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A novel saliva-based mirNA profile to diagnose and predict oral cancer

International Journal of Oral science 2024年第1期16卷 97-109页

作者： Jaikrishna Balakittnen Chameera Ekanayake Weeramange Daniel F.Wallace Pascal H.G.Duijf Alexandre s.Cristino Gunter Hartel roberto A.Barrero Touraj Taheri Liz Kenny sarju Vasani Martin Batstone Omar Breik Chamindie Punyadeera saliva&Liquid Biopsy Translational Laboratory Griffith Institute for Drug DiscoveryGriffith UniversityNathanQLDAustralia Department of Medical Laboratory sciences Faculty of Allied Health SciencesUniversity of JaffnaJaffnaSri Lanka Menzies Health Institute Griffith UniversityGold CoastQLDAustralia school of Biomedical sciences Faculty of HealthQueensland University of TechnologyBrisbaneQLDAustralia Centre for Cancer Biology Clinical and Health SciencesUniversity of South Australia&SA PathologyAdelaideSAAustralia Institute of Clinical Medicine Faculty of MedicineUniversity of OsloOsloNorway Department of Medical Genetics Oslo University HospitalOsloNorway Griffith Institute for Drug Discovery Griffith UniversityNathanQLDAustralia QIMr Berghofer Medical research Institute Statistics UnitBrisbaneQLDAustralia school of Public Health The University of QueenslandBrisbaneQLDAustralia school of Nursing Queensland University of TechnologyBrisbaneQLDAustralia eresearch Research InfrastructureAcademic DivisionQueensland University of TechnologyBrisbaneQLDAustralia Department of Anatomical Pathology Royal Brisbane and Women’s HospitalHerstonQLDAustralia Faculty of Medicine The University of QueenslandBrisbaneQLDAustralia royal Brisbane and Women’s Hospital Cancer Care ServicesHerstonQLDAustralia Department of Otolaryngology Royal Brisbane and Women’s HospitalHerstonQLDAustralia Department of Oral and Maxillofacial surgery Royal Brisbane and Women’s HospitalHerstonQLDAustralia

Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microrNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD).The Cancer Genome Atlas (TCGA) mirNA sequencing data and small rNA sequencing data of saliva samples were used to discover differentially expressed mirNAs. Identified mirNAs were validated in saliva samples of OC (n=50), OPMD (n=52), and controls(n=60) using quantitative real-time PCr. Eight differentially expressed mirNAs (mir-7-5p, mir-10b-5p, mir-182-5p, mir-215-5p,mir-431-5p, mir-486-3p, mir-3614-5p, and mir-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-mirNA signature to discriminate OC and controls was:area under curve (AUC):0.954, sensitivity:86%, specificity:90%,positive predictive value (PPV):87.8%and negative predictive value (NPV):88.5%whereas between OC and OPMD was:AUC:0.911,sensitivity:90%, specificity:82.7%, PPV:74.2%and NPV:89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary mirNA signature that can aid in diagnosing and predicting OC,revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary mirNAs to the clinical utility of using mirNAs derived from saliva samples.

关键词： specificity salivary diagnosis

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Dynamic Patterns of Gene Expression Additivity and regulatory Variation throughout Maize Development

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Molecular Plant 2019年第3期12卷 410-425页

作者： Peng Zhou Candice N.Hirsch steven P.Briggs nathan M.springer Department of Plant and Microbial Biology University of MinnesotaSaint PaulMN 55108USA Department of Agronomy and Plant Genetics University of MinnesotaSaint PaulMN 55108USA Division of Biological sciences University of CaliforniaSanDiegoLaJollaCA92093USA

Gene expression variation is a key component underlying phenotypic variation and heterosis. Transcriptome profiling was performed on 23 different tissues or developmental stages of two maize inbreds, B73 and Mo17, as well as their hybrid. The obtained large-scale datasets provided opportunities to monitor the developmental dynamics of differential expression, additivity for gene expression, and regulatory variation. The transcriptome can be divided into .30 000 genes that are expressed in at least one tissue of one in bred and an additional ~10 000 “silent” genes that are not expressed in any tissue of any genotype, 90% of which are non-syntenic relative to other grasses. Many (.74%) of the expressed genes exhibit differential expression in at least one tissue. However, the majority of genes with differential expression do not exhibit consistent differential expression in different tissues. These genes often exhibit tissue-specific differential expression with equivalent expression in other tissues, and in many cases they switch the directionality of differential expression in different tissues. This suggests widespread variation for tissue-specific regulation of gene expression between the two maize inbreds B73 and Mo17. Nearly 5000 genes are expressed in only one parent in at least one tissue (single parent expression) and 97% of these genes are expressed at mid-parent levels or higher in the hybrid, providing extensive opportunities for hybrid complementation in heterosis. In general, additive expression patterns are much more common than non-additive patterns, and this trend is more pronounced for genes with strong differential expression or single pare nt expressi on. There is relatively little evidence for non-additive expression patterns that are maintained in multiple tissues. The analysis of allele-specific expression allowed classification of cis. and trans-regulatory variation. Genes with c/s-regulatory variation often exhibit additive expression and tend

关键词： maize gene expression heterosis differential expression non-additive expression allele-specific expression

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Proposing new indicators for glaucoma healthcare service

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Eye and Vision 2017年第1期4卷 26-29页

作者： Yuan Bo Liang Ye Zhang David C.Musch nathan Congdon Clinical and Epidemiological Eye research Center The Eye Hospital of Wenzhou Medical UniversityWenzhouChina Centre for Public Health Queens UniversityBelfastUK Beijing Tongren Eye Center Beijing Tongren HospitalCapital Medical UniversityBeijingChina Kellogg Eye Center University of MichiganAnn ArborMIUSA Eye Hospital School of Optometry and OphthalmologyWenzhou Medical CollegeNo.270Xue Yuan Xi RoadWenzhouZhejiang 3250027China

Glaucoma is the first leading cause of irreversible blindness worldwide with increasing importance in public *** of glaucoma care quality as well as efficiency would benefit public health assessments,but are *** propose three such ***,the glaucoma coverage rate(GCr),which is the number of people known to have glaucoma divided by the total number of people with glaucoma as estimated from population-based studies multiplied by 100%.second,the glaucoma detection rate(GDr),which is number of newly diagnosed glaucoma patients in one year divided by the population in a defined area in ***,the glaucoma follow-up adherence rate(GFAr),calculated as the number of patients with glaucoma who visit eye care provider(s)at least once a year over the total number of patients with glaucoma in given eye care provider(s)in a specific *** tracking and reporting these three indicators may help to improve the healthcare system performance at national or regional levels.

关键词： Glaucoma coverage rate Glaucoma detection rate Glaucoma follow-up adherence rate Healthcare indicator

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News coverage of Confucius Institutes in the pre-Trump era

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Economic and Political studies 2022年第2期10卷 155-180页

作者： Muhammad Akhtaruzzaman nathan Berg Donald Lien Ying Wue Faculty of Health Education and Environment Toi Ohomai Institute of TechnologyRotoruaNew Zealand Otago Business school University of OtagoDunedinNew Zealand Department of Economics University of NewcastleCallaghanAustralia Department of Economics University of Texas-San AntonioSan AntonioTXUSA school of Journalism and Communication Shanghai International Studies UniversityShanghaiChina

A novel dataset is presented that reveals a general pattern of declining favourability in news stories about Confucius Institutes(CIs)from 2006 through 2015 in six English-speaking countries:the Us,the UK,Canada,Australia,India and *** are sig-nificant differences in mean favourability and time trends across countries,*** trends in favourability are observed in the Us and Canada,in particular,whereas Kenya and India’s time trends are nil or possibly *** report empir-ical models of favourability conditional on GDP per capita,trade with China and the number of CIs across country-year *** with Pew polling data,our data reveal an inter-esting pair of conflicting income ***-income countries tend to be more negative and less positive on CIs than low-income countries ***-country positive shocks to real GDP per capita,however,are positively associated with favourabil-ity after cross-country differences in income levels are absorbed by country fixed *** number of CIs in a country has mixed effects on the favourability of news coverage about CIs across country-year *** billions of dollars spent on public diplomacy by the Chinese government,our findings suggest that its return on investment in public diplomacy in the form of CIs may not be as expected.

关键词： Confucius Institute China English-speaking news-paper public diplomacy soft power

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A study of real-world micrograph data quality and machine learning model robustness

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npj Computational Materials 2021年第1期7卷 1463-1473页

作者： Xiaoting Zhong Brian Gallagher Keenan Eves Emily robertson T.nathan Mundhenk T.Yong-Jin Han Materials science Division Lawrence Livermore National LaboratoryLivermoreCAUSA Center for Applied scientific Computing Lawrence Livermore National LaboratoryLivermoreCAUSA Defense Technologies Engineering Division Lawrence Livermore National LaboratoryLivermoreCAUSA Computational Engineering Division Lawrence Livermore National LaboratoryLivermoreCAUSA

Machine-learning(ML)techniques hold the potential of enabling efficient quantitative micrograph analysis,but the robustness of ML models with respect to real-world micrograph quality variations has not been carefully *** collected thousands of scanning electron microscopy(sEM)micrographs for molecular solid materials,in which image pixel intensities vary due to both the microstructure content and microscope instrument *** then built ML models to predict the ultimate compressive strength(UCs)of consolidated molecular solids,by encoding micrographs with different image feature descriptors and training a random forest regressor,and by training an end-to-end deep-learning(DL)*** show that instrument-induced pixel intensity signals can affect ML model predictions in a consistently negative *** a remedy,we explored intensity normalization *** is seen that intensity normalization helps to improve micrograph data quality and ML model robustness,but microscope-induced intensity variations can be difficult to eliminate.

关键词： instrument image eliminate

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New insights into estrogenic regulation of O^6-methylguanine DNA-methyltransferase (MGMT) in human breast cancer cells： Co-degradation of Er-α and MGMT proteins by fulvestrant or O^6-benzylguanine indicates fresh avenues for therapy

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The Journal of Biomedical research 2016年第5期30卷 393-410页

作者： Ameya Paranjpe nathan I. Bailes santhi Konduri George C. Bobustuc Francis Ali-Osman Mohd. A. Yusuf surendra r. Punganuru Hanumantha rao Madal Debasish Basak AGM Mostofa Kalkunte s. srivenugopa Department of Biomedical sciences and Cancer Biology Center School of Pharmacy Texas Tech University Health Sciences Center Amarillo TX 79106 USA Neuro-Oncology section Aurora Advanced Cancer Care Milwaukee WI 53215 USA Department of surgery The Preston Robert Tisch Brain Tumor Center Duke University Durham NC 27710 USA

Endocrine therapy using estrogen receptor-u （Er-α） antagonists for attenuating horm2one-driven cell proliferation is a major treatment modality for breast cancers. To exploit any DNA repair deficiencies associated with endocrine therapy, we investigated the functional and physical interactions of Er-α with O^6-methylguanine DNA methyltransferase （MGMT）, a unique DNA repair protein that confers tumor resistance to various anticancer alkylating agents. The Er-α -positive breast cancer cell lines （MCF-7, T47D） and Er- negative cell lines （MDAMB- 468, MDAMB-231）, and established inhibitors of Er-α and MGMT, namely, ICI-182,780 （Faslodex） and O^6- benzylguanine, respectively, were used to study MGMT- Er interactions. The MGMT gene promoter was found to harbor one full and two half estrogen-responsive elements （ErEs） and two antioxidant-responsive elements （ArEs）. MGMT expression was upregulated by estrogen, downregulated by tamoxifen in Western blot and promoter-linked reporter assays. similarly, both transient and stable transfections of Nrf-2 （nuclear factor-erythroid 2-related factor-2） increased the levels of MGMT protein and activity 3 to 4-fold reflecting novel regulatory nodes for this dragresistance determinant. Of the different Er-α antagonists tested, the pure anti-estrogen fulvestrant was most potent in inhibiting the MGMT activity in a dose, time and Er-α dependent manner, similar to O^6-benzylguanine. Interestingly, fulvestrant exposure led to a degradation of both Er-α and MGMT proteins and O^6-benzylguanine also induced a specific loss of Er-a and MGMT proteins in MCF-7 and T47D breast cancer cells with similar kinetics. Immunoprecipitation revealed a specific association of Er-a and MGMT proteins in breast cancer cells. Furthermore, silencing of MGMT gene expression triggered a decrease in the levels of both MGMT and Er-a proteins. The involvement of proteasome in the drug-induced degradation of both proteins was also demonstrated. Fulvestrant enhanced th

关键词： estrogen signaling MGMT DNA repair ubiquitin-proteasome pathway breast cancer anti-estrogens

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A new software for automated counting of glistenings in intraocular lenses in vivo

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International Journal of Ophthalmology(English edition) 2023年第8期16卷 1237-1242页

作者： Nick stanojcic Christopher C.Hull Eduardo Mangieri nathan Little David O’Brart Department of Ophthalmology Guy’s and St Thomas’NHS Foundation TrustLondon SE17EHUK Centre for Applied Vision research School of Health SciencesUniversity of LondonLondon EC1V 0HBUK sparca Ltd CroydonSurrey CR01QQUK King’s College London WC2R 2LSUK

AIM:To assess the performance of a bespoke software for automated counting of intraocular lens(IOL)glistenings in slit-lamp ***:IOL glistenings from slit-lamp-derived digital images were counted manually and automatically by the bespoke *** images of one randomly selected eye from each of 34 participants were used as a training set to determine the threshold setting that gave the best agreement between manual and automatic grading.A second set of 63 images,selected using randomised stratified sampling from 290 images,were used for software *** images were obtained using a previously described ***-derived automated glistenings counts were compared to manual counts produced by three ***:A threshold value of 140 was determined that minimised the total deviation in the number of glistenings for the 34 images in the training *** this threshold value,only slight agreement was found between automated software counts and manual expert counts for the validating set of 63 images(κ=0.104,95%CI,0.040-0.168).Ten images(15.9%)had glistenings counts that agreed between the software and manual *** were 49 images(77.8%)where the software overestimated the number of ***:The low levels of agreement show between an initial release of software used to automatically count glistenings in in vivo slit-lamp images and manual counting indicates that this is a non-trivial *** improvement involving a dialogue between software developers and experienced ophthalmologists is required to optimise *** results suggest that validation of software is necessary for studies involving semi-automatic evaluation of glistenings.

关键词： new software automated counting glistenings intraocular lenses slit-lamp images

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How to perform gastrointestinal ultrasound: anatomy and normal findings

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World Journal of Gastroenterology 2017年第38期23卷 6931-6941页

作者： nathan s s Atkinson robert V Bryant Yi Dong Christian Maaser Torsten Kucharzik Giovanni Maconi Anil K Asthana Michael Blaivas Adrian Goudie Odd Helge Gilja Dieter Nuernberg Dagmar schreiber-Dietrich Christoph F Dietrich Translational Gastroenterology Unit Oxford University Hospitals NHS Foundation Trust school of Medicine University of Adelaide Department of Gastroenterology and Hepatology Royal Adelaide Hospital Department of Ultrasound Zhongshan Hospital Fudan University Ambulanzzentrum Gastroenterologie Klinikum Lüneburg Department of Gastroenterology Stadtisches Klinikum Luneburg gGmbH Gastrointestinal Unit Department of Biomedical and Clinical Sciences 'L.Sacco' University Hospital Department of Gastroenterology and Hepato-logy The Alfred Hospital Monash University Piedmont Hospital Department of Emergency Medicine Fremantle Hospital and Health service Emergency Department National Centre for Ultrasound in Gastro- enterology Haukeland University Hospital Department of Clinical Medicine University of Bergen Department of Gastroenterology Brandenburg Medical School Med. Klinik 2 Caritas-Krankenhaus Bad Mergentheim

Gastrointestinal ultrasound is a practical, safe, cheap and reproducible diagnostic tool in inflammatorybowel disease gaining global prominence amongst clinicians. Understanding the embryological processes of the intestinal tract assists in the interpretation of abnormal sonographic findings. In general terms, the examination principally comprises interrogation of the colon, mesentery and small intestine using both lowfrequency and high-frequency probes. Interpretation of findings on GIUs includes assessment of bowel wall thickness, symmetry of this thickness, evidence of transmural changes, assessment of vascularity using Doppler imaging and assessment of other specific features including lymph nodes, mesentery and luminal motility. In addition to B-mode imaging, transperineal ultrasonography, elastography and contrast-enhanced ultrasonography are useful adjuncts. This supplement expands upon these features in more depth.

关键词： Ultrasound Intestinal Inflammatory bowel disease Guidelines Teaching

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万想不到的征程

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作者： (新加坡)纳丹(s.r. nathan)

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选择萃取火焰原子吸收法测定地质物质中的铋

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地质地球化学 1993年第2期21卷 62-64页

作者： P.Chattopadhyay s.s.nathan 杨喜增米瑞华南开大学化学系南开大学测试中心

研究了用带有增强输出(boosted output)空心阴极灯的火焰原子吸收光谱仪快速测定地质样品(尤其是化探样品)中铋含量的方法。先用甲基异丁基酮萃取碘化铋,然后用乙二胺四乙酸水溶液反萃取铋,将萃取的水相吸喷到空气-乙炔火焰中以原子化... 详细信息

研究了用带有增强输出(boosted output)空心阴极灯的火焰原子吸收光谱仪快速测定地质样品(尤其是化探样品)中铋含量的方法。先用甲基异丁基酮萃取碘化铋,然后用乙二胺四乙酸水溶液反萃取铋,将萃取的水相吸喷到空气-乙炔火焰中以原子化。为了检验方法的准确性,对美国地质调查局的化探参考样和其他一些国际参考样进行了分析,所测结果与其他原子吸收法测定结果进行了比较,发现本方法适用于各种地质样品中低至0.4ppm铋的测定。

关键词：地质物质采样铋火焰原子吸收

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