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Stress-activated kinases as therapeutic targets in pancreatic cancer

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World Journal of Gastroenterology 2021年第30期27卷 4963-4984页

作者： Benno Traub Aileen Roth marko Kornmann Uwe Knippschild Joachim Bischof Department of General and Visceral Surgery Ulm University HospitalUlm 89081Germany

pancreatic cancer is a dismal disease with high incidence and poor survival *** the aim to improve overall survival of pancreatic cancer patients,new therapeutic approaches are urgently *** kinases are key regulatory players in basically all stages of development,maintaining physiologic functions but also being involved in pathogenic processes.c-Jun N-terminal kinases(JNK)and p38 kinases,representatives of the mitogen-activated protein kinases,as well as the casein kinase 1(CK1)family of protein kinases are important mediators of adequate response to cellular stress following inflammatory and metabolic stressors,DNA damage,and *** their physiologic roles,they are responsible for the regulation of cell cycle progression,cell proliferation and differentiation,and *** of the underlying pathways consequently has been identified in various cancer types,including pancreatic *** targeting of those pathways has been the field of interest for several *** success in earlier studies was limited due to lacking specificity and off-target effects,more recent improvements in small molecule inhibitor design against stress-activated protein kinases and their use in combination therapies have shown promising in vitro ***,targeting of JNK,p38,and CK1 protein kinase family members may actually be of particular interest in the field of precision medicine in patients with highly deregulated kinase pathways related to these ***,further studies are warranted,especially involving in vivo investigation and clinical trials,in order to advance inhibition of stress-activated kinases to the field of translational medicine.

关键词： pancreatic cancer Stress-activated protein kinases Mitogen-activated protein kinases c-Jun N-terminal kinases Casein kinase 1 Small molecule inhibitor

The influence of physiobiomechanical parameters,technical aspects of shooting,and psychophysiological factors on biathlon performance:A review

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Journal of Sport and Health Science 2018年第4期7卷 394-404页

作者： marko s.laaksonen thomas finkenzeller hans-christer holmberg gerold sattlecker department of health sciences swedish winter sports research centremid sweden universityOstersund 83125Sweden department of sport science and kinesiology paris lodron university of salzburgSalzburg 5020Austria school of sport sciences uit the arctic university of norwayTromso 9019Norway

The biathlon, an Olympic sporting discipline that combines cross-country skiing with rifle marksmanship, entails considerable physiological demands, as well as fine motor control while shooting after intense exercise and under mental pressure. Although much of our knowledge about cross-country skiing is probably also applicable to the biathlon, carrying the rifle and shooting under stress make this discipline somewhat unique. The present review summarizes and examines the scientific literature related to biathlon performance, with a focus on physiological and biomechanical factors and shooting technique, as well as psychophysiological aspects of shooting performance. We conclude with suggestions for future research designed to extend our knowledge about the biathlon, which is presently quite limited.

关键词：射击技术射击性能竞赛评论奥林匹克心理压力马达控制上海大学

Multi-national observational study to assess quality of life and treatment preferences in patients with Crohn’s perianal fistulas

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World Journal of Gastrointestinal Surgery 2023年第11期15卷 2537-2552页

作者： Chitra Karki Amod Athavale Vijay Abilash Gary Hantsbarger parnia Geransar Kate Lee Slobodan Milicevic marko p.rovic Leanne Raven Magdalena Sajak-Szczerba Abigail Silber Annabelle Yoon phil Tozer Global Evidence and Outcomes-Gastroenterology Takeda Pharmaceuticals United StatesIncCambridgeMA 02139United States Trinity partners LLCWalthamMA 02451-7528United States Observational Research Takeda Pharmaceuticals United StatesIncCambridgeMA 02139United States Medical Affairs Takeda Pharmaceuticals International Co.Opfikon 8152ZurichSwitzerland Research and patient programs Crohn’s and Colitis Canada600-60 St.Clair Avenue EastToronto M4T 1N5OntarioCanada Treasurer European Federation of Crohn’s&Ulcerative Colitis AssociationsBrussels B 1000Belgium Crohn’s and Colitis Australia Camberwell SouthVIC 3124Australia European Federation of Crohn’s&Ulcerative Colitis Associations Brussels B 1000Belgium Japan Medical Office Takeda Pharmaceutical Company LimitedTokyo 103-8668Japan Department of Colorectal Surgery St Mark’s Hospital and Academic InstituteLondon HA13UJUnited Kingdom

BACKGROUND patients with Crohn’s disease(CD)are at risk of developing complications such as perianal *** with Crohn’s perianal fistulas(CpF)are affected by fecal incontinence(FI),bleeding,pain,swelling,and purulent perianal discharge,and METHODS This cross-sectional observational study was conducted in patients with CD aged 21-90 years via a web-enabled questionnaire in seven countries(April-August 2021).patients were recruited into three cohorts:Cohort 1 included patients without perianal fistulas;cohort 2 included patients with perianal fistulas without fistula-related surgery;and cohort 3 included patients with perianal fistulas and fistula-related *** patient-reported outcome measures were used to assess quality of *** of treatment preferences were measured using a discrete choice experiment(DCE).RESULTS In total,929 patients were recruited(cohort 1,n=620;cohort 2,n=174;cohort 3,n=135).Short Inflammatory Bowel Disease Questionnaire scores were worse for patients with CpF(cohorts 2 and 3)than for those with CD without CpF(cohort 1):Mean score 3.8 and 3.7 vs 4.1,respectively,(ppatients with CpF than for those with CD without *** of Life with Anal Fistula scores were similar in patients with CpF with or without CpF-related surgery(cohorts 2 and 3):Mean score 41 and 42,*** the DCE,postoperative discomfort and fistula healing rate were the most important treatment attributes influencing treatment choice:Mean relative importance 35.7 and 24.7,*** The burden of illness in CD is significantly higher for patients with CpF and patients rate lower postoperative discomfort and higher healing rates as the most desirable treatment attributes.

关键词： Burden of illness Crohn’s disease Discrete choice experiment perianal fistulas patient-reported outcomes Treatment preferences

Raman lasing and soliton mode-locking in lithium niobate microresonators

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Light(Science & Applications) 2020年第1期9卷 1925-1931页

作者： Mengjie Yu Yoshitomo Okawachi Rebecca Cheng Cheng Wang Mian Zhang Alexander L.Gaeta marko Loncar Department John A.paulson School of Engineering and Applied Sciences Harvard UniversityCambridgeMA 02138USA Department of Applied physics and Applied Mathematics Columbia UniversityNew YorkNY 10027USA Department of Electronic Engineering&State Key Laboratory of Terahertz and Millimeter Waves City University of Hong KongKowloonHong KongChina HyperLight Corporation 501 Massachusetts AvenueCambridgeMA 02139USA

The recent advancement in lithium-niobite-on-insulator(LNOI)technology is opening up new opportunities in optoelectronics,as devices with better performance,lower power consumption and a smaller footprint can be realised due to the high optical confinement in the *** LNOI platform offers both largeχ(2)andχ(3)nonlinearities along with the power of dispersion engineering,enabling brand new nonlinear photonic devices and applications for the next generation of integrated photonic ***,Raman scattering and its interaction with other nonlinear processes have not been extensively studied in dispersion-engineered LNOI *** this work,we characterise the Raman radiation spectra in a monolithic lithium niobate(LN)microresonator via selective excitation of Raman-active phonon *** dominant mode for the Raman oscillation is observed in the backward direction for a continuous-wave pump threshold power of 20mW with a high differential quantum efficiency of 46%.We explore the effects of Raman scattering on Kerr optical frequency comb *** achieve mode-locked states in an X-cut LNOI chip through sufficient suppression of the Raman effect via cavity geometry *** analysis of the Raman effect provides guidance for the development of future chip-based photonic devices on the LNOI platform.

关键词： scattering pump lithium

First determination of the highly genotoxic fungal contaminant altertoxin II in a naturally infested apple sample

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Emerging Contaminants 2020年第1期6卷 82-86页

作者： Hannes puntscher Doris marko Benedikt Warth Department of Food Chemistry and Toxicology Faculty of ChemistryUniversity of ViennaWahringer Str.381090ViennaAustria

Altertoxin II is an epoxide-holding perylene quinone and secondary metabolite produced by Alternaria *** genotoxic potential and the high concentrations determined in laboratory fungal cultures resulted in an increased scientific interest in this emerging ***,no natural occurrence in food has been reported to date to the best of our ***,we unambiguously identified altertoxin II in a naturally infected,unprocessed *** a validated LC-MS/MS method,fruit peel spots(approx.1 mm in diameter),typically associated with Alternaria infestation,were tested for 17 mycotoxins produced by this *** concentrations of tentoxin were determined 24 h after harvest,and the dibenzopyrones alternariol,alternariol monomethyl ether(AME)and AME-3-sulfate after six months of ***,these contamination patterns can be considered unlikely to be of toxicological concern for ***,an inconspicuous peel lesion(0.5×1 cm)separately sampled from a stored apple,exhibited considerably high concentrations of 14 Alternaria toxins,including dibenzopyrones,their barely studied modified forms(glucosides and sulfates),as well as genotoxic perylene quinones including altertoxin *** the toxicological potential of this compound,contaminations in such infected fruit parts should not be underestimated,*** the case of exposure through the consumption of fresh smoothies or fruit juices.

关键词： Alternaria alternata Emerging contaminants Genotoxicity Food safety plant pathology Liquid chromatography tandem mass spectrometry

Role of novel biomarkers in diabetic cardiomyopathy

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World Journal of Diabetes 2021年第6期12卷 685-705页

作者： marko Kumric Tina Ticinovic Kurir Josip A Borovac Josko Bozic Department of pathophysiology University of Split School of MedicineSplit 21000Croatia Department of Endocrinology University Hospital of SplitSplit 21000Croatia Emergency Medicine Institute of Emergency Medicine of Split-Dalmatia CountySplit 21000Croatia

Diabetic cardiomyopathy(DCM)is commonly defined as cardiomyopathy in patients with diabetes mellitus in the absence of coronary artery disease and *** DCM is now recognized as a cause of substantial morbidity and mortality among patients with diabetes mellitus and clinical diagnosis is still inappropriate,various expert groups struggled to identify a suitable biomarker that will help in the recognition and management of DCM,with little success so ***,we thought it important to address the role of biomarkers that have shown potential in either human or animal studies and which could eventually result in mitigating the poor outcomes of *** the array of biomarkers we thoroughly analyzed,long noncoding ribonucleic acids,soluble form of suppression of tumorigenicity 2 and galectin-3 seem to be most beneficial for DCM detection,as their plasma/serum levels accurately correlate with the early stages of *** combination of relatively inexpensive and accurate speckle tracking echocardiography with some of the highlighted biomarkers may be a promising screening method for newly diagnosed diabetes mellitus type 2 *** purpose of the screening test would be to direct affected patients to more specific confirmation *** perspective is in concordance with current guidelines that accentuate the importance of an interdisciplinary team-based approach.

关键词： Diabetic cardiomyopathy Heart failure Biomarkers Diabetes mellitus Cardiomyopathy

Origins of high ductility exhibited by an extruded magnesium alloy Mg-1.8Zn-0.2Ca:Experiments and crystal plasticity modeling

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Journal of Materials Science & Technology 2021年第25期84卷 27-42页

作者： Jie Wang Gaoming Zhu Leyun Wang Evgenii Vasilev Jun-Sang park Gang Sha Xiaoqin Zeng marko Knezevic National Engineering Research Center of Light Alloy Net Forming Shanghai Jiao Tong UniversityShanghai200240China Department of Mechanical Engineering University of New HampshireDurhamNH03824USA Advanced photon Source Argonne National LaboratoryLemontIL60439USA School of Materials Science and Engineering Nanjing University of Science and TechnologyNanjing210094China State Key Laboratory of Metal Matrix Composites Shanghai Jiao Tong UniversityShanghai200240China

Low ductility and strength are major bottlenecks against Mg alloys’wide *** this work,we systematically design the composition and fabrication process for a low-alloyed Mg-Zn-Ca alloy,showing that it can be extruded at low temperatures(~250℃)and high speeds(~2 mm/s).After the extrusion,this alloy exhibits a substantially weakened basal texture,relatively small grain size,very high tensile elongation(~30%),and good *** origin of the considerably improved ductility was studied using a combination of three-dimensional atom probe tomography(3D-ApT),transmission electron microscopy(TEM),electron backscattered diffraction(EBSD)in conjunction with surface slip trace analysis,in-situ synchrotron X-ray diffraction,and elasto-plastic self-consistent(EpSC)***-segregation of Zn and Ca atoms at a grain boundary is observed and associated with texture weakening and grain boundary mediated plasticity,both improving the *** basal slip and prismatic slip are identified as the dominant deformation systems in the alloy,the ratio between their slip resistances is substantially reduced relative to pure Mg and most other Mg alloys,significantly contributing to the improved ductility of the *** Mg-Zn-Ca alloy exhibiting excellent mechanical properties and low fabrication cost is a promising candidate for industrial productions.

关键词： Mg-Zn-Ca alloy Ductility Deformation mechanisms Crystal plasticity modeling Grain boundary mediated plasticity

Adherence to Mediterranean diet and advanced glycation endproducts in patients with diabetes

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World Journal of Diabetes 2021年第11期12卷 1942-1956页

作者： marko Grahovac marko Kumric Marino Vilovic Dinko Martinovic Ante Kreso Tina Ticinovic Kurir Josip Vrdoljak Karlo prizmic Joško Božić Department of pharmacology University of Split School of MedicineSplit 21000Croatia Department of pathophysiology University of Split School of MedicineSplit 21000Croatia Department of Endocrinology University Hospital of SplitSplit 21000Croatia

BACKGROUND In recent years,American Diabetes Association started to strongly advocate the Mediterranean diet(MD)over other diets in patients with diabetes mellitus(DM)because of its beneficial effects on glycemic control and cardiovascular(CV)risk *** levels of advanced glycation endproducts(AGEs)emerged as an indicator of CV risk in *** biopsy being invasive,the use of AGE Reader has been shown to reflect tissue AGEs *** To examine the association between adherence to MD and AGEs in patients with DM type *** This cross-sectional study was conducted on 273 patients with DM type II.A survey questionnaire was composed of 3 separate *** first part of the questionnaire included general data and the habits of the *** second part aimed to assess the basic parameters of participants’diseases and associated *** third part of the questionnaire was the Croatian version of the 14-item MD service score(MDSS).AGEs levels and associated CV risk were measured using AGE Reader(DiagnOptics Technologies BV,Groningen,The Netherlands).RESULTS A total of 27(9.9%)patients fulfilled criteria for adherence to MD,with a median score of 8.0(6.0-10.0).patients with none/limited CV risk had significantly higher percentage of MD adherence in comparison to patients with increased/definite CV risk(15.2%vs 6.9%,p=0.028),as well as better adherence to guidelines for nuts(23.2%vs 12.6%,p=0.023)and legumes(40.4%vs 25.9%,p=0.013)*** number of patients with glycated hemoglobin(HbA1c)pared to patients with HbA1c>7%(14.9%vs 7.3%,p=0.045).Moreover,those patients followed the MDSS guidelines for eggs(33.0%vs 46.8%,p=0.025)and wine(15.6%vs 29.8%,p=0.006)consumption more *** score had significant positive correlation with disease duration(r=0.179,p=0.003)and negative correlation with body mass index(BMI)values(r=-0.159,p=0.008).In the multiple linear regression model,BMI(β±SE,-0.09±0.04,p=0.037

关键词： Mediterranean diet Cardiovascular disease Diabetes mellitus Advanced glycation endproducts Dietary habits Atherosclerosis

periodic Solutions in Unbounded Domains for the Boussinesq System

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Acta Mathematica Sinica,English Series 2010年第5期26卷 837-862页

作者： Elder Jesús VILLAMIZAR-ROA María ngeles RODRíGUEZ-BELLIDO marko Antonio ROJAS-MEDAR Escuela de Matemáticas Universidad Nacional de Colombia Dpto. Ecuaciones Diferenciales y Análisis Numérico Universidad de Sevilla Aptdo Dpto. de Ciencias Básicas Facultad de Ciencias Universidad del Bío BíoCampus Fernando May

Assuming that the external forces of the system are small enough, the reference temperature being a periodic function, we study the existence, the uniqueness and the regularity of time-periodic solutions for the Boussinesq equations in several classes of unbounded domains of Rn. Our analysis is based on the framework of weak-Lp spaces.

关键词： Boussinesq equations strong periodic solutions unbounded domains