bluuebunny/crossref_metadata_2025_split huggingface dataset:
Informing patients about their mutation tests: CDKN2A c.256G>A in melanoma as an example
Authors: Hemminki Kari , Srivastava Aayushi , Rachakonda Sivaramakrishna , Bandapalli Obul , Nagore Eduardo , Hemminki Akseli , Kumar Rajiv 
Published: July 2020

Abstract
Background
When germline mutations are suspected as causal in cancer, patient DNA may be sequenced to detect variants in relevant genes. If a particular mutation has not been reported in reliable family studies, genetic counselors are facing a dilemma of appropriately informing patients. Many sequencing facilities provide an interpretation of the findings based on the available sequence databases or on prediction tools that are curated from bioinformatics and mechanistic datasets. The counseling dilemma is exacerbated if the pedigree data are not informative but the in silico predictions suggest pathogenicity.

Methods
We present here a real world example of the c.256G > A CDKN2A variant, which was detected in one melanoma patient where two siblings were diagnosed with melanoma in situ. We investigated a detailed family history of the affected siblings in order to survey probability of the cancer risks within the context to this mutation.

Results
This c.256G > A CDKN2A variant was detected in one of the brothers and in the melanoma-free mother while the other brother in the family tested negative. The variant had been previously described in one patient from a melanoma family. In the family under investigation, the mother’s 16 first-and second-degree relatives had survived past the median onset age for melanoma and none presented melanoma. We tested the variant using multiple bioinformatic tools that all predicted deleteriousness of the variant. The genetic counseling report to the melanoma patient stated that the CDKN2A variant was ‘likely pathogenic’ and the disease was defined as ‘likely hereditary melanoma’.

Conclusions
The pedigree data showed at the most a low penetrance variant, which, if taken into consideration, might have altered the provided diagnosis. When dealing with ‘practically’ unknown variants the counselors would be advised to incorporate a detailed family history rather than basing predictions on functionality provided by sequencing facilities.
A risk-associated Active transcriptome phenotype expressed by histologically normal human breast tissue and linked to a pro-tumorigenic adipocyte population
Authors: Kang Taekyu , Yau Christina , Wong Christopher K. , Sanborn John Z. , Newton Yulia , Vaske Charlie , Benz Stephen C. , Krings Gregor , Camarda Roman , Henry Jill E. , Stuart Josh , Powell Mark , Benz Christopher C. 
Published: July 2020

Abstract
Background
Previous studies have identified and validated a risk-associated Active transcriptome phenotype commonly expressed in the cancer-adjacent and histologically normal epithelium, stroma, and adipose containing peritumor microenvironment of clinically established invasive breast cancers, conferring a 2.5- to 3-fold later risk of dying from recurrent breast cancer. Expression of this Active transcriptome phenotype has not yet been evaluated in normal breast tissue samples unassociated with any benign or malignant lesions; however, it has been associated with increased peritumor adipocyte composition.

Methods
Detailed histologic and transcriptomic (RNAseq) analyses were performed on normal breast biopsy samples from 151 healthy, parous, non-obese (mean BMI = 29.60 ± 7.92) women, ages 27–66 who donated core breast biopsy samples to the Komen Tissue Bank, and whose average breast cancer risk estimate (Gail score) at the time of biopsy (1.27 ± 1.34) would not qualify them for endocrine prevention therapy.

Results
Full genome RNA sequencing (RNAseq) identified 52% (78/151) of these normal breast samples as expressing the Active breast phenotype. While Active signature genes were found to be most variably expressed in mammary adipocytes, donors with the Active phenotype had no difference in BMI but significantly higher Gail scores (1.46 vs. 1.18; p = 0.007). Active breast samples possessed 1.6-fold more (~ 80%) adipocyte nuclei, larger cross-sectional adipocyte areas (p < 0.01), and 0.5-fold fewer stromal and epithelial cell nuclei (p < 1e−6). Infrequent low-level expression of cancer gene hotspot mutations was detected but not enriched in the Active breast samples. Active samples were enriched in gene sets associated with adipogenesis and fat metabolism (FDR q ≤ 10%), higher signature scores for cAMP-dependent lipolysis known to drive breast cancer progression, white adipose tissue browning (Wilcoxon p < 0.01), and genes associated with adipocyte activation (leptin, adiponectin) and remodeling (CAV1, BNIP3), adipokine growth factors (IGF-1, FGF2), and pro-inflammatory fat signaling (IKBKG, CCL13).

Conclusions
The risk-associated Active transcriptome phenotype first identified in cancer-adjacent breast tissues also occurs commonly in healthy women without breast disease who do not qualify for breast cancer chemoprevention, and independently of breast expressed cancer-associated mutations. The risk-associated Active phenotype appears driven by a pro-tumorigenic adipocyte microenvironment that can predate breast cancer development.
First multilocus sequence typing (MLST) of Giardia duodenalis isolates from humans in Romania
Authors: Costache Carmen , Kalmár Zsuzsa , Colosi Horațiu Alexandru , Baciu Alina Mihaela , Opriş Răzvan Vlad , Györke Adriana , Colosi Ioana Alina 
Published: July 2020

Abstract
Background
Giardia duodenalis is one of the most prevalent and highly diverse human parasites, encompassing a complex of eight genetically distinct assemblages, each further divided into sub-assemblages. While in recent years, G. duodenalis genotype distribution patterns in humans have been intensely studied, there is still very little information available on the diversity of Giardia genotypes and sub-assemblages infecting people in Romania. In the present study, we investigated the genetic diversity of Giardia duodenalis in asymptomatic patients from Romania.

Methods
Over an 11-month period, human feces from 7805 healthy adults were screened by microscopic analysis for G. duodenalis cysts during their obligatory periodic check-ups. DNA extraction was performed from microscopic-positive fecal samples, followed by multilocus sequence typing of four genetic loci of the ITS region, gdh, tpi and bg genes, followed by DNA sequencing and phylogenetic analysis. Statistical analysis was performed using EpiInfo 2000 software.

Results
The prevalence of giardiasis in the present study was 0.42% (33/7805). Twenty-three samples (76.67%) were successfully genotyped at each locus. The bg and tpi genes had the highest typing success rate (100%). The identified assemblages were assemblage A in 27 cases (subtypes A2 and A3), and B in 3 cases.

Conclusions
To our knowledge, the present study is the first report of multilocus sequence typing of G. duodenalis isolated from humans in Romania. The present results may shed light on G. duodenalis infection in humans at a regional and national level, thus increasing awareness against this parasitic infection.
The role of the oncostatin M/OSM receptor β axis in activating dermal microvascular endothelial cells in systemic sclerosis
Authors: Marden G. , Wan Q. , Wilks J. , Nevin K. , Feeney M. , Wisniacki N. , Trojanowski M. , Bujor A. , Stawski L. , Trojanowska M. 
Published: July 2020

Abstract
Background
Scleroderma (SSc) is a rare autoimmune disease characterized by vascular impairment and progressive fibrosis of the skin and other organs. Oncostatin M, a member of the IL-6 family, is elevated in SSc serum and was recognized as a significant player in various stages of fibrosis. The goal of this study was to assess the contribution of the OSM/OSMRβ pathway to endothelial cell (EC) injury and activation in SSc.

Methods
IHC and IF were used to assess the distribution of OSM and OSMRβ in SSc (n = 14) and healthy control (n = 7) skin biopsies. Cell culture experiments were performed in human dermal microvascular endothelial cells (HDMECs) and included mRNA and protein analysis, and cell migration and proliferation assays. Ex vivo skin organoid culture was used to evaluate the effect of OSM on perivascular fibrosis.

Results
OSMRβ protein was elevated in dermal ECs and in fibroblasts of SSc patients. Treatments of HDMECs with OSM or IL-6+sIL-6R have demonstrated that both cytokines similarly stimulated proinflammatory genes and genes related to endothelial to mesenchymal transition (EndMT). OSM was more effective than IL-6+sIL-6R in inducing cell migration, while both treatments similarly induced cell proliferation. The effects of OSM were mediated via OSMRβ and STAT3, while the LIFR did not contribute to these responses. Both OSM and IL-6+sIL-6R induced profibrotic gene expression in HDMECs, as well as expansion of the perivascular PDGFRβ+ cells in the ex vivo human skin culture system. Additional studies in HDMECs showed that siRNA-mediated downregulation of FLI1 and its close homolog ERG resulted in increased expression of OSMRβ in HDMECs.

Conclusions
This work provides new insights into the role of the OSM/OSMRβ axis in activation/injury of dermal ECs and supports the involvement of this pathway in SSc vascular disease.
Paediatric, pedestrian road traffic injuries in the city of Mashhad in north-eastern Iran 2015–2019: a data note
Authors: Tabari Parinaz , Shabanikiya Hamidreza , Bagheri Nasser , Bergquist Robert , Hashtarkhani Soheil , Kiani Fatemeh , Mohammadi Alireza , Kiani Behzad 
Published: July 2020

Abstract
Objectives
The leading factors of paediatric, pedestrian road traffic injuries (PPRTIs) are associated with the characteristics of immediate environment. Spatial analysis of data related to PPRTIs could provide useful knowledge for public health specialists to prevent and decrease the number of accidents. Therefore, we aim to release the datasets which have been used to conduct a multiple-scale spatial analysis of PPRTIs in the city of Mashhad, Iran, between 2015-2019.

Data description
The data include four datasets. The base PPRTIs dataset includes motor vehicle accidents and their attributes in the city of Mashhad between March 2015 and March 2019. The attribute data includes the month, day of the week, hour of the day, place (longitude and latitude) of each accident, age range of the child and gender. Furthermore, three spatial datasets about the city of Mashhad are introduced; (1) the digital boundaries of Neighbourhood, (2) road network dataset (street lines) and (3) urban suburbs of Mashhad.
AHRR cg05575921 methylation in relation to smoking and PM2.5 exposure among Taiwanese men and women
Authors: Tantoh Disline Manli , Wu Ming-Chi , Chuang Chun-Chao , Chen Pei-Hsin , Tyan Yeu Sheng , Nfor Oswald Ndi , Lu Wen-Yu , Liaw Yung-Po 
Published: July 2020

Abstract
Background
Polycyclic aromatic hydrocarbon (PAH)-rich substances like cigarette smoke and PM2.5 induce aryl hydrocarbon receptor (AHR)-mediated aryl hydrocarbon receptor repressor (AHRR) methylation. AHRR cg05575921 and coagulation factor II (thrombin) receptor-like 3 (F2RL3) cg03636183 methylation patterns are well-established biomarkers for smoking. Even though AHRR cg05575921 methylation has recently been associated with PM2.5, the interaction between smoking and PM2.5 on AHRR methylation is yet to be fully explored. We evaluated AHRR and F2RL3 CpG sites to identify potential significant markers in relation to PM2.5 and smoking in Taiwanese adults.

Methods
DNA methylation and smoking data of 948 participants aged 30–70 years were obtained from the Taiwan Biobank Database (2008–2015), while PM2.5 data were obtained from the Air Quality Monitoring Database (2006–2011).

Results
Smoking and PM2.5 were independently associated with hypomethylation (lower levels) of AHRR cg05575921, AHRR cg23576855, F2RL3 cg03636183, and F2LR3 cg21911711 after multiple-comparison correction (Bonferroni P < 0.00028409). Cg05575921 was the most hypomethylated AHRR CpG site, while cg03636183 was the most hypomethylated F2RL3 CpG site. Overall, cg05575921 was the most hypomethylated CpG site: β = − 0.03909, P < 0.0001; − 0.17536, P < 0.0001 for former and current smoking, respectively (P-trendsmoking < 0.0001) and − 0.00141, P < 0.0001 for PM2.5. After adjusting for F2RL3 cg03636183, smoking and PM2.5 remained significantly associated with cg05575921 hypomethylation: β − 0.02221, P < 0.0001; − 0.11578, P < 0.0001 for former and current smoking, respectively (P-trendsmoking < 0.0001) and − 0.0070, P = 0.0120 for PM2.5. After stratification by sex, smoking and PM2.5 remained associated (P < 0.05) with cg05575921 hypomethylation in both men (β = − 0.04274, − 0.17700, and − 0.00163 for former smoking, current smoking, and PM2.5, respectively) and women (β = − 0.01937, − 0.17255, and − 0.00105 for former smoking, current smoking, and PM2.5, respectively). After stratification by residential area, former and current smoking remained associated (P < 0.05) with cg05575921 hypomethylation: β = − 0.03918 and − 0.17536, respectively (P-trendsmoking < 0.0001). Living in the central and southern areas was also associated (P < 0.05) with cg05575921 hypomethylation: β = − 0.01356 and − 0.01970, respectively (P-trendarea < 0.0001).

Conclusion
Smoking and PM2.5 were independently associated with hypomethylation of cg05575921, cg23576855, cg03636183, and cg21911711. The most hypomethylated CpG site was cg05575921 and its association with smoking and PM2.5 was dose-dependent.
Evaluation of the reproductive system development and egg-laying performance of hens infected with TW I-type infectious bronchitis virus
Authors: Zhang Xiaorong , Liao Kai , Chen Shuqin , Yan Kun , Du Xubin , Zhang Chengcheng , Guo Mengjiao , Wu Yantao 
Published: July 2020

AbstractThe prevalence of TW I-type infectious bronchitis virus (IBV) has been increasing rapidly, and it has become the second most common genotype of IBV in China threatening the poultry industry. In this study, 1-day-old specific-pathogen-free (SPF) chickens infected with TW I-type IBV were continuously observed for 200 days. TW I-type IBV affected the respiratory, urinary, and female reproductive systems, resulting in a mortality rate of 10% as well as a decrease in egg quantity and an increase in inferior eggs. During the monitoring period, serious lesions occurred in the female reproductive system, such as yolk peritonitis, a shortened oviduct, and cysts of different sizes with effusion in the degenerated right oviduct. The infective viruses persisted in vivo for a long time, and due to the stress of laying, virus shedding was detected again after the onset of egg production. Our findings suggest that TW I-type IBV is deadly to chickens and could cause permanent damage to the oviduct, resulting in the poor laying performance of female survivors and decreasing the breeding value and welfare of the infected flock.
Toward better control of classical swine fever in wild boars: susceptibility of boar-pig hybrids to a recent Japanese isolate and effectiveness of a bait vaccine
Authors: Fukai Katsuhiko , Nishi Tatsuya , Yamada Manabu , Ikezawa Mitsutaka 
Published: July 2020

AbstractWe analyzed the pathogenicity of a recent Japanese classical swine fever virus (CSFV) to wild boars via an experimental infection using boar-pig hybrids as an alternative to wild boars. We also investigated the effectiveness of a bait vaccine against the CSFV. Naïve boar-pig hybrids and pigs showed clinical signs such as fever, leucopenia, anorexia and conjunctivitis following the experimental infection. In contrast, the boar-pig hybrids administered the bait vaccine did not show any clinical signs. Our data indicated that boar-pig hybrids and domestic pigs have similar susceptibility to the recent Japanese CSFV. Additionally, the bait vaccine is effective against the CSFV.
The Glaesserella parasuis phosphoglucomutase is partially required for lipooligosaccharide synthesis
Authors: Feng Saixiang , Chen Aihua , Wang Xiaobing , Pan Zhichao , Xu Siqi , Yu Huiwen , Zhang Bin , Liao Ming 
Published: July 2020

AbstractLipooligosaccharides (LOSs) are virulence determinants of Glaesserella parasuis, a pathogen of the respiratory tract of pigs. We previously reported that disruption of the galU or galE gene in G. parasuis results in increased sensitivity to porcine serum, indicating that the galactose catabolism pathway is required for polysaccharide formation in G. parasuis. Here, we evaluated the role of the HAPS_0849 gene in LOS synthesis. The G. parasuis SC096 HAPS_0849 mutant produced a highly truncated LOS molecule, although a small fraction of intact LOS was still observed, and this mutant was found to be more sensitive to serum than the parental strain. HAPS_0849 was overexpressed and purified for biochemical assays, and this protein exhibited phosphoglucomutase (PGM) activity. Heterologous expression of a pgm gene from Escherichia coli in the HAPS_0849 mutant led to restoration of the wild-type LOS glycoform, further demonstrating the PGM function of HAPS_0849 in G. parasuis. The autoagglutination and biofilm formation ability of this strain were also investigated. Disruption of HAPS_0849 led to an increased tendency to autoagglutinate and form more biofilms, and these enhanced phenotypes were observed in the absence of glucose. In addition, LOSs from HAPS_0849, galU and lgtB mutants had similar truncated glycoforms, while LOSs from the galE and lex-1 mutants exhibited another type of defective LOS pattern. These findings imply that HAPS_0849 may function upstream of GalU in the generation of glucose 1-phosphate. In conclusion, our results preliminarily described the functions of HAPS_0849 in G. parasuis, and this gene was partially required for LOS synthesis.
RETRACTED ARTICLE: MicroRNA-143 targets MAPK3 to regulate the proliferation and bone metastasis of human breast cancer cells
Authors: Du Yiqun , Zhang Jian , Meng Yanchun , Huang Mingzhu , Yan Wangjun , Wu Zhiqiang 
Published: July 2020

AbstractMicroRNAs (miRs) have shown tremendous potential to act as therapeutic targets for cancer treatment. In this context, the present study was designed to investigate the potential of miR-143 in the treatment of breast cancer. Results showed that miR-143 to be significantly (P < 0.05) downregulated in breast cancer tissues and cell lines. The miR-143 has inhibitory effect on CAMA-1cell growth which was manifested as significant (P < 0.05) decline in loss of viability of cancer cells. The loss of cell viability was revealed to be due to the induction of apoptotic cell death as evident from acridine orange/ethidium bromide (AO/EB) and 4′,6-diamidino-2-phenylindole (DAPI) staining assays. The apoptotic cell percentage was found to be 35.7% in miR-143 mimics transfected in comparison to 6.4% in miR-NC transfected cells. The western blot analysis showed that miR-143 caused enhancement in Bax and suppression in Bcl-2 expression in CAMA-1 cells. The miR-143 also suppressed the bone metastasis of the CAMA-1 cells by suppressing the expression of Jag1 and deactivation of the Rho-signalling pathway. The transwell assays also showed considerable anti-metastatic effects of miR-143 on CAMA-1 cells. Taken together, miR-143 has growth inhibitory anti-metastatic effect on breast cancer and thus may prove beneficial in breast cancer treatment.
Existence and multiplicity of solutions for nonlocal fourth-order elliptic equations with combined nonlinearities
Authors: Yuanfang Ru , Yukun An 
Published: July 2020

AbstractThis paper is concerned with the following nonlocal fourth-order elliptic problem:$$\begin{aligned} \textstyle\begin{cases} \Delta ^{2}u-m(\int _{\varOmega } \vert \nabla u \vert ^{2} \,dx)\Delta u=a(x) \vert u \vert ^{s-2}u+f(x,u), \quad x\in \varOmega , \\ u=\Delta u=0,\quad x\in \partial \varOmega , \end{cases}\displaystyle \end{aligned}$${Δ2u−m(∫Ω|∇u|2dx)Δu=a(x)|u|s−2u+f(x,u),x∈Ω,u=Δu=0,x∈∂Ω,by using the mountain pass theorem, the least action principle, and the Ekeland variational principle, the existence and multiplicity results are obtained.
Predicting the success of entrepreneurial campaigns in crowdfunding: a spatio-temporal approach
Authors: Woods Clinton , Yu Han , Huang Hong 
Published: July 2020

AbstractAs an alternative to traditional venture capital investment, crowdfunding has emerged as a novel method and potentially disruptive innovation for financing a variety of new entrepreneurial ventures without standard financial intermediaries. It is still unknown to scholars and people who use crowdfunding services whether the crowdfunding efforts reinforce or contradict existing theories about the dynamics of successful entrepreneurial financing as well as the general distribution and use of crowdfunding mechanisms. This paper presents new results obtained from investigating the Kickstarter campaign data of over ninety-nine thousand projects totaling about 1 billion USD in pledges from 2009 until the most recent 2017 through dynamical spatio-temporal modeling. The funding level, the percentage of a project’s goal actually raised from online communities, is used as the outcome of interest in the modeling to associate with dollar pledged and backer count that reflect the signals of underlying project quality. Evidence from the results was found to support the dynamic impact of the geographic location of a Kickstarter on its success and the associations between the observed project traits and the success of the entrepreneurial effort in the presence of the unmeasured spatio-temporal confounding. These results offer further insight into the empirical dynamics of the emerging phenomenon of online entrepreneurial financing about the role the spatio-temporal component plays in both the type of projects proposed and the association of sociocultural traits of successful fundraising with the underlying quality.
Are three antiseptic paints needed for safe preparation of the surgical field? A prospective cohort study with 239 patients
Authors: Roth Jan A. , Schwab Cyrill , Atkinson Andrew , von Flüe Markus , Kettelhack Christoph , Eckstein Friedrich S. , Battegay Manuel , Klimke Steffi , Frei Reno , Widmer Andreas F. 
Published: July 2020

Abstract
Background
Preoperative skin antisepsis is an essential component of safe surgery. However, it is unclear how many antiseptic paints are needed to eliminate bacteria prior to incision. This study compared microbial skin counts after two and three antiseptic paints.

Methods
We conducted a prospective cohort study in non-emergency patients receiving a cardiac/abdominal surgery with standardized, preoperative skin antisepsis consisting of an alcoholic compound and either povidone iodine (PI) or chlorhexidine (CHX). We obtained three skin swabs from the participant’s thorax/abdomen using a sterile template with a 25 cm2 window: After collection of the first swab prior to skin antisepsis, and once the second and third application of PI/CHX had dried out, we obtained a second and third swab, respectively. Our primary outcome was the reduction in microbial skin counts after two and three paints of PI/CHX.

Results
Among the 239 enrolled patients, there was no significant difference in the reduction of mean square root-transformed microbial skin counts with three versus two paints (P = 0.2). But distributions of colony forming units (CFUs) decreased from paint 2 to 3 in a predefined analysis (P = 0.002). There was strong evidence of an increased proportion of patients with zero CFU after paint 3 versus paint 2 (P = 0.003). We did not identify risk factors for insufficient reduction of microbial skin counts after two paints, defined as the detection of > 5 CFUs and/or ≥ 1 pathogens.

Conclusions
In non-emergency surgical patients, three antiseptic paints may be superior to two paints in reducing microbial skin colonization prior to surgery.