bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic analysis of α-linolenic acid content and biosynthesis in Paeonia ostii fruits and seeds
Authors: Yu Shui-Yan , Zhang Xiao , Huang Liang-Bo , Lyu Yu-Ping , Zhang Ying , Yao Zu-Jie , Zhang Xiao-Xiao , Yuan Jun-Hui , Hu Yong-Hong 
Published: April 2021

Abstract
Background
Paeonia ostii is a potentially important oilseed crop because its seed yield is high, and the seeds are rich in α-linolenic acid (ALA). However, the molecular mechanisms underlying ALA biosynthesis during seed kernel, seed testa, and fruit pericarp development in this plant are unclear. We used transcriptome data to address this knowledge gap.

Results
Gas chromatograph-mass spectrometry indicated that ALA content was highest in the kernel, moderate in the testa, and lowest in the pericarp. Therefore, we used RNA-sequencing to compare ALA synthesis among these three tissues. We identified 227,837 unigenes, with an average length of 755 bp. Of these, 1371 unigenes were associated with lipid metabolism. The fatty acid (FA) biosynthesis and metabolism pathways were significantly enriched during the early stages of oil accumulation in the kernel. ALA biosynthesis was significantly enriched in parallel with increasing ALA content in the testa, but these metabolic pathways were not significantly enriched during pericarp development. By comparing unigene transcription profiles with patterns of ALA accumulation, specific unigenes encoding crucial enzymes and transcription factors (TFs) involved in de novo FA biosynthesis and oil accumulation were identified. Specifically, the bell-shaped expression patterns of genes encoding SAD, FAD2, FAD3, PDCT, PDAT, OLE, CLE, and SLE in the kernel were similar to the patterns of ALA accumulation in this tissue. Genes encoding BCCP, BC, KAS I– III, and FATA were also upregulated during the early stages of oil accumulation in the kernel. In the testa, the upregulation of the genes encoding SAD, FAD2, and FAD3 was followed by a sharp increase in the concentrations of ALA. In contrast, these genes were minimally expressed (and ALA content was low) throughout pericarp development.

Conclusions
We used three tissues with high, moderate, and low ALA concentrations as an exemplar system in which to investigate tissue-specific ALA accumulation mechanisms in P. ostii. The genes and TFs identified herein might be useful targets for future studies of ALA accumulation in the tree peony. This study also provides a framework for future studies of FA biosynthesis in other oilseed plants.
Concentrations of estradiol, progesterone and testosterone in serum and cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage correlate weakly with transcranial Doppler flow velocities
Authors: Martin Jan , Plank Eva , Ulm Bernhard , Gempt Jens , Wostrack Maria , Jungwirth Bettina , Kagerbauer Simone M. 
Published: April 2021

Abstract
Background
The implication of the steroids estradiol, progesterone and testosterone in cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) has not been comprehensively assessed. In rodents, studies suggested beneficial effects of steroids on cerebral vasospasm after experimental SAH. Studies in humans are warranted, however, a general dilemma of human studies on neuroactive substances is that the brain is not directly accessible and that concentrations in the periphery may not adequately parallel concentrations in the central compartments. In the present study, concentrations of estradiol, progesterone and testosterone in serum and cerebrospinal fluid (CSF) of patients with aSAH were determined. Blood flow velocities in cerebral arteries were measured by transcranial Doppler sonography (TCD). The aim of this study was to evaluate the correlations between the cerebral blood flow velocities and levels of estradiol, progesterone and testosterone in CSF and serum.

Results
Samples of serum and CSF of 42 patients with aSAH were collected concomitantly daily or every other day via the arterial line and the external ventricular drainage for two weeks after the hemorrhage. Blood flow velocities in the cerebral arteries were determined by TCD. Total estradiol, progesterone and testosterone concentrations were measured by electro-chemiluminescence immunoassay. The strength of correlation was assessed by Spearman’s rank correlation coefficient. The correlation analysis revealed very weak correlations between cerebral blood flow velocities and concentrations of estradiol, progesterone and testosterone levels in both compartments with correlation coefficients below 0.2.

Conclusions
In humans with aSAH, merely very weak correlations between flow velocities in cerebral arteries and concentrations of estradiol, progesterone and testosterone in serum and CSF were demonstrated. These results suggest a limited influence of the respective steroids on cerebral vascular tone although vasodilatory effects were described in rodent studies. Thus, the implication of steroids in processes of neurological deterioration warrants further clarification.
Circulating miRNA-202-3p is a potential novel biomarker for diagnosis of type 1 gastric neuroendocrine neoplasms
Authors: Dou Dou , Li Xiao-kou , Xia Qi-sheng , Chen Ying-ying , Li Yuan-liang , Wang Chao , Qi Zhi-rong , Tan Huang-ying 
Published: April 2021

AbstractBackgroundCurrently, there are no circulating diagnostic biomarkers for gastric neuroendocrine neoplasms (g-NENs). In previous studies, we found that miRNA-202-3p is overexpressed in the tumour tissue of type 1 g-NEN. We speculated that miRNA-202-3p is also likely to be highly expressed in circulating blood.MethodsA total of 27 patients with type 1 g-NEN and 27 age- and sex-matched control participants were enrolled in this study. The miRNA-202-3p levels in serum obtained from the participants were measured by qRT‐PCR. The expression level of miRNA-202-3p in the samples was calculated by comparison with a standard curve.ResultsThe clinical characteristics of the patients were similar to those of the patient samples in previous reports. Expression of miRNA-202-3p was significantly higher in the patient group (3.84 × 107copies/nl) than in the control group (0.635 × 107copies/nl). The area under the ROC curve (AUC) was 0.878 (95% CI: 0.788–0.968), and the optimal cut-off point was approximately 1.12 × 107copies/nl. The sensitivity and specificity were 88.9% and 77.8%, respectively.ConclusionThis study suggests that miRNA-202-3p is potentially useful as a biomarker of type 1 g-NEN; further investigation and verification should be performed in future research.
Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations
Authors: Mikasi Sello Given , Isaacs Darren , Chitongo Rumbidzai , Ikomey George Mondide , Jacobs Graeme Brendon , Cloete Ruben 
Published: April 2021

Abstract
Background
The Integrase (IN) strand transfer inhibitor (INSTI), Dolutegravir (DTG), has been given the green light to form part of first-line combination antiretroviral therapy (cART) by the World Health Organization (WHO). DTG containing regimens have shown a high genetic barrier against HIV-1 isolates carrying specific resistance mutations when compared with other class of regimens.

Methods
We evaluated the HIV-1 CRF02_AG IN gene sequences from Cameroon for the presence of resistance-associated mutations (RAMs) against INSTIs and naturally occurring polymorphisms (NOPs), using study sequences (n = 20) and (n = 287) sequences data derived from HIV Los Alamos National Laboratory database. The possible impact of NOPs on protein structure caused by HIV-1 CRF02_AG variations was addressed within the context of a 3D model of the HIV-1 IN complex and interaction analysis was performed using PyMol to validate DTG binding to the Wild type and seven mutant structures.

Results
We observed 12.8% (37/287) sequences to contain RAMs, with only 1.0% (3/287) of the sequences having major INSTI RAMs: T66A, Q148H, R263K and N155H. Of these,11.8% (34/287) of the sequences contained five different IN accessory mutations; namely Q95K, T97A, G149A, E157Q and D232N. NOPs occurred at a frequency of 66% on the central core domain (CCD) position, 44% on the C-terminal domain (CTD) position and 35% of the N-terminal domain (NTD) position. The interaction analysis revealed that DTG bound to DNA, 2MG ions and DDE motif residues for T66A, T97A, Q148H, N155H and R263K comparable to the WT structure. Except for accessory mutant structure E157Q, only one MG contact was made with DTG, while DTG had no MG ion contacts and no DDE motif residue contacts for structure D232N.

Conclusions
Our analysis indicated that all RAM’s that resulted in a change in the number of interactions with encompassing residues does not affect DTG binding, while accessory mutations E157Q and D232N could affect DTG binding leading to possible DTG resistance. However, further experimental validation is required to validate the in silico findings of our study.
Prevalence of sexually transmitted infections among cervical cancer suspected women at University of Gondar Comprehensive Specialized Hospital, North-west Ethiopia
Authors: Abebe Milkias , Eshetie Setegn , Tessema Belay 
Published: April 2021

Abstract
Background
Sexually transmitted infections (STIs) such as Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and Syphilis have continued a significant public health problem, especially in areas with substandard infection prevention and control programs. It is known that STIs are largely associated with the increased occurrence of cervical cancer. To date, little is known about the burden of STIs among cervical cancer suspected women in Ethiopia.

Objectives
To assess the seroprevalence of STIs and associated risk factors among cervical cancer suspected women with special emphasis on HIV, HBV, HCV, and Syphilis.

Methods
A hospital-based cross-sectional study was conducted among cervical cancer suspected women at the University of Gondar Comprehensive Specialized Hospital from February to April 2017. A pre-tested and structured questionnaire was used to collect data on patients’ characteristics. The patient’s serum or plasma samples were tested for HIV, HBV, HCV, and syphilis using enzyme-linked immunosorbent assay. In all aspects, the standard operational procedure was strictly followed. Data were analyzed using SPSS version 20 software and presented using tables. Statistical associations were measured using bivariate and multivariable logistic regression. A p-value of below 0.05 was considered statistically significant.

Result
A total of 403 cervical cancer suspected women with the mean age of 42.54 (SD + 11. 24) years were enrolled in the study. The overall prevalence of STIs was 16.6% (67/403) and the prevalence of HIV, HBV, HCV, and syphilis was 36/403 (8.9%), 10/403 (2.5%), 4/403 (1%), and 29/403 (7.2%) respectively. History of multiple sexual partners (Adjusted OR = 3.02, 95%CI 1.57–5.79, P = 0.001), alcohol addiction (Adjusted OR = 2.2, 95%CI 1.07–4.5, P = 0.031), history of STI (Adjusted OR = 3.38; 95% CI: 1.76–6.47, P = 0.00) and not use of condom (Adjusted OR = 4.99; 95% CI: 1.5–16.16, P = 0.007) were significantly associated with STIs.

Conclusion
The prevalence of STIs was generally higher among cervical cancer suspected patients. Health education is encouraged to promote awareness about the prevention of STIs.
Efficacy of galcanezumab in patients with migraine who did not benefit from commonly prescribed preventive treatments
Authors: Kuruppu Dulanji K. , Tobin Joshua , Dong Yan , Aurora Sheena K. , Yunes-Medina Laura , Green A. Laine 
Published: April 2021

AbstractBackgroundGalcanezumab is a calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) indicated for the preventive treatment of migraine. While galcanezumab has demonstrated efficacy in patients who did not respond to prior preventive medications in general, its efficacy in patients who did not benefit from individual, commonly prescribed preventive treatments due to inadequate efficacy or safety/tolerability remains unknown.MethodsCONQUER was a 3-month, randomized, double-blind, placebo-controlled, phase 3b study that enrolled patients with episodic or chronic migraine who had 2 to 4 migraine preventive medication category failures in the past 10 years. Patients were randomly assigned 1:1 to receive placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose;N = 232). Post hoc analyses were conducted to determine the efficacy of galcanezumab in patients who had not benefited from six of the most commonly prescribed migraine preventive medications. The mean change from baseline in monthly migraine headache days and ≥ 50 % response rates were assessed over months 1–3. Improvement in Migraine-Specific Questionnaire Role Function-Restrictive (MSQ-RFR) scores were assessed at month 3. The endpoints were estimated via mixed model with repeated measures.ResultsThe most common treatment failures due to inadequate efficacy or safety/tolerability, which at least 20 % of patients reported trying without benefit, included topiramate, amitriptyline, propranolol, valproate or divalproex, onabotulinum toxin A, and metoprolol. Patients who had not previously benefited from these treatments had a greater mean reduction in monthly migraine headache days across months 1–3 in the galcanezumab group compared to placebo (allp < 0.01). More patients treated with galcanezumab experienced a ≥ 50 % reduction from baseline in monthly migraine headache days across months 1–3 compared to placebo (allp < 0.05). Galcanezumab-treated patients had a greater improvement in mean MSQ-RFR scores at month 3 compared to placebo (allp < 0.01).ConclusionsIn this population, galcanezumab was effective in reducing monthly migraine headache days, improving response rates, and enhancing quality of life in patients who had not previously benefited from topiramate, amitriptyline, propranolol, valproate or divalproex, onabotulinum toxin A, and/or metoprolol due to inadequate efficacy or safety/tolerability.Trial registrationClinicalTrials.govNCT03559257(CONQUER).
Integrating approaches for quality guideline development in LactaMap, an online lactation care support system
Authors: Boss Melinda , Turner Jennifer , Boss Patrick , Hartmann Peter , Pritchard Douglas , Clifford Rhonda 
Published: April 2021

Abstract
Background
Health professionals caring for women and infants experiencing difficulty with breastfeeding have reported deficiencies in evidence-based lactation knowledge. LactaMap is an online lactation care support system with more than 100 clinical practice guidelines to support breastfeeding care. Clinical practice guidelines support medical decision-making by summarising scientific evidence into systematically developed statements for specific clinical circumstances. Both common-sense and theory-based approaches have been used for guideline development and debate continues regarding which is superior. LactaMap clinical practice guidelines were created over the course of 5 years using a common-sense approach that was refined inductively. The aim of this study was to incorporate a theory-based framework approach into the methodology for ongoing update and review of LactaMap clinical practice guidelines.

Methods
The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument was chosen as the framework-based approach to appraise LactaMap guideline quality. The study was conducted in two phases. The first phase appraised all 103 original LactaMap guidelines. The second phase appraised a subset of 15 updated LactaMap guidelines using improved methodology guided by phase 1, as well as 15 corresponding original (un-updated) guidelines.

Results
Mean Domain scores for 103 LactaMap original guidelines were above 75% in 3 of the 6 AGREE II quality Domains and no mean Domain score rated poorly. Update of guideline methodology was guided by phase 1 appraisals. Improved documentation of methods relating to questions in the Rigour of Development Domain resulted in improvement in mean Domain score from 39 to 72%.

Conclusions
This study showed that a theory-based approach to guideline development methodology can be readily integrated with a common-sense approach. Factors identified by AGREE II theory-based framework provided practical guidance for changes in methodology that were integrated prior to LactaMap website publication. Demonstration of high quality in LactaMap clinical practice guideline methodology ensures clinicians and the public can have trust that the content founded on them is robust, scientific and of highest possible quality.
A high level of lncFGD5-AS1 inhibits epithelial-to-Mesenchymal transition by regulating the miR-196a-5p/SMAD6/BMP axis in gastric Cancer
Authors: Liu Lin , Zhang Cheng , Wang Jizhao , Liu Xu , Qu Hangying , Zhang Guangjian , Liang Ting , Wang Jiansheng , Zhang Jia 
Published: April 2021

Abstract
Background
Long non-coding RNA (lncRNA) was a vital factor in the progression and initiation of human cancers. This study found a new lncRNA, FGD5-AS1, which can inhibit EMT process, proliferation, and metastasis in vitro and in vivo.

Methods
qRT-PCR was employed to test the expression of lncFGD5-AS1 in 30 gastric cancer patients’ cancer tissue and para-cancer tissue. Overexpressed lncFGD5-AS1 cells shown sharply decrease of proliferation, migration, and epithelial-mesenchymal transition (EMT). miR-196a-5p/SMAD6 was confirmed as downstream molecular mechanism of lncFGD5-AS1 by expression correlation analysis and mechanism experiments. In vivo study illustrated overexpression of lncFGD5-AS1 suppression tumor growth.

Results
LncFGD5-AS1 served as a ceRNA of miR-196a-5p to release its inhibition on SMAD6, a conventional inhibitor on the BMP pathway. Comparing with normal gastric cancer cells, FGD5-AS1 overexpressed group had fewer migration cells, lower cell viability, and lower EMT transformation rate. Meanwhile, xenografts nude mice injecting with overexpressed-FGD5-AS1 cells also shown smaller tumor weight and volume.

Conclusion
In conclusion, this research supported the first evidence that FGD5-AS1 suppressed proliferation and metastasis in gastric cancer by regulating miR-196a-5p/SMAD6/BMP axis and suggested a potential therapeutic candidate for gastric cancer.
GNA14 stimulation of KLF7 promotes malignant growth of endometrial cancer through upregulation of HAS2
Authors: Wang Jing , Teng Fei , Chai Hongxia , Zhang Caixia , Liang Xiaolei , Yang Yongxiu 
Published: April 2021

Abstract
Background
Endometrial cancer (UCEC) is one of the most common gynecological malignancies. We previously found that overexpression of G protein α subunit 14 (GNA14) promoted UCEC growth. Krüppel-like factor 7 (KLF7) acts as an oncogene in various cancer types, whereas the connection between GNA14 and KLF7 in UCEC is unclear. We herein explored the involvement of GNA14/KLF7 in UCEC development.

Methods
Clinical relevance of GNA14, KLF7 and HAS2 in UCEC was analyzed from TCGA and by immunohistochemical staining. Knockdown and overexpression of indicated genes were conducted by transfecting the cells with siRNAs and lentivirus, respectively. mRNA and protein expression was detected by qRT-PCR and Western blot. CCK8, colony formation, cell cycle, apoptosis, transwell and wound healing were performed to check cell biology function in vitro. Tumor growth in nude mice was conducted to check in vivo function. RNA sequencing was used to determine dys-regulated genes.

Results
We demonstrated that GNA14 stimulated the expression of KLF7 in UCEC cells. There was a positive correlation between GNA14 and KLF7 in normal and UCEC tissues. In vitro, KLF7 promoted cell proliferation, colony formation, cell cycle progression, and migration of UCEC cells. Apoptosis was inhibited by KLF7. Xenografted tumorigenesis of UCEC cells was suppressed by KLF7 knockdown. Furthermore, RNA sequencing results showed that KLF7 regulated the expression of a large amount of genes, among which hyaluronan synthase 2 (HAS2) was downregulated in KLF7 knockdown cells. Based on TCGA database and immunoblotting assays, KLF7 positively regulated HAS2 in UCEC cells and tissues. Lastly, knockdown of HAS2 reversed the oncogenic role of KLF7 on UCEC cell proliferation, migration, and xenografted tumor development.

Conclusion
Taken together, we reveal that GNA14/KLF7/HAS2 signaling cascade exerts tumor promoting function during UCEC development.
A genomic-clinicopathologic Nomogram for the preoperative prediction of lymph node metastasis in gastric cancer
Authors: Zhong Xin , Xuan Feichao , Qian Yun , Pan Junhai , Wang Suihan , Chen Wenchao , Lin Tianyu , Zhu Hepan , Wang Xianfa , Wang Guanyu 
Published: April 2021

Abstract
Background
Preoperative evaluation of lymph node (LN) state is of pivotal significance for informing therapeutic decisions in gastric cancer (GC) patients. However, there are no non-invasive methods that can be used to preoperatively identify such status. We aimed at developing a genomic biosignature based model to predict the possibility of LN metastasis in GC patients.

Methods
We used the RNA profile retrieving strategy and performed RNA expression profiling in a large GC cohort (GSE62254, n = 300) from Gene Expression Ominus (GEO). In the exploratory stage, 300 GC patients from GSE62254 were involved and the differentially expressed RNAs (DERs) for LN-status were determined using the R software. GC samples in GSE62254 were randomly allocated into a learning set (n = 210) and a verification set (n = 90). By using the Least absolute shrinkage and selection operator (LASSO) regression approach, a set of 23-RNA signatures were established and the signature based nomogram was subsequently built for distinguishing LN condition. The diagnostic efficiency, as well as the clinical performance of this model were assessed using the decision curve analysis (DCA). Metascape was used for bioinformatic analysis of the DERs.

Results
Based on the genomic signature, we established a nomogram that robustly distinguished LN status in the learning (AUC = 0.916, 95% CI 0.833–0.999) and verification sets (AUC = 0.775, 95% CI 0.647–0.903). DCA demonstrated the clinical value of this nomogram. Functional enrichment analysis of the DERs was performed using bioinformatics methods which revealed that these DERs were involved in several lymphangiogenesis-correlated cascades.

Conclusions
In this study, we present a genomic signature based nomogram that integrates the 23-RNA biosignature based scores and Lauren classification. This model can be utilized to estimate the probability of LN metastasis with good performance in GC. The functional analysis of the DERs reveals the prospective biogenesis of LN metastasis in GC.