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| 2. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Kim, Joon Tae, et al.
(author)
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Dual antiplatelet Use for extended period taRgeted to AcuTe ischemic stroke with presumed atherosclerotic OrigiN (DURATION) trial : Rationale and design
- 2023
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In: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 18:8, s. 1015-1020
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Journal article (peer-reviewed)abstract
- Rationale: The optimal duration of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin for the large artery atherosclerotic (LAA) stroke subtype has been debated. Aims: To determine whether the 1-year risk of recurrent vascular events could be reduced by a longer duration of DAPT in patients with the LAA stroke subtype. Methods and study design: A total of 4806 participants will be recruited to detect a statistically significant relative risk reduction of 22% with 80% power and a two-sided alpha error of 0.05, including a 10% loss to follow-up. This is a registry-based, multicenter, prospective, randomized, open-label, blinded end point study designed to evaluate the efficacy and safety of a 12-month duration of DAPT compared with a 3-month duration of DAPT in the LAA stroke subtype. Patients will be randomized (1:1) to either DAPT for 12 months or DAPT for 3 months, followed by monotherapy (either aspirin or clopidogrel) for the remaining 9 months. Study outcomes: The primary efficacy outcome of the study is a composite of stroke (ischemic or hemorrhagic), myocardial infarction, and all-cause mortality for 1 year after the index stroke. The secondary efficacy outcomes are (1) stroke, (2) ischemic stroke or transient ischemic attack, (3) hemorrhagic stroke, and (4) all-cause mortality. The primary safety outcome is major bleeding. Discussion: This study will help stroke physicians determine the appropriate duration of dual therapy with clopidogrel-aspirin for patients with the LAA stroke subtype. Trial registration: URL: https://cris.nih.go.kr/cris. CRIS Registration Number: KCT0004407.
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| 4. |
- Kwon, Hyuk Sung, et al.
(author)
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Early increment of soluble triggering receptor expressed on myeloid cells 2 in plasma might be a predictor of poor outcome after ischemic stroke
- 2020
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In: Journal of clinical neuroscience. - : ELSEVIER SCI LTD. - 0967-5868 .- 1532-2653. ; 73, s. 215-218
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Journal article (peer-reviewed)abstract
- Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is derived from cleavage of TREM2, which is expressed on the cell surface of microlgia and other tissue-specific macrophages. In the present study, the changes in the sTREM2 levels after ischemic stroke (IS) and their association with clinical outcomes were evaluated. A total of 43 patients diagnosed with non-cardioembolic IS between June 2011 and May 2014 were consecutively included in this study. Patients treated with intravenous thrombolysis or intra-arterial thrombectomy were excluded. Plasma samples were collected three times (days 1, 7, and 90) after ictus. The sTREM2 level was measured in the samples using the highly sensitive solid-phase proximity ligation assay (SP-PLA). Among the 43 subjects, higher initial NIH stroke scale (NIHSS) score (P = 0.005), early increment of sTREM2 (P < 0.001), and late decrement of sTREM2 (P = 0.002), were more common in patients with poor outcome. Based on multivariate analysis, initial NIHSS score (P = 0.015) and early increment of sTREM2 (P = 0.032) were independently associated with poor outcome. The results from the present study indicate that increment of sTREM2 level at the early phase was a predictor of poor outcome. Serial follow-up of sTREM2 may aid prognosis after stroke.
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| 5. |
- Cho, Eun, et al.
(author)
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Clinical experience of tensor-valued diffusion encoding for microstructure imaging by diffusional variance decomposition in patients with breast cancer
- 2022
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In: Quantitative Imaging in Medicine and Surgery. - : AME Publishing Company. - 2223-4292 .- 2223-4306. ; 12:3, s. 2002-2017
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Journal article (peer-reviewed)abstract
- Background: Diffusion-weighted imaging plays a key role in magnetic resonance imaging (MRI) of breast tumors. However, it remains unclear how to interpret single diffusion encoding with respect to its link with tissue microstructure. The purpose of this retrospective cross-sectional study was to use tensor-valued diffusion encoding to investigate the underlying microstructure of invasive ductal carcinoma (IDC) and evaluate its potential value in a clinical setting. Methods: We retrospectively reviewed biopsy-proven breast cancer patients who underwent preoperative breast MRI examination from July 2020 to March 2021. We reviewed the MRI of 29 patients with 30 IDCs, including analysis by diffusional variance decomposition enabled by tensor-valued diffusion encoding. The diffusion parameters of mean diffusivity (MD), total mean kurtosis (MKT), anisotropic mean kurtosis (MKA), isotropic mean kurtosis (MKI), macroscopic fractional anisotropy (FA), and microscopic fractional anisotropy (μFA) were estimated. The parameter differences were compared between IDC and normal fibroglandular breast tissue (FGBT), as well as the association between the diffusion parameters and histopathologic items. Results: The mean value of MD in IDCs was significantly lower than that of normal FGBT (1.07±0.27 vs. 1.34±0.29, P<0.001); however, MKT, MKA, MKI, FA, and μFA were significantly higher (P<0.005). Among all the diffusion parameters, MKI was positively correlated with the tumor size on both MRI and pathological specimen (rs=0.38, P<0.05 vs. rs=0.54, P<0.01), whereas MKT had a positive correlation with the tumor size in the pathological specimen only (rs=0.47, P<0.02). In addition, the lymph node (LN) metastasis group had significantly higher MKT, MKA, and μFA compared to the metastasis negative group (P<0.05). Conclusions: Tensor-valued diffusion encoding enables a useful non-invasive method for characterizing breast cancers with information on tissue microstructures. Particularly, μFA could be a potential imaging biomarker for evaluating breast cancers prior to surgery or chemotherapy.
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| 6. |
- Schweiker, Marcel, et al.
(author)
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Evaluating assumptions of scales for subjective assessment of thermal environments – Do laypersons perceive them the way, we researchers believe?
- 2020
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In: Energy and Buildings. - : Elsevier BV. - 0378-7788. ; 211
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Journal article (peer-reviewed)abstract
- People's subjective response to any thermal environment is commonly investigated by using rating scales describing the degree of thermal sensation, comfort, and acceptability. Subsequent analyses of results collected in this way rely on the assumption that specific distances between verbal anchors placed on the scale exist and that relationships between verbal anchors from different dimensions that are assessed (e.g. thermal sensation and comfort) do not change. Another inherent assumption is that such scales are independent of the context in which they are used (climate zone, season, etc.). Despite their use worldwide, there is indication that contextual differences influence the way the scales are perceived and therefore question the reliability of the scales’ interpretation. To address this issue, a large international collaborative questionnaire study was conducted in 26 countries, using 21 different languages, which led to a dataset of 8225 questionnaires. Results, analysed by means of robust statistical techniques, revealed that only a subset of the responses are in accordance with the mentioned assumptions. Significant differences appeared between groups of participants in their perception of the scales, both in relation to distances of the anchors and relationships between scales. It was also found that respondents’ interpretations of scales changed with contextual factors, such as climate, season, and language. These findings highlight the need to carefully consider context-dependent factors in interpreting and reporting results from thermal comfort studies or post-occupancy evaluations, as well as to revisit the use of rating scales and the analysis methods used in thermal comfort studies to improve their reliability.
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| 7. |
- Schweiker, Marcel, et al.
(author)
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The Scales Project, a cross-national dataset on the interpretation of thermal perception scales
- 2019
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In: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 6:1
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Journal article (peer-reviewed)abstract
- Thermal discomfort is one of the main triggers for occupants' interactions with components of the built environment such as adjustments of thermostats and/or opening windows and strongly related to the energy use in buildings. Understanding causes for thermal (dis-)comfort is crucial for design and operation of any type of building. The assessment of human thermal perception through rating scales, for example in post-occupancy studies, has been applied for several decades; however, long-existing assumptions related to these rating scales had been questioned by several researchers. The aim of this study was to gain deeper knowledge on contextual influences on the interpretation of thermal perception scales and their verbal anchors by survey participants. A questionnaire was designed and consequently applied in 21 language versions. These surveys were conducted in 57 cities in 30 countries resulting in a dataset containing responses from 8225 participants. The database offers potential for further analysis in the areas of building design and operation, psycho-physical relationships between human perception and the built environment, and linguistic analyses.
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| 8. |
- Hellwig, Runa T., et al.
(author)
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A framework for adopting adaptive thermal comfort principles in design and operation of buildings
- 2019
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In: Energy and Buildings. - : Elsevier BV. - 0378-7788. ; 205
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Journal article (peer-reviewed)abstract
- The concept of adaptive thermal comfort was formulated many decades ago and has been validated in numerous field studies. As a result, wider acceptable indoor temperature ranges based on adaptive models have been included in international and national standards and the adaptive approach to thermal comfort is regarded as a significant contributor in achieving low energy building design and operation. Despite the ever-increasing scientific literature on adaptive comfort around the world, the overall understanding of how to translate the adaptive principles into design practice and concepts for operating buildings is still limited, which suggests a gap between the scientific outcomes and the real-world applications. This discussion paper identifies the challenges and gaps in using the principles of adaptive thermal comfort by design practitioners and discusses them in light of relevant research findings. More than 100 literature sources were reviewed in support of the discussion. The paper then proposes a framework that aims to facilitate the adoption of adaptive comfort principles in design and operation of buildings and describes the outline of an imminent guideline for low energy building design based on the concept of adaptive thermal comfort.
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| 9. |
- Hellwig, Runa T., et al.
(author)
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Applying adaptive principles: Developing guidance for planning practice
- 2019
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In: PROCEEDINGS OF THE 1ST INTERNATIONAL CONFERENCE ON COMFORT AT THE EXTREMES: ENERGY, ECONOMY AND CLIMATE.
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Conference paper (peer-reviewed)abstract
- One of the major challenges of building industry today is to provide indoor spaces allowing the occupants to make themselves comfortable while achieving low energy consumption. Considering the observed increasing temperatures and a more extreme climate, this becomes even more urgent and difficult to accomplish. It is therefore necessary to rely on approaches than contribute to sustainable building design, such as the adaptive approach to thermal comfort which postulates that people are not passive recipients of their environment but adapt behaviourally, physiologically and psychologically. The concept of adaptive thermal comfort was formulated many decades ago and has been validated in numerous field studies. Temperature thresholds based on adaptive models have been included in international and national standards. However, the overall understanding of how to translate the adaptive principles into design practice and concepts for operating buildings is still limited. Subtask B of IEA Annex 69 addresses this gap: “Strategy and practice of adaptive thermal comfort in low energy buildings”. The subtask aims to develop guidelines for low energy buildings that include the principle of adaptive comfort. This paper discusses the challenges and gaps identified in using the principles of adaptive thermal comfort in building design and operation and outlines the contents of the imminent guideline.
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| 10. |
- Hellwig, Runa T., et al.
(author)
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Design of adaptive opportunities for people in buildings
- 2022
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In: Routledge Handbook of Resilient Thermal Comfort. - London : Routledge. - 9781003244929 ; , s. 193-209
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Book chapter (other academic/artistic)abstract
- Adaptive opportunities for people are a key element in the adaptive thermal comfort approach. Research has led to a broad and solid foundation of knowledge, but design processes on how to support people’s behavioural control through building design are still missing. This chapter presents a design process for incorporating adaptive opportunities and discusses how such an approach enhances thermal resilience. The design process is facilitated with tools and exemplary design or operation actions for stakeholders. Non-energy using adaptive opportunities and the passive performance a building affords are the means to enhance not only human thermal comfort in buildings but also human resilience. This is because they offer people concrete options for acting and supporting their belief in their ability and skills to act in case of extreme weather events and can hence facilitate physiological adaptation. They are therefore paramount to build a resilient human-building interaction in a changing environment.
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