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Article: Framework for the ISO 52016 standard accuracy prediction based on the in-depth sensitivity analysis

Zakula, Tea / Badun, Nikola / Ferdelji, Nenad / Ugrina, Ivo

Applied energy. 2021 Sept. 15, v. 298

2021

Abstract: We present here a comprehensive study on the accuracy of ISO 52016-1:2017 standard (the Standard), and provide a novel, widely applicable framework for its assessment. The global sensitivity analysis and predictive modeling have been utilized to explore ... ...

Abstract	We present here a comprehensive study on the accuracy of ISO 52016-1:2017 standard (the Standard), and provide a novel, widely applicable framework for its assessment. The global sensitivity analysis and predictive modeling have been utilized to explore the intricacies of differences between the Standard and dynamic simulations in TRNSYS. The study includes more than 147 thousand cases with diverse combinations of building characteristics and all international climate zones. The main conclusion is that the Standard has good accuracy in the calculation of heating energy needs, while it is much less accurate in the calculation of cooling energy needs. For climates in which heating is dominant, 100% of cases had acceptable accuracy; in contrast, only 30–70% of cases in moderate climates had an acceptable accuracy. Consequently, we propose improvements to the Standard, suggesting that considerable benefits could be obtained if the variability of window properties based on the boundary conditions at each time step is implemented. The proposed method results in significant improvements since the number of acceptable cases for cooling in moderate climates has increased to 75–100%. This has been quantified for a great variety of window properties and for all climates. An online tool has been provided, enabling the estimation of the expected relative difference between the Standard and TRNSYS for a specific building.
Keywords	computer software ; energy ; prediction
Language	English
Dates of publication	2021-0915
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	2000772-3
ISSN	0306-2619
ISSN	0306-2619
DOI	10.1016/j.apenergy.2021.117089
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Vitamin D Supplementation and Clinical Outcomes in Severe COVID-19 Patients-Randomized Controlled Trial.

Domazet Bugarin, Josipa / Dosenovic, Svjetlana / Ilic, Darko / Delic, Nikola / Saric, Ivana / Ugrina, Ivo / Stojanovic Stipic, Sanda / Duplancic, Bozidar / Saric, Lenko

Nutrients

2023 Volume 15, Issue 5

Abstract: COVID-19 symptoms vary from asymptomatic cases to moderate and severe illness with patients needing hospitalization and intensive care treatment. Vitamin D is associated with severity of viral infections and has an immune-modulatory effect in immune ... ...

Abstract	COVID-19 symptoms vary from asymptomatic cases to moderate and severe illness with patients needing hospitalization and intensive care treatment. Vitamin D is associated with severity of viral infections and has an immune-modulatory effect in immune response. Observational studies showed a negative association of low vitamin D levels and COVID-19 severity and mortality outcomes. In this study, we aimed to determine whether daily supplementation of vitamin D during intensive care unit (ICU) stay in COVID-19 patients with severe illness affects clinically relevant outcomes. Patients with COVID-19 disease in need of respiratory support admitted to the ICU were eligible for inclusion. Patients with low vitamin D levels were randomized into one of two groups: the intervention group received daily supplementation of vitamin D and the control group did not receive vitamin D supplementation. In total, 155 patients were randomized: 78 into the intervention group and 77 into the control group. There was no statistically significant difference in number of days spent on respiratory support, although the trial was underpowered for the main outcome. There was no difference in any of the secondary outcomes analyzed between two groups. Our study suggests no benefit in vitamin D supplementation to patients with severe COVID-19 disease admitted to the ICU and in need of respiratory support in any of the analyzed outcomes.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Vitamins ; Vitamin D ; Dietary Supplements
Chemical Substances	Vitamins ; Vitamin D (1406-16-2)
Language	English
Publishing date	2023-02-28
Publishing country	Switzerland
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15051234
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Laboratory Experimental Design for a Glycomic Study.

Ugrina, Ivo / Campbell, Harry / Vučković, Frano

Methods in molecular biology (Clifton, N.J.)

2017 Volume 1503, Page(s) 13–19

Abstract: Proper attention to study design before, careful conduct of procedures during, and appropriate inference from results after scientific experiments are important in all scientific studies in order to ensure valid and sometimes definitive conclusions can ... ...

Abstract	Proper attention to study design before, careful conduct of procedures during, and appropriate inference from results after scientific experiments are important in all scientific studies in order to ensure valid and sometimes definitive conclusions can be made. The design of experiments, also called experimental design, addresses the challenge of structuring and conducting experiments to answer the questions of interest as clearly and efficiently as possible.
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-6493-2_2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Chitosan-Based Thermogelling System for Nose-to-Brain Donepezil Delivery: Optimising Formulation Properties and Nasal Deposition Profile.

Perkušić, Mirna / Nižić Nodilo, Laura / Ugrina, Ivo / Špoljarić, Drago / Jakobušić Brala, Cvijeta / Pepić, Ivan / Lovrić, Jasmina / Safundžić Kučuk, Maša / Trenkel, Marie / Scherließ, Regina / Zadravec, Dijana / Kalogjera, Livije / Hafner, Anita

Pharmaceutics

2023 Volume 15, Issue 6

Abstract: Donepezil nasal delivery strategies are being continuously investigated for advancing therapy in Alzheimer's disease. The aim of this study was to develop a chitosan-based, donepezil-loaded thermogelling formulation tailored to meet all the requirements ... ...

Abstract	Donepezil nasal delivery strategies are being continuously investigated for advancing therapy in Alzheimer's disease. The aim of this study was to develop a chitosan-based, donepezil-loaded thermogelling formulation tailored to meet all the requirements for efficient nose-to-brain delivery. A statistical design of the experiments was implemented for the optimisation of the formulation and/or administration parameters, with regard to formulation viscosity, gelling and spray properties, as well as its targeted nasal deposition within the 3D-printed nasal cavity model. The optimised formulation was further characterised in terms of stability, in vitro release, in vitro biocompatibility and permeability (using Calu-3 cells), ex vivo mucoadhesion (using porcine nasal mucosa), and in vivo irritability (using slug mucosal irritation assay). The applied research design resulted in the development of a sprayable donepezil delivery platform characterised by instant gelation at 34 °C and olfactory deposition reaching a remarkably high 71.8% of the applied dose. The optimised formulation showed prolonged drug release (
Language	English
Publishing date	2023-06-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15061660
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Article ; Online: Unravelling Immunoglobulin G Fc N-Glycosylation: A Dynamic Marker Potentiating Predictive, Preventive and Personalised Medicine.

Russell, Alyce / Adua, Eric / Ugrina, Ivo / Laws, Simon / Wang, Wei

International journal of molecular sciences

2018 Volume 19, Issue 2

Abstract: Multiple factors influence immunoglobulin G glycosylation, which in turn affect the glycoproteins' function on eliciting an anti-inflammatory or pro-inflammatory response. It is prudent to underscore these processes when considering the use of ... ...

Abstract	Multiple factors influence immunoglobulin G glycosylation, which in turn affect the glycoproteins' function on eliciting an anti-inflammatory or pro-inflammatory response. It is prudent to underscore these processes when considering the use of immunoglobulin G
MeSH term(s)	Biomarkers/metabolism ; Glycomics/methods ; Glycosylation ; Humans ; Precision Medicine/methods ; Protein Processing, Post-Translational ; Receptors, Fc/chemistry ; Receptors, Fc/metabolism
Chemical Substances	Biomarkers ; Receptors, Fc
Language	English
Publishing date	2018-01-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms19020390
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Article ; Online: In situ gelling nanosuspension as an advanced platform for fluticasone propionate nasal delivery.

Nižić Nodilo, Laura / Perkušić, Mirna / Ugrina, Ivo / Špoljarić, Drago / Jakobušić Brala, Cvijeta / Amidžić Klarić, Daniela / Lovrić, Jasmina / Saršon, Vesna / Safundžić Kučuk, Maša / Zadravec, Dijana / Kalogjera, Livije / Pepić, Ivan / Hafner, Anita

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

2022 Volume 175, Page(s) 27–42

Abstract: In this work we present the development of in situ gelling nanosuspension as advanced form for fluticasone propionate nasal delivery. Drug nanocrystals were prepared by wet milling technique. Incorporation of drug nanocrystals into polymeric in situ ... ...

Abstract	In this work we present the development of in situ gelling nanosuspension as advanced form for fluticasone propionate nasal delivery. Drug nanocrystals were prepared by wet milling technique. Incorporation of drug nanocrystals into polymeric in situ gelling system with pectin and sodium hyaluronate as constitutive polymers was fine-tuned attaining appropriate formulation surface tension, viscosity and gelling ability. Drug nanonisation improved the release profile and enhanced formulation mucoadhesive properties. QbD approach combining formulation and administration parameters resulted in optimised nasal deposition profile, with 51.8% of the dose deposited in the middle meatus, the critical region in the treatment of rhinosinusitis and nasal polyposis. Results obtained in biocompatibility and physico-chemical stability studies confirmed the leading formulation potential for safe and efficient nasal corticosteroid delivery.
MeSH term(s)	Administration, Intranasal ; Fluticasone ; Gels ; Nose ; Polymers/chemistry ; Viscosity
Chemical Substances	Gels ; Polymers ; Fluticasone (CUT2W21N7U)
Language	English
Publishing date	2022-04-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1065368-5
ISSN	1873-3441 ; 0939-6411
ISSN (online)	1873-3441
ISSN	0939-6411
DOI	10.1016/j.ejpb.2022.04.009
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Article ; Online: Tailoring functional spray-dried powder platform for efficient donepezil nose-to-brain delivery.

Perkušić, Mirna / Nižić Nodilo, Laura / Ugrina, Ivo / Špoljarić, Drago / Jakobušić Brala, Cvijeta / Pepić, Ivan / Lovrić, Jasmina / Matijašić, Gordana / Gretić, Matija / Zadravec, Dijana / Kalogjera, Livije / Hafner, Anita

International journal of pharmaceutics

2022 Volume 624, Page(s) 122038

Abstract: Shortcomings of oral donepezil administration in the treatment of Alzheimer's disease have paved the way for ongoing investigations towards more efficient and safe donepezil nose-to-brain delivery. Herein we present the development of advantageous powder ...

Abstract	Shortcomings of oral donepezil administration in the treatment of Alzheimer's disease have paved the way for ongoing investigations towards more efficient and safe donepezil nose-to-brain delivery. Herein we present the development of advantageous powder platform for donepezil nose-to-brain delivery, coupling careful design of chitosan and mannitol-based carrier matrix with spray-drying technology advantages and early consideration of adequate nasal administration mode, employing QbD approach. Unprecedentedly, ultrasonic nozzle was used to atomise the drying feed in response to size-related requirements for nasal aerosol particles. The optimised spray-drying process resulted in free-flowable dry powder with a great majority of particles larger than 10 µm, ensuring localised nasal deposition upon aerosolization, as evidenced by using 3D-printed nasal cavity model. QbD approach coupling formulation, process and administration parameters enabled optimisation of drug deposition profile reaching tremendously high 65.5 % of the applied dose deposited in the olfactory region. The leading formulation exhibited favourable swelling, mucoadhesion, drug release and permeation-enhancing properties, suiting the needs for efficient brain-targeted delivery. Results of in vitro biocompatibility and physico-chemical stability studies confirmed the leading formulation potential for safe and efficient donepezil nose-to-brain delivery. The obtained results encourage extending the study to an appropriate in vivo model needed for the final proof-of-concept.
MeSH term(s)	Administration, Inhalation ; Administration, Intranasal ; Aerosols ; Brain ; Donepezil ; Dry Powder Inhalers ; Particle Size ; Powders
Chemical Substances	Aerosols ; Powders ; Donepezil (8SSC91326P)
Language	English
Publishing date	2022-07-20
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	428962-6
ISSN	1873-3476 ; 0378-5173
ISSN (online)	1873-3476
ISSN	0378-5173
DOI	10.1016/j.ijpharm.2022.122038
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Article ; Online: Choosing proper normalization is essential for discovery of sparse glycan biomarkers.

Uh, Hae-Won / Klarić, Lucija / Ugrina, Ivo / Lauc, Gordan / Smilde, Age K / Houwing-Duistermaat, Jeanine J

Molecular omics

2020 Volume 16, Issue 3, Page(s) 231–242

Abstract: Rapid progress in high-throughput glycomics analysis enables the researchers to conduct large sample studies. Typically, the between-subject differences in total abundance of raw glycomics data are very large, and it is necessary to reduce the ... ...

Abstract	Rapid progress in high-throughput glycomics analysis enables the researchers to conduct large sample studies. Typically, the between-subject differences in total abundance of raw glycomics data are very large, and it is necessary to reduce the differences, making measurements comparable across samples. Essentially there are two ways to approach this issue: row-wise and column-wise normalization. In glycomics, the differences per subject are usually forced to be exactly zero, by scaling each sample having the sum of all glycan intensities equal to 100%. This total area (row-wise) normalization (TA) results in so-called compositional data, rendering many standard multivariate statistical methods inappropriate or inapplicable. Ignoring the compositional nature of the data, moreover, may lead to spurious results. Alternatively, a log-transformation to the raw data can be performed prior to column-wise normalization and implementing standard statistical tools. Until now, there is no clear consensus on the appropriate normalization method applied to glycomics data. Nor is systematic investigation of impact of TA on downstream analysis available to justify the choice of TA. Our motivation lies in efficient variable selection to identify glycan biomarkers with regard to accurate prediction as well as interpretability of the model chosen. Via extensive simulations we investigate how different normalization methods affect the performance of variable selection, and compare their performance. We also address the effect of various types of measurement error in glycans: additive, multiplicative and two-component error. We show that when sample-wise differences are not large row-wise normalization (like TA) can have deleterious effects on variable selection and prediction.
MeSH term(s)	Algorithms ; Biomarkers/analysis ; Calibration ; Glycomics/methods ; Mass Spectrometry
Chemical Substances	Biomarkers
Language	English
Publishing date	2020-03-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2515-4184
ISSN (online)	2515-4184
DOI	10.1039/c9mo00174c
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Fine-Mapping of the Human Blood Plasma N-Glycome onto Its Proteome.

Suhre, Karsten / Trbojević-Akmačić, Irena / Ugrina, Ivo / Mook-Kanamori, Dennis O / Spector, Tim / Graumann, Johannes / Lauc, Gordan / Falchi, Mario

Metabolites

2019 Volume 9, Issue 7

Abstract: Most human proteins are glycosylated. Attachment of complex oligosaccharides to the polypeptide part of these proteins is an integral part of their structure and function and plays a central role in many complex disorders. One approach towards ... ...

Abstract	Most human proteins are glycosylated. Attachment of complex oligosaccharides to the polypeptide part of these proteins is an integral part of their structure and function and plays a central role in many complex disorders. One approach towards deciphering this human glycan code is to study natural variation in experimentally well characterized samples and cohorts. High-throughput capable large-scale methods that allow for the comprehensive determination of blood circulating proteins and their glycans have been recently developed, but so far, no study has investigated the link between both traits. Here we map for the first time the blood plasma proteome to its matching N-glycome by correlating the levels of 1116 blood circulating proteins with 113 N-glycan traits, determined in 344 samples from individuals of Arab, South-Asian, and Filipino descent, and then replicate our findings in 46 subjects of European ancestry. We report protein-specific N-glycosylation patterns, including a correlation of core fucosylated structures with immunoglobulin G (IgG) levels, and of trisialylated, trigalactosylated, and triantennary structures with heparin cofactor 2 (SERPIND2). Our study reveals a detailed picture of protein N-glycosylation and suggests new avenues for the investigation of its role and function in the associated complex disorders.
Language	English
Publishing date	2019-06-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo9070122
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Article ; Online: Significant Associations of IgG Glycan Structures With Chronic Graft-Versus-Host Disease Manifestations: Results of the Cross-Sectional NIH Cohort Study.

Prenc, Ema / Pulanic, Drazen / Pucic-Bakovic, Maja / Ugrina, Ivo / Desnica, Lana / Milosevic, Milan / Pirsl, Filip / Mitchell, Sandra / Rose, Jeremy / Vrhovac, Radovan / Nemet, Damir / Lauc, Gordan / Pavletic, Steven Z

Frontiers in immunology

2021 Volume 12, Page(s) 633214

Abstract: Chronic graft-versus-host disease (cGvHD) is a systemic alloimmune and autoimmune disorder and a major late complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). The disease is characterized by an altered homeostasis of the ... ...

Abstract	Chronic graft-versus-host disease (cGvHD) is a systemic alloimmune and autoimmune disorder and a major late complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). The disease is characterized by an altered homeostasis of the humoral immune response. Immunoglobulin G (IgG) glycoprotein is the main effector molecule of the humoral immune response. Changes in IgG glycosylation are associated with a number of autoimmune diseases. IgG glycosylation analysis was done by the means of liquid chromatography in the National Institutes of Health (NIH) cohort of 213 cGvHD patients. The results showed statistically significant differences with regards to cGvHD NIH joint/fascia and skin score, disease activity and intensity of systemic immunosuppression. ROC analysis confirmed that IgG glycosylation increases specificity and sensitivity of models using laboratory parameters and markers of inflammation associated with cGvHD (eosinophil count, complement components C3 and C4 and inflammation markers: albumin, CRP and thrombocyte count). This research shows that IgG glycosylation may play a significant role in cGvHD pathology. Further research could contribute to the understanding of the disease biology and lead to the clinical biomarker development to allow personalized approaches to chronic GvHD therapy.
MeSH term(s)	Adolescent ; Adult ; Aged ; Biomarkers ; Child ; Child, Preschool ; Chronic Disease ; Cohort Studies ; Complement System Proteins/metabolism ; Cross-Sectional Studies ; Eosinophils/pathology ; Female ; Glycosylation ; Graft vs Host Disease/immunology ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunity, Humoral ; Immunoglobulin G/chemistry ; Immunoglobulin G/metabolism ; Inflammation Mediators/metabolism ; Male ; Middle Aged ; Polysaccharides/chemistry ; Precision Medicine ; Severity of Illness Index ; Skin/pathology ; Transplantation, Homologous ; Young Adult
Chemical Substances	Biomarkers ; Immunoglobulin G ; Inflammation Mediators ; Polysaccharides ; Complement System Proteins (9007-36-7)
Language	English
Publishing date	2021-07-14
Publishing country	Switzerland
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.633214
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