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Article ; Online: Flipped or traditional online teaching? Two different strategies to handle teaching in nursing education during the COVID-19 pandemic.

Holm, Patrik / Beckman, Linda

International journal of nursing education scholarship

2022 Volume 19, Issue 1

Abstract: Objectives: The aim of this study was to investigate differences in academic achievement between two groups of students who were taught the same course online within the nursing program but through two different teaching strategies and to examine the ... ...

Abstract	Objectives: The aim of this study was to investigate differences in academic achievement between two groups of students who were taught the same course online within the nursing program but through two different teaching strategies and to examine the students' attitudes towards flipped classroom. Methods: Online lectures using Zoom was given to teach a course regarding the immune system and another course was taught the same subject in flipped classroom approach using video lectures followed by seminars. Academic achievement were compared between the groups, and perspectives on flipped classroom were investigated using a questionnaire. Results: The main findings were that participation in flipped classroom seminars had a positive effect on academic achievement (OR 2.3 (CI [1.001-5.1]), and that students preferred the flipped classroom approach over traditional lectures. Conclusions: This study suggests that a student centered teaching strategy like flipped classroom is an effective way to increase the students' engagement and academic achievements.
MeSH term(s)	COVID-19 ; Curriculum ; Education, Nursing ; Humans ; Pandemics ; Problem-Based Learning ; SARS-CoV-2 ; Teaching
Language	English
Publishing date	2022-02-21
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2162109-3
ISSN	1548-923X ; 2194-5772
ISSN (online)	1548-923X
ISSN	2194-5772
DOI	10.1515/ijnes-2021-0119
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Article ; Online: Synthesis of Site-Specific Antibody-[60]Fullerene-Oligonucleotide Conjugates for Cellular Targeting.

Äärelä, Antti / Räsänen, Kati / Holm, Patrik / Salo, Harri / Virta, Pasi

ACS applied bio materials

2023 Volume 6, Issue 8, Page(s) 3189–3198

Abstract: An ideal therapeutic antibody-oligonucleotide conjugate (AOC) would be a uniform construct, contain a maximal oligonucleotide (ON) payload, and retain the antibody (Ab)-mediated binding properties, which leads to an efficient delivery of the ON cargo to ... ...

Abstract	An ideal therapeutic antibody-oligonucleotide conjugate (AOC) would be a uniform construct, contain a maximal oligonucleotide (ON) payload, and retain the antibody (Ab)-mediated binding properties, which leads to an efficient delivery of the ON cargo to the site of therapeutic action. Herein, [60]fullerene-based molecular spherical nucleic acids (MSNAs) have been site-specifically conjugated to antibodies (Abs), and the Ab-mediated cellular targeting of the MSNA-Ab conjugates has been studied. A well-established glycan engineering technology and robust orthogonal click chemistries yielded the desired uniform MSNA-Ab conjugates (MW ∼ 270 kDa), with an oligonucleotide (ON):Ab ratio of 24:1, in 20-26% isolated yields. These AOCs retained the antigen binding properties (Trastuzumab's binding to human epidermal growth factor receptor 2, HER2), studied by biolayer interferometry. In addition, Ab-mediated endocytosis was demonstrated with live-cell fluorescence and phase-contrast microscopy on BT-474 breast carcinoma cells, overexpressing HER2. The effect on cell proliferation was analyzed by label-free live-cell time-lapse imaging.
MeSH term(s)	Humans ; Fullerenes ; Oligonucleotides ; Antibodies ; Immunoconjugates/chemistry
Chemical Substances	Fullerenes ; Oligonucleotides ; Antibodies ; Immunoconjugates
Language	English
Publishing date	2023-07-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2576-6422
ISSN (online)	2576-6422
DOI	10.1021/acsabm.3c00318
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Article ; Online: Development of an in vitro aggregation assay for long synthetic polypeptide, amyloidogenic gelsolin fragment AGelD187N 173-242.

Leimu, Laura / Haavisto, Oskar / Nesati, Victor / Holm, Patrik / Haapalinna, Antti / Salbo, Rune / Pesonen, Ullamari

PloS one

2023 Volume 18, Issue 8, Page(s) e0290179

Abstract: Aggregation of the gelsolin protein fragment is the hallmark of the hereditary systemic disease gelsolin amyloidosis. As with other protein misfolding diseases, there is an urgent need for efficient disease-modifying treatment for gelsolin amyloidosis. ... ...

Abstract	Aggregation of the gelsolin protein fragment is the hallmark of the hereditary systemic disease gelsolin amyloidosis. As with other protein misfolding diseases, there is an urgent need for efficient disease-modifying treatment for gelsolin amyloidosis. The formation of amyloids can be reproduced by incubating the disease-causing amyloidogenic 8 kDa polypeptide, 70-residue gelsolin protein fragment, AGelD187N 173-242, in vitro and monitoring the process by thioflavin T dye. However, for screening of potential aggregation inhibitors, the required protein amounts are large and the biotechnological production of amyloidogenic proteins has many challenges. Conversely, use of shorter synthetic regions of AGelD187N 173-242 does not mimic the in vivo aggregation kinetics of full-length fragment as they have different aggregation propensity. In this study, we present an in vitro aggregation assay for full-length AGelD187N 173-242 that has been produced by solid-phase chemical synthesis and after that monomerized carefully. Chemical synthesis allows us to produce high quantities of full-length fragment efficiently and at low cost. We demonstrate that the generated aggregates are fibrillar in nature and how the purity, terminal modification, initial aggregates and seeding affect the aggregation kinetics of a synthetic gelsolin fragment. We also present sufficient quality criteria for the initial monomerized synthetic polypeptide.
MeSH term(s)	Humans ; Gelsolin ; Peptides ; Amyloid Neuropathies, Familial ; Amyloidogenic Proteins ; Biotechnology
Chemical Substances	Gelsolin ; Peptides ; Amyloidogenic Proteins
Language	English
Publishing date	2023-08-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0290179
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Article ; Online: Development of benzodioxine-heteroarylpiperazines as highly potent and selective α2c antagonists.

Wang, Shouming / Haikarainen, Anssi / Pohjakallio, Antti / Sipilä, Julius / Kaskinoro, Janne / Juhila, Satu / Jalava, Niina / Koskinen, Mikko / Vesajoki, Marja / Kumpulainen, Esa / Pystynen, Jarmo / Koskelainen, Tuula / Holm, Patrik / Din Belle, David

Bioorganic & medicinal chemistry letters

2022 Volume 77, Page(s) 129005

Abstract: Here is reported the design and synthesis of a series of highly potent and selective α2C antagonists using benzodioxine methyl piperazine as a central scaffold by pharmacophoric analysis to improve the pharmacokinetics of suboptimal clinical candidate ... ...

Abstract	Here is reported the design and synthesis of a series of highly potent and selective α2C antagonists using benzodioxine methyl piperazine as a central scaffold by pharmacophoric analysis to improve the pharmacokinetics of suboptimal clinical candidate molecules.
MeSH term(s)	Receptors, Adrenergic, alpha-2
Chemical Substances	Receptors, Adrenergic, alpha-2
Language	English
Publishing date	2022-09-26
Publishing country	England
Document type	Journal Article
ZDB-ID	1063195-1
ISSN	1464-3405 ; 0960-894X
ISSN (online)	1464-3405
ISSN	0960-894X
DOI	10.1016/j.bmcl.2022.129005
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Article ; Online: 2,3-Dihydrobenzo-dioxine piperidine derivatives as potent and selective α2c antagonists.

Bioorganic & medicinal chemistry letters

2022 Volume 69, Page(s) 128783

Abstract: In this manuscript, we report a series of benzodioxine methyl piperidine derivatives as highly potent and selective α2C antagonists by ligand design to improve the pharmacokinetics of a previous candidate molecule. ...

Abstract	In this manuscript, we report a series of benzodioxine methyl piperidine derivatives as highly potent and selective α2C antagonists by ligand design to improve the pharmacokinetics of a previous candidate molecule.
MeSH term(s)	Dioxins ; Piperidines/pharmacology ; Receptors, Adrenergic, alpha-2
Chemical Substances	Dioxins ; Piperidines ; Receptors, Adrenergic, alpha-2
Language	English
Publishing date	2022-05-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1063195-1
ISSN	1464-3405 ; 0960-894X
ISSN (online)	1464-3405
ISSN	0960-894X
DOI	10.1016/j.bmcl.2022.128783
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Article ; Online: Drug-to-Antibody Ratio Estimation via Proteoform Peak Integration in the Analysis of Antibody-Oligonucleotide Conjugates with Orbitrap Fourier Transform Mass Spectrometry.

Nagornov, Konstantin O / Gasilova, Natalia / Kozhinov, Anton N / Virta, Pasi / Holm, Patrik / Menin, Laure / Nesatyy, Victor J / Tsybin, Yury O

Analytical chemistry

2021 Volume 93, Issue 38, Page(s) 12930–12937

Abstract: The therapeutic efficacy and pharmacokinetics of antibody-drug conjugates (ADCs) in general, and antibody-oligonucleotide conjugates (AOCs) in particular, depend on the drug-to-antibody ratio (DAR) distribution and average value. The DAR is considered a ... ...

Abstract	The therapeutic efficacy and pharmacokinetics of antibody-drug conjugates (ADCs) in general, and antibody-oligonucleotide conjugates (AOCs) in particular, depend on the drug-to-antibody ratio (DAR) distribution and average value. The DAR is considered a critical quality attribute, and information pertaining to it needs to be gathered during ADC/AOC development, production, and storage. However, because of the high structural complexity of ADC/AOC samples, particularly in the initial drug-development stages, the application of the current state-of-the-art mass spectrometric approaches can be limited for DAR analysis. Here, we demonstrate a novel approach for the analysis of complex ADC/AOC samples, following native size-exclusion chromatography Orbitrap Fourier transform mass spectrometry (FTMS). The approach is based on the integration of the proteoform-level mass spectral peaks in order to provide an estimate of the DAR distribution and its average value with less than 10% error. The peak integration is performed via a truncation of the Orbitrap's unreduced time-domain ion signals (transients) before mass spectra generation via FT processing. Transient recording and processing are undertaken using an external data acquisition system, FTMS Booster X2, coupled to a Q Exactive HF Orbitrap FTMS instrument. This approach has been applied to the analysis of whole and subunit-level trastuzumab conjugates with oligonucleotides. The obtained results indicate that ADC/AOC sample purification or simplification procedures, for example, deglycosylation, could be omitted or minimized prior to the DAR analysis, streamlining the drug-development process.
MeSH term(s)	Fourier Analysis ; Immunoconjugates/analysis ; Mass Spectrometry ; Oligonucleotides ; Pharmaceutical Preparations
Chemical Substances	Immunoconjugates ; Oligonucleotides ; Pharmaceutical Preparations
Language	English
Publishing date	2021-09-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.1c02247
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Article ; Online: Evaluation of decentralised model-based selection of head and neck cancer patients for a proton treatment study. DAHANCA 35.

Hansen, Christian Rønn / Jensen, Kenneth / Smulders, Bob / Holm, Anne Ivalu Sander / Samsøe, Eva / Nielsen, Martin Skovmos / Sibolt, Patrik / Skyt, Peter / Elstrøm, Ulrik Vindelev / Nielsen, Camilla Panduro / Johansen, Jørgen / Zukauskaite, Ruta / Eriksen, Jesper Grau / Farhadi, Mohamma / Andersen, Maria / Andersen, Elo / Overgaard, Jens / Grau, Cai / Friborg, Jeppe

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

2023 Volume 190, Page(s) 109812

Abstract: Introduction: Proton treatment can potentially spare patients with H&N cancer for substantial treatment-related toxicities. The current study investigated the reproducibility of a decentralised model-based selection of patients for a proton treatment ... ...

Abstract	Introduction: Proton treatment can potentially spare patients with H&N cancer for substantial treatment-related toxicities. The current study investigated the reproducibility of a decentralised model-based selection of patients for a proton treatment study when the selection plans were compared to the clinical treatment plans performed at the proton centre. Methods: Sixty-three patients were selected for proton treatment in the six Danish Head and Neck Cancer (DAHANCA) centres. The patients were selected based on normal tissue complication probability (NTCP) estimated from local photon and proton treatment plans, which showed a ΔNTCP greater than 5%-point for either grade 2 + dysphagia or grade 2 + xerostomia at six months. The selection plans were compared to the clinical treatment plans performed at the proton centre. Results: Of the 63 patients, 49 and 25 were selected based on an estimated benefit in risk of dysphagia and xerostomia, respectively. Eleven patients had a potential gain in both toxicities. The mean ΔNTCP changed from the local selection plan comparison to the clinical comparison from 6.9 to 5.3 %-points (p = 0.01) and 7.3 to 4.9 %-points (p = 0.03) for dysphagia and xerostomia, respectively. Volume differences in both CTV and OAR could add to the loss in ΔNTCP. 61 of the 63 clinical plans had a positive ΔNTCP, and 38 had a ΔNTCP of 5%-points for at least one of the two endpoints. Conclusion: A local treatment plan comparison can be used to select candidates for proton treatment. The local comparative proton plan overestimates the potential benefit of the clinical proton plan. Continuous quality assurance of the delineation procedures and planning is crucial in the subsequent randomised clinical trial setting.
MeSH term(s)	Humans ; Protons ; Organs at Risk ; Deglutition Disorders/etiology ; Reproducibility of Results ; Radiotherapy Dosage ; Proton Therapy/adverse effects ; Proton Therapy/methods ; Head and Neck Neoplasms/radiotherapy ; Head and Neck Neoplasms/etiology ; Xerostomia/etiology ; Radiotherapy Planning, Computer-Assisted/methods ; Radiotherapy, Intensity-Modulated/methods
Chemical Substances	Protons
Language	English
Publishing date	2023-07-20
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	605646-5
ISSN	1879-0887 ; 0167-8140
ISSN (online)	1879-0887
ISSN	0167-8140
DOI	10.1016/j.radonc.2023.109812
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Article ; Online: Base-catalysed

Meyer, Denise N / Cortés González, Miguel A / Jiang, Xingguo / Johansson-Holm, Linus / Pourghasemi Lati, Monireh / Elgland, Mathias / Nordeman, Patrik / Antoni, Gunnar / Szabó, Kálmán J

Chemical communications (Cambridge, England)

2021 Volume 57, Issue 68, Page(s) 8476–8479

Abstract: A new method for the fluorine-18 labelling of trifluoromethyl ketones has been developed. This method is based on the conversion of a- ... ...

Abstract	A new method for the fluorine-18 labelling of trifluoromethyl ketones has been developed. This method is based on the conversion of a-COCF
MeSH term(s)	Fluorine Radioisotopes/chemistry ; Ketones/chemistry ; Molecular Structure ; Proteinase Inhibitory Proteins, Secretory/chemical synthesis ; Proteinase Inhibitory Proteins, Secretory/chemistry
Chemical Substances	Fluorine Radioisotopes ; Ketones ; Proteinase Inhibitory Proteins, Secretory ; Fluorine-18 (GZ5I74KB8G)
Language	English
Publishing date	2021-08-04
Publishing country	England
Document type	Journal Article
ZDB-ID	1472881-3
ISSN	1364-548X ; 1359-7345 ; 0009-241X
ISSN (online)	1364-548X
ISSN	1359-7345 ; 0009-241X
DOI	10.1039/d1cc03624f
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Article: Base-catalysed ¹⁸F-labelling of trifluoromethyl ketones. Application to the synthesis of ¹⁸F-labelled neutrophil elastase inhibitors

Meyer, Denise N. / Cortés González, Miguel A. / Jiang, Xingguo / Johansson-Holm, Linus / Pourghasemi Lati, Monireh / Elgland, Mathias / Nordeman, Patrik / Antoni, Gunnar / Szabó, Kálmán J.

Chemical communications. 2021 Aug. 25, v. 57, no. 68

2021

Abstract: A new method for the fluorine-18 labelling of trifluoromethyl ketones has been developed. This method is based on the conversion of a–COCF₃ functional group to a difluoro enol silyl ether followed by halogenation and fluorine-18 labelling. The utility of ...

Abstract	A new method for the fluorine-18 labelling of trifluoromethyl ketones has been developed. This method is based on the conversion of a–COCF₃ functional group to a difluoro enol silyl ether followed by halogenation and fluorine-18 labelling. The utility of this new method was demonstrated by the synthesis of fluorine-18 labelled neutrophil elastase inhibitors, which are potentially useful for detection of inflammatory disorders.
Keywords	elastase ; enols ; neutrophils
Language	English
Dates of publication	2021-0825
Size	p. 8476-8479.
Publishing place	The Royal Society of Chemistry
Document type	Article
ZDB-ID	1472881-3
ISSN	1364-548X ; 1359-7345 ; 0009-241X
ISSN (online)	1364-548X
ISSN	1359-7345 ; 0009-241X
DOI	10.1039/d1cc03624f
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Article ; Online: SANS: high-throughput retrieval of protein sequences allowing 50% mismatches.

Koskinen, J Patrik / Holm, Liisa

Bioinformatics (Oxford, England)

2012 Volume 28, Issue 18, Page(s) i438–i443

Abstract: ... http://ekhidna.biocenter.helsinki.fi/downloads/sans.: Contact: liisa.holm@helsinki.fi. ...

Abstract	Motivation: The genomic era in molecular biology has brought on a rapidly widening gap between the amount of sequence data and first-hand experimental characterization of proteins. Fortunately, the theory of evolution provides a simple solution: functional and structural information can be transferred between homologous proteins. Sequence similarity searching followed by k-nearest neighbor classification is the most widely used tool to predict the function or structure of anonymous gene products that come out of genome sequencing projects. Results: We present a novel word filter, suffix array neighborhood search (SANS), to identify protein sequence similarities in the range of 50-100% identity with sensitivity comparable to BLAST and 10 times the speed of USEARCH. In contrast to these previous approaches, the complexity of the search is proportional only to the length of the query sequence and independent of database size, enabling fast searching and functional annotation into the future despite rapidly expanding databases. Availability and implementation: The software is freely available to non-commercial users from our website http://ekhidna.biocenter.helsinki.fi/downloads/sans. Contact: liisa.holm@helsinki.fi.
MeSH term(s)	Algorithms ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Databases, Protein ; Genome ; Metagenome ; Sequence Alignment ; Sequence Analysis, Protein/methods ; Sequence Homology, Amino Acid ; Software
Chemical Substances	Bacterial Proteins
Language	English
Publishing date	2012-09-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/bts417
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