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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. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is 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 verify an autophagic response.
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| 4. |
- Mozes, Ferenc E., et al.
(författare)
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Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis
- 2023
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Ingår i: The Lancet Gastroenterology & Hepatology. - : ELSEVIER INC. - 2468-1253. ; 8:8, s. 704-713
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Tidskriftsartikel (refereegranskat)abstract
- Background Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD. Methods This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score >= 15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10 vs 10 to <20 vs >= 20 kPa; FIB-4: <1<middle dot>3 vs 1<middle dot>3 to <= 2<middle dot>67 vs >2<middle dot>67; NFS: <-1<middle dot>455 vs -1<middle dot>455 to <= 0<middle dot>676 vs >0<middle dot>676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.Findings Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44<middle dot>7%] were female, median age was 54 years [IQR 44-63), and 1161 [46<middle dot>1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5<middle dot>8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0<middle dot>0001 for all comparisons). The tAUC at 5 years were 0<middle dot>72 (95% CI 0<middle dot>62-0<middle dot>81) for histology, 0<middle dot>76 (0<middle dot>70-0<middle dot>83) for LSM-VCTE, 0<middle dot>74 (0<middle dot>64-0<middle dot>82) for FIB-4, and 0<middle dot>70 (0<middle dot>63-0<middle dot>80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression.Interpretation Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases.
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- Berman, Anne H., Professor, et al.
(författare)
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Transdiagnostic and tailored internet intervention to improve mental health among university students : Research protocol for a randomized controlled trial
- 2024
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Ingår i: Trials. - : Springer Nature. - 1745-6215. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Emerging adulthood is often associated with mental health problems. About one in three university students report symptoms of depression and anxiety that can negatively affect their developmental trajectory concerning work, intimate relationships, and health. This can interfere with academic performance, as mood and anxiety disorders are key predictors of dropout from higher education. A treatment gap exists, where a considerable proportion of students do not seek help for mood and anxiety symptoms. Offering internet interventions to students with mental health problems could reduce the treatment gap, increase mental health, and improve academic performance. A meta-analysis on internet interventions for university students showed small effects for depression and none for anxiety. Larger trials are recommended to further explore effects of guidance, transdiagnostic approaches, and individual treatment components.Methods: This study will offer 1200 university students in Sweden participation in a three-armed randomized controlled trial (RCT) evaluating a guided or unguided transdiagnostic internet intervention for mild to moderate depression and anxiety, where the waitlist control group accesses the intervention at 6-month follow-up. Students reporting suicidal ideation/behaviors will be excluded and referred to treatment within the existing healthcare system. An embedded study within the trial (SWAT) will assess at week 3 of 8 whether participants in the guided and unguided groups are at higher risk of failing to benefit from treatment. Those at risk will be randomized to an adaptive treatment strategy, or to continue the treatment as originally randomized. Primary outcomes are symptoms of depression and anxiety. Follow-ups will occur at post-treatment and at 6-, 12-, and 24-month post-randomization. Between-group outcome analyses will be reported, and qualitative interviews about treatment experiences are planned.Discussion: This study investigates the effects of a transdiagnostic internet intervention among university students in Sweden, with an adaptive treatment strategy employed during the course of treatment to minimize the risk of treatment failure. The study will contribute knowledge about longitudinal trajectories of mental health and well-being following treatment, taking into account possible gender differences in responsiveness to treatment. With time, effective internet interventions could make treatment for mental health issues more widely accessible to the student group.
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| 6. |
- Guex, Anne Geraldine, et al.
(författare)
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Highly porous scaffolds of PEDOT:PSS for bone tissue engineering
- 2017
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Ingår i: Acta Biomaterialia. - : ELSEVIER SCI LTD. - 1742-7061 .- 1878-7568. ; 62, s. 91-101
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Tidskriftsartikel (refereegranskat)abstract
- Conjugated polymers have been increasingly considered for the design of conductive materials in the field of regenerative medicine. However, optimal scaffold properties addressing the complexity of the desired tissue still need to be developed. The focus of this study lies in the development and evaluation of a conductive scaffold for bone tissue engineering. In this study PEDOT:PSS scaffolds were designed and evaluated in vitro using MC3T3-E1 osteogenic precursor cells, and the cells were assessed for distinct differentiation stages and the expression of an osteogenic phenotype. Ice-templated PEDOT:PSS scaffolds presented high pore interconnectivity with a median pore diameter of 53.6 +/- 5.9 mu m and a total pore surface area of 7.72 +/- 1.7 m(2).g(-1). The electrical conductivity, based on I-V curves, was measured to be 140 mu S.cm(-1) with a reduced, but stable conductivity of 6.1 mu S.cm(-1) after 28 days in cell culture media. MC3T3-E1 gene expression levels of ALPL, COL1A1 and RUNX2 were significantly enhanced after 4 weeks, in line with increased extracellular matrix mineralisation, and osteocalcin deposition. These results demonstrate that a porous material, based purely on PEDOT:PSS, is suitable as a scaffold for bone tissue engineering and thus represents a promising candidate for regenerative medicine. Statement of Significance Tissue engineering approaches have been increasingly considered for the repair of non-union fractions, craniofacial reconstruction or large bone defect replacements. The design of complex biomaterials and successful engineering of 3-dimensional tissue constructs is of paramount importance to meet this clinical need. Conductive scaffolds, based on conjugated polymers, present interesting candidates to address the piezoelectric properties of bone tissue and to induce enhanced osteogenesis upon implantation. However, conductive scaffolds have not been investigated in vitro in great measure. To this end, we have developed a highly porous, electrically conductive scaffold based on PEDOT:PSS, and provide evidence that this purely synthetic material is a promising candidate for bone tissue engineering. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd.
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| 7. |
- Lindmark, Gudrun, et al.
(författare)
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qRT-PCR analysis of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN in colon cancer lymph nodes : An improved method for assessment of tumor stage and prognosis
- 2024
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 154:3, s. 573-584
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Tidskriftsartikel (refereegranskat)abstract
- One fourth of colorectal cancer patients having curative surgery will relapse of which the majority will die. Lymph node (LN) metastasis is the single most important prognostic factor and a key factor when deciding on postoperative treatment. Presently, LN metastases are identified by histopathological examination, a subjective method analyzing only a small LN volume and giving no information on tumor aggressiveness. To better identify patients at risk of relapse we constructed a qRT-PCR test, ColoNode, that determines levels of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN mRNAs. Combined these biomarkers estimate the tumor cell load and aggressiveness allocating patients to risk categories with low (0, −1), medium (1), high (2) and very high (3) risk of recurrence. Here we present result of a prospective, national multicenter study including 196 colon cancer patients from 8 hospitals. On average, 21 LNs/patient, totally 4698 LNs, were examined by both histopathology and ColoNode. At 3-year follow-up, 36 patients had died from colon cancer or lived with recurrence. ColoNode identified all patients that were identified by histopathology and in addition 9 patients who were undetected by histopathology. Thus, 25% of the patients who recurred were identified by ColoNode only. Multivariate Cox regression analysis proved ColoNode (1, 2, 3 vs 0, −1) as a highly significant risk factor with HR 4.24 [95% confidence interval, 1.42-12.69, P =.01], while pTN-stage (III vs I/II) lost its univariate significance. In conclusion, ColoNode surpassed histopathology by identifying a significantly larger number of patients with future relapse and will be a valuable tool for decisions on postoperative treatment.
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| 8. |
- Luo, Yifei, et al.
(författare)
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Technology Roadmap for Flexible Sensors
- 2023
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Ingår i: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 17:6, s. 5211-5295
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Forskningsöversikt (refereegranskat)abstract
- Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.
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| 10. |
- Ritschl, Valentin, et al.
(författare)
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Educational readiness among health professionals in rheumatology: low awareness of EULAR offerings and unfamiliarity with the course content as major barriers-results of a EULAR-funded European survey
- 2023
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Ingår i: RMD Open. - : BMJ PUBLISHING GROUP. - 2056-5933. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundOngoing education of health professionals in rheumatology (HPR) is critical for high-quality care. An essential factor is education readiness and a high quality of educational offerings. We explored which factors contributed to education readiness and investigated currently offered postgraduate education, including the European Alliance of Associations for Rheumatology (EULAR) offerings.Methods and participantsWe developed an online questionnaire, translated it into 24 languages and distributed it in 30 European countries. We used natural language processing and the Latent Dirichlet Allocation to analyse the qualitative experiences of the participants as well as descriptive statistics and multiple logistic regression to determine factors influencing postgraduate educational readiness. Reporting followed the Checklist for Reporting Results of Internet E-Surveys guideline.ResultsThe questionnaire was accessed 3589 times, and 667 complete responses from 34 European countries were recorded. The highest educational needs were professional development, prevention and lifestyle intervention. Older age, more working experience in rheumatology and higher education levels were positively associated with higher postgraduate educational readiness. While more than half of the HPR were familiar with EULAR as an association and the respondents reported an increased interest in the content of the educational offerings, the courses and the annual congress were poorly attended due to a lack of awareness, comparatively high costs and language barriers.ConclusionsTo promote the uptake of EULAR educational offerings, attention is needed to increase awareness among national organisations, offer accessible participation costs, and address language barriers.
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