bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the potential correlation between gastric cancer and gastrointestinal microbiota via in-silico data mining
Authors: Ding Xuelu , Zhu Yukun , She Zhaoyuan , Liu Xuewen , Zhang Cancan , Ma Xuying , Wang Feng , Wang Fei , Geng Xin
Published: December 2019

Background Emerging evidence shows the gastrointestinal microbiome might play an important role in the carcinogenesis of gastric cancer. While Helicobactor pylori has been reported to be a specific risk factor of gastric cancer, it is still controversial whether significant difference of non- H. pylori microbiota exists between gastric cancer patients and healthy control.Results In this study, we employed multiple bioinformatic databases to excavate the potential correlation between gastrointestinal microbiome and gastric cancer. The databases involved in this investigation include HMDB, STITCH, OMIM, GWAS Catalog, WebGestalt, Toppgene, GeneMANIA. In addition, the network diagrams were built by use of Cytoscape software. Notably, our results showed that 33 common genes participate in both gastrointestinal microbiome and gastric cancer. The further analysis of these common genes suggested that there was a wide array of interactions and pathways in which the correlation between gastrointestinal microbiome and gastric cancer is involved.Conclusions Our present study gives a bioinformatic insight into possible pathways in which the gastrointestinal microbiome play roles in gastric cancer. Future efforts are necessary to be paid to elicit the exact mechanisms as well as potential therapeutic targets of gastric cancer.
Ada-WHIPS: Explaining AdaBoost Classification with Applications in the Health Sciences
Authors: Hatwell Julian , Gaber Mohamed Medhat , Azad R.M. Atif
Published: December 2019

Background Computer Aided Diagnostics (CAD) can support medical practitioners to make critical decisions about their patients' disease conditions. Practitioners require access to the chain of reasoning behind CAD to build trust in the CAD advice and to supplement their own expertise. Yet, CAD systems might be based on black box machine learning (ML) models and high dimensional data sources (electronic health records, MRI scans, cardiotocograms, etc). These foundations make interpretation and explanation of the CAD advice very challenging. This challenge is recognised throughout the machine learning research community. eXplainable Artificial Intelligence (XAI) is emerging as one of the most important research areas of recent years, because it addresses the interpretability and trust concerns of medical practitioners and other critical decision makers. Method In this work, we focus on AdaBoost, a black box model that has been widely adopted in the CAD literature. We address the challenge -- to explain AdaBoost classification -- with a novel algorithm that extracts simple, logical rules from AdaBoost models. Our algorithm, \textit{Adaptive-Weighted High Importance Path Snippets} (Ada-WHIPS), makes use of AdaBoost's adaptive classifier weights; using a novel formulation, Ada-WHIPS uniquely redistributes the weights among individual decision nodes at the internals of the AdaBoost model. Then, a simple heuristic search of the weighted nodes finds a single rule that dominated the model's decision. We compare the explanations generated by our novel approach with the state of the art in an experimental study. We evaluate the derived explanations with simple statistical tests of well-known quality measures, precision and coverage, and a novel measure \textit{stability} that is better suited to the XAI setting. Results In this paper, our experimental results demonstrate the benefits of using our novel algorithm for explaining AdaBoost classification. The simple rule-based explanations have better generalisation (mean coverage 15\%-68\%) while remaining competitive for specificity (mean precision 80\%-99\%). A very small trade-off in specificity is shown to guard against over-fitting. Conclusions This research demonstrates that interpretable, classification rule-based explanations can be generated for computer aided diagnostic tools based on AdaBoost, and that a tightly coupled, AdaBoost-specific approach can outperform model-agnostic methods.
Categorising UK Biobank Self-Reported Medication Data using Text Matching
Authors: Appleby Philip Duncan , Buchan Natalie S , Doney Alexander SF , Jefferson Emily R
Published: December 2019

Introduction There are multiple potential sources of information about medications taken by participants in large population and patient cohorts such as the UK Biobank (UKBB) study, including from self-reported information and from linkage to electronic health records. At the time of writing, only self-reported medication data from UKBB participants have been released, in the form of medication codes that are assigned at the time of assessment centre interviews. Prescribing data is due to be released by UKBB in the near future. UKBB self-reported medication codes and descriptions do not have any published structure, which means that grouping medications into broader categories to contribute to clinical phenotyping is not possible. The motivation for the software project described here was to develop an automated means of classifying UKBB self-reported medications, for clinical phenotyping purposes.Methods We describe software tools, developed to match UKBB medication descriptions with terms from drug classification systems. The WHO’s Anatomical Therapeutic Chemical (ATC) Classification System and the British National Formulary (BNF) were selected as classification systems and were matched separately against UKBB medication coded descriptions. Manual matches can be added, for the cases where matching either fails or results in ambiguity. Manual matched codes would need to be added from the target classification system.Results Of the 3,646 medications reported as having been used by UKBB participants, 2,935 (80.5%) were matched with ATC system codes and 3,338 (91.6%) were matched with BNF codes. In general, medications remaining unmatched after manually matching those considered important according to clinician opinion, were either over the counter medicines with general descriptions or had very low participant report counts. A case study was conducted in which genetic associations between individual medications as phenotypes versus a Blood Pressure Genetic Risk Score were found less significant than those found once the medications had been automatically grouped. Conclusion Use of the matching software has been proven to assist in building medication-based phenotype proxies and to increase association significance over single UKBB medication codes. The matching software developed is available for general use and should also be applicable to other classification problems where descriptive text can be matched. https://github.com/PhilAppleby/ukbb-srmed/
On-farm management and participatory evaluation of pigeonpea (Cajanus cajan [L.] Millspaugh) diversity across the agro-ecological zones of Benin Republic
Authors: KINHOEGBE Géofroy , Djèdatin Gustave , Loko Laura Estelle Yêyinou , Favi Abraham Gnimassou , Adomou Aristide , Agbangla Clément , Dansi Alexandre
Published: December 2019

Background: Pigeonpea is a multipurpose food legume that contributes to food security in Benin. However, its production declined and some landraces are being threatened of disappearance. Previous investigations on pigeonpea in Benin have been restricted to South and Central Benin. Therefore, pigeonpea diversity in northern is still unknown. This study aimed to have a better knowledge of pigeonpea genetic diversity, for its promotion and valorization.Methods: 500 producers of pigeonpea belonging to thirteen sociolinguistic groups were selected through 50 villages. Data were collected using methods and tools of participatory research appraisal. Folk nomenclatures, taxonomy of pigeonpea and seed system were investigated. The distribution and extent of pigeonpea landraces were evaluated using Four Square Analysis method. A comparative analysis of pigeonpea uses categories, production systems, pigeonpea production constraints, famers’ preference criteria and participative evaluation for existing landraces across agro-ecological zones was done.Result: Folk nomenclature and taxonomy were mainly based on seed coat colour and size colour. Seven pigeonpea uses category were recorded including sacrifice, grain processing and fertilization. The results showed that pigeonpea seed system is informal. Based on seed characteristics, fifteen landraces were recorded with seven new landraces. A high rate of landraces threatened of disappearance was observed across the ecological zones. Ten constraints are known affecting pigeonpea production in Benin with pests and diseases as the most important in all agro-ecological zones. This study revealed that pigeonpea cultivation is increasing in the Sudanian zone. Landraces to be produced must be selected on the basis of 11 criteria among them precocity and resistance to pests and diseases, in the three ecological zones and adaptability to any type of soil in the Sudanian zone were the most important. The participatory evaluation revealed the existence of a few performing landraces.Conclusions: The development of performing varieties is important to enhance pigeonpea production in Benin. Morphological and molecular characterizations of identified landrace are highly recommended to help select suitable varieties for breeding programs. In situ and ex situ conservation strategies are important to preserve landraces threatened of disappearance.
Melatonin regulates the neurotransmitter secretion disorder induced by caffeine through the gut-brain axis in zebrafish (Danio rerio)
Authors: Peng Qiannan , Zhang Zeng , Huo Dongxue , Jiang Shuaiming , Ma Chenchen , Chang Haibo , Reiter Russel , Shi Haitao , Zhang Jiachao
Published: December 2019

Background : Melatonin has been widely used as a "probiotic agent" capable of producing strong neurotransmitter secretion regulatory effects. In the present study, a zebrafish neural hyperactivity model was established using caffeine induction, and the regulation and mechanism of melatonin and probiotic on zebrafish neurotransmitter secretion disorder were explored. Results : Disorders of brain neurotransmitter secretion caused by caffeine, including that of dopamine (DA), γ-aminobutyric acid (γ-GABA), and 5-hydroxytryptamine (5-HT), were improved after interference treatment with melatonin or the probiotic. Metagenomic sequencing demonstrated that the melatonin-treated zebrafish gradually restored their normal intestinal microbial structure, while probiotic supplementation may restructure a new microbiome. Additionally, supplementation with melatonin significantly regulated intestinal microbial functional features. Based on this activity, we supposed that gut microbes play an essential role in the regulation of neurotransmitter secretion disorder via a process that involves melatonin. Germ-free (GF) zebrafish were used to verify the hypotheses. Validation experiment results revealed that the effect on the zebrafish in the GF group could not achieve that on the zebrafish in the melatonin group after adding the same dose of melatonin, and subsequent real-time PCR and metabolic pathway analysis confirmed the conclusion. Meanwhile, the content of acetic acid and propionic acid in the zebrafish gut decreased after caffeine induction and increased significantly after melatonin treatment. Conclusions : In the present research, we identified the potential mechanism of melatonin regulation of neurotransmitter secretion disorder through the gut-brain axis, laying a foundation for exploring the prevention and treatment of some neuropsychiatric disorders by improving the intestinal microbiota.
Opportunistic detection of Fusobacterium nucleatum as a marker for the early gut microbial dysbiosis
Authors: Huh Ji-Won , Roh Tae-Young
Published: December 2019

Background Gastrointestinal microbiome has a great impact on human health and diseases. Fusobacterium nucleatum , an oral resident gram-negative microorganism, has been reported to differentially prevail in colorectal cancer (CRC). However, the effect of its enrichment was not clearly explored in terms of microbial homeostasis and stability at the early stage of disease development. Result Our analysis on longitudinal metagenomic data generated by the Integrative Human Microbiome Project (iHMP) showed that F. nucleatum significantly proliferated in IBD subjects with decrease in microbial diversity. Using non-parametric LDA effect size (LEfSe) algorithm, 12 IBD- and 14 non-IBD-specific marker species were identified. IBD-specific marker species were found more in the F. nucleatum -experienced subjects than in not-experienced ones. In addition, F. nucleatum experience severely abrogated intra-personal stability of microbiome in IBD patients and induced highly variable gut microenvironment. From the longitudinal comparison between prior and posterior distributions to F. nucleatum detection, 41 species could be regarded as indicative “classifiers” of dysbiotic state. Multiple logistic regression models were built to predict the probability experiencing F. nucleatum and showed that the high probability at the points following F. nucleatum observation was significantly associated with microbial dysbiosis. Finally, clustering all detected microbes based on the longitudinal distribution revealed that marker species for IBD and non-IBD conditions as well as pre-documented signature biomarkers of CRC were well distinguishable and could be utilized for explaining gut symbiosis and dysbiosis. Conclusion F. nucleatum opportunistically appeared under early gut dysbiosis, and a group of discriminative marker species associated with F. nucleatum , screened from the longitudinal analysis of microbial changes, was successfully applied to predict early microbiota alterations in both IBD and non-IBD conditions. Our prediction model and development of microbial biomarkers for estimating gut dysbiosis should provide a novel aspect of microbial homeostasis/dynamics and useful information on non-invasive biomarker screening.
Effect of flavophospholipol on fecal microbiota in weaned pigs challenged with Salmonella Typhimurium
Authors: Nair Saranya , Farzan Vahab , Weese J Scott , Poljak Zvonimir , Friendship Robert M
Published: December 2019

Background The heightened prevalence of Salmonella Typhimurium in nursery pigs remains a public health and food safety concern. Studies have reported antibiotic, flavophospholipol, may have the ability to reduce Salmonella in swine, as well as alter the gut microbiota in favour of beneficial bacteria by inhibiting pathogenic bacteria. Thus, the objective of this study was to investigate the fecal microbiota of weaned pigs receiving in-feed flavophospholipol and challenged with Salmonella Typhimurium. Results Twenty-one weaned pigs were fed either a diet containing 4 ppm of flavophospholipol (treatment group) or a non-medicated feed (control group) for 36 days post-weaning (Day 1 to Day 36). The pigs were orally challenged with a 2 mL dose of 10 8 CFU/mL of S. Typhimurium at Day 7 and Day 8. Community bacterial DNA extracted from fecal samples collected at Day 6 (before challenge) and Day 36 (28 days after challenge) were used to assess the fecal microbiota using the V4 region of the 16S rRNA gene with Illumina MiSeq next-generation sequencing. Sequencing data were visualized using mothur, and analyzed in JMP and R. The fecal microbiota of pigs in treatment group had significant differences in abundance of phyla (Firmicutes, Proteobacteria) and genera ( Lactobacillus, Roseburia , Treponema, unclassified Ruminococcaceae, Blautia , Streptococcus , Megasphaera , Dorea , Sporobacter , Peptococcus , unclassified Firmicutes, Clostridium IV and Campylobacter) when compared to pigs that controls 28 days after challenge with Salmonella ( P <0.05). Specifically, results demonstrated a significant increase in phylum Proteobacteria ( P= 0.001) and decrease in Firmicutes ( P =0.012) and genus Roseburia ( P =0.003) in the treated pigs suggestive of possible microbial dysbiosis. An increased abundance of genera Treponema ( P =0.012) and Lactobacillus ( P =0.012) was also noted in the treated group in comparison to the control. Conclusion Based on these findings, it is difficult to conclude whether treatment with 4 ppm of flavophospholipol is aiding in reducing Salmonella and promoting favorable indigenous bacteria in the pig microbiota as previous literature has suggested.
Suicide risk within one year of cognitive impairment diagnosis in older adults: a nationwide retrospective cohort study
Authors: Choi Jae Woo , Lee Kang Soo , Han Euna
Published: December 2019

Background This study aims to investigate suicide risk within one year of receiving a diagnosis of cognitive impairment in older adults without mental disorders. Methods This study used National Health Insurance Service-Senior Cohort data on older adults with newly diagnosed cognitive impairment including Alzheimer’s disease, vascular dementia, other/unspecified dementia, and mild cognitive impairment from 2004 to 2012. We selected 41,195 older adults without cognitive impairment through 1:1 propensity score matching using age, gender, Charlson Comorbidity Index, and index year, with follow-up throughout 2013. We eliminated subjects with mental disorders and estimated adjusted hazard ratios (AHR) of suicide deaths within one year after diagnosis using the Cox proportional hazards models. Results We identified 49 suicide deaths during the first year after cognitive impairment diagnosis. The proportion of observed suicide deaths was the highest within one year after cognitive impairment diagnosis (48.5% of total); older adults with cognitive impairment were at a higher suicide risk than those without cognitive impairment (AHR, 1.89; 95% confidence interval [CI], 1.18–3.04). Subjects with Alzheimer’s disease and other/unspecified dementia were at greater suicide risk than those without cognitive impairment (AHR, 1.94, 1.94; 95% CI, 1.12–3.38, 1.05–3.58). Suicide risk in female and young-old adults (60–74 years) with cognitive impairment was higher than in the comparison group (AHR, 2.61, 5.13; 95% CI, 1.29–5.28, 1.48–17.82). Conclusions Older patients with cognitive impairment were at increased suicide risk within one year of diagnosis. Early intervention for suicide prevention should be provided to older adults with cognitive impairment.
Long non-coding RNA MEG3 silencing and microRNA-214 restoration elevate osteoprotegerin expression to ameliorate osteoporosis by limiting TXNIP
Authors: Ding Rui , Gu ZhengTao , Yang ChangSheng , Huang CaiQiang , Li QingChu , Xie DengHui , Zhang RongKai , Qiu YiYan
Published: December 2019

BackgroundLong non-coding RNAs (LncRNAs) have been found to regulate innumerable diseases, yet the role of lncRNA MEG3 in osteoporosis (OP) has rarely been discussed. Here, we intend to probe into the mechanism of MEG3 on OP development by modulating microRNA-214 (miR-214) and thioredoxin-interacting protein (TXNIP)MethodsRat models of OP were established. MEG3, miR-214, and TXNIP mRNA expression in rat femoral tissues was detected, along with TXNIP, PCNA, cyclin D1, OCN, RUNX2, Osteolix, OPG, and PANKL protein expression. Ca, P and ALP contents in rat blood samples were also determined. Primary osteoblasts were isolated and cultured. Viability, COL-I, COL-II and COL-Χ contents, ALP content and activity, and mineralized nodule area of rat osteoblasts in each group were further detected.ResultsMEG3 and TXNIP were overexpressed while miR-214 was underexpressed in femoral tissues of OP rats. MEG3 silencing and miR-214 overexpression increased BMD, BV/TV, Tb.N, Tb.Th, the number of osteoblasts, collagen area and OPG expression, and downregulated PANKL of femoral tissues in OP rats. MEG3 silencing and miR-214 overexpression elevated Ca and P contents and reduced ALP content in OP rats’ blood, elevated viability, differentiation ability, COL-I and COL-Χ contents and ALP activity, and abated COL-II content of osteoblasts. MEG3 specifically bound to miR-214 to regulate TXNIP.ConclusionCollectively, we demonstrated that MEG3 silencing and miR-214 overexpression promote proliferation and differentiation of osteoblasts in OP by downregulating TXNIP, which further improves OP.
Every athlete has a unique trajectory: Knee-related quality of life in young athletes following anterior cruciate ligament reconstruction
Authors: Le Christina Y. , Hui Catherine , Emery Carolyn A. , Manns Patricia J. , Whittaker Jackie L.
Published: December 2019

Background Although the physical, psychological, and social consequences of sustaining an anterior cruciate ligament (ACL) tear in young athletes are well documented, little is known about how ACL tears influence health-related quality of life (QOL). This case series describes changes in knee-related QOL over the first 12 months following an ACL reconstruction (ACLR) in young athletes and explores the association between 6-month knee symptoms, moderate-to-vigorous-intensity physical activity (MVPA), kinesiophobia, and 12-month knee-related QOL.Methods Twenty young athletes (15-20 years old, 70% female) who underwent primary ACLR were evaluated pre-ACLR (baseline) and post-ACLR at 3, 6, 9, and 12 months. Knee-related QOL was assessed with the Knee injury and Osteoarthritis Outcome Score (KOOS) QOL subscale. Knee symptoms (KOOS symptoms subscale), average daily minutes of MVPA (tri-axial accelerometer), and kinesiophobia (Tampa Scale for Kinesiophobia; TSK) were also tracked. Descriptive statistics (median with range, mean with standard deviation, or proportion with 95%CI) were calculated for demographic and outcome variables. Individual changes in KOOS QOL scores over the 12-month study period were compared to minimal clinically important difference, patient acceptable symptoms state, treatment failure, and normative reference values. Associations between 6-month KOOS symptoms, MVPA, TSK, and 12-month KOOS QOL were explored using Spearman’s rank correlation coefficient (ρ).Results Considerable individual variability in the trajectory of KOOS QOL scores was observed over the study period with 13 (65%) participants achieving clinically important improvements. At 12 months, the median KOOS QOL score was 53 (range 6-100) and only 7 (35%) participants reported acceptable QOL and 4 (20%) exceeded normative reference values. A moderate association was detected between 6-month KOOS symptoms and 12-month KOOS QOL scores (ρ=0.53, p=0.02).ConclusionsThis case series reveals that young athletes experience unique knee-related QOL trajectories in the first 12 months following an ACLR and that deficits in knee-related QOL still exist at 12 months. These findings highlight the individual and dynamic nature of QOL and the importance of considering QOL as an indicator of recovery in injured young athletes.
Upregulation of microRNA-96 alleviates the neurological damage in acute seizure rats by down-regulating RAC1 and inhibiting the activation of RhoA/ROCK signaling pathway
Authors: Wang Zhihan , Jiang Wei , Ren Dabin , Chen Wei , Zheng Ping
Published: December 2019

Objective Today, the research about the involvement of non-coding RNAs on neurological disorders is still scarce. Hence, we aimed to investigate the effect of miR-96 targeted RAC1 to mediate RhoA/ROCK signaling pathway in neurological damage in acute seizure rats.MethodsThe acute seizure rat model was constructed by using classical chlorinated-pilocarpine injection, which was treated with miR-96 mimics, RAC1-siRNA or their controls. The number of BrdU positive cells, neuronal changes and apoptosis, expression of NGF, BDNF and GFAP were detected by different staining assays. At the same time, the activity of SOD, the content of MDA and the protein contents of TNF-α and IL-6 in rat hippocampus were detected as well. Next, the expression of NGF, BDNF, GFAP, Bax, Bcl-2, caspase-3, RAC1, RhoA and ROCK were determined by RT-qPCR and western blot analysis. Then, the binding site between miR-96 and RAC1 was analyzed by bioinformatics software and luciferase assay. Finally, the altered expression of miRNAs was investigated in exosomes released from excitotoxic neurons with a customized rat miRNA chipset.Results After upregulation of miR-96 or downregulation RAC1, BrdU-positive cells, TUNEL-positive cells, NGF, GFAP, MDA, TNF-α, IL-6, Bax, caspase-3, and pathway related proteins in rat hippocampus decreased while Bcl-2, BDNF, and the activity of SOD increased. Furthermore, RAC1 was found to be the target gene of miR-96 and their relationship was validated in in-vitro studies. Finally, the decreased expression of miR-96 in exosomes from kainic acid treated neurons was identified as well.Conclusion This study suggests that upregulation of miR-96 could downregulate RAC1 and inhibit the activation of RhoA/ROCK signaling pathway, thus alleviated the neurological damage in acute seizure rats.
Serum soluble ST2 is a predictor for poor long-term prognosis after transient ischemic attack and ischemic stroke: a cohort study
Authors: Tian Xuan , Guo Yinan , Wang Xiao , Pei Lulu , Wang Xin , Wu Jun , Sun Shilei , Li Yusheng , Ning Mingming , Buonanno Ferdinando S. , Xu Yuming , Song Bo
Published: December 2019

Background Soluble ST2 (sST2) is a novel inflammation marker for the prediction of adverse outcomes in patients with cardiovascular disease and diabetes mellitus. The aim of the present study was to examine the predictive value of serum sST2 for prognostic outcomes in patients with transient ischemic attack (TIA)/ischemic stroke.Methods Patients within 24 h after symptom onset were prospectively enrolled based on the TIA/ischemic stroke database of the First Affiliated Hospital of Zhengzhou University. The 1-year prognostic outcomes were composite adverse events (including ischemic and hemorrhagic stroke, myocardial infarction, and all-cause death) and a combination of major disability and death [modified Rankin Scale (mRS), 3-6]. Cox proportional hazard and logistic regression models were used to evaluate the association between serum sST2 and TIA/ischemic stroke prognosis. The C statistic, net reclassiﬁcation index (NRI), and integrated discrimination index (IDI) were used to present improvement in risk classification.Results Serum sST2 levels were positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores. Kaplan-Meier analysis indicated a significantly different risk in composite adverse events between patients with higher and those with lower levels of sST2 (P=0.006). Serum sST2 was an independent predictor for composite adverse events (HR: 2.517, 95% CI: 1.279-4.956, P=0.008) and major disability or death (OR: 3.126, 95% CI: 1.452-6.728, P=0.004) after multivariate adjustment. The addition of the sST2 to the NIHSS score significantly improved the predictive value for prognostic outcomes in patients with TIA/ischemic stroke (C statistic: 0.021, IDI: 1.91%, P=0.042 for composite adverse events; NRI: 32.82%, P=0.042 for major disability or death).Conclusions Serum sST2 levels were positively associated with the severity of TIA/ischemic stroke and could independently predict composite adverse events and major disability or death, indicating that sST2 may be a potential prognostic marker for TIA/ischemic stroke.
Tumor microenvironmental prognosis analysis and molecular labeling of immune-related genes in Luminal B type breast cancer
Authors: Gan Fengjiao , Hu Kang , Li Xiaomei , Jiang Ni , Wu Qiaoyuan , Li Yi , Xu Mengxi , Sun Suhong , Luo Qing
Published: December 2019

Background: Tumor microenvironment (TME) cells is one of the important elements, constitute the tumor tissues and in predicting tumor clinical results and treatment effect has the important significance of clinical pathology. However, a detailed map for prognostic landscape of TME in Luminal B breast cancer is still lacking. Methods: ownloaded the expression profile and clinical follow-up information of luminal B breast cancer from TCGA and GEO, and used CIBERSORT to evaluate the infiltration mode of TME in 209 patients, and constructed the molecular subtype of luminal B breast cancer based on TME, further evaluated the relationship between molecular subtype and prognosis. DESeq2 was used to analyze the differentially expressed genes among molecular subtypes of luminal B breast cancer, and cox multivariate regression analysis was used for feature selection to construct TME signature. Results: ased on the median value of TMEscore, the samples were divided into High TMEscore and Low TMEscroe, and the relationship with prognosis, clinical features, immune gene expression and genomic variation was further evaluated. Different TME cells have significant correlation in luminal B breast cancer. These TME cells stratified different clinical results of luminal B breast cancer, and further TMEscore was established by Cox regression analysis. High TME score is associated with poor prognosis. Meanwhile, this study showed that CXCL10, CXCL9, GZMB and other immune activation genes and PDCD1LG2 and other immune checkpoint genes have higher expression levels in high TME score, and the mutation frequency of TP53 gene was lower in risk-H than that in risk-L. Conclusion: In this study, we systematically evaluated the TME infiltration patterns of 209 TCGA luminal B breast cancer patients and developed the TME score approach. It was found that TME score is a powerful prognostic biomarker and predictor of response to immunocheckpoint inhibitors and provides a new strategy for luminal B breast cancer immunotherapy.
Anti-Müllerian hormone predictive levels to determine the likelihood of ovarian hyper-response in infertile women with polycystic ovarian morphology
Authors: Sene Azadeh Akbari , Ashrafi Mahnaz , Alaghmand-Fard Nasim , Mohammadi Neda , Alisaraie Mona Mortezapour , Alizadeh Ahad
Published: December 2019

Background: The objective of this study was to investigate how the serum levels of Anti-Müllerian hormone (AMH) in normal-ovulatory infertile women with polycystic ovarian morphology (PCOM) is associated with ovarian hyper-response? Methods: This prospective cohort study was carried out on 100 infertile women with PCOM who were treated by antagonist/agonist-triggered stimulation protocol in Shahid Akbar-Abadi Hospital IVF center, Tehran, Iran. Serum AMH levels were measured before starting the ART cycle and the ovarian hyper-response was evaluated by retrieved oocyte numbers, estradiol levels on triggering day and the incidence of OHSS clinical signs and symptoms. Logistic regression and the area under the curve (AUC) were used to estimate the effects of AMH and accuracy of test. Results: ROC curve analysis showed that AMH had a significant performance to predict ovarian hyper-response in PCOM patients (AUC = 0.73). The estimated threshold value was 4.95 ng/ml, specificity was 74.58% (95%CI: [50.85, 93.22]), and sensitivity was 73.17% (95%CI: [48.78, 92.68]). The results of logistic regression showed that there was a significant interaction between AMH and BMI (P = 0.008) so BMI had a moderation effect. In other words, the AMH cut-off values to predict the ovarian hyper-response were different for different BMI. Conclusions: Considering the AMH cut-offs for different BMI categories would be valuable to adapt a tailored, effective and safe stimulation program for infertile women with PCOM.
Identification of lncRNA–miRNA–mRNA regulatory network associated with Primary Open Angle Glaucoma
Authors: Zhou Minwen , Lu Bing , Tan Wei , Fu Mingshui
Published: December 2019

Background Primary open angle glaucoma (POAG) is a complicated disorder characterized by a progressive permanent degeneration of retinal ganglion cell (RGCs) death. An increasing number of studies have suggested that long noncoding RNAs (lncRNAs) have the ability to regulate gene expression; however, thus far, the mechanisms and functions of lncRNAs in the development of POAG are still unclear.Methods Using the data from Gene Expression Omnibus (GEO), differentially expressed lncRNAs and differentially expressed mRNAs between POAG patients and controls were identified. Then, the lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) network was constructed, and the key lncRNAs in POAG were identified. A Gene Ontology (GO) analysis and a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to assess the enriched biological functions of mRNA in the ceRNA network.Results During this study, a POAG-related ceRNA network with 37 miRNA nodes, 248 lncRNA nodes, 178 mRNA nodes, and 1985 edges was constructed. In addition, four lncRNAs (DNAJC27-AS1, AF121898, OIP5-AS1, and SNX29P2) were established as hub RNAs in this ceRNA network. The functional assay showed that 18 GO terms and 17 pathways were enriched.Conclusion This study provides novel insights into the lncRNA-related ceRNA network in POAG, and the four lncRNAs were identified in the development of POAG.
Analysis of relationship between key genes and astaxanthin biosynthesis in Phaffia rhodozyma by transcript level and gene knock-out
Authors: Li Zhipeng , Chen Lina , Li Tianli , Du Xiping , He Ning , Jiang Zedong , Li Lijun , Ni Hui
Published: December 2019

Background Phaffia rhodozyma is a potential industrial source for production of natural astaxanthin. The synthetic mechanism of astaxanthin in P. rhodozyma is complex and unclear that blocked its development. Results In this study, eight genes related to dicyclic and monocyclic pathway in three different strains of P. rhodozyma were analyzed, and the relationship between the expression and astaxanthin biosynthesis was explored. Among these genes, crtYB (R=0.75, P<0.05) and asy genes (R=0.74, P<0.05) showed the most closely correlation with astaxanthin biosynthesis. In order to further study exact relationship, crtYB and asy genes were knocked out by homologous recombination. After crtYB knock-out, astaxanthin was decreased to be under detected line. It suggested crtYB played a role in dicyclic and monocyclic pathway. Meanwhile, the asy gene was in dicyclic pathway of astaxanthin biosynthesis, and its knock-out would promote the astaxanthin biosynthesis in monocyclic pathway, resulting in a 25.04% increase in astaxanthin production. Conclusion The possible rate-limiting enzymes were asy gene and crtYB illustrated by analysis of regression. Knock-out of asy and crtYB gene was great helpful to understand the synthetic pathway of astaxanthin, and significant to the industrial application of producing astaxanthin.
Antibacterial effect of silver nanorings
Authors: González-Fernández Sara , Lozano-Iturbe Víctor , García Beatriz , Andrés Luis J. , Menéndez Mª Fe , Rodríguez David , Vazquez Fernando , Martín Carla , Quiros Luis M
Published: December 2019

Background The emergence and expansion of antibiotic resistance makes it necessary to have alternative anti-infective agents, among which silver nanoparticles (AgNPs) display especially interesting properties. AgNPs carry out their antibacterial action through various molecular mechanisms, and the magnitude of the observed effect is dependent on multiple, not fully understood, aspects, particle shape being one of the most important. In this article, we conduct a study of the antibacterial effect of a new type of AgNP: silver nanorings (AgNRs), and compare it with other alternative types of AgNP synthesized in parallel using the same methodology.Results When they act on planktonic forms, AgNRs produce a smaller effect on the viability of different bacteria than nanoparticles with other structures although their effect on growth is more intense over a longer period. When their action on biofilms is analyzed, AgNRs show a greater concentration-dependent effect. In both cases it was observed that the effect on inhibition depends on the microbial species, but not its Gram positive or negative nature. Growth patterns in silver-resistant Salmonella strains suggest that AgNRs work through different mechanisms to other AgNPs. The antibacterial effect is also produced to some extent by the conditioning of culture media or water by contact with AgNPs but, at least over short periods of time, this is not due to the release of Ag ions.Conclusions AgNRs constitute a new type of AgNP, whose antibacterial properties depend on their shape, and is capable of acting efficiently on both planktonic bacteria and biofilms.
αβ-Dehydrocurvularin isolated from the fungus Aspergillus welwitschiae effectively inhibited the behaviour and development of the root-knot nematode Meloidogyne graminicola in rice roots
Authors: xiang Chao , Liu Ying , Liu Shi-Ming , Huang Ya-Fei , Kong Ling-An , Peng Huan , Liu Mao-Yan , Liu Jing , Peng De-Liang , Huang Wen-Kun
Published: December 2019

Background: The root-knot nematode Meloidogyne graminicola has become a serious threat to rice production as a result of the cultivation changes from transplanting to direct seeding. The nematicidal metabolites of Aspergillus welwitschiae have been investigated in vitro, and the disease control efficacy of the active compound has been evaluated under greenhouse and field conditions.Results: The active compound αβ-dehydrocurvularin (αβ-DC), isolated by nematicidal assay-directed fractionation, showed significant nematicidal activity against M. graminicola, with an median lethal concentration (LC50) value of 122.2 μg mL−1. αβ-DC effectively decreased the attraction of rice roots to nematodes and the infection of nematodes and also suppressed the development of nematodes under greenhouse conditions. Moreover, αβ-DC efficiently reduced the root gall index under field conditions.Conclusion: To our knowledge, this is the first report to describe the nematicidal activity of αβ-DC against M. graminicola. The results obtained under greenhouse and field conditions provide a basis for developing commercial formulations from αβ-DC to control M. graminicola in the future.
The role of DRAM1 in mitophagy contributes to preeclampsia regulation in mice
Authors: Chen Guoqing , Lin Ying , Chen Lu , Zeng Fa , Zhang Li , Huang Yan , Huang Pingping , Liao Lingling , Yu Yuanlan
Published: December 2019

Background: Preeclampsia (PE) is a pregnancy complication that is diagnosed by the new onset of hypertension and proteinuria. Although the pathogenesis of PE is still not fully understood, growing evidence indicates that oxidative stress and mitochondrial dysfunction may contribute to the progression of PE. Therefore, we aimed to determine the role of mitophagy in mitochondrial dysfunction and oxidative stress in PE. Moreover, we aimed to evaluate the role of DNA damage-regulated autophagy modulator 1 (DRAM1) in the development of PE. Results: In this study, we first constructed a mouse model of PE induced by Hif-1α and found a high level of oxidative stress, apoptosis and mitochondrial dysfunction in the placentas of PE mice. Additionally, the activity of mitophagy was decreased, and the level of DRAM1 was significantly decreased in the placentas of PE mice. To further explore the role of DRAM1 in mitophagy, DRAM1 was overexpressed in the placental tissues of PE mice. It was found that the overexpression of DRAM1 effectively improved the symptoms of PE mice and that blood lipid and urine protein levels were significantly reduced. Furthermore, DRAM1 overexpression also improved mitochondrial function and reduced oxidative stress in the placentas of PE mice. In addition, it improved mitochondrial fusion and fission and enhanced mitophagy.Conclusions: our results indicate a key role of DRAM1 in mitophagy in contributing to the regulation of PE. To our knowledge, this is the first study to confirm the role of DRAM1 in PE, and the study provides a new understanding of the pathophysiological mechanisms of PE.
Apatinib in treating clinical and biochemical recurrent ovarian cancer
Authors: Wang Zhongyu , Huang Yake , Long Ling , Zhou Li , Huang Yan , Gan Lei , Pu Aiming , Li Sufen , xie rongkai
Published: December 2019

Background: Apatinib, a small molecule inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), exerts antiangiogenic effects. Taken orally, apatinib shows clinical activity in the treatment of recurrent or platinum-resistant ovarian cancer (OC) as monotherapy or in combination with other chemotherapeutic agents. We investigated the efficacy of apatinib in recurrent OC and preliminarily evaluated the clinical activity of apatinib in biochemical-only recurrent OC patients. Results: We retrospectively analyzed clinical material of 41 recurrent patients who had received apatinib monotherapy or apatinib plus chemotherapy between June 2016 and August 2018. Apatinib was administered at a 500 mg daily dose. Response was determined according to measurable disease or serum carbohydrate antigen (CA)-125 levels. Progression-free survival (PFS) was estimated by Kaplan-Meier method. All patients were evaluable, 19 (46.34%) had biochemical relapse and 22 (53.66%) had clinical relapse. The objective response rate (ORR) and disease control rate (DCR) in the overall population were 31.71% and 78.05%, respectively. The median PFS was 7 months (95% confidence interval 5.43-8.57). In patients with biochemical relapse only, the median PFS was 6 months, with ORR of 26.32% and DCR of 89.47%. Conclusions: Apatinib is a well-tolerated and effective agent in patients with recurrent OC and has the potential to delay clinical progression in patients with asymptomatic biochemical relapse.
Influential factors of postoperative outcomes of symptomatic lateral discoid meniscus
Authors: Yang ShunJie , Ding Zhong-Jun , Li Jian , Xue Yang , Chen Gang
Published: December 2019

Background: Discoid lateral meniscus (DLM) have a higher rate of tear and degeneration for its abnormal shape and structure. Arthroscopy is the main treatment for symptomatic DLM, however, postoperative clinical outcomes vary widely resulting from effects of diverse factors. Therefore, the present research aims to explore the factors influencing postoperative clinical outcomes of symptomatic DLM. Methods: Patients with discoid meniscus who underwent arthroscopic surgery at our hospital from 9/2008 to 9/2015 were selected according to the inclusion and exclusion criteria. Gender, body mass index (BMI), and 18 other factors were selected as potential predictors that might affect postoperative outcomes. Knee function was assessed by the Lysholm, Tegner, International Knee Documentation Committee (IKDC) and Ikeuchi scales. Univariate analyses (rank-sum test and chi-squared test) and multivariate analyses (ordered logistic regression and logistic regression) were used to detect the risk factors bearing on postoperative outcomes. P<0.05 was considered statistically significant.Results: A total of 502 patients were enrolled. Female gender was an influencing factor for Lysholm (P=0.002, odds ratio (OR)=2.713), Tegner (P=0.001, OR=2.526), IKDC (P=0.022, OR=1.735) and Ikeuchi scores (P=0.010, OR=2.164). BMI was negatively correlated with Lysholm (P=0.007, OR=1.119) and IKDC (P=0.029, OR=1.088) scores. Work intensity was negatively related to IKDC (P=0.038, OR=1.492) and Ikeuchi (P=0.014, OR=1.689) scores. Age of onset was inversely correlated with Tegner (P<0.001, OR=1.109) score. Symptoms duration and IKDC (P=0.002, OR=1.020) had an inverse correlation. Lack of cartilage lesions was a protective factor in terms of Tegner score (P<0.001, OR=0.261). Outerbridge grade was negatively correlated with Lysholm (P=0.016, OR=1.589) and Ikeuchi (P=0.017, OR=1.582) scores. Saucerization with repair was a risk factor for poor Ikeuchi scores (P=0.037, OR=4.328) in terms of subtotal/total meniscectomy.Conclusion: Arthroscopic treatment of symptomatic DLM is safe and effective. Female sex, cartilage lesions and saucerization with repair may be related to unfavourable postoperative outcomes. Clinical efficacy may worsen with increasing BMI, work intensity, symptomatic duration, age of onset and Outerbridge grade.
A Novel Mutation in the Kringle IV Domain of LPA gene leading to Familial Hyperlipoproteinemia
Authors: Li Youran , Zhang Xinyue , Wang Yizhong , Gong Fan , Yu Xiaofei , Zhang Ting
Published: December 2019

Background This study aims to investigate the clinical characterization and causative genetic defect of a four-generation Chinese Han family with hyperlipoproteinemia. Methods The combined use of next-generation sequencing and qPCR technique was performed to investigate genetic pathology of familial hyperlipoproteinemia. Results The clinical manifestations of the family members include hyperlipoproteinemia, early-onset hypertension, coronary heart disease, lipoma, cerebral infarction and even sudden death, and a novel heterozygous deletion of 3-16 exon of LPA gene was identified to be causative for the symptoms in the family. Conclusions A novel deletion in the LPA gene was identified in a Chinese family associated with hyperlipoproteinemia, which expands the spectrum of the LPA mutation and its associated phenotype. Keywords Copy number variation; Hyperlipoproteinemia; Kringle IV; Lipoprotein(a); LPA;
Identifying no-harm incidents in home healthcare: a cohort study using trigger tool methodology
Authors: Lindblad Marléne , Unbeck Maria , Nilsson Lena , Schildmeijer Kristina , Ekstedt Mirjam
Published: December 2019

Background Patient safety in home healthcare is largely unexplored. No-harm incidents may give valuable information about risk areas and system failures as a source for proactive patient safety work. We hypothesized that it would be feasible to retrospectively identify no-harm incidents and thus aimed to explore the cumulative incidence, preventability, types, and potential contributing causes of no-harm incidents that affected adult patients admitted to home Healthcare. Methods A structured retrospective record review using a trigger tool designed for home healthcare. A random sample of 600 home healthcare records from ten different organizations across Sweden was reviewed. Results In the study, 40,735 days were reviewed. In all, 313 no-harm incidents affected 177 (29.5%) patients; of these, 198 (63.2%) no-harm incidents, in 127 (21.2%) patients, were considered preventable. The most common no-harm incident types were “fall without harm,” “deficiencies in medication management,” and “moderate pain.” The type“deficiencies in medication management” was deemed to have a preventability rate twice as high as those of “fall without harm” and “moderate pain.” The most common potential contributing cause was “deficiencies in nursing care and treatment, i.e., delayed, erroneous, omitted or incomplete treatment or care.” Conclusion This study suggests that it is feasible to identify no-harm incidents and potential contributing causes such as omission of care using record review with a trigger tool adapted to the context. No-harm incidents and potential contributing causes are valuable sources of knowledge for improving patient safety, as they highlight system failures and indicate risks before an adverse event reach the patient. Keywords No-harm incident, Trigger tool, Retrospective record review, Home healthcare, Patient safety