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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)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. |
- Kurilshikov, Alexander, et al.
(författare)
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Large-scale association analyses identify host factors influencing human gut microbiome composition
- 2021
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53:2, s. 156-165
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Tidskriftsartikel (refereegranskat)abstract
- To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
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| 4. |
- Ballantyne, Kaye N., et al.
(författare)
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Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats
- 2014
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 35:8, s. 1021-1032
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Tidskriftsartikel (refereegranskat)abstract
- Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, greater than99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RMY-STRs in identifying and separating unrelated and related males and provides a reference database.
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| 5. |
- Kristan, Matej, et al.
(författare)
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The Visual Object Tracking VOT2016 Challenge Results
- 2016
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Ingår i: COMPUTER VISION - ECCV 2016 WORKSHOPS, PT II. - Cham : SPRINGER INT PUBLISHING AG. - 9783319488813 - 9783319488806 ; , s. 777-823
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2016 aims at comparing short-term single-object visual trackers that do not apply pre-learned models of object appearance. Results of 70 trackers are presented, with a large number of trackers being published at major computer vision conferences and journals in the recent years. The number of tested state-of-the-art trackers makes the VOT 2016 the largest and most challenging benchmark on short-term tracking to date. For each participating tracker, a short description is provided in the Appendix. The VOT2016 goes beyond its predecessors by (i) introducing a new semi-automatic ground truth bounding box annotation methodology and (ii) extending the evaluation system with the no-reset experiment.
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| 6. |
- Lee, Christine J., et al.
(författare)
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Clinical manifestations of COVID-19 breakthrough infections: A systematic review and meta-analysis
- 2022
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Ingår i: Journal of Medical Virology. - : WILEY. - 0146-6615 .- 1096-9071. ; 94:9, s. 4234-4245
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Forskningsöversikt (refereegranskat)abstract
- To provide a comparative meta-analysis and systematic review of the risk and clinical outcomes of coronavirus 2019 (COVID-19) infection between fully vaccinated and unvaccinated groups. Eighteen studies of COVID-19 infections in fully vaccinated ("breakthrough infections") and unvaccinated individuals were reviewed from Medline/PubMed, Scopus, Embase, and Web of Science databases. The meta-analysis examined the summary effects and between-study heterogeneity regarding differences in the risk of infection, hospitalization, treatments, and mortality between vaccinated and unvaccinated individuals. he overall risk of infection was lower for the fully vaccinated compared to that of the unvaccinated (relative risk [RR] 0.20, 95% confidence interval [CI]: 0.19-0.21), especially for variants other than Delta (Delta: RR 0.29, 95% CI: 0.13-0.65; other variants: RR 0.06, 95% CI: 0.04-0.08). The risk of asymptomatic infection was not statistically significantly different between fully vaccinated and unvaccinated (RR 0.56, 95% CI: 0.27-1.19). There were neither statistically significant differences in risk of hospitalization (RR 1.06, 95% CI: 0.38-2.93), invasive mechanical ventilation (RR 1.65, 95% CI: 0.90-3.06), or mortality (RR 1.19, 95% CI: 0.79-1.78). Conversely, the risk of supplemental oxygen during hospitalization was significantly higher for the unvaccinated (RR 1.40, 95% CI: 1.08-1.82). Unvaccinated people were more vulnerable to COVID-19 infection than fully vaccinated for all variants. Once infected, there were no statistically significant differences in the risk of hospitalization, invasive mechanical ventilation, or mortality. Still, unvaccinated showed an increased need for oxygen supplementation. Further prospective analysis, including patients risk factors, COVID-19 variants, and the utilized treatment strategies, would be warranted.
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| 7. |
- Sung, Sang Hyun, et al.
(författare)
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Flexible wireless powered drug delivery system for targeted administration on cerebral cortex
- 2018
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Ingår i: Nano Energy. - : ELSEVIER SCIENCE BV. - 2211-2855 .- 2211-3282. ; 51, s. 102-112
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Tidskriftsartikel (refereegranskat)abstract
- The controlled drug delivery devices helps timely drug administrations and maintenance of effective dose to maximize curing effects with minimal side effects. Application of this technology to various body parts has been limited, especially in organs with curved surface, such as the brain and the eye. Herein, we report a flexible drug delivery microdevice (f-DDM) for controlled administration on the curved organ surface. The unique structure of the f-DDM consists of freestanding gold membranes over the multireservoir array was implemented by reversing the typical fabrication order of the reservoir and sealing membrane. We optimized the design of the f-DDM by a finite element analysis to prevent thermal damage during the laser transfer and the applying current density for reliable drug release through an electrochemical analysis. The wireless power transfer system was applied to f-DDM, which shows stable wirelessly powered operation. The f-DDM was flexible enough to be implantable on the curved cerebral cortex and successfully adopted for delivery of two different chemicals or prevention of seizure activity using an anti-epileptic drug. Our study opens a new avenue for the controlled, region-specific, and combinatorial application of drugs, the key factors for precision medicine.
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| 8. |
- Aubert, Salome, et al.
(författare)
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Global Matrix 3.0 Physical Activity Report Card Grades for Children and Youth: Results and Analysis From 49 Countries
- 2018
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Ingår i: Journal of Physical Activity and Health. - : HUMAN KINETICS PUBL INC. - 1543-3080 .- 1543-5474. ; 15, s. S251-S273
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accumulating sufficient moderate to vigorous physical activity is recognized as a key determinant of physical, physiological, developmental, mental, cognitive, and social health among children and youth (aged 5-17 y). The Global Matrix 3.0 of Report Card grades on physical activity was developed to achieve a better understanding of the global variation in child and youth physical activity and associated supports. Methods: Work groups from 49 countries followed harmonized procedures to develop their Report Cards by grading 10 common indicators using the best available data. The participating countries were divided into 3 categories using the United Nations human development index (HDI) classification (low or medium, high, and very high HDI). Results: A total of 490 grades, including 369 letter grades and 121 incomplete grades, were assigned by the 49 work groups. Overall, an average grade of "C-," "D+," and "C-" was obtained for the low and medium HDI countries, high HDI countries, and very high HDI countries, respectively. Conclusions: The present study provides rich new evidence showing that the situation regarding the physical activity of children and youth is a concern worldwide. Strategic public investments to implement effective interventions to increase physical activity opportunities are needed.
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| 9. |
- Aubert, Salome, et al.
(författare)
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Report Card Grades on the Physical Activity of Children and Youth Comparing 30 Very High Human Development Index Countries
- 2018
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Ingår i: Journal of Physical Activity and Health. - : HUMAN KINETICS PUBL INC. - 1543-3080 .- 1543-5474. ; 15, s. S298-S314
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Tidskriftsartikel (refereegranskat)abstract
- Background: To better understand the childhood physical inactivity crisis, Report Cards on physical activity of children and youth were prepared concurrently in 30 very high Human Development Index countries. The aim of this article was to present, describe, and compare the findings from these Report Cards. Methods: The Report Cards were developed using a harmonized process for data gathering, assessing, and assigning grades to 10 common physical activity indicators. Descriptive statistics were calculated after converting letter grades to interval variables, and correlational analyses between the 10 common indicators were performed using Spearmans rank correlation coefficients. Results: A matrix of 300 grades was obtained with substantial variations within and between countries. Low grades were observed for behavioral indicators, and higher grades were observed for sources of influence indicators, indicating a disconnect between supports and desired behaviors. Conclusion: This analysis summarizes the level and context of the physical activity of children and youth among very high Human Development Index countries, and provides additional evidence that the situation regarding physical activity in children and youth is very concerning. Unless a major shift to a more active lifestyle happens soon, a high rate of noncommunicable diseases can be anticipated when this generation of children reaches adulthood.
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| 10. |
- Nous, Fay M. A., et al.
(författare)
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Comparison of the Diagnostic Performance of Coronary Computed Tomography Angiography-Derived Fractional Flow Reserve in Patients With Versus Without Diabetes Mellitus (from the MACHINE Consortium)
- 2019
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Ingår i: American Journal of Cardiology. - : EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. - 0002-9149 .- 1879-1913. ; 123:4, s. 537-543
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Tidskriftsartikel (refereegranskat)abstract
- Coronary computed tomography angiography-derived fractional flow reserve (CT-FFR) is a noninvasive application to evaluate the hemodynamic impact of coronary artery disease by simulating invasively measured FFR based on CT data. CT-FFR is based on the assumption of a normal coronary microvascular response. We assessed the diagnostic performance of a machine-learning based application for on-site computation of CT-FFR in patients with and without diabetes mellitus with suspected coronary artery disease. The study population included 75 diabetic and 276 nondiabetic patients who were enrolled in the MACHINE consortium. The overall diagnostic performance of coronary CT angiography alone and in combination with CT-FFR were analyzed with direct invasive FFR comparison in 110 coronary vessels of the diabetic group and in 415 coronary vessels of the nondiabetic group. Per-vessel discrimination of lesion-specific ischemia by CT-FFR was assessed by the area under the receiver operating characteristic curves. The overall diagnostic accuracy of CT-FFR in diabetic patients was 83% and in nondiabetic patients 75% (p = 0.088), showing improvement over the diagnostic accuracy of coronary CT angiography, which was 58% and 65% (p = 0.223), respectively. In addition, the diagnostic accuracy of CT-FFR was similar between diabetic and nondiabetic patients per stratified CT-FFR group (CT-FFR amp;lt; 0.6, 0.6 to 0.69, 0.7 to 0.79, 0.8 to 0.89, amp;gt;= 0.9). The area under the curves for diabetic and nondiabetic patients were also comparable, 0.88 and 0.82 (p = 0.113), respectively. In conclusion, on-site machine-learning CT-FFR analysis improved the diagnostic performance of coronary CT angiography and accurately discriminated lesion-specific ischemia in both diabetic and nondiabetic patients suspected of coronary artery disease. (C) 2018 Elsevier Inc. All rights reserved.
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