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Real-world effectiveness and safety of direct-acting antivirals in hepatitis C virus patients with mental disorders

World Journal of Gastroenterology 2023年第25期29卷 4085-4098页

作者： dorota Dybowska dorota zarebska-michaluk Piotr Rzymski Hanna Berak Beata Lorenc Marek Sitko Michal Dybowski Wlodzimierz Mazur Magdalena Tudrujek-Zdunek Justyna Janocha-Litwin Ewa Janczewska Jakub Klapaczynski Anna Parfieniuk-Kowerda Anna Piekarska Barbara Sobala-Szczygiel Krystyna Dobrowolska Malgorzata Pawlowska Robert Flisiak Department of Infectious Diseases and Hepatology Faculty of MedicineNicolaus Copernicus UniversityBydgoszcz 85-030Poland Department of Infectious Diseases and Allergology Jan Kochanowski UniversityKielce 25-317Poland Department of Infectious Diseases Provincial HospitalKielce 25-317Poland Department of Environmental Medicine University of Medical SciencesPoznań60-806Poland Integrated Science Association Universal Scientific Education and Research NetworkPoznań60-806Poland Outpatient Clinic Hospital for Infectious Diseases in WarsawWarsaw 01-201Poland Pomeranian Center of Infectious Diseases Medical UniversityGdańsk 80-214Poland Department of Infectious and Tropical Diseases Jagiellonian UniversityKraków 31-088Poland Utrecht University School of Economics Utrecht UniversityUtrecht 3584 ECNetherlands Clinical Department of Infectious Diseases Medical University of SilesiaChorzów 41-500Poland Department of Infectious Diseases Medical University of LublinLublin 20-059Poland Department of Infectious Diseases and Hepatology Medical University of WrocławWrocław 50-367Poland Department of Basic Medical Sciences Faculty of Public Health in BytomMedical University of SilesiaKatowice 40-007Poland Department of Internal Medicine and Hepatology Central Clinical Hospital of the Ministry of Internal Affairs and AdministrationWarsaw 00-241Poland Department of Infectious Diseases and Hepatology Medical University of BiałystokBiałystok 15-089Poland Department of Infectious Diseases and Hepatology Medical University ofŁódźŁódź91-347Poland Department of Infectious Diseases and Hepatology Medical University of SilesiaBytom 41-902Poland Collegium Medicum Jan Kochanowski UniversityKielce 25-317Poland

BACKGROUND It is estimated that 58 million people worldwide are infected with the hepatitis C virus(HCV).Patients with severe psychiatric disorders could not be treated with previously available interferon-based therapies due to their unfavorable side effect *** has changed with the introduction of direct-acting antivirals(DAA),although their real-life tolerance and effectiveness in patients with different psychiatric disorders remain to be *** To evaluate the effectiveness and safety of DAA in patients with various mental *** This was a retrospective observational study encompassing 14272 patients treated with DAA for chronic hepatitis C in 22 Polish hepatology centers,including 942 individuals diagnosed with a mental disorder(anxiety disorder,bipolar affective disorder,depression,anxiety-depressive disorder,personality disorder,schizophrenia,sleep disorder,substance abuse disorder,and mental illness without a specific diagnosis).The safety and effectiveness of DAA in this group were compared to those in a group without psychiatric illness(n=13330).Antiviral therapy was considered successful if serum ribonucleic acid(RNA)of HCV was undetectable 12 wk after its completion[sustained virologic response(SVR)].Safety data,including the incidence of adverse events(AEs),serious AEs(SAEs),and deaths,and the frequency of treatment modification and discontinuation,were collected during therapy and up to 12 wk after treatment *** entire study population was included in the intent-to-treat(ITT)***-protocol(PP)analysis concerned patients who underwent HCV RNA evaluation 12 wk after completing *** Among patients with mental illness,there was a significantly higher percentage of men,treatmentnaive patients,obese,human immunodeficiency virus and hepatitis B virus-coinfected,patients with cirrhosis,and those infected with genotype 3(GT3)while infection with GT1b was more frequent in the population without psychia

关键词： Hepatitis C Mental disorders Direct-acting antivirals

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Antiviral factors and their counteraction by HIV-1: many uncovered and more to be discovered

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Journal of Molecular Cell Biology 2024年第2期16卷 1-10页

作者： dorota Kmiec Frank Kirchhoff Institute of Molecular Virology Ulm University Medical Center89081 UlmGermany

Extensive studies on HIV-1 have led to the discovery of a variety of structurally and functionally diverse innate defense factors that target various steps of the retroviral replication *** of them,such as APOBEC3,tetherin,and SERINC5,are well *** importance is evident from the fact that HIV-1 uses its accessory proteins Vif,Vpu,and Nef to counteract ***,the list of antiviral factors is constantly increasing,and accumulating evidence suggests that innate defense mechanisms,which restrict HIV-1 and/or are counteracted by viral proteins,remain to be *** antiviral factors are relevant to diseases other than HIV/AIDS,since they are commonly active against various viral *** this review,we provide an overview of recently reported antiretroviral factors and viral countermeasures,present the evidence suggesting that more innate defense mechanisms remain to be discovered,and discuss why this is a challenging but rewarding task.

关键词： HIV-1 restriction factors viral antagonists interferon-stimulated genes antiviral factors

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Daclatasvir vs telaprevir plus peginterferon alfa/ribavirin for hepatitis C virus genotype 1

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World Journal of Gastroenterology 2016年第12期22卷 3418-3431页

作者： Ira Jacobson Stefan Zeuzem Robert Flisiak Brygida Knysz Stefan Lueth dorota zarebska-michaluk Ewa Janczewska Peter Ferenci Moises Diago Anna Linda Zignego Rifaat Safadi Yaacov Baruch Dzhamal Abdurakhmanov Stephen Shafran Dominique Thabut Rafael Bruck Adrian Gadano Alexander James Thompson Justin Kopit Fiona Mc Phee Tracy Michener Eric A Hughes Philip D Yin Stephanie Noviello Weill Cornell Medical College New YorkNY 10029United States Icahn School of Medicine at Mount Sinai New YorkNY 10029United States JW Goethe University Hospital 60323 FrankfurtGermany Uniwersytet Medyczny w Bialymstoku 15-089 BialystokPoland EMC and Medical University 50-220 WroclawPoland Universitatsklinikum Hamburg-Eppendorf 20246 HamburgGermany Wojewodzki Szpital Zespolony w Kielcach 25-736 KielcePoland ID Clinic 41-400 MyslowicePoland Medizinische Universitat Wien 1090 ViennaAustria Clinica Quiron 46010 ValenciaSpain Universita degli Studi di Firenze 50121 FlorenceItaly Holy Family Hospital Nazareth 6004Israel Rambam Medical Center Haifa 31096Israel 1st Moscow State Medical University N.A.I.M.Sechenov 119991 MoscowRussia University of Alberta Hospital EdmontonAlberta T6G 2B7Canada Groupe Hospitalier Pitie-Salpetriere 75013 ParisFrance Tel Aviv Sourasky Medical Center and Tel Aviv University Tel Aviv 64239Israel Hospital Italiano de Buenos Aires Buenos Aires C1181ACHArgentina St.Vincents Hospital and the University of Melbourne Melbourne 3065Australia Fiona McPhee Bristol-Myers Squibb Research and DevelopmentWallingfordCT 06492United States Bristol-Myers Squibb Research and Development PrincetonNJ 08450United States

AIM: To evaluate daclatasvir vs telaprevir, each combined with peginterferon alfa-2a/ribavirin(peg IFN/RBV), in treatment-naive hepatitis C virus(HCV) genotype(GT) 1-infected ***: In this phase 3, randomized, open-label, noninferiority study, 602 patients were randomly assigned(2:1) to daclatasvir vs telaprevir, stratified by IL28 B rs12979860 host genotype(CC vs non-CC), cirrhosis status(compensated cirrhosis vs no cirrhosis), and HCV GT1 subtype(GT1a vs GT1b). Patients were selected by study inclusion criteria from a total of 793 enrolled patients. Patients received daclatasvir 60 mg once daily or telaprevir 750 mg 3 times daily plus peg IFN/RBV. Daclatasvir recipients received 24 wk of daclatasvir plus peg IFN/RBV; those without an extended rapid virologic response(e RVR; undetectable HCV-RNA at weeks 4 and 12) received an additional 24 wk of peg IFN/RBV. Telaprevir-treated patients received 12 wk of telaprevir plus peg IFN/RBV followed by 12(with e RVR) or 36(no e RVR) wk of peg IFN/RBV. The primary objective was to compare for noninferiority of sustained virologic response rates at posttreatment week 12(SVR12) in GT1b-infected patients. Key secondary objectives were to demonstrate that the rates of anemia(hemoglobin < 10 g/d L) and rashrelated events, through week 12, were lower with daclatasvir + peg IFN/RBV than with telaprevir + peg IFN/RBV among GT1b-infected patients. Resistance testing was performed using population-based sequencing of the NS5 A region for all patients at baseline, and for patients with virologic failure or relapse and HCV-RNA ≥ 1000 IU/m L, to investigate any link between NS5 A polymorphisms associated with daclatasvir resistance and virologic outcome. RESULTS: Patient demographics and disease characteristics were generally balanced across treatment arms; however, there was a higher proportion of black/African Americans in the daclatasvir groups(6.0% and 8.2% in the GT1 b and GT1 a groups, respectively) than in the telaprevi

关键词： Direct-acting antiviral Chronic hepatitis C Daclatasvir Genotype 1b NS5A inhibitor Liver disease

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Changes in the adult sex ratio of six duck species breeding populations over two decades

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Avian Research 2024年第2期15卷 202-210页

作者： Monika Homolkova Petr Musil Diego Pavon-Jordan dorota Gajdosova Zuzana Musilova Sarka Neuzilova Jan Zouhar Department of Ecology Faculty of Environmental SciencesCzech University of Life Sciences PragueKamýcka 129CZ-16521Prague–SuchdolCzech Republic Department of Terrestrial Ecology Norwegian Institute for Nature Research(NINA)PO Box 5685 TorgardenTrondheimN-7485Norway Department of Econometrics Faculty of Informatics and StatisticsUniversity of Economicsnam.W.Churchilla 4CZ-13067Prague 3Czech Republic

Despite all efforts,long-term changes in the adult sex ratios of breeding duck populations are still unclear;this uncertainty is especially true for male-bias populations,which are often under the scrutiny of researchers lacking convenient results for the active protection of endangered *** with male-bias populations are usually strongly affected by a decline in population size that leads to a higher extinction *** this study,we examined our long-term data of the abundance of breeding populations in six duck species(Mallard Anas platyrhynchos,Gadwall Mareca strepera,Red-crested Pochard Netta rufina,Common Pochard Aythya ferina,Tufted Duck Aythya fuligula,and Common Goldeneye Bucephala clangula)from fishponds in South Bohemia,Czechia,between 2004 and *** evidence was used to assess long-term changes in the adult sex ratio in these breeding populations and investigate the possible effects of the NAO index(North Atlantic Oscillation index)on them,indicating climate conditions in *** determined a long-term decrease of the proportion of females in the breeding season in two of the six examined species:Common Pochard and Red-crested Pochard,which is driven by the long-term increase in the number of males in contrast to the decreasing or stable number of females likely caused by different migration behaviours between females and *** the case of Common Pochard,in breeding populations,we estimated 60-65%of males in the early 2000s rising to 75-80%in the early ***,we establish no significant effects linked to climate conditions of the previous winter in these species as a crucial cause of the changes of the proportion of females in the breeding population.

关键词： Adult sex ratio Breeding population Population dynamics Red-listed species Waterfowl Winter weather conditions

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A single degenerated primer significantly improves COX1 barcoding performance in soil nematode community profiling

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Soil Ecology Letters 2024年第2期6卷 31-44页

作者： Yincai Ren dorota L. Porazinska Quanhui Ma Shuhan Liu Hongmei Li Xue Qing Department of Plant Pathology Nanjing Agricultural UniversityNanjing210095China Department of Entomology and Nematology University of FloridaGainesvilleFL32611USA Institute of Grassland Science Key Laboratory of Vegetation Ecology of the Ministry of EducationJilin Songnen Grassland Ecosystem National Observation and Research StationNortheast Normal UniversityChangchun130024China

A new COX1 primer for soil nematode metabarcoding was designed,and this primer outperforms other commonly used COX1 primer pairs in species recovery and quantity of PCR products.•The lack of reference database is the main reason that led to the low species recovery in COX1 metabarcoding.•We expanded current NCBI database by adding 51 newly generated COX1 reference *** nematodes play important roles in soil ecosystems and often serve as bioindicators of soil *** identification of soil nematodes is often difficult due to their limited diagnostic characters and high phenotypic *** barcoding and metabarcoding techniques are promising but lack universal primers,especially for mitochondrial COX1 *** this study a degenerated COX1 forward primer COIFGED was *** primer pair(COIFGED/JB5GED)outperforms other four commonly used COX1 primer pairs in species recovery and quantity of polymerase chain reaction(PCR)*** metabarcoding analysis,the reads obtained from the new primer pair had the highest sequencing saturation threshold and amplicon sequence variant(ASV)diversity in comparison to other COX1 as well as 18S rRNA *** annotation of ASVs suggested the new primer pair initially recovered 9 and 6 out of 25 genera from mock communities,respectively,outperformed other COX1 primers,but underperformed the widely used 18S NF1/18Sr2b primers(16 out of 25 genera).By supplementing the COX1 database with our reference sequences,we recovered an additional 6 mock community species bringing the tally closer to that obtained with 18S *** summary,our newly designed COX1 primers significantly improved species recovery and thus can be supplementary or alternative to the conventional 18S metabarcoding.

关键词： degenerated primers DNA metabarcoding mitochondrial cytochrome oxidase c subunit I gene phylogeny ribosomal RNA gene soil nematodes

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Genotype 3-hepatitis C virus’last line of defense

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World Journal of Gastroenterology 2021年第11期27卷 1006-1021页

作者： dorota Zarębska-michaluk Department of Infectious Diseases Jan Kochanowski UniversityKielce 25-369ŚwiętokrzyskiePoland

Chronic infection with hepatitis C virus(HCV)is one of the leading causes of liver disease globally,affecting approximately 71 million *** majority of them are infected with genotype(GT)1 but infections with GT3 are second in *** many years,GT3 was considered to be less pathogenic compared to other GTs in the HCV family due to its favorable response to interferon(IFN)-based ***,the growing evidence of a higher rate of steatosis,more rapid progression of liver fibrosis,and lower efficacy of antiviral treatment compared to infection with other HCV GTs has changed this *** review presents the specifics of the course of GT3 infection and the development of therapeutic options for GT3-infected patients in the era of direct-acting antivirals(DAA).The way from a standard of care therapy with pegylated IFNalpha(pegIFNα)and ribavirin(RBV)through a triple combination of pegIFNα+RBV and DAA to the highly potent IFN-free pangenotypic DAA regimens is discussed along with some treatment options which appeared to be dead *** the implementation of highly effective pangenotypic regimens is the most recent stage of revolution in the treatment of GT3 infection,there is still room for improvement,especially in patients with liver cirrhosis and those who fail to respond to DAA therapies,particularly those containing inhibitors of HCV nonstructural protein 5A.

关键词： Hepatitis C virus Genotype 3 Antiviral treatment Interferon Direct-acting antivirals Pangenotypic

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Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C

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World Journal of Gastroenterology 2023年第6期29卷 949-966页

作者： MichałBrzdęk dorota Zarębska-michaluk Federica Invernizzi Marta Cilla Krystyna Dobrowolska Robert Flisiak Collegium Medicum Jan Kochanowski UniversityKielce 25-516Poland of Infectious Diseases Jan Kochanowski UniversityKielce 25-516Poland Center for Liver Disease Division of Internal Medicine and HepatologyIRCCS Ospedale San RaffaeleMilan 20-132Italy Department of Infectious Diseases and Hepatology Medical University of BiałystokBiałystok 15-540Poland

Chronic infection with the hepatitis C virus(HCV)remains a major health problem affecting approximately 58 million people *** the era of interferon(IFN)-based regimens,patients particularly infected with genotypes 1 and 4 achieved a low response *** implementation of direct-acting antivirals changed the landscape of HCV *** increase in effectiveness provided us with the hope of eliminating HCV as a significant public threat by *** the following years,there was an observed improvement in the treatment of HCV with genotype-specific regimens and highly effective pangenotypic options that are the most recent stage of the *** optimization of therapy was accompanied by changes in the patient profile from the beginning of the IFN-free era over *** treated with antiviral therapies were younger in successive periods,less burdened with comorbidities and comedications,more frequently treatment-naïve and had less advanced liver *** the IFN-free era,specific subpopulations such as patients with HCV/HIV coinfection,those with a history of previous treatment,patients with renal impairment or with cirrhosis had lower chances for a virologic ***,these populations should no longer be considered difficult to *** the high effectiveness of HCV therapy,there is a small percentage of patients with treatment ***,they can be effectively retreated with pangenotypic rescue regimens.

关键词： Hepatitis C virus Interferon Direct-acting antiviral Epidemiology Chronic hepatitis C

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Fuel poverty and low carbon emissions: a comparative study of the feasibility of the hybrid renewable energy systems incorporating combined heat and power technology

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Frontiers in Energy 2022年第2期16卷 336-356页

作者： dorota RZETELSKA Madeleine COMBRINCK Department of Mechanical and Construction Engineering Faculty of Engineering and EnvironmentNorthumbria UniversityNewcastle-upon-TyneNE18STUK

Fuel poverty is most prevalent in North East England with 14.4%of fuel poor households in Newcastle upon *** aim of this paper was to identify a grid connected renewable energy system coupled with natural gas reciprocating combined heat and power unit,that is cost-effective and technically feasible with a potential to generate a profit from selling energy excess to the grid to help alleviate fuel *** system was also aimed at low carbon *** models were designed and optimized with the aid of the HOMER Pro *** were compared with respect to their economic,technical,and environmental performance.A solution was proposed where restrictions were placed on the size of renewable energy *** configuration consists of 150 kW CHP,300 kW PV cells,and 30 kW wind *** renewable fraction is 5.10%and the system yields a carbon saving of 7.9%in comparison with conventional *** initial capital investment is$1.24 million which enables the system to have grid sales of 582689 kWh/a.A conservative calculation determined that 40%of the sales can be used to reduce the energy cost of fuel poor households by$706 per *** solution has the potential to eliminate fuel poverty at the site analyzed.

关键词： greenhouse gas control low carbon target grid connected renewable fraction fuel poverty combined heat and power HOMER Pro

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Effects of hyperbaric oxygen therapy on human psychomotor performance:A review

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结合医学学报:英文版 2023年第5期21卷 430-440页

作者： dorota Olex-Zarychta Institute of Sport Sciences Academy of Physical Education in Katowice40-065 KatowicePoland

Psychomotor performance is the coordination of a sensory or ideational(cognitive)process and a motor *** sensorimotor processes involved in planning and execution of voluntary movements need oxygen supply and seem to be significantly disrupted in states of *** oxygen therapy has become a widely used treatment in routine medicine and sport medicine due to its beneficial effects on different aspects of human physiology and *** paper presents state-of-the-art data on the effects of hyperbaric oxygen therapy on different aspects of human psychomotor *** therapy’s influence on musculoskeletal properties and motor abilities as well as the effects of hyperbaric oxygenation on cognitive,myocardial and pulmonary functions are *** this review the molecular and physiological processes related to human psychomotor performance in response to hyperbaric oxygen are discussed to contribute to this fast-growing field of research in integrative medicine.

关键词： Hyperbaric oxygen therapy Hypoxia Psychomotor performance Oxidative metabolism

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Application of monodispersive anion exchangers in sorption and separation of Y^3＋ from Nd^3＋ and Sm^3＋ complexes with dcta

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Journal of Rare Earths 2008年第5期26卷 619-625页

作者： Halina Hubicka dorota Kolodynska Department of Inorganic Chemistry Faculty of Chemistry Maria Curie-Sklodowska University Maria Curie-Sklodowska Sq.3 20-031 Lublin Poland

Rare earth complexes with trans-1,2-diaminocyclohexane-N,N,N ,N -tetraacetic acid （DCTA） of the Ln（dcta） type exhibited an unusual sequence of affinity on the polystyrene anion exchangers： pm^3＋〉Nd^3＋〉Sm^3＋〉Pr^3＋〉Ce^3＋〉Eu^3＋〉Gd^3＋〉La^3＋〉Sc^3＋〉Tb^3＋〉Dy^3＋〉 Ho^3＋〉Y^3＋〉Er^3＋〉Tm^3＋〉Yb3＋〉Lu^3＋[1]. Taking into account the position of Y^3＋, Sm^3＋, and Nd^3＋ in this affinity series, for the monodispersive polystyrene anion exchangers, Lewatit MonoPlus M 500, Lewatit MonoPlus M 600, Lewatit MonoPlus MP 500, Lewatit MonoPlus MP 64, and for the heterodispersive anion exchanger, Lewatit MP 62, the weight （Dg） and bed （Dv） distribution coefficients of these complexes and working ion exchange capacities （Cw） were determined. Based on these values, purifications of Y^3＋ from Nd^3＋ and Y^3＋ from Sm^3＋ in the macro-micro component system on these anion exchangers were studied. The application potential of this method was highlighted for the separation of Y^3＋ in the presence of Nd^3＋ and Sm^3＋. With 1 L of monodispersive and strongly basic polystyrene gel anion exchanger Lewatit MonoPlus M 500 in the acetate form, it is possible to obtain approximately 79 g Y2O3 purified from Nd2O3 and 70 g Y2O3 purified from Sm2O3 in the same process condition.

关键词： DCTA rare earth complexes anion exchange

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