bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health risk assessments of arsenic and toxic heavy metal exposure in drinking water in northeast Iran
Authors: Alidadi Hosein , Tavakoly Sany Seyedeh Belin , Zarif Garaati Oftadeh Batoul , Mohamad Tafaghodi , Shamszade Hosein , Fakhari Maryam 
Published: September 2019

Abstract

Background
Arsenic and heavy metals are the main cause of water pollution and impact human health worldwide. Therefore, this study aims to assess the probable health risk (non-carcinogenic and carcinogenic risk) for adults and children that are exposed to arsenic and toxic heavy metals (Pb, Ni, Cr, and Hg) through ingestion and dermal contact with drinking water.

Method
In this study, chemical analysis and testing were conducted on 140 water samples taken from treated drinking water in Mashhad, Iran. The health risk assessments were evaluated using hazard quotient (HQ), hazard index (HI), and lifetime cancer risk (CR).

Results
The results of the HQ values of arsenic and heavy metals for combined pathways were below the safety level (HQ < 1) for adults, while the HI for children were higher than the safety limit in some stations. Likewise, Cr showed the highest average contribution of HItotal elements (55 to 71.2%) for adult and children population. The average values of total carcinogenic risk (TCR) through exposure to drinking water for children and adults were 1.33 × 10−4 and 7.38 × 10−5, respectively.

Conclusion
Overall, the CRtotal through exposure to drinking water for children and adults was borderline or higher than the safety level of US EPA risk, suggesting the probability of carcinogenic risk for the children and adults to the carcinogenic elements via ingestion and dermal routes. Therefore, appropriate purification improvement programs and control measures should be implemented to protect the health of the residents in this metropolitan city.
Decision-making under uncertainty in environmental health policy: new approaches
Authors: Reis Jacques , Spencer Peter S. 
Published: September 2019

Abstract
Decision-making in environmental health policy is a complex procedure even in well-known conditions. Thus, in the case of uncertainty, decision-making becomes a hurdle race. We address scientific uncertainty, methods to reduce uncertainty, biomedical doubt and science communication, and the role of stakeholders, activists, lobbies and media that together influence policy decisions. We also consider the major responsibility and role of the medico-scientific community in this process. This community can and should teach the principle of scientific uncertainty to all stakeholders, advise policy-makers and underline the ethical issues, considering that our brains are not only the deposit of our humanity but also the route to environmental health and societal harmony.
Identifying protein complexes based on an edge weight algorithm and core-attachment structure
Authors: Wang Rongquan , Liu Guixia , Wang Caixia 
Published: September 2019

AbstractBackgroundProtein complex identification from protein-protein interaction (PPI) networks is crucial for understanding cellular organization principles and functional mechanisms. In recent decades, numerous computational methods have been proposed to identify protein complexes. However, most of the current state-of-the-art studies still have some challenges to resolve, including their high false-positives rates, incapability of identifying overlapping complexes, lack of consideration for the inherent organization within protein complexes, and absence of some biological attachment proteins.ResultsIn this paper, to overcome these limitations, we present a protein complex identification method based on an edge weight method and core-attachment structure (EWCA) which consists of a complex core and some sparse attachment proteins. First, we propose a new weighting method to assess the reliability of interactions. Second, we identify protein complex cores by using the structural similarity between a seed and its direct neighbors. Third, we introduce a new method to detect attachment proteins that is able to distinguish and identify peripheral proteins and overlapping proteins. Finally, we bind attachment proteins to their corresponding complex cores to form protein complexes and discard redundant protein complexes. The experimental results indicate that EWCA outperforms existing state-of-the-art methods in terms of both accuracy andp-value. Furthermore, EWCA could identify many more protein complexes with statistical significance. Additionally, EWCA could have better balance accuracy and efficiency than some state-of-the-art methods with high accuracy.ConclusionsIn summary, EWCA has better performance for protein complex identification by a comprehensive comparison with twelve algorithms in terms of different evaluation metrics. The datasets and software are freely available for academic research athttps://github.com/RongquanWang/EWCA.
A purely bioinformatic pipeline for the prediction of mammalian odorant receptor gene enhancers
Authors: Degl’Innocenti Andrea , Meloni Gabriella , Mazzolai Barbara , Ciofani Gianni 
Published: September 2019

Abstract

Background
In most mammals, a vast array of genes coding for chemosensory receptors mediates olfaction. Odorant receptor (OR) genes generally constitute the largest multifamily (> 1100 intact members in the mouse). From the whole pool, each olfactory neuron expresses a single OR allele following poorly characterized mechanisms termed OR gene choice. OR genes are found in genomic aggregations known as clusters. Nearby enhancers, named elements, are crucial regulators of OR gene choice. Despite their importance, searching for new elements is burdensome. Other chemosensory receptor genes responsible for smell adhere to expression modalities resembling OR gene choice, and are arranged in genomic clusters — often with chromosomal linkage to OR genes. Still, no elements are known for them.

Results
Here we present an inexpensive framework aimed at predicting elements. We redefine cluster identity by focusing on multiple receptor gene families at once, and exemplify thirty — not necessarily OR-exclusive — novel candidate enhancers.

Conclusions
The pipeline we introduce could guide future in vivo work aimed at discovering/validating new elements. In addition, our study provides an updated and comprehensive classification of all genomic loci responsible for the transduction of olfactory signals in mammals.
Towards pixel-to-pixel deep nucleus detection in microscopy images
Authors: Xing Fuyong , Xie Yuanpu , Shi Xiaoshuang , Chen Pingjun , Zhang Zizhao , Yang Lin 
Published: September 2019

AbstractBackgroundNucleus or cell detection is a fundamental task in microscopy image analysis and supports many other quantitative studies such as object counting, segmentation, tracking, etc. Deep neural networks are emerging as a powerful tool for biomedical image computing; in particular, convolutional neural networks have been widely applied to nucleus/cell detection in microscopy images. However, almost all models are tailored for specific datasets and their applicability to other microscopy image data remains unknown. Some existing studies casually learn and evaluate deep neural networks on multiple microscopy datasets, but there are still several critical, open questions to be addressed.ResultsWe analyze the applicability of deep modelsspecificallyfor nucleus detection across a wide variety of microscopy image data. More specifically, we present a fully convolutional network-based regression model and extensively evaluate it on large-scale digital pathology and microscopy image datasets, which consist of 23 organs (or cancer diseases) and come from multiple institutions. We demonstrate that for a specific target dataset, training with images from the same types of organs might be usually necessary for nucleus detection. Although the images can be visually similar due to the same staining technique and imaging protocol, deep models learned with images from different organs might not deliver desirable results and would require model fine-tuning to be on a par with those trained with target data. We also observe that training with a mixture of target and other/non-target data does not always mean a higher accuracy of nucleus detection, and it might require proper data manipulation during model training to achieve good performance.ConclusionsWe conduct a systematic case study on deep models for nucleus detection in a wide variety of microscopy images, aiming to address several important but previously understudied questions. We present and extensively evaluate an end-to-end, pixel-to-pixel fully convolutional regression network and report a few significant findings, some of which might have not been reported in previous studies. The model performance analysis and observations would be helpful to nucleus detection in microscopy images.
Biological variation of immunological blood biomarkers in healthy individuals and quality goals for biomarker tests
Authors: Aziz Najib , Detels Roger , Quint Joshua J. , Gjertson David , Ryner Timothy , Butch Anthony W. 
Published: September 2019

AbstractBackgroundCytokines, chemokines, adipocytokines, soluble cell receptors, and immune activation markers play an important role in immune responsiveness and can provide prognostic value since they reflect underlying conditions and disease states. This study was undertaken to investigate the components of biological variation for various laboratory tests of blood immunological biomarkers.ResultsEstimates of intra-individual coefficient of variation (CVI) and inter-individual coefficient of variation (CVG) were examined for blood immunological biomarkers. Biomarkers with CVI < 10% for both genders were CD3, CD4, and CD8 T-cells, serum levels of soluble cluster of differentiation 14 (sCD14), sCD163, and soluble glycoprotein 130 (sgp130). The CVIfor serum levels of adiponectin, interleukin-1 receptor antagonist (IL-1Ra), macrophage inflammatory protein 1 beta (MIP-1β), soluble CD40 Ligand (sCD40L), soluble interleukin-2 receptor alpha (sIL-2Rα), soluble interleukin-6 receptor (sIL-6R), soluble tumor necrosis factor receptor II (sTNF-RII), and tumor necrosis factor alpha (TNF-α) were between 11 and 20%. Biomarkers with CVG < 20% were CD3 T-cell, and serum concentrations of sCD14, sCD40L, and sgp130. The biomarkers with CVG > 40% were adiponectin, IL-1ra, leptin, MIP-1β, sCD163, and sIL-2Rα.ConclusionThe biological variations of biomarkers have important monitoring value for longitudinal investigation and are essential for quality specification of tests that are performed in the laboratory. The CVIwas relatively small while CVGwas comparatively large and mean values of each biomarker vary between subjects. The individuality of biomarkers significantly influences reference interval values. A majority of the biomarkers in this study had strong individuality and the result of each biomarker should be cautiously interpreted if using established reference interval values. Comparison of a patient’s test result with previous ones may be more useful than the usage of conventional reference values.
Genome wide search to identify reference genes candidates for gene expression analysis in Gossypium hirsutum
Authors: Smitha P. K. , Vishnupriyan K. , Kar Ananya S. , Anil Kumar M. , Bathula Christopher , Chandrashekara K. N. , Dhar Sujan K. , Das Manjula 
Published: September 2019

Abstract

Background
Cotton is one of the most important commercial crops as the source of natural fiber, oil and fodder. To protect it from harmful pest populations number of newer transgenic lines have been developed. For quick expression checks in successful agriculture qPCR (quantitative polymerase chain reaction) have become extremely popular. The selection of appropriate reference genes plays a critical role in the outcome of such experiments as the method quantifies expression of the target gene in comparison with the reference. Traditionally most commonly used reference genes are the “house-keeping genes”, involved in basic cellular processes. However, expression levels of such genes often vary in response to experimental conditions, forcing the researchers to validate the reference genes for every experimental platform. This study presents a data science driven unbiased genome-wide search for the selection of reference genes by assessing variation of > 50,000 genes in a publicly available RNA-seq dataset of cotton species Gossypium hirsutum.

Result
Five genes (TMN5, TBL6, UTR5B, AT1g65240 and CYP76B6) identified by data-science driven analysis, along with two commonly used reference genes found in literature (PP2A1 and UBQ14) were taken through qPCR in a set of 33 experimental samples consisting of different tissues (leaves, square, stem and root), different stages of leaf (young and mature) and square development (small, medium and large) in both transgenic and non-transgenic plants. Expression stability of the genes was evaluated using four algorithms - geNorm, BestKeeper, NormFinder and RefFinder.

Conclusion
Based on the results we recommend the usage of TMN5 and TBL6 as the optimal candidate reference genes in qPCR experiments with normal and transgenic cotton plant tissues. AT1g65240 and PP2A1 can also be used if expression study includes squares. This study, for the first time successfully displays a data science driven genome-wide search method followed by experimental validation as a method of choice for selection of stable reference genes over the selection based on function alone.
Transcriptional regulation of stilbene synthases in grapevine germplasm differentially susceptible to downy mildew
Authors: Ciaffi Mario , Paolacci Anna Rita , Paolocci Marco , Alicandri Enrica , Bigini Valentina , Badiani Maurizio , Muganu Massimo 
Published: September 2019

AbstractBackgroundTo limit the impact of the downy mildew disease of grapevine and reduce the need to recur to chemical treatments, an effective strategy might be recovering adaptive resistance traits in both cultivated and wildV. viniferagermplasm.Considering that stilbenes represent the most important class of phytoalexins in theVitaceae, the constitutive expression and transcriptional activation of all the functional members of the stilbene synthase gene family were analysed in a group of nine grapevine genotypes following artificial infection with the oomycetePlasmopara viticola, the causal agent of the disease. In addition, in the same genotypes we analyzed the expression of genes encoding for two transcription factors involved in the transcriptional regulation of the stilbene synthase genes, namelyVvMYB14andVvMYB15, and of genes encoding for chalcone synthases.ResultsDowny mildew incidence and severity ranged from nihil to high in the grapevine genotypes considered, being low to moderate in a subgroup ofV. viniferagenotypes. The constitutive expression of the stilbene synthase genes as well as the extent of their transcriptional activation followingP. viticolainoculation appeared to be inversely related to the proneness to develop disease symptoms upon infection. In a specular manner, followingP. viticolainoculation all the chalcone synthase genes were up-regulated in the susceptible grapevine genotypes and down-regulated in the resistant ones. The infection brought byP. viticolaappeared to elicit a co-ordinated and sequential transcriptional activation of distinct stilbene synthase genes subsets, each of which may be regulated by a distinct and specific MYB transcription factor.ConclusionsThe present results suggest that the induction of stilbene biosynthesis may contribute to the basal immunity against the downy mildew of grapevine, thus representing an adaptive resistance trait to recover, in both cultivated and wildV. viniferagermplasm. During the early stages ofP. viticolainfection, an antagonistic interaction between flavonol and stilbene biosynthesis might occur, whose outcome might determine the subsequent extent of disease symptoms. Further studies are needed to decipher the possible regulatory mechanisms involved in the antagonistic crosstalk between these two metabolic pathways in resistant and susceptible genotypes in response toP. viticola.
Apolipoprotein E gene polymorphism and the risk of cardiovascular disease and type 2 diabetes
Authors: Liu Sudong , Liu Jing , Weng Ruiqiang , Gu Xiaodong , Zhong Zhixiong 
Published: September 2019

Abstract

Background
The role of apolipoprotein E gene (APOE) in lipid metabolism has been well established, and APOE is associated with the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). However, the relationship between APOE polymorphisms and type 2 diabetes (T2DM) with or without CVD remains unclear.

Methods
In this cross-sectional study, a total of 924 participants including 211 controls (CVD-T2DM-), 247 T2DM patients with CVD (CVD-T2DM+), 232 CVD patients without T2DM (CVD + T2DM-) and 234 T2DM patients with CVD (CVD + T2DM+), were genotyped using chip platform. The association between APOE polymorphisms and T2DM patients with or without CVD was analyzed by univariable and multivariable logistic analysis.

Results
The present study showed that the frequency of E3/E4 increased in T2DM patients with CVD (p < 0.01). The ε4 allele was higher in CVD patients without T2DM (p < 0.01) and T2DM patients with CVD (p < 0.01) as compared with the controls.

Conclusions
The subjects carrying ε4 allele have increased risk of CVD and T2DM, and exhibit higher level of lipid profiles.
A rare case of Colistin-resistant Salmonella Enteritidis meningitis in an HIV-seropositive patient
Authors: Rule Roxanne , Mbelle Nontombi , Sekyere John Osei , Kock Marleen , Hoosen Anwar , Said Mohamed 
Published: September 2019

Abstract

Background
Non-typhoidal salmonellae (NTS) have been associated with invasive disease, notably meningitis, in immunocompromised individuals. Infections of this nature carry high rates of morbidity and mortality. Colistin resistance in salmonellae is a rare finding, more so in an invasive isolate such as cerebrospinal fluid (CSF). Colistin resistance has important infection control implications and failure to manage this phenomenon may lead to the loss of our last line of defence against multi-drug resistant Gram-negative organisms. To our knowledge, this is the first reported clinical case of colistin-resistant Salmonella Enteritidis meningitis in South Africa.

Case presentation
We report a case of a young male patient with advanced human immunodeficiency virus (HIV) infection who presented to hospital with symptoms of meningitis. Cerebrospinal fluid (CSF) cultured a Salmonella Enteritidis strain. Antimicrobial susceptibility testing (AST) of the isolate, revealed the strain to be colistin resistant. Despite early and aggressive antimicrobial therapy, the patient succumbed to the illness after a short stay in hospital. Subsequent genomic analysis of the isolate showed no presence of the mcr genes or resistance-conferring mutations in phoPQ, pmrAB, pmrHFIJKLME/arnBCADTEF, mgrB, and acrAB genes, suggesting the presence of a novel colistin resistance mechanism.

Conclusion
Invasive non-typhoidal salmonellae infection should be suspected in patients with advanced immunosuppression who present with clinical features of meningitis. Despite early and appropriate empiric therapy, these infections are commonly associated with adverse outcomes to the patient. Combination therapy with two active anti-Salmonella agents may be a consideration in the future to overcome the high mortality associated with NTS meningitis. Colistin resistance in clinical Salmonella isolates, although a rare finding at present, has significant public health and infection control implications. The causative mechanism of resistance should be sought in all cases.
“Enterocytozoon bieneusi and Cryptosporidium: a cross-sectional study conducted throughout Thailand”
Authors: Prasertbun Rapeepun , Mori Hirotake , Sukthana Yaowalark , Popruk Supaluk , Kusolsuk Teera , Hagiwara Katsuro , Mahittikorn Aongart 
Published: September 2019

Abstract

Background
Enterocytozoon bieneusi and Cryptosporidium spp. are prevalent zoonotic parasites associated with a high burden among children. To date only limited molecular epidemiological data on E. bieneusi and Cryptosporidium spp. in humans living in Thailand has been published.

Methods
PCR-based tools were used to detect and characterize E. bieneusi and Cryptosporidium spp. The internal transcribed spacer (ITS) region of the rRNA gene was used to investigate E. bieneusi, and the small subunit (SSU) rRNA gene was used to investigate Cryptosporidium spp., and 697 fecal samples from villagers and school children in rural areas in Thailand were analyzed.

Results
The infection rates were 2.15% (15/697) for E. bieneusi and 0.14% (1/697) for Cryptosporidium spp. The prevalence of E. bieneusi was significantly high in Loei province. Sequence analysis indicated that the Cryptosporidium isolate was C. parvum. Nine E. bieneusi genotypes were identified, EbpC, Peru12, TMH6, TMH3, TMH7, H, D, and two novel genotypes TMLH1 and TMLH2. E. bieneusi prevalence was significantly higher in male participants than in female participants, and in children aged 3–15 years than in participants aged > 15 years.

Conclusions
The prevalence, genotypes, and zoonotic potential of E. bieneusi were found to vary significantly high even in one country. Transmission routes and key animal carriers of E. bieneusi may be associated with differences in hygiene, sanitation, and cultural behaviors. Further molecular studies including longitudinal studies will be required to unveil epidemiological characteristics of these opportunistic intestinal protozoa in all over the countries.
Molecular mechanisms of hydrogen sulfide against uremic accelerated atherosclerosis through cPKCβII/Akt signal pathway
Authors: Xiong Ruifang , Lu Xiangxue , Song Jinghong , Li Han , Wang Shixiang 
Published: September 2019

Abstract

Background
Cardiovascular disease is the most common complication and leading cause of death in maintenance hemodialysis patients. The protection mechanism of hydrogen sulfide (H2S) and the specific role of conventional protein kinase C βII (cPKCβII)/Akt signaling pathway in the formation of atherosclerosis is still controversial.

Methods
8-week-old male ApoE−/− mice were treated with 5/6 nephrectomy and high-fat diet to make uremia accelerated atherosclerosis (UAAS) model. Mice were divided into normal control group (control group), sham operation group (sham group), UAAS group, L-cysteine group (UAAS+L-cys group), sodium hydrosulfide group (UAAS+NaHS group), and propargylglycine group (UAAS+PPG group). Western blot was used to detect cPKCβII activation, Akt phosphorylation and endothelial nitric oxide synthase (eNOS) expression in mice aorta.

Results
The membrane translocation of cPKCβII in UAAS group was higher than sham group, and L-cys or NaHS injection could suppress the membrane translocation, but PPG treatment resulted in more membrane translocation of cPKCβII (P < 0.05, n = 6 per group). Akt phosphorylation and the eNOS expression in UAAS group was lower than sham group, and L-cys or NaHS injection could suppress the degradation of Akt phosphorylation and the eNOS expression, but PPG treatment resulted in more decrease in the Akt phosphorylation and the eNOS expression (P < 0.05, n = 6 per group).

Conclusion
Endogenous cystathionine-γ-lyase (CSE)/H2S system protected against the formation of UAAS via cPKCβII/Akt signal pathway. The imbalance of CSE/H2S system may participate in the formation of UAAS by affecting the expression of downstream molecule eNOS, which may be mediated by cPKCβII/Akt signaling pathway.