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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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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Jin, Ying-Hui, et al.
(författare)
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Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
- 2020
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Ingår i: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
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| 5. |
- Chen, Hui, et al.
(författare)
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Age- and sex-specific modifiable risk factor profiles of dementia : evidence from the UK Biobank
- 2023
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 38:1, s. 83-93
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Tidskriftsartikel (refereegranskat)abstract
- Dementia constitutes a worldwide concern. To characterize the age- and sex-specific modifiable risk factor profiles of dementia, we included 497,401 UK Biobank participants (mean age = 56.5 years) without dementia at baseline (2006–2010) and followed them until March 2021. Cox proportional hazard models were used to estimate the age- and sex-specific hazard ratios (HRs) of incident dementia associated with socioeconomic (less education and high Townsend deprivation index), lifestyle (non-moderate alcohol intake, current smoking, suboptimal diet, physical inactivity, and unhealthy sleep duration), and health condition factors (hypertension, diabetes, cardiovascular diseases, and depressive symptoms). We also calculated the population attributable fractions (PAFs) of these factors. During follow-up (mean = 11.6 years), we identified 6564 dementia cases. HRs for the risk factors were similar between the sexes, while most factors showed stronger associations among younger participants. For example, the HRs of smoking were 1.74 (95% CI: 1.23, 2.47) for individuals aged < 50 years, and 1.18 (1.05, 1.33) for those aged ≥ 65 years. Overall, 46.8% (37.4%, 55.2%) of dementia cases were attributable to the investigated risk factors. The PAFs of the investigated risk factors also decreased with age, but that for health condition risk factors decreased with lower magnitude than socioeconomic and lifestyle risk factors. The stronger associations and greater PAFs of several modifiable risk factors for dementia among younger adults than older participants underscored the importance of dementia prevention from an earlier stage across the adult life course.
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| 6. |
- Chen, Hui, et al.
(författare)
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Association of Long-Term Body Weight Variability With Dementia : A Prospective Study
- 2021
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 77:10, s. 2116-2122
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Tidskriftsartikel (refereegranskat)abstract
- Background: Body weight variability (BWV) refers to intraindividual weight loss and gain over a period. The association of long-term BWV with dementia remains unclear and whether this association is beyond body weight change is undetermined.Methods: In the Health and Retirement Study, a total of 5 547 dementia-free participants (56.7% women; mean [SD] age, 71.1 [3.2] years) at baseline (2008) were followed up to 8 years (mean = 6.8 years) to detect incident dementia. Body weight was self-reported biennially from 1992 to 2008. BWV was measured as the coefficient of variation utilizing the body weight reported 9 times across 16 years before baseline. Cox-proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI).Results: Among the 5 547 participants, a total of 427 incident dementia cases were identified during follow-up. Greater long-term BWV was significantly associated with a higher risk of dementia (HR comparing extreme quartiles: 2.01, 95% CI: 1.48-2.72; HR of each SD increment: 1.21, 95% CI: 1.10-1.32; p-trend < .001) independent of mean body weight and body weight change. This significant association was even observed for BWV estimated approximately 15 years preceding dementia diagnosis (HR of each SD increment: 1.13, 95% CI: 1.03-1.23) and was more pronounced for that closer to diagnosis.Conclusion: Our prospective study suggested that greater BWV may be a novel risk factor for dementia.
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| 7. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 8. |
- Meng, Qing-Ling, et al.
(författare)
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Anatomic study of maximum intensity projection of the membranous labyrinth and the internal auditory meatus- MRI scan in 16 Chinese adults
- 2007
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 127:11, s. 1150-6
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Tidskriftsartikel (refereegranskat)abstract
- CONCLUSION: Three-dimensional reconstruction of maximum intensity projection (MIP) might document objectively, stereoscopically and directly the minute structures of the membranous labyrinth and internal auditory meatus. In this study, we establish magnetic resonance imaging (MRI) measurement criteria of the inner ear in Chinese adults.OBJECTIVE: The goal of this study was to provide an anatomic basis for otolosurgery and neurosurgery in Chinese adults.MATERIALS AND METHODS: Sixteen healthy volunteer subjects were scanned by a GE-signa 1.5T MRI scanner. All original images were transferred to an MRI workstation and all the structures of the inner ear were reconstructed, rotated at various angles and measured with an MIP program.RESULTS: Anatomic structures of the membranous labyrinth and internal auditory meatus were well demonstrated in MIP images in all volunteers. All inner ear structures including utricle, saccule, cochlear duct, internal auditory meatus and three semicircular ducts produced high intensity signals.
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| 9. |
- Proletov, Ian, et al.
(författare)
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Primary and secondary glomerulonephritides 1.
- 2014
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 29 Suppl 3:May, s. 186-200
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Takeuchi, Fumihiko, et al.
(författare)
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Interethnic analyses of blood pressure loci in populations of East Asian and European descent
- 2018
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.
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