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转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化

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Engineering 2024年第1期32卷 57-68页

作者： Vedrana Vicic Bockor Nika Foglar Goran Josipovic Marija Klasic Ana Vujic Branimir Plavsa toma Keser Samira Smajlovic Aleksandar Vojta Vlatka Zoldos Laboratory for Epigenetics Department of BiologyFaculty of ScienceUniversity of ZagrebZagreb 10000Croatia Genos Glycoscience Research Laboratory Zagreb 10000Croatia Faculty of Pharmacy and Biochemistry University of ZagrebZagreb 10000Croatia

Hepatocyte nuclear factor 1 alpha(HNF1A),hepatocyte nuclear factor 4 alpha(HNF4A),and forkhead box protein A2(FOXA2)are key transcription factors that regulate a complex gene network in the liver,cre-ating a regulatory transcriptional loop.The Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase genes.Our in silico analysis of HNF1A,HNF4A.and FOXA2 binding to the ten candidate glyco-genes studied in this work confirms a significant enrich-ment of these transcription factors specifically in the liver.Our previous studies identified HNF1A as a master regulator of fucosylation,glycan branching,and galactosylation of plasma glycoproteins.Here,we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan phenotype.We used the state-of-the-art clus-tered regularly interspaced short palindromic repeats/dead Cas9(CRISPR/dCas9)molecular tool for the downregulation of the HNF1A,HNF4A,and FOXA2 genes in HepG2 cells-a human liver cancer cell line.The results show that the downregulation of all three genes individually and in pairs affects the transcrip-tional activity of many glyco-genes,although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan structures.The effect is better seen as an overall change in the total HepG2 N-glycome,primarily due to the extension of biantennary glycans.We propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan structure.We also propose a model showing feedback loops with the mutual activation of HNF1A-FOXA2 and HNF4A-FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.

关键词： Clustered regularly interspaced short palindromic repeats/dead Cas9(CRISPR/dCas9) Epigenetics Hepatocyte nuclear factor 1 alpha(HNF1A) Hepatocyte nuclear factor 4 alpha(HNF4A) Forkhead box protein A2(FOXA2) N-glycosylation HepG2 cells

A fixed point theorem for Proinov mappings with a contractive iterate

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Applied Mathematics(A Journal of Chinese Universities) 2023年第3期38卷 403-412页

作者： Erdal Karapnar andreea Fulga Department of Medical Research China Medical UniversityTaichungTaiwanChina Department of Mathematics Cankaya University06790EtimesgutAnkaraTurkey Department of Mathematics and Computer Science Transilvania University of BrasovBrasovRo-mania.

In this paper,we consider the fixed point theorem for Proinov mappings with a contractive iterate at a point.In other words,we combine and unify the basic approaches of Proinov and Sehgal in the framework of the compl... 详细信息

关键词： contractive iterate at a point Proinov mappings fixed point theorems

Allergic rhinitis facts from an Irish pediatric population

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2023年第4期9卷 333-339页

作者： andreea Nae Colleen B.Heffernan Michael Colreavy Department of Otorhinolaryngology Ireland

Objective:Assessing the main allergens in the pediatric population from the largest urban area in the country.Methods:Clinical letters of patients referred with possible allergic rhinitis(AR)were retrospectively reviewed over the past 5 years.Results:Five hundred and fifty‐five patients were included.Males suffer twice as often with AR than females and have high titers of allergens.House dust mites(44.7%)and grass pollen(29%)were the main allergens in our area,with 48%of patients sensitized to both allergens.Half of the patients had the diagnosis of AR confirmed with positive allergen‐specific tests.For the other half,the diagnosis was based on a clinical assessment performed by a pediatric otolaryngologist.Conclusions:Half of suspected AR children have environmental allergen sensitivity confirmed by testing,and a large number had a clinical diagnosis of AR after an otolaryngology consultation.Our findings can help clinicians to initiate AR treatment considering the most problematic allergens in the area.

关键词： aeroallergens allergic rhinitis grass pollens house dust mites skin prick

Risk factors for carotid plaque progression after optimising the risk factor treatment: substudy results of the Atherosclerotic Plaque Characteristics Associated with a Progression Rate of the Plaque and a Risk of Stroke in Patients with the carotid Bifurcation Plaque Study (ANTIQUE)

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Stroke & Vascular Neurology 2022年第2期7卷 132-139页

作者： David Školoudik Petra Kešnerova tomaš Hrbač David Netuka Jaroslav Vomačka Kateřina Langova Roman Herzig tomaš Belšan Center for Health Research Faculty of MedicineUniversity of OstravaOstravaCzech Republic Department of Neurology University Hospital OstravaOstravaCzech Republic Department of Neurology Second Faculty of MedicineCharles UniversityPrahaCzech Republic Department of Neurology Motol University HospitalPrahaCzech Republic Department of Neurosurgery Faculty of MedicineUniversity of OstravaOstravaCzech Republic Department of Neurosurgery University Hospital OstravaOstravaCzech Republic Department of Neurosurgery Military University Hospital PraguePrahaCzech Republic Department of Radiological Assistance Faculty of Health SciencesPalacky University OlomoucOlomoucCzech Republic Deaprtment of Radiology University Hospital OlomoucOlomoucCzech Republic Department of Biophysics Faculty of MedicinePalacky University OlomoucOlomoucCzech Republic Department of Neurology University Hospital Hradec KrálovéHradec KraloveCzech Republic Department of Neurology Faculty of Medicine in Hradec KrálovéCharles UniversityHradec KrálovéCzech Republic Department of Radiology Military University Hospital PraguePrahaCzech Republic

Background and aim Carotid plaque progression contributes to increasing stroke risk.The study aims to identify factors influencing carotid plaque thickness progression after changing the preventive treatment to the‘treating arteries instead of risk factors’strategy,that is,change in treatment depending on the progression of atherosclerosis.Methods The study participants who completed sonographic controls over the course of 3 years were enrolled to the analysis.Duplex sonography of cervical arteries was performed in 6-month intervals with measurement of carotid plaque thickness.Plaque thickness measurement error(σ)was set as 3 SD.Only evidently stable and progressive plaques(defined as plaque thickness difference between initial and final measurements of˂σand>2σ,respectively)were included to analysis.Univariate and multivariate logistic regression analysis was performed to identify factors influencing plaque progression.Results A total of 1391 patients(466 males,age 67.2±9.2 years)were enrolled in the study.Progressive plaque in at least one carotid artery was detected in 255(18.3%)patients.Older age,male sex,greater plaque thickness,coronary heart disease,vascular surgery/stenting history and smoking were more frequently present in patients with progressive plaque(p˂0.05 in all cases).Multivariate logistic regression analysis identified only the plaque thickness(OR 1.850 for left side,95%CI 1.398 to 2.449;and OR 1.376 for right side,95%CI 1.070 to 1.770)as an independent factor influencing plaque progression.Conclusion Carotid plaque thickness corresponding to stenosis severity is the only independent risk factor for plaque thickness progression after optimising the prevention treatment.

关键词： prevention treatment Duplex

Artificial intelligence as a noninvasive tool for pancreatic cancer prediction and diagnosis

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World Journal of Gastroenterology 2023年第12期29卷 1811-1823页

作者： Alexandra Corina Faur Daniela Cornelia Lazar Laura andreea Ghenciu Department of Anatomy and Embriology “Victor Babeș”University of Medicine and Pharmacy TimișoaraTimișoara 300041TimișRomania Department V of Internal Medicine I Discipline of Internal Medicine IVUniversity of Medicine and Pharmacy“Victor Babes”TimișoaraTimișoara 300041TimișRomania DepartmentⅢ Discipline of Pathophysiology“Victor Babeș”University of Medicine and PharmacyTimișoara 300041TimișRomania

Pancreatic cancer(PC)has a low incidence rate but a high mortality,with patients often in the advanced stage of the disease at the time of the first diagnosis.If detected,early neoplastic lesions are ideal for surgery,offering the best prognosis.Preneoplastic lesions of the pancreas include pancreatic intraepithelial neoplasia and mucinous cystic neoplasms,with intraductal papillary mucinous neoplasms being the most commonly diagnosed.Our study focused on predicting PC by identifying early signs using noninvasive techniques and artificial intelligence(AI).A systematic English literature search was conducted on the PubMed electronic database and other sources.We obtained a total of 97 studies on the subject of pancreatic neoplasms.The final number of articles included in our study was 44,34 of which focused on the use of AI algorithms in the early diagnosis and prediction of pancreatic lesions.AI algorithms can facilitate diagnosis by analyzing massive amounts of data in a short period of time.Correlations can be made through AI algorithms by expanding image and electronic medical records databases,which can later be used as part of a screening program for the general population.AI-based screening models should involve a combination of biomarkers and medical and imaging data from different sources.This requires large numbers of resources,collaboration between medical practitioners,and investment in medical infrastructures.

关键词： Pancreatic cancer Early pancreatic lesions Pancreatic neoplasia Artificial intelligence Deep learning Machine learning Radiomics Diagnosis Pancreas

Intra-ampullary papillary-tubular neoplasm combined with ampullary neuroendocrine carcinoma:A case report

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World Journal of Clinical Cases 2022年第22期10卷 8045-8053页

作者： Hana Zavrtanik Boštjan Luzar Aleštomažič Department of Abdominal Surgery University Medical Centre LjubljanaLjubljana 1000Slovenia Institute of Pathology Faculty of MedicineUniversity of LjubljanaLjubljana 1000Slovenia Faculty of Medicine University of LjubljanaLjubljana 1000Slovenia

BACKGROUND The ampulla of Vater is an anatomically and histologically complex region giving rise to a heterogenous group of tumors.This is,to the best of our knowledge,the first case of intra-ampullary papillary-tubular neoplasm combined with ampullary neuroendocrine carcinoma reported in the literature.CASE SUMMARY A 61-year-old woman presented to the emergency department for evaluation of painless jaundice.Contrast-enhanced computed tomography(CT)of the abdomen and chest showed a periampullary tumor mass measuring 15 mm×12 mm×14 mm,with no evidence of locoregional and distant metastases,for which she underwent pancreatoduodenectomy.Histopathologic examination of a resected specimen revealed an intra-ampullary papillary tubular neoplasm with highgrade dysplasia in combination with poorly differentiated grade 3 neuroendocrine carcinoma with a mitotic count of more than 20 mitoses per 10 high power fields and Ki-67 index of 100%.No positive lymph nodes were identified.Her postoperative course was uneventful.Postoperatively,she remained under close surveillance.Multiple liver metastases were observed on follow-up CT 8 mo after the surgery,so systemic therapy with cisplatin and etoposide was initiated.CONCLUSION The simultaneous occurrence of neuroendocrine and non-neuroendocrine tumors in the ampulla of Vater is rare and the pathogenesis of such tumors is largely unknown.Due to unpredictable clinical behavior and lack of solid evidence on optimal treatment strategy,close patient surveillance is advised after radical resection of the primary tumor.

关键词： Ampulla of Vater Neuroendocrine carcinoma Mixed tumour Pancreaticoduodenectomy Prognosis Case report

Probability of informed trading during the COVID‑19 pandemic:the case of the Romanian stock market

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Financial Innovation 2023年第1期9卷 889-915页

作者： Cosmin Octavian Cepoi Victor Dragotă Ruxandra Trifan andreea Iordache Department of Money and Banking and CEFIMO Faculty of Finance and BankingBucharest University of Economic StudiesBucharestRomania Department of Finance and CEFIMO Faculty of Finance and BankingBucharest University of Economic StudiesBucharestRomania Doctoral School of Finance Faculty of Finance and BankingBucharest University of Economic StudiesBucharestRomania

Using data from the Bucharest Stock Exchange,we examine the factors influencing the probability of informed trading(PIN)during February—October 2020,a COVID-19 pandemic period.Based on an unconditional quantile regression approach,we show that PIN exhibit asymmetric dependency with liquidity and trading costs.Furthermore,building a customized database that contains all insider transactions on the Bucharest Stock Exchange,we reveal that these types of orders monotonically increase the infor-mation asymmetry from the 50th to the 90th quantile throughout the PIN distribution.Finally,we bring strong empirical evidence associating the level of information asym-metry to the level of fake news related to the COVID-19 pandemic.This novel result suggests that during episodes when the level of PIN is medium to high(between 15 and 50%),any COVID-19 related news classified as misinformation released during the lockdown period,is discouraging informed traders to place buy or sell orders condi-tioned by their private information.

关键词： PIN COVID-19 Market microstructure Insider trading

Classification of osteogenesis imperfecta:Importance for prophylaxis and genetic counseling

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World Journal of Clinical Cases 2023年第12期11卷 2604-2620页

作者： Monica-Cristina Panzaru andreea Florea Lavinia Caba Eusebiu Vlad Gorduza Department of Medical Genetics Faculty of Medicine“Grigore T.Popa”University of Medicine and PharmacyIasi 700115Romania Department of Medical Genetics-Medical Genetics resident “Grigore T.Popa”University of Medicine and PharmacyIasi 700115Romania

Osteogenesis imperfecta(OI)is a genetically heterogeneous monogenic disease characterized by decreased bone mass,bone fragility,and recurrent fractures.The phenotypic spectrum varies considerably ranging from prenatal fractures with lethal outcomes to mild forms with few fractures and normal stature.The basic mechanism is a collagen-related defect,not only in synthesis but also in folding,processing,bone mineralization,or osteoblast function.In recent years,great progress has been made in identifying new genes and molecular mechanisms underlying OI.In this context,the classification of OI has been revised several times and different types are used.The Sillence classification,based on clinical and radiological characteristics,is currently used as a grading of clinical severity.Based on the metabolic pathway,the functional classification allows identifying regulatory elements and targeting specific therapeutic approaches.Genetic classification has the advantage of identifying the inheritance pattern,an essential element for genetic counseling and prophylaxis.Although genotype-phenotype correlations may sometimes be challenging,genetic diagnosis allows a personalized management strategy,accurate family planning,and pregnancy management decisions including options for mode of delivery,or early antenatal OI treatment.Future research on molecular pathways and pathogenic variants involved could lead to the development of genotype-based therapeutic approaches.This narrative review summarizes our current understanding of genes,molecular mechanisms involved in OI,classifications,and their utility in prophylaxis.

关键词： Osteogenesis imperfecta Heterogeneity Classification Molecular mechanism Genetic counseling Prophylaxis

A simple,stroke-based method for gesture drawing

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Virtual Reality & Intelligent Hardware 2022年第5期4卷 381-392页

作者： Lesley ISTEAD Joe ISTEAD andreea POCOL Craig S.KAPLAN School of Information Technology Carleton UniversityOttawaOntarioCanada School of Computer Science University of WaterlooWaterlooOntarioCanada

Background Gesture drawing is a type of fluid,fast sketch with loose and roughly drawn lines that captures the motion and feeling of a subject.Although style transfer methods,which are able to learn a style from an input image and apply it to a secondary image,can reproduce many styles,they are currently unable to produce the flowing strokes of gesture drawings.Method In this paper,we present a method for producing gesture drawings that roughly depict objects or scenes with loose dancing contours and frantic textures.By following a gradient field,our method adapts stroke-based painterly rendering algorithms to produce long curved strokes.A rough,overdrawn appearance is created through a progressive refinement.In addition,we produce rough hatch strokes by altering the stroke direction.These add optional shading to gesture drawings.Results A wealth of parameters provide users the ability to adjust the output style,from short and rapid strokes to long and fluid strokes,and from swirling to straight lines.Potential stylistic outputs include pen-and-ink and colored pencil.We present several generated gesture drawings and discuss the application of our method to video.Conclusion Our stroke-based rendering algorithm produces convincing gesture drawings with numerous controllable parameters,permitting the creation of a variety of styles.

关键词： Gesture drawing Sketching Non-photorealistic rendering