bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel R2R3-MYB from grape hyacinth, MaMybA, which is different from MaAN2, confers intense and magenta anthocyanin pigmentation in tobacco
Authors: Chen Kaili , Du Lingjuan , Liu Hongli , Liu Yali 
Published: September 2019

Abstract

Background
The primary pigments in flowers are anthocyanins, the biosynthesis of which is mainly regulated by R2R3-MYBs. Muscari armeniacum is an ornamental garden plant with deep cobalt blue flowers containing delphinidin-based anthocyanins. An anthocyanin-related R2R3-MYB MaAN2 has previously been identified in M. armeniacum flowers; here, we also characterized a novel R2R3-MYB MaMybA, to determine its function and highlight similarities and differences between MaMybA and MaAN2.

Results
In this study, a novel anthocyanin-related R2R3-MYB gene was isolated from M. armeniacum flowers and functionally identified. A sequence alignment showed that MaMybA contained motifs typically conserved with MaAN2 and its orthologs. However, the shared identity of the entire amino acid sequence between MaMybA and MaAN2 was 43.5%. Phylogenetic analysis showed that they were both clustered into the AN2 subgroup of the R2R3-MYB family, but not in the same branch. We also identified a IIIf bHLH protein, MabHLH1, in M. armeniacum flowers. A bimolecular fluorescence complementation assay showed that MabHLH1 interacted with MaMybA or MaAN2 in vivo; a dual luciferase assay indicated that MaMybA alone or in interaction with MabHLH1 could regulate the expression of MaDFR and AtDFR, but MaAN2 required MabHLH1 to do so. When overexpressing MaMybA in Nicotiana tabacum ‘NC89’, the leaves, petals, anthers, and calyx of transgenic tobacco showed intense and magenta anthocyanin pigments, whereas those of OE-MaAN2 plants had lighter pigmentation. However, the ovary wall and seed skin of OE-MaMybA tobacco were barely pigmented, while those of OE-MaAN2 tobacco were reddish-purple. Moreover, overexpressing MaMybA in tobacco obviously improved anthocyanin pigmentation, compared to the OE-MaAN2 and control plants, by largely upregulating anthocyanin biosynthetic and endogenous bHLH genes. Notably, the increased transcription of NtF3′5′H in OE-MaMybA tobacco might lead to additional accumulation of delphinidin 3-rutinoside, which was barely detected in OE-MaAN2 and control plants. We concluded that the high concentration of anthocyanin and the newly produced Dp3R caused the darker color of OE-MaMybA compared to OE-MaAN2 tobacco.

Conclusion
The newly identified R2R3-MYB transcription factor MaMybA functions in anthocyanin biosynthesis, but has some differences from MaAN2; MaMybA could also be useful in modifying flower color in ornamental plants.
Microbiological and clinical characteristics of Streptococcus gallolyticus subsp. pasteurianus infection in China
Authors: Li Yi , Chen Xingchun , Zhang Zhijun , Wang Lijun , Wang Junrui , Zeng Ji , Yang Junwen , Lu Binghuai 
Published: September 2019

Abstract

Background
Infections by Streptococcus gallolyticus subsp. pasteurianus (SGSP) is often underestimated. Herein, the epidemiological features and resistant characteristics of SGSP in mainland China are characterized to enable a better understanding of its role in clinical infections.

Methods
In the present work, 45 SGSP isolates were collected from the samples of bloodstream, urine, aseptic body fluid, and fetal membrane/placenta from patients in 8 tertiary general hospitals of 6 cities/provinces in China from 2011 to 2017. The identification of all isolates was performed using traditional biochemical methods, 16S rRNA and gyrB sequencing, followed by the characterization of their antibiotic resistance profiling and involved genes.

Results
Among 34 non-pregnancy-related patients, 4 (4/34,11.8%) patients had gastrointestinal cancer, 10 (10/34, 29.4%) patients had diabetes, and one patient had infective endocarditis. Moreover, 11 cases of pregnant women were associated with intrauterine infection (9/11, 81.2%) and urinary tract infection (1/11, 9.1%), respectively. Except one, all other SGSP isolates were correctly identified by the BD Phoenix automated system. We found that all SGSP isolates were phenotypically susceptible to penicillin, ampicillin, cefotaxime, meropenem, and vancomycin. Forty strains (40/45, 88.9%) were both erythromycin and clindamycin-resistant, belonging to the cMLSB phenotype, and the majority of them carried erm(B) gene (39/40, 97.5%). Although the cMLSB/erm(B) constituted the most frequently identified phenotype/genotype combination (25/40, 62.5%) among all erythromycin-resistant cMLSB isolates, erm(B)/erm(A), erm(B)/mef(A/E), and erm(B)/erm(T) was detected in 7, 4, and 3 isolates, respectively. Furthermore, 43 strains (43/45, 95.6%) were tetracycline-resistant, and out of these, 39 strains (39/45, 86.7%) carried tet(L), 27(27/45, 60.0%) strains carried tet(O), and 7 (7/45, 15.6%) strains carried tet(M), alone or combined, respectively. All erythromycin-resistant isolates were also resistant to tetracycline.

Conclusions
It is important to study and draw attention on SGSP, an underreported opportunistic pathogen targeting immunodeficient populations, notably elderly subjects, pregnant women and neonates.
“If there are no female nurses to attend to me, I will just go and deliver at home”: a qualitative study in Garissa, Kenya
Authors: N’Gbichi Coralie , Ziraba Abdhalah Kasiira , Wambui David Wainaina , Bakibinga Pauline , Kisiangani Isaac , Njoroge Pauline , Noor Rumana , Njoroge Ngugi , Salah Raha Abdi , Mohamed Elmi 
Published: September 2019

Abstract

Background
The North Eastern region in Kenya experiences challenges in the utilization of maternal and newborn health services. In this region, culture and religion play a major role in influencing healthcare seeking behaviour of the community. This study was conducted to (i) understand key inherent barriers to health facility delivery in the Somali community of North Eastern Kenya and (ii) inform interventions on specific needs of this community.

Methods
The study was conducted among community members of Garissa sub-County as part of a baseline assessment before the implementation of an intervention package aimed at creating demand and increasing utilization of maternal and newborn services. Focus group discussions and key informant interviews were conducted with clan leaders, Imams, health managers, member of the county assembly, and service users (women and men) in three locations of Garissa sub-County. Data were analysed through content analysis, by coding recurrent themes and pre-established themes.

Results
Using health facility for delivery was widely acceptable and most respondents acknowledged the advantages and benefits of skilled birth delivery. However, a commonly cited barrier in using health facility delivery was the issue of male nurses and doctors attending to women in labour. According to participants, it is against their culture and thus a key disincentive to using maternity services. Living far from the health facility and lack of a proper and reliable means of transportation was also highlighted as a reason for home delivery. At the health facility level, respondents complained about the poor attitude of health care providers, especially female nurses being disrespectful; and the limited availability of healthcare workers, equipment and supplies. Lack of awareness and information on the importance of skilled birth attendance was also noted.

Conclusion
To increase health facility delivery, interventions need to offer services that take into consideration the sociocultural aspect of the recipients. Culturally acceptable and sensitive services, and awareness on the benefits of skilled birth attendance among the community members are likely to attract more women to use maternity services and thus reduce adverse maternal and newborn health outcomes.
A validated natural language processing algorithm for brain imaging phenotypes from radiology reports in UK electronic health records
Authors: Wheater Emily , Mair Grant , Sudlow Cathie , Alex Beatrice , Grover Claire , Whiteley William 
Published: September 2019

Abstract

Background
Manual coding of phenotypes in brain radiology reports is time consuming. We developed a natural language processing (NLP) algorithm to enable automatic identification of brain imaging in radiology reports performed in routine clinical practice in the UK National Health Service (NHS).

Methods
We used anonymized text brain imaging reports from a cohort study of stroke/TIA patients and from a regional hospital to develop and test an NLP algorithm. Two experts marked up text in 1692 reports for 24 cerebrovascular and other neurological phenotypes. We developed and tested a rule-based NLP algorithm first within the cohort study, and further evaluated it in the reports from the regional hospital.

Results
The agreement between expert readers was excellent (Cohen’s κ =0.93) in both datasets. In the final test dataset (n = 700) in unseen regional hospital reports, the algorithm had very good performance for a report of any ischaemic stroke [sensitivity 89% (95% CI:81–94); positive predictive value (PPV) 85% (76–90); specificity 100% (95% CI:0.99–1.00)]; any haemorrhagic stroke [sensitivity 96% (95% CI: 80–99), PPV 72% (95% CI:55–84); specificity 100% (95% CI:0.99–1.00)]; brain tumours [sensitivity 96% (CI:87–99); PPV 84% (73–91); specificity: 100% (95% CI:0.99–1.00)] and cerebral small vessel disease and cerebral atrophy (sensitivity, PPV and specificity all > 97%). We obtained few reports of subarachnoid haemorrhage, microbleeds or subdural haematomas. In 110,695 reports from NHS Tayside, atrophy (n = 28,757, 26%), small vessel disease (15,015, 14%) and old, deep ischaemic strokes (10,636, 10%) were the commonest findings.

Conclusions
An NLP algorithm can be developed in UK NHS radiology records to allow identification of cohorts of patients with important brain imaging phenotypes at a scale that would otherwise not be possible.
The effectiveness of military hospital-based drug treatment program (PMK) when compared with the traditional community-based drug treatment program (FAST)
Authors: Kaewkham Niramon , Leelahanaj Thawatchai , Yingwiwattanapong Jatsada , Rattanasumawong Wanida 
Published: September 2019

Abstract

Background
In Thailand, two community-based drug treatment approaches are common. The first one is the traditional community-based treatment program (FAST) which brings the principles of community therapy as a guideline for treatment. The second one is the military hospital-based drug treatment program (PMK), derived from the basic military training, the Buddhist Twelve Steps, CBT and the Minnesota Rehabilitation Model. This study aimed to investigate and compare the efficacy of PMK vs. FAST.

Method
The experiment was conducted from January–March 2016 at the rehabilitation center for patients with drug addiction in Thailand. Quasi-experimental methods were introduced, and ASSIST, WHOQOL-BRIEF-THAI and self-efficacy interview form were applied. After completing the drug rehabilitation program at a total duration of 120 days, the researcher continued at follow up times at 3 and 6 months.

Results
Compared with baseline scores, both programs significantly reduced the severity of drugs and increased self-efficacy at 6-month follow-up. PMK had better improved scores in the relationship and environment dimensions of quality of life at 3-month follow-up (P = 0.026, 0.006). The mean quality of life scores in PMK at 3 and 6 months showed better results than mean scores at baseline (P = < 0.001).

Conclusion
Both community-based programs in Thailand significantly reduced the severity of drugs and increased self-efficacy scores at 6-month follow-up. PMK and FAST has not shown any significant difference in treatment outcome results in the aspects of self-efficacy and reduced severity of drugs used. However, PMK had significant positive effects on the quality of life.
Enhancer variants associated with Alzheimer’s disease affect gene expression via chromatin looping
Authors: Kikuchi Masataka , Hara Norikazu , Hasegawa Mai , Miyashita Akinori , Kuwano Ryozo , Ikeuchi Takeshi , Nakaya Akihiro 
Published: September 2019

Abstract

Background
Genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms (SNPs) that may be genetic factors underlying Alzheimer’s disease (AD). However, how these AD-associated SNPs (AD SNPs) contribute to the pathogenesis of this disease is poorly understood because most of them are located in non-coding regions, such as introns and intergenic regions. Previous studies reported that some disease-associated SNPs affect regulatory elements including enhancers. We hypothesized that non-coding AD SNPs are located in enhancers and affect gene expression levels via chromatin loops.

Methods
To characterize AD SNPs within non-coding regions, we extracted 406 AD SNPs with GWAS p-values of less than 1.00 × 10− 6 from the GWAS catalog database. Of these, we selected 392 SNPs within non-coding regions. Next, we checked whether those non-coding AD SNPs were located in enhancers that typically regulate gene expression levels using publicly available data for enhancers that were predicted in 127 human tissues or cell types. We sought expression quantitative trait locus (eQTL) genes affected by non-coding AD SNPs within enhancers because enhancers are regulatory elements that influence the gene expression levels. To elucidate how the non-coding AD SNPs within enhancers affect the gene expression levels, we identified chromatin-chromatin interactions by Hi-C experiments.

Results
We report the following findings: (1) nearly 30% of non-coding AD SNPs are located in enhancers; (2) eQTL genes affected by non-coding AD SNPs within enhancers are associated with amyloid beta clearance, synaptic transmission, and immune responses; (3) 95% of the AD SNPs located in enhancers co-localize with their eQTL genes in topologically associating domains suggesting that regulation may occur through chromatin higher-order structures; (4) rs1476679 spatially contacts the promoters of eQTL genes via CTCF-CTCF interactions; (5) the effect of other AD SNPs such as rs7364180 is likely to be, at least in part, indirect through regulation of transcription factors that in turn regulate AD associated genes.

Conclusion
Our results suggest that non-coding AD SNPs may affect the function of enhancers thereby influencing the expression levels of surrounding or distant genes via chromatin loops. This result may explain how some non-coding AD SNPs contribute to AD pathogenesis.
LncRNA SNHG6 promotes chemoresistance through ULK1-induced autophagy by sponging miR-26a-5p in colorectal cancer cells
Authors: Wang Xinke , Lan Zhixian , He Juan , Lai Qiuhua , Yao Xiang , Li Qingyuan , Liu Yongfeng , Lai Huasheng , Gu Chuncai , Yan Qun , Fang Yuxin , Zhang Yue , Li Aimin , Liu Side 
Published: September 2019

Abstract

Background
Chemotherapy resistance is one of the main causes of recurrence in colorectal cancer (CRC) patients and leads to poor prognosis. Long noncoding RNAs (lncRNAs) have been reported to regulate chemoresistance. We aimed to determine the role of the lncRNA small nucleolar RNA host gene 6 (SNHG6) in CRC cell chemoresistance.

Methods
Cell drug sensitivity tests and flow cytometry were performed to analyze CRC cell chemoresistance. Animal models were used to determine chemoresistance in vivo, and micro RNA (miRNA) binding sites were detected by dual-luciferase reporter assays. Bioinformatics analysis was performed to predict miRNAs binding to SNHG6 and target genes of miR-26a-5p. SNHG6/miR-26a-5p/ULK1 axis and autophagy-related proteins were detected by qRT-PCR and western blotting. Furthermore, immunofluorescence was employed to confirm the presence of autophagosomes.

Results
SNHG6 enhanced CRC cell resistance to 5-fluorouracil (5-FU), promoted autophagy, inhibited 5-FU-induced apoptosis, and increased 5-FU resistance in vivo. Bioinformatics analysis showed that miR-26a-5p might bind to SNHG6 and target ULK1, and dual-luciferase reporter assays confirmed this activity. qRT-PCR and western blotting showed that SNHG6 was able to negatively regulate miR-26a-5p but correlated positively with ULK1.

Conclusion
SNHG6 may promote chemoresistance through ULK1-induced autophagy by sponging miR-26a-5p in CRC cells.
Adaptive step size algorithm to increase efficiency of proton macro Monte Carlo dose calculation
Authors: Kueng Reto , Frei Daniel , Volken Werner , Stuermlin Fabian , M. Stampanoni Marco F. , Aebersold Daniel M. , Manser Peter , Fix Michael K. 
Published: September 2019

Abstract

Purpose
To provide fast and accurate dose calculation in voxelized geometries for proton radiation therapy by implementing an adaptive step size algorithm in the proton macro Monte Carlo (pMMC) method.

Methods
The in-house developed local-to-global MMC method for proton dose calculation is extended with an adaptive step size algorithm for efficient proton transport through a voxelized geometry by sampling transport parameters from a pre-simulated database. Adaptive choice of an adequate slab size in dependence of material interfaces in the proton’s longitudinal and lateral vicinity is investigated. The dose calculation algorithm is validated against the non-adaptive pMMC and full MC simulation for pencil and broad beams with various energies impinging on academic phantoms as well as a head and neck patient CT.

Results
For material interfaces perpendicular to a proton’s direction, choice of nearest neighbor slab thickness shows best trade-off between dosimetric accuracy and calculation efficiency. Adaptive reduction of chosen slab size is shown to be required for material interfaces closer than 0.5 mm in lateral direction. For the academic phantoms, dose differences of within 1% or 1 mm compared to full Geant4 MC simulation are found, while achieving an efficiency gain of up to a factor of 5.6 compared to the non-adaptive algorithm and 284 compared to Geant4. For the head and neck patient CT, dose differences are within 1% or 1 mm with an efficiency gain factor of up to 3.4 compared to the non-adaptive algorithm and 145 compared to Geant4.

Conclusion
An adaptive step size algorithm for proton macro Monte Carlo was implemented and evaluated. The dose calculation provides the accuracy of full MC simulations, while achieving an efficiency gain factor of three compared to the non-adaptive algorithm and two orders of magnitude compared to full MC for a complex patient CT.
Human papilloma virus (HPV) genotypes concordance between Iranian couples referrals
Authors: Davarmanesh Mehrdad , Dezfulian Mehrouz , Gharavi Mohammad Javad , Younesi Sarang , Saadati Pourandokht , Amin Mohammad Mehdi Taheri , Jazayeri Seyed Mohammad 
Published: September 2019

Abstract

Background
Human Papilloma Virus (HPV) genotypes concordance among sexual couples has been evaluated in many investigations with considerable variations in the concordance. However, no such study has carried out between Iranian couples yet.

Methods
Urogenital specimen from both males and females of couples were taken and transferred to Nilou laboratory for molecular analysis. HPV DNA extraction and typing were carried out using cobas 4800 platform. Demographic and virological data were analyzed afterwards.

Results
One hundred fourteen couples were enrolled in the study. The mean age of participants were 36 ± 8 and 32 ± 7 for males and females, respectively. 64 (28%) of specimens were positive for at least one HPV genotype. The positive rates within genders were 30.7 and 25.4% for females and males, respectively with a considerable association (P value 0.021). Within the positive samples, 13(5.7%), 8 (7%) and 31(13.5%) were belonged to 16, 18 and other HR genotypes. 59 (51.8%) couples who were negative for HPV showed negative concordance. Of the total positive HPV patients (55 couples, 48.2%), 9 (16.3%) couples had positive concordance and the rest of 46 (83.7%) couples (either of spouse being negative and the other being positive for HPV) showed neither kinds of concordance.

Conclusion
Recognition of the dynamics of HPV infection not only in women, but in their sexual partners could impact the implementation of preventive measures like HPV vaccination for cervical cancer and other HPV-related diseases for both sexual partners.
Body weight at 10 years of age and change in body composition between 8 and 10 years of age were related to survival in a longitudinal study of 39 Labrador retriever dogs
Authors: Penell Johanna Christina , Morgan David Mark , Watson Penny , Carmichael Stuart , Adams Vicki Jean 
Published: September 2019

AbstractBackgroundOverweight and obesity have been adversely associated with longevity in dogs but there is scarce knowledge on the relation between body composition and lifespan. We aimed to investigate the effects of body composition, and within-dog changes over time, on survival in adult Labradors using a prospective cohort study design. The dogs had a median age of 6.5 years at study start and were kept in similar housing and management conditions throughout. The effects of the various predictors, including the effect of individual monthly-recorded change in body weight as a time varying covariate, were evaluated using survival analysis.ResultsAll dogs were followed to end-of-life; median age at end-of-life was 14.0 years. Body composition was measured annually with dual-energy x-ray absorptiometer (DEXA) scans between 6.2 and 17.0 years. All 39 dogs had DEXA recorded at 8, 9 and 10 years of age. During the study the mean (± SD) percent of fat (PF) and lean mass (PL) was 32.8 (± 5.6) and 64.2 (± 5.5) %, respectively, with a mean lean:fat ratio (LFR) of 2.1 (± 0.6); body weight (BW) varied from 17.5 to 44.0 kg with a mean BW change of 9.9 kg (± 3.0). There was increased hazard of dying for every kg increase in BW at 10 years of age; for each additional kg of BW at 10 years, dogs had a 19% higher hazard (HR = 1.19, P = 0.004). For the change in both lean mass (LM) and LFR variables, it was protective to have a higher lean and/or lower fat mass (FM) at 10 years of age compared to 8 years of age, although the HR for change in LM was very close to 1.0. For age at study start, older dogs had an increased hazard. There was no observed effect for the potential confounders sex, coat colour and height at shoulders, or of the time-varying covariate.ConclusionsThese results suggest that even rather late-life control efforts on body weight and the relationship between lean and fat mass may influence survival in dogs. Such “windows of opportunity” can be used to develop healthcare strategies that would help promote an increased healthspan in dogs.
CUT&RUNTools: a flexible pipeline for CUT&RUN processing and footprint analysis
Authors: Zhu Qian , Liu Nan , Orkin Stuart H. , Yuan Guo-Cheng 
Published: September 2019

Abstract
We introduce CUT&RUNTools as a flexible, general pipeline for facilitating the identification of chromatin-associated protein binding and genomic footprinting analysis from antibody-targeted CUT&RUN primary cleavage data. CUT&RUNTools extracts endonuclease cut site information from sequences of short-read fragments and produces single-locus binding estimates, aggregate motif footprints, and informative visualizations to support the high-resolution mapping capability of CUT&RUN. CUT&RUNTools is available at https://bitbucket.org/qzhudfci/cutruntools/.