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- Schiller, D, et al.
(author)
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The Human Affectome
- 2024
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In: Neuroscience and biobehavioral reviews. - 1873-7528. ; 158, s. 105450-
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Journal article (peer-reviewed)
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- Altersberger, V. L., et al.
(author)
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Intravenous Thrombolysis in Patients With Ischemic Stroke Aged ≥90 Years: A Cohort Study From the TRISP Collaboration
- 2022
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In: Stroke. - 1524-4628. ; 53:12, s. 3557-3563
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Journal article (peer-reviewed)abstract
- BACKGROUND: The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly. METHODS: In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those <90 years using symptomatic intracranial hemorrhage (ECASS [European Cooperative Acute Stroke Study]-II criteria), death, and poor functional outcome in survivors (modified Rankin Scale score 3-5 for patients with prestroke modified Rankin Scale score ≤2 and modified Rankin Scale score 4-5 for patients prestroke modified Rankin Scale ≥3) at 3 months as outcomes. We calculated adjusted odds ratio with 95% CI using logistic regression models. RESULTS: Of 16974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratioadjusted 1.14 [0.83-1.57]) did not differ significantly between both groups. However, the probability of death (odds ratioadjusted 3.77 [3.14-4.53]) and poor functional outcome (odds ratioadjusted 2.63 [2.13-3.25]) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar. CONCLUSIONS: The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.
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- Westphal, L. P., et al.
(author)
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Association of prestroke metformin use, stroke severity, and thrombolysis outcome
- 2020
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 95:4
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Journal article (peer-reviewed)abstract
- Objective To evaluate whether pretreatment with metformin (MET) is associated with less stroke severity and better outcome after IV thrombolysis (IVT), we analyzed a cohort of 1,919 patients with stroke with type 2 diabetes mellitus in a multicenter exploratory analysis. Methods Data from patients with diabetes and ischemic stroke treated with IVT were collected within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration. We applied propensity score matching (PSM) to obtain balanced baseline characteristics of patients treated with and without MET. Results Of 1,919 patients with stroke with type 2 diabetes who underwent IVT, 757 (39%) had received MET before stroke (MET+), whereas 1,162 (61%) had not (MET-). MET+ patients were younger with a male preponderance. Hypercholesterolemia and pretreatment with statins, antiplatelets, or antihypertensives were more common in the MET+ group. After PSM, the 2 groups were well balanced with respect to demographic and clinical aspects. Stroke severity on admission (NIH Stroke Scale 10.0 +/- 6.7 vs 11.3 +/- 6.5), 3-month degree of independence on modified Rankin Scale (2 [interquartile range (IQR) 1.0-4.0] vs 3 [IQR 1.0-4.0]), as well as mortality (12.5% vs 18%) were significantly lower in the MET+ group. The frequency of symptomatic intracerebral hemorrhages did not differ between groups. HbA1c levels were well-balanced between the groups. Conclusions Patients with stroke and diabetes on treatment with MET receiving IVT had less severe strokes on admission and a better functional outcome at 3 months. This suggests a protective effect of MET resulting in less severe strokes as well as beneficial thrombolysis outcome.
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- Phadke, R., et al.
(author)
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RBCK1-related disease: A rare multisystem disorder with polyglucosan storage, auto-inflammation, recurrent infections, skeletal, and cardiac myopathy—Four additional patients and a review of the current literature
- 2020
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In: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 43:5, s. 1002-1013
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Journal article (peer-reviewed)abstract
- In this article, we report four new patients, from three kindreds, with pathogenic variants in RBCK1 and a multisystem disorder characterised by widespread polyglucosan storage. We describe the clinical presentation of progressive skeletal and cardiac myopathy, combined immunodeficiencies and auto-inflammation, illustrate in detail the histopathological findings in multiple tissue types, and report muscle MRI findings. © 2020 SSIEM
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- Welsh, Joshua A., et al.
(author)
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Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches
- 2024
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In: Journal of Extracellular Vesicles. - : John Wiley and Sons Inc. - 2001-3078. ; 13:2
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Journal article (peer-reviewed)abstract
- Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.
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- Tinyanont, S., et al.
(author)
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Infrared spectropolarimetric detection of intrinsic polarization from a core-collapse supernova
- 2021
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In: Nature Astronomy. - : Springer Nature. - 2397-3366. ; 5:6, s. 544-551
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Journal article (peer-reviewed)abstract
- Massive stars die an explosive death as a core-collapse supernova (CCSN). The exact physical processes that cause the collapsing star to rebound into an explosion are not well understood1–3, and the key to resolving this issue may lie in the measurement of the shape of CCSNe ejecta. Spectropolarimetry is the only way to perform this measurement for CCSNe outside the Milky Way and Magellanic Clouds. We present the infrared spectropolarimetric detection of a CCSN enabled by the new highly sensitive WIRC+Pol instrument at Palomar Observatory, which can observe CCSNe (magnitude M = −17 mag) out to 20 Mpc at ~0.1% polarimetric precision. Infrared spectropolarimetry is less affected than optical spectropolarimetry by dust scattering in the circumstellar and interstellar media, thereby providing a less biased probe of the intrinsic geometry of the supernova ejecta. SN 2018hna, a SN 1987A-like explosion, shows 2.0 ± 0.3% continuum polarization in the J band oriented at ~160° on sky 182 days after the explosion. Assuming a prolate geometry as in SN 1987A, we infer an ejecta axis ratio of <0.48 with the axis of symmetry pointing at a 70° position angle. The axis ratio is similar to that of SN 1987A, suggesting that the two CCSNe may share intrinsic geometry and inclination angles. Our data do not rule out oblate ejecta. We also observe one other CCSN and two thermonuclear supernovae in the J band. Supernova 2020oi, a stripped-envelope type Ic SN in Messier 100 has broadband p = 0.37 ± 0.09% at peak light, indicative of either a 10% asymmetry or host interstellar polarization. The type Ia SNe 2019ein and 2020ue have <0.33% and <1.08% polarization near peak light, indicative of asymmetries of less than 10% and 20%, respectively.
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- Walther, G, et al.
(author)
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Report on challenges for SCIs
- 2021
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Reports (other academic/artistic)abstract
- This report discusses the challenges posed by four types of threats – terrorist attacks, cyber-attacks, extreme weather and social unrest – on the following eight smart critical infrastructure systems:a.ALPHA - Finance (financial system): The analysis focuses on disturbed information flow and disabling/manipulating IT and communication systems, including attacks on the “physical layer” using the example of IEMI/HPEM threats, as well as the software layer.b. BRAVO - Energy supply (system): The analysis focuses on disruption of “smart” energy supply in a “smart city”, caused by natural hazards, in this case flooding, leading to cascading effects and severe consequences for other energy-depending SCIs.c. CHARLIE - Health care (system):Focus of the analysis is on all threats that might cause large increases in the numbers of injuries or sick patients within a densely populated area. This will include indirect impacts, e.g. large numbers of injuries caused by a disaster or terrorist attacks or disease epidemics, but also direct impacts, e.g. service disruptions in critical health infrastructures, such as hospitals, due to attacks or disasters hitting the infrastructure itself.d.DELTA - Transportation (system) – airports: According to the framework situation, threats on Smart Airports will be assessed under circumstances of (i) blocked traffic, (ii) passenger and airplane traffic exceeding capacity (iii) flood.e. ECHO - Industry (in zones in cities) "Industrial Production Plants":The analysis focuses mainly on technological accidents within the refinery complex, but also accidents caused by natural hazards affecting refinery property outside the main refinery complex, e.g. accident on jetty belonging to refinery on the river Danube during unloading/loading oil products from barge to a tank, damages by a gale or storm on process installations (pipes, hoses) resulting in river pollution. Both scenarios could lead to cascading effects for other SCIs in close vicinity.f. FOXTROT - Water supply (systems): The analysis focuses on three cases of local and regional drinking water supply chains, with different kinds of vulnerabilities in terms of climate threats, ICT challenges, security issues and human error.g.GOLF - Urban flood protection (systems): The analysis focuses in the disruption of water and transport caused through tidal and fluvial flooding events.h. HOTEL: City of Helsinki - Flooding underground coal storage. Resilience of the energy infrastructure (city environment).The way this analysis was conducted was by assessing these threats using a 5x5 framework matrix. The two axes of the matrix were phases (understand risks, anticipate/prepare, absorb/withstand, respond/recover, adapt/learn) and dimensions (system/physical, information/data, organizational/business, societal/political, cognitive/decision-making).Each individual matrix block was discussed by subject experts who identified specific challenges and implications for each matrix element and rated its relevance (high, medium, low).In terms of the results, the system/physical dimension received the highest number of important challenges.Overall, the most important singular element was to understand risks in the organizational/business dimension. The least importance was attributed to the adapt/learn phase.
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- Dhiman, Vinit, et al.
(author)
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Multiband optical variability of the TeV blazar PG 1553+113 in 2019
- 2022
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 519:2, s. 2796-2811
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Journal article (peer-reviewed)abstract
- We report the flux and spectral variability of PG 1553 + 113 on intra-night (IDV) to short-term time-scales using BVRI data collected over 91 nights from 28 February to 8 November 2019 employing 10 optical telescopes: three in Bulgaria, two each in India and Serbia, and one each in Greece, Georgia, and Latvia. We monitored the blazar quasi-simultaneously for 16 nights in the V and R bands and 8 nights in the V, R, I bands and examined the light curves (LCs) for intra-day flux and colour variations using two powerful tests: the power-enhanced F-test and the nested ANOVA test. The source was found to be significantly (>99 per cent) variable in 4 nights out of 27 in R-band, 1 out of 16 in V-band, and 1 out of 6 nights in I-band. No temporal variations in the colours were observed on IDV time-scale. During the course of these observations the total variation in R-band was 0.89 mag observed. We also investigated the spectral energy distribution (SED) using B-, V-, R-, and I-band data. We found optical spectral indices in the range of 0.878 +/- 0.029 to 1.106 +/- 0.065 by fitting a power law (F-nu proportional to nu(-alpha)) to these SEDs of PG 1553 + 113. We found that the source follows a bluer-when-brighter trend on IDV time-scales. We discuss possible physical causes of the observed spectral variability.
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- Nordanstig, Annika, 1974, et al.
(author)
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EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:8
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Journal article (peer-reviewed)abstract
- The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.
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- Ristivojevic, MK, et al.
(author)
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Alpha-Gal on the Protein Surface Hampers Transcytosis through the Caco-2 Monolayer
- 2020
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In: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 21:16
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Journal article (peer-reviewed)abstract
- Transepithelial transport of proteins is an important step in the immune response to food allergens. Mammalian meat allergy is characterized by an IgE response against the carbohydrate moiety galactosyl-α-1,3-galactose (α-Gal) present on mammalian glycoproteins and glycolipids, which causes severe allergic reactions several hours after red meat consumption. The delayed reaction may be related to the processing of α-Gal carrying proteins in the gastrointestinal tract. The aim of this study was to investigate how protein glycosylation by α-Gal affects the susceptibility to gastric digestion and transport through the Caco-2 cell monolayer. We found that α-Gal glycosylation altered protein susceptibility to gastric digestion, where large protein fragments bearing the α-Gal epitope remained for up to 2 h of digestion. Furthermore, α-Gal glycosylation of the protein hampered transcytosis of the protein through the Caco-2 monolayer. α-Gal epitope on the intact protein could be detected in the endosomal fraction obtained by differential centrifugation of Caco-2 cell lysates. Furthermore, the level of galectin-3 in Caco-2 cells was not affected by the presence of α-Gal glycosylated BSA (bovine serum albumin) (BSA-α-Gal). Taken together, our data add new knowledge and shed light on the digestion and transport of α-Gal glycosylated proteins.
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- Stupar, D., et al.
(author)
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Posttraumatic stress disorder symptoms among trauma-exposed adolescents from low- and middle-income countries
- 2021
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In: Child and Adolescent Psychiatry and Mental Health. - : Springer Science and Business Media LLC. - 1753-2000. ; 15:1
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Journal article (peer-reviewed)abstract
- Background Exposure to traumatic events in childhood is associated with the development and maintenance of various psychiatric disorders, but most frequently with posttraumatic stress disorder (PTSD). The aim of this study was to evaluate the types of traumatic events experienced and the presence and predictors of PTSD symptoms among adolescents from the general population from ten low- and middle-income countries (LMICs). Methods Data were simultaneously collected from 3370 trauma-exposed adolescents (mean age = 15.41 [SD = 1.65] years, range 12-18; 1465 (43.5%) males and 1905 (56.5%) females) in Brazil, Bulgaria, Croatia, Indonesia, Montenegro, Nigeria, the Palestinian Territories, the Philippines, Romania, and Serbia, with Portugal, a high-income country, as a reference point. The UCLA PTSD Reaction Index for the DSM-5 (PTSD-RI-5) was used for the assessment of traumatic events and PTSD symptoms. Results The most frequently reported traumatic events were death of a close person (69.7%), witnessing violence other than domestic (40.5%), being in a natural disaster (34.4%) and witnessing violent death or serious injury of a close person (33.9%). In total, 28.5% adolescents endorsed two to three DSM-5 PTSD criteria symptoms. The rates of adolescents with symptoms from all four DSM-5 criteria for PTSD were 6.2-8.1% in Indonesia, Serbia, Bulgaria, and Montenegro, and 9.2-10.5% in Philippines, Croatia and Brazil. From Portugal, 10.7% adolescents fall into this category, while 13.2% and 15.3% for the Palestinian Territories and Nigeria, respectively. A logistic regression model showed that younger age, experiencing war, being forced to have sex, and greater severity of symptoms (persistent avoidance, negative alterations in cognitions and mood, and alterations in arousal and reactivity) were significant predictors of fulfilling full PTSD criteria. Conclusions Nearly every third adolescent living in LMICs might have some PTSD symptoms after experiencing a traumatic event, while nearly one in ten might have sufficient symptoms for full DSM-5 PTSD diagnosis. The findings can inform the generation of PTSD burden estimates, allocation of health resources, and designing and implementing psychosocial interventions for PTSD in LMICs.
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- Novicic, Zorana Kurbalija, et al.
(author)
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Lithium influences whole-organism metabolic rate inDrosophila subobscura
- 2021
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In: Journal of Neuroscience Research. - : John Wiley & Sons. - 0360-4012 .- 1097-4547. ; 99:1, s. 407-418
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Journal article (peer-reviewed)abstract
- Lithium is widely used to treat bipolar disorder. However, the efficacy and vulnerability as to its side effects are known to differ. Although the specific biochemical mechanism of action is still elusive, lithium may influence mitochondrial function, and consequently, metabolism. Lithium exposure in this study was conducted on a unique set of mito-nuclear introgression lines ofDrosophila subobscurato disentangle the independent effects of mitochondrial DNA (mtDNA) against a common nuclear DNA background. The study addressed three issues: (a) whether lithium has a dose-dependent effect on whole-organism metabolic rate, (b) whether mtDNA haplotypes show divergent metabolic efficiency measured by metabolic rate to lithium exposure and (c) whether lithium influences the whole-organism metabolic rate across sexes. The results confirm that lithium influenced the whole-organism metabolic rate, showing a subtle balance between efficacy and adverse effects within a narrow dose range. In addition, lithium exposure was found to influence metabolism differently based on mtDNA haplotypes and sex. This preliminary research may have a range of biological implications for the role of mitochondrial variability in psychiatric disease and treatment by contributing to the understanding and predicting of the lithium treatment response and risk for toxic side effects.
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- Saqr, M., et al.
(author)
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Is there order in the mess? : A single paper meta-analysis approach to identification of predictors of success in learning analytics
- 2022
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In: Studies in Higher Education. - : Informa UK Limited. - 0307-5079 .- 1470-174X. ; 47:12, s. 2370-2391
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Journal article (peer-reviewed)abstract
- Predictors of student academic success do not always replicate well across different learning designs, subject areas, or educational institutions. This suggests that characteristics of a particular discipline and learning design have to be carefully considered when creating predictive models in order to scale up learning analytics. This study aimed to examine if and to what extent frequently used predictors of study success are portable across a homogenous set of courses. The research was conducted in an integrated blended problem-based curriculum with trace data (n = 2,385 students) from 50 different course offerings across four academic years. We applied the statistical method of single paper meta-analysis to combine correlations of several indicators with students’ success. Total activity and the forum indicators exhibited the highest prediction intervals, where the former represented proxies of the overall engagement with online tasks, and the latter with online collaborative learning activities. Indicators of lecture reading (frequency of lecture view) showed statistically insignificant prediction intervals and, therefore, are less likely to be portable across course offerings. The findings show moderate amounts of variability both within iterations of the same course and across courses. The results suggest that the use of the meta-analytic statistical method for the examination of study success indicators across courses with similar learning design and subject area can offer valuable quantitative means for the identification of predictors that reasonably well replicate and consequently can be reliably portable in the future.
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- Thomsen, Christer, 1977, et al.
(author)
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Proteomic characterisation of polyglucosan bodies in skeletal muscle in RBCK1 deficiency
- 2022
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In: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 48:1
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Journal article (peer-reviewed)abstract
- Aims Several neurodegenerative and neuromuscular disorders are characterised by storage of polyglucosan, consisting of proteins and amylopectin-like polysaccharides, which are less branched than in normal glycogen. Such diseases include Lafora disease, branching enzyme deficiency, glycogenin-1 deficiency, polyglucosan body myopathy type 1 (PGBM1) due to RBCK1 deficiency and others. The protein composition of polyglucosan bodies is largely unknown. Methods We combined quantitative mass spectrometry, immunohistochemical and western blot analyses to identify the principal protein components of polyglucosan bodies in PGBM1. Histologically stained tissue sections of skeletal muscle from four patients were used to isolate polyglucosan deposits and control regions by laser microdissection. Prior to mass spectrometry, samples were labelled with tandem mass tags that enable quantitative comparison and multiplexed analysis of dissected samples. To study the distribution and expression of the accumulated proteins, immunohistochemical and western blot analyses were performed. Results Accumulated proteins were mainly components of glycogen metabolism and protein quality control pathways. The majority of fibres showed depletion of glycogen and redistribution of key enzymes of glycogen metabolism to the polyglucosan bodies. The polyglucosan bodies also showed accumulation of proteins involved in the ubiquitin-proteasome and autophagocytosis systems and protein chaperones. Conclusions The sequestration of key enzymes of glycogen metabolism to the polyglucosan bodies may explain the glycogen depletion in the fibres and muscle function impairment. The accumulation of components of the protein quality control systems and other proteins frequently found in protein aggregate disorders indicates that protein aggregation may be an essential part of the pathobiology of polyglucosan storage.
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