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Targeting triple-negative breast cancer:A clinical perspective

Oncology Research 2023年第3期31卷 221-238页

作者： LAZAR S.POPOVIC GORANA MATOVINA-BRKO maja POPOVIC KEVIN PUNIE ANA CVETANOVIC MATTEO LAMBERTINI Department of Medical Oncology Oncology Institute of VojvodinaSremska KamenicaSerbia Faculty of Medicine University of Novi SadNovi SadSerbia Department of General Medical Oncology and Multidisciplinary Breast Centre Leuven Cancer InstituteUniversity Hospitals LeuvenLeuvenBelgium Department for Oncology Medical Faculty NisUniversity of NisNisSerbia Clinic of Oncology Clinical Centre NisNisSerbia Department of Internal Medicine and Medical Sciences(DiMI) School of MedicineUniversity of GenovaGenovaItaly Department of Medical Oncology U.O.C Clinica di Oncologia MedicaIRCCS Ospedale Policlinico San MartinoGenovaItaly

Triple-negative breast cancer(TNBC)is a disease with often an aggressive course and a poor prognosis compared to other subtypes of breast *** accounts for approximately 10%–15%of all diagnosed breast cancer cases and represents a high unmet need in the *** to just a few years ago,chemotherapy was the only systemic treatment option for this subtype(1).To date,TNBC is considered a heterogeneous *** of the existing classifications is based on the analysis of mRNA expression in 587 TNBC cases,in which Lehman et *** six subtypes of TNBC as follows:two basal-like(BL1 and BL2)subtypes,a mesenchymal(M)subtype,a mesenchymal stem-like(MSL)subtype,an immunomodulatory(IM)subtype,and a luminal androgen receptor(LAR)subtype(2).Later studies have demonstrated that the IM and MSL subtypes do not correlate with independent subtypes but reflect background expression by dense infiltration of tumor-infiltrating lymphocytes(TILs)or stromal *** to this finding,the classification of TNBC has been revised into the following four subtypes:basal 1,basal 2,LAR,and mesenchymal subtypes(3).Over the last years,several new strategies have been investigated for the treatment of patients with *** them,immunotherapy,antibody drug conjugates,new chemotherapy agents,and targeted therapy have been and are currently being *** present article aims to provide an updated overview on the different treatment options that are now available or are still under investigation for patients with TNBC.

关键词： Triple-negative breast cancer Immunotherapy Antibody-drug conjugates Target therapy

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Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure

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World Journal of Cardiology 2024年第8期16卷 448-457页

作者： Petra Grubić Rotkvić Luka Rotkvić Ana Đuzel Čokljat maja Cigrovski Berković Department of Cardiology University Hospital Centre ZagrebZagreb 10000Croatia Department of Cardiology Magdalena Clinic for Cardiovascular DiseaseKrapinske Toplice 49217Croatia Department of Internal Medicine General Hospital DubrovnikDubrovnik 20000Croatia Department for Sport and Exercise Medicine University of Zagreb Faculty of KinesiologyZagreb 10000Croatia

BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of *** previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic *** groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic *** To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body *** The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood *** evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was *** There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of *** independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy *** SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic *** control contributes to the i

关键词： Sodium-dependent glucose transporter 2 inhibitors Dipeptidyl peptidase-4 inhibitors Type 2 diabetes mellitus Heart failure Diabetic cardiomyopathy Cardiovascular disease

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Exploring new treatment options for polycystic ovary syndrome: Review of a novel antidiabetic agent SGLT2 inhibitor

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World Journal of Diabetes 2021年第7期12卷 932-938页

作者： Jelena Marinkovic-Radosevic maja Cigrovski Berkovic Egon Kruezi Ines Bilic-Curcic Anna Mrzljak Department of Endocrinology Diabetes and MetabolismSisters of Charity Clinical Hospital CentreZagreb 10000Croatia Department of Endocrinology DiabetesMetabolism and Clinical PharmacologyClinical Hospital DubravaZagreb 10000Croatia Department of Kinesiological Anthropology and Methodology Faculty of KinesiologyUniversity of ZagrebZagreb 10000Croatia Department of Gynecology and Obstetrics Sisters of Charity Clinical Hospital CentreZagreb 10000Croatia Department of Pharmacology Faculty of MedicineUniversity of J.J.Strossmayer OsijekOsijek 31000Croatia Clinical Hospital Center Osijek Osijek 31000Croatia School of Medicine University of ZagrebZagreb 10000Croatia Department of Gastroenterology and Hepatology University Hospital Centre ZagrebZagreb 10000Croatia

Polycystic ovary syndrome(PCOS)is the most common endocrinopathy in women of reproductive age associated with long-term metabolic and cardiovascular consequences.A plethora of symptoms and their severity differentiate on an individual level,giving the syndrome numerous *** to menstrual cycle abnormalities,women suffer from irregular menstrual bleeding,difficulty in conception,and ***,the risk of pregnancy complications such as gestational diabetes mellitus,hypertensive disorders of pregnancy,and preterm birth are higher in women with PCOS than in the general ***,women with PCOS have comorbidities such as dyslipidemia,obesity,glucose intolerance or diabetes type 2,non-alcoholic fatty liver disease,and metabolic syndrome,which all influence the treatment *** insulinsensitizing agents,although good for some of the metabolic derangements,do not offer long-term cardiovascular benefits;therefore,new treatment options are of paramount ***-glucose co-transporter-2(SGLT-2)inhibitors,a new class of antidiabetic agents with beneficial cardiovascular,bodyweight,and antihyperglycemic effects,although not approved for the treatment of PCOS,might be an attractive therapeutic addition in the PCOS ***,recent studies with SGLT-2 inhibitors showed promising improvements in anthropometric parameters and body composition in patients with *** is important to further explore the SGLT-2 inhibitors potential as an early therapeutic option because of the PCOS-related risk of metabolic,reproductive,and psychological consequences.

关键词： Polycystic ovary syndrome Sodium-glucose co-transporter-2 inhibitors Metabolic risk Cardiovascular risk Metabolic syndrome Insulin resistance Obesity Type 2 diabetes mellitus Dyslipidemia

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A web-based, component-oriented application for spatial modelling of habitat suitability of mosquito vectors

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International Journal of Digital Earth 2009年第4期2卷 327-342页

作者： P.Zeilhofer P.S.Arraes Neto W.Y.maja D.A.Vecchiato Department of Geography Universidade Federal de Mato GrossoBrazilAv.F.Correa da Costas/nCoxipo78.060-900 Cuiaba´-MTBrazil Department of Computer Science Universidade Federal de UberlandiaBrazil Universidade Federal de Mato Grosso Brazil

This paper proposes a web-enabled computational environment for the spatial modelling of habitat suitability of mosquito *** a component-based architecture and implemented using an object-oriented data model,we integrate database interfaces,Web feature services(WFS)based on the open GIS consortium(OGC)protocols,and the data-mining tool WEKA,coupled through Java servlet scripts(JSP).The prototype,based exclusively on freely available libraries and software components,provides basic dynamic spatial simulation capabilities using logistic regression to end-users engaged in local and regional health administration and planning but who lack access to specific software and/or detailed knowledge of spatial modelling *** component-based approach facilitates system maintenance and future expansion of functionality,and guarantees the reusability of developed modules in new spatial modelling applications of health and environmental-related *** of the WWW-application was validated in a study of habitat suitability mapping of the Malaria vector Anopheles darlingi,in an area surrounding the Manso River hydropower plant,Central Brazil.

关键词： habitat mapping component and service orientation WWW

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Prehabilitation of overweight and obese patients with dysglycemia awaiting bariatric surgery: Predicting the success of obesity treatment

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World Journal of Diabetes 2022年第12期13卷 1096-1105页

作者： maja Cigrovski Berkovic Ines Bilic-Curcic Anna Mrzljak Silvija Canecki Varzic Vjekoslav Cigrovski Department of Endocrinology Diabetes and Clinical PharmacologyClinical Hospital DubravaZagreb 10000Croatia Faculty of Kinesiology University of ZagrebZagreb 10000Croatia Faculty of Medicine University of Osijek Osijek 31000Croatia Department of Endocrinology and Diabetes Clinical Hospital Centre OsijekOsijek 31000Croatia Department of Gastroenterology and Hepatology University Hospital Center ZagrebZagreb 10000Croatia School of Medicine University of ZagrebZagreb 10000Croatia

Bariatric surgery offers the best health results in overweight and obese patients but is not a risk and/or complication-free *** cases with additional hyperglycemia,the burden of surgery can be even higher and alter both shortterm and long-term *** bariatric surgery offers glycemic improvements and in the case of early onset diabetes disease remission,weight loss results are lower than for obese patients without *** multimodal programs,usually including interventions related to patients’performance,nutritional and psychological status as well as currently available pharmacotherapy before the surgery itself might considerably improve the immediate and late postoperative ***,there are still no clear guidelines addressing the prehabilitation of obese patients with dysglycemia undergoing bariatric surgery and therefore no unique protocols to improve patients’*** this minireview,we summarize the current knowledge on prehabilitation before bariatric surgery procedures in patients with obesity and dysglycemia.

关键词： Bariatric surgery Obesity Dysgylcemia Diabetes outcome Prehabilitation

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Hepatitis E virus in professionally exposed: A reason for concern?

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World Journal of Hepatology 2021年第7期13卷 723-730页

作者： Anna Mrzljak Ivan Balen Ljubo Barbic maja ilic Tatjana Vilibic-Cavlek Department of Gastroenterology and Hepatology University Hospital Centre ZagrebZagreb 10000Croatia School of Medicine University of ZagrebZagreb 10000Croatia Department of Gastroenterology and Endocrinology General Hospital“Dr.Josip Bencevic”Slavonski Brod 35000Croatia Faculty of Veterinary Medicine University of ZagrebZagreb 10000Croatia Department of Epidemiology Croatian Institute of Public HealthSchool of MedicineUniversity of ZagrebZagreb 10000Croatia Department of Virology Croatian Institute of Public HealthSchool of MedicineUniversity of ZagrebZagreb 10000Croatia

The zoonotic risk of hepatitis E virus(HEV)is well *** HEV seroprevalence rates vary according to geographical region,assays used,and study *** infection is still underdiagnosed,implying the need to evaluate the disease's burden in the general population and specific risk groups,such as professionally *** contact with various animal reservoirs such as pigs,rabbits,sheep,dogs,wild boars,and deer has been associated with higher anti-HEV seroprevalence as a part of occupational *** exact transmission routes remain to be determined,some general preventive measures such as proper hand hygiene,the usage of personal protective equipment,and the thermal processing of food before consumption should be followed.A“One-Health”multisectoral approach should be implemented to achieve optimal health and well-being outcomes,recognizing the interconnections between humans,animals,plants,and their shared environment,in which a vaccine against the zoonotic genotypes 3 and 4 and swine vaccination should be considered as a possible public health *** opinion review comprehensively addresses the HEV burden of professional exposure for butchers,slaughterhouse workers,veterinarians,farmers,hunters,and forestry workers delineates the current limits of protective work measures,and tackles future directions.

关键词： Hepatitis E virus Zoonotic infection Occupational disease Veterinarians Farmers Butchers Slaughterhouse workers Forestry workers Hunters

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Coagulation and Endothelial Dysfunction Associated with NAFLD:Current Status and Therapeutic Implications

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Journal of Clinical and Translational Hepatology 2022年第2期10卷 339-355页

作者： Doris Ogresta Anna Mrzljak maja Cigrovski Berkovic Ines Bilic-Curcic Sanja Stojsavljevic-Shapeski Lucija Virovic-Jukic Department of Gastroenterology and Hepatology Sestre Milosrdnice University Hospital CenterZagrebCroatia Depart-ment of Gastroenterology and Hepatology University Hospital Center ZagrebZagrebCroatia Department of Medicine University of ZagrebSchool of MedicineZagrebCroatia Department for Endocrinology Diabetes and PharmacologyUniversity Hospital DubravaZagrebCroatia Department of Kinesiological Anthropology and Methodology Faculty of KinesiologyUniversity of Zagreb Department of Pharmacology Faculty of MedicineUniversity of JJ StrossmayerOsijekCroatia Department of Diabetes Endocrinology and Metabolism DisordersUniversity Hospital OsijekOsijekCroatia

Non-alcoholic fatty liver disease(NAFLD)is closely related to insulin resistance,type 2 diabetes mellitus,and *** is nowadays considered a multisystem disease with a strong association with cardiovascular disease and arterial hypertension,which interfere with changes in the coagulation *** disorders are common in patients with hepatic impairment and are dependent on the degree of liver *** with NAFLD may have preserved overall hemostatic profile,but many studies suggest a trend toward a procoagulant *** state in NAFLD patients may even induce progression of hepatic *** dysfunction is present in the systemic and portal vein circulation in NAFLD patients,and platelets are being recognized as modulators of liver diseases through various *** a literature review,we discuss possible disorders in the coagulation cascade and fibrinolysis,endothelial dysfunction,and platelet abnormalities in patients with *** the processes and mechanisms involved in the hemostatic abnormalities associated with NAFLD,directly related to liver disease or indirectly related through inflam-matory processes and metabolic disorders,several potential therapeutic targets have been identified and reviewed here.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Insulin resistance Coagulation Endothelial dysfunction Platelet dysfunction Thrombosis

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Shifting perspectives-interplay between non-alcoholic fatty liver disease and insulin resistance in lean individuals

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World Journal of Hepatology 2021年第1期13卷 80-93页

作者： Ines Bilic-Curcic maja Cigrovski Berkovic Lucija Virovic-Jukic Anna Mrzljak Department of Pharmacology Faculty of MedicineUniversity of J.J.Strossmayer OsijekOsijek 31000Croatia Clinical Hospital Center Osijek Osijek 31000Croatia Department of Kinesiological Anthropology and Methodology Faculty of KinesiologyUniversity of ZagrebZagreb 10000Croatia Clinical Hospital Dubrava Zagreb 10000Croatia Department of Medicine Division of Gastroenterology and HepatologySisters of Charity University HospitalZagreb 10000Croatia School of Medicine University of ZagrebZagreb 10000Croatia Department of Medicine Merkur University HospitalZagreb 10000Croatia

Non-alcoholic fatty liver disease(NAFLD)has become a significant public health burden affecting not only obese individuals but also people with normal *** opposed to previous beliefs,this particular subset of patients has an increased risk of all-cause mortality and worse outcomes than their obese *** development of NAFLD in lean subjects seems to be interconnected with metabolic phenotype,precisely visceral fat tissue,sarcopenia,and insulin ***,we summarize available data focusing on the co-dependent relationship between metabolic phenotype,insulin resistance,and development of NAFLD in lean individuals,suggesting more appropriate tools for measuring body fat distribution for the screening of patients at risk.

关键词： Non-alcoholic fatty liver disease Metabolic phenotype Lean individuals Insulin resistance Visceral fat tissue Sarcopenia

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Association between cardiorespiratory fitness level and insulin resistance in adolescents with various obesity categories

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World Journal of Diabetes 2023年第7期14卷 1126-1136页

作者： Lavinia La Grasta Sabolic Marija Pozgaj Sepec Bernardica Valent Moric maja Cigrovski Berkovic Department of Pediatric Endocrinology and Diabetology University Hospital Centre Sestre milosrdniceZagreb 10000Croatia School of Medicine Catholic UniversityZagreb 10000Croatia Department for Sport and Exercise Medicine Faculty of Kinesiology University of ZagrebZagreb 10000Croatia

BACKGROUND An association between cardiorespiratory fitness(CRF)and insulin resistance in obese adolescents,especially in those with various obesity categories,has not been systematically *** is a lack of knowledge about the effects of CRF on insulin resistance in severely obese adolescents,despite their continuous *** To investigate the association between CRF and insulin resistance in obese adolescents,with special emphasis on severely obese *** We performed a prospective,cross-sectional study that included 200 pubertal adolescents,10 years to 18 years of age,who were referred to a tertiary care center due to *** to body mass index(BMI),adolescents were classified as mildly obese(BMI 100% to 120% of the 95^(th)percentile for age and sex)or severely obese(BMI≥120% of the 95^(th)percentile for age and sex or≥35 kg/m^(2),whichever was lower).Participant body composition was assessed by bioelectrical impedance analysis.A homeostatic model assessment of insulin resistance(HOMA-IR)was *** oxygen uptake(VO_(2)max)was determined from submaximal treadmill exercise *** was expressed as VO_(2)max scaled by total body weight(TBW)(mL/min/kg TBW)or by fat free mass(FFM)(mL/min/kg FFM),and then categorized as poor,intermediate,or good,according to VO_(2)max *** were analyzed by statistical software package SPSS(IBM SPSS Statistics for Windows,Version 24.0).P<0.05 was considered statistically *** A weak negative correlation between CRF and HOMA-IR was found[Spearman’s rank correlation coefficient(rs)=-0.28,P<0.01 for CRF_(TBW);(r_(s))=-0.21,P<0.01 for CRF_(FFM)].One-way analysis of variance(ANOVA)revealed a significant main effect of CRF on HOMA-IR[F(2200)=6.840,P=0.001 for CRF_(TBW);F_((2200))=3.883,P=0.022 for CRF_(FFM)].Subsequent analyses showed that obese adolescents with poor CRF had higher HOMA-IR than obese adolescents with good CRF(P=0.001 for CRF_(TBW);P=0.018 for CRF_(FFM)).Two-w

关键词： Cardiorespiratory fitness Insulin resistance Obese adolescents Severe obesity Obesity category

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Pancreatic exocrine insufficiency, diabetes mellitus and serum nutritional markers after acute pancreatitis

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World Journal of Gastroenterology 2014年第48期20卷 18432-18438页

作者： Miroslav Vujasinovic Bojan Tepes Jana Makuc Sasa Rudolf Jelka Zaletel Tjasa Vidmar maja Seruga Bostjan Birsa Miroslav Vujasinovic Jana Makuc Tjasa Vidmar Department of Internal Medicine Slovenj Gradec General Hospital Slovenj Gradec 2380 Slovenia Abakus Medico Diagnostic Centre Rogaska Slatina 3250 Slovenia Department of Radiology University Medical Centre Maribor Maribor 2000 Slovenia Department of Endocrinology Diabetes and Metabolic Diseases University Medical Centre Ljubljana Ljubljana 1000 Slovenia Department of Internal Medicine Murska Sobota General Hospital Murska Sobota 9001 Slovenia Department of Internal Medicine Celje General Hospital Celje 3000 Slovenia

AIM: To investigate impairment and clinical significance of exocrine and endocrine pancreatic function in patients after acute pancreatitis (AP).

关键词： Acute pancreatitis Diabetes mellitus Pancreatic exocrine insufficiency Serum nutritional markers

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