to other variables (i.e. risky sexual behaviour) and measurement invariance between men and women.ConclusionsThe multidimensional scale of sexual self-concept has adequate psychometric properties to assess sexual self-concept in equivalent samples.