| 1. |
|
|
| 2. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
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.
|
|
| 3. |
- Lensink, Marc F., et al.
(författare)
-
Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment
- 2023
-
Ingår i: Proteins. - : WILEY. - 0887-3585 .- 1097-0134.
-
Tidskriftsartikel (refereegranskat)abstract
- We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average similar to 70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21 941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their five best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% of the targets compared to 8% two years earlier. This remarkable improvement is due to the wide use of the AlphaFold2 and AlphaFold2-Multimer software and the confidence metrics they provide. Notably, expanded sampling of candidate solutions by manipulating these deep learning inference engines, enriching multiple sequence alignments, or integration of advanced modeling tools, enabled top performing groups to exceed the performance of a standard AlphaFold2-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem.
|
|
| 4. |
- Mavroidis, Panayiotis, et al.
(författare)
-
Comparison of the helical tomotherapy and MLC-based IMRT radiation modalities in treating brain and cranio-spinal tumors.
- 2009
-
Ingår i: Technology in Cancer Research & Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 8:1, s. 3-14
-
Tidskriftsartikel (refereegranskat)abstract
- The investigation of the clinical efficacy and effectiveness of Intensity Modulated Radiotherapy (IMRT) using Multileaf Collimators (MLC) and Helical Tomotherapy (HT) has been an issue of increasing interest over the past few years. In order to assess the suitability of a treatment plan, dosimetric criteria such as dose-volume histograms (DVH), maximum, minimum, mean, and standard deviation of the dose distribution are typically used. Nevertheless, the radiobiological parameters of the different tumors and normal tissues are often not taken into account. The use of the biologically effective uniform dose (D=) together with the complication-free tumor control probability (P(+)) were applied to evaluate the two radiation modalities. Two different clinical cases of brain and cranio-spinal axis cancers have been investigated by developing a linac MLC-based step-and-shoot IMRT plan and a Helical Tomotherapy plan. The treatment plans of the MLC-based IMRT were developed on the Philips treatment planning station using the Pinnacle 7.6 software release while the dedicated Tomotherapy treatment planning station was used for the HT plan. With the use of the P(+) index and the D(=) concept as the common prescription point, the different treatment plans were compared based on radiobiological measures. The tissue response probabilities were plotted against D(=) for a range of prescription doses. The applied plan evaluation method shows that in the brain cancer, the HT treatment gives slightly better results than the MLC-based IMRT in terms of optimum expected clinical outcome (P(+) of 66.1% and 63.5% for a D(=) to the PTV of 63.0 Gy and 62.0 Gy, respectively). In the cranio-spinal axis cancer, the HT plan is significantly better compared to the MLC-based IMRT plan over the clinically useful dose prescription range (P(+) of 84.1% and 28.3% for a D(=) to the PTV of 50.6 Gy and 44.0 Gy, respectively). If a higher than 5% risk for complications could be allowed, the complication-free tumor control could be increased by almost 30% compared to the initial dose prescription. In comparison to MLC based-IMRT, HT can better encompass the often large PTV while minimizing the volume of the OARs receiving high dose. A radiobiological treatment plan evaluation can provide a closer association of the delivered treatment with the clinical outcome by taking into account the dose-response relations of the irradiated tumors and normal tissues. The use of P - (D=) diagrams can complement the traditional tools of evaluation such as DVHs, in order to compare and effectively evaluate different treatment plans.
|
|
| 5. |
- Mavroidis, Panayiotis, et al.
(författare)
-
Treatment plan comparison between helical tomotherapy and MLC-based IMRT using radiobiological measures.
- 2007
-
Ingår i: Phys Med Biol. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 52:13, s. 3817-36
-
Tidskriftsartikel (refereegranskat)abstract
- The rapid implementation of advanced treatment planning and delivery technologies for radiation therapy has brought new challenges in evaluating the most effective treatment modality. Intensity-modulated radiotherapy (IMRT) using multi-leaf collimators (MLC) and helical tomotherapy (HT) are becoming popular modes of treatment delivery and their application and effectiveness continues to be investigated. Presently, there are several treatment planning systems (TPS) that can generate and optimize IMRT plans based on user-defined objective functions for the internal target volume (ITV) and organs at risk (OAR). However, the radiobiological parameters of the different tumours and normal tissues are typically not taken into account during dose prescription and optimization of a treatment plan or during plan evaluation. The suitability of a treatment plan is typically decided based on dosimetric criteria such as dose-volume histograms (DVH), maximum, minimum, mean and standard deviation of the dose distribution. For a more comprehensive treatment plan evaluation, the biologically effective uniform dose (D) is applied together with the complication-free tumour control probability (P(+)). Its utilization is demonstrated using three clinical cases that were planned with two different forms of IMRT. In this study, three different cancer types at different anatomical sites were investigated: head and neck, lung and prostate cancers. For each cancer type, a linac MLC-based step-and-shoot IMRT plan and a HT plan were developed. The MLC-based IMRT treatment plans were developed on the Philips treatment-planning platform, using the Pinnacle 7.6 software release. For the tomotherapy HiArt plans, the dedicated tomotherapy treatment planning station was used, running version 2.1.2. By using D as the common prescription point of the treatment plans and plotting the tissue response probabilities versus D for a range of prescription doses, a number of plan trials can be compared based on radiobiological measures. The applied plan evaluation method shows that in the head and neck cancer case the HT treatment gives better results than MLC-based IMRT in terms of expected clinical outcome P(+) of 62.2% and 46.0%, D to the ITV of 72.3 Gy and 70.7 Gy, respectively). In the lung cancer and prostate cancer cases, the MLC-based IMRT plans are better over the clinically useful dose prescription range. For the lung cancer case, the HT and MLC-based IMRT plans give a P(+) of 66.9% and 72.9%, D to the ITV of 64.0 Gy and 66.9 Gy, respectively. Similarly, for the prostate cancer case, the two radiation modalities give a P(+) of 68.7% and 72.2%, D to the ITV of 86.0 Gy and 85.9 Gy, respectively. If a higher risk of complications (higher than 5%) could be allowed, the complication-free tumour control could increase by over 40%, 2% and 30% compared to the initial dose prescription for the three cancer cases, respectively. Both MLC-based IMRT and HT can encompass the often-large ITV required while they minimize the volume of the organs at risk receiving high doses. Radiobiological evaluation of treatment plans may provide an improved correlation of the delivered treatment with the clinical outcome by taking into account the dose-response characteristics of the irradiated targets and normal tissues. There may exist clinical cases, which may look dosimetrically similar but in radiobiological terms may be quite different. In such situations, traditional dose-based evaluation tools can be complemented by the use of P(+)--D diagrams to effectively evaluate and compare treatment plans.
|
|
| 6. |
- Roland, Teboh, et al.
(författare)
-
Tradeoffs for Assuming Rigid Target Motion in Mlc-Based Real Time Target Tracking Radiotherapy : A Dosimetric and Radiobiological Analysis
- 2010
-
Ingår i: Technology in Cancer Research & Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 9:2, s. 199-210
-
Tidskriftsartikel (refereegranskat)abstract
- We report on our assessment of two types of real time target tracking modalities for lung cancer radiotherapy namely (1) single phase propagation (SPP) where motion compensation assumes a rigid target and (2) multi-phase propagation (MPP) where motion compensation considers a deformable target. In a retrospective study involving 4DCT volumes from six (n=6) previously treated lung cancer patients, four-dimensional treatment plans representative of the delivery scenarios were generated per modality and the corresponding dose distributions were derived. The modalities were then evaluated (a) Dosimetrically for target coverage adequacy and normal tissue sparing by computing the mean GTV dose, relative conformity gradient index (CGI), mean lung dose (MLD) and lung V-20; (b) Radiobiologically by calculating the biological effective uniform dose ((sic)) for the target and organs at risk (OAR) and the complication free tumor control probability (P+). As a reference for the comparative study, we included a 40 Static modality, which was a conventional approach to account for organ motion and involved the use of individualized motion margins. With reference to the 4D Static modality, the average percent decrease in lung V-20 and MLD were respectively (13.1 +/- 6.9) % and (11.4 +/- 5.6) % for the MPP modality, whereas for the SPP modality they were (9.4 +/- 6.2) % and (7.2 +/- 4.7) %. On the other hand, the CGI was observed to improve by 15.3 +/- 13.2 and 9.6 +/- 10.0 points for the MPP and SPP modalities, respectively while the mean GTV dose agreed to better than 3% difference across all the modalities. A similar trend was observed in the radiobiological analysis where the P+ improved on average by (6.7 +/- 4.9) % and (4.1 +/- 3.6) % for the MPP and SPP modalities, respectively while the (sic) computed for the OAR decreased on average by (6.2 +/- 3.6) % and (3.8 +/- 3.5) % for the MPP and SPP tracking modalities, respectively. The (sic) calculated for the GTV for all the modalities was in agreement to better than 2% difference. In general, respiratory motion induces target displacement and deformation and therefore the complex MPP real time target tracking modality is the preferred. On the other hand, the SPP approach affords simplicity in implementation at the expense of failing to account for target deformation. Radiobiological and dosimetric analyses enabled us to investigate the consequences of failing to compensate for deformation and assess the impact if any on the clinical outcome. While it is not possible to draw any general conclusions on a small patient cohort, our study suggests that the two tracking modalities can lead to comparable clinical outcomes and as expected are advantageous when compared with the static conventional modality.
|
|
| 7. |
- Shi, Xue, et al.
(författare)
-
A strong, biodegradable, and recyclable all-lignocellulose fabricated triboelectric nanogenerator for self-powered disposable medical monitoring
- 2023
-
Ingår i: Journal of Materials Chemistry A. - 2050-7488 .- 2050-7496. ; 11:22, s. 11730-11739
-
Tidskriftsartikel (refereegranskat)abstract
- The growing demand for fast, reliable, and accessible information in the vastly connected world makes disposable sensors increasingly important. However, reducing their costs, environmental impact, and usability remains challenging. Here, we report a low-cost, biodegradable, and recyclable all-lignocellulosic triboelectric nanogenerator (AL-TENG) for self-powered disposable medical monitoring. Based on a facile in situ lignin regeneration & chemical crosslinking modification strategy, a high-performance lignocellulosic bioplastic is synthesized from resource-abundant and renewable biomass for fabricating the AL-TENG. The whole device has a low environmental impact as it can be easily recycled and biodegraded at its end-of-life. Furthermore, a self-powered smart ward system and a self-powered contactless medical monitoring system are developed to improve the convenience for patients and reduce the risk of mutual infection. This work can expand the application of self-powered systems to disposable medical sensing, which may greatly promote the development of intelligent wards and disposable electronics.
|
|
| 8. |
- Stathakis, Sotirios, et al.
(författare)
-
gamma(+) index : A new evaluation parameter for quantitative quality assurance
- 2014
-
Ingår i: Computer Methods and Programs in Biomedicine. - : Elsevier BV. - 0169-2607 .- 1872-7565. ; 114:1
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The accuracy dose delivery and the evaluation of differences between calculated and delivered dose distributions, has been studied by several groups. The aim of this investigation is to extend the gamma index by including radiobiological information and to propose a new index that we will here forth refer to as the gamma plus (gamma(+)). Further more, to validate the robustness of this new index in performing a quality control analysis of an IMRT treatment plan using pure radiobiological measures such as the biologically effective uniform dose ((D) over bar) and complication-free tumor control probability (P+). Material and methods: A new quality assurance index, the (gamma(+)), is proposed based on the theoretical concept of gamma index presented by Low et al. (1998). In this study, the dose difference, including the radiobiological dose information (biological effective dose, BED) is used instead of just the physical dose difference when performing the gamma(+) calculation. An in-house software was developed to compare different dose distributions based on the gamma(+) concept. A test pattern for a two-dimensional dose comparison was built using the in-house software platform. The gamma(+) index was tested using planar dose distributions (exported from the treatment planning system) and delivered (film) dose distributions acquired in a solid water phantom using a test pattern and a theoretical clinical case. Furthermore, a lung cancer case for a patient treated with IMRT was also selected for the analysis. The respective planar dose distributions from the treatment plan and the film were compared based on the gamma(+) index and were evaluated using the radiobiological measures of P+ and (D) over bar. Results: The results for the test pattern analysis indicate that the gamma(+) index distributions differ from those of the gamma index since the former considers radiobiological parameters that may affect treatment outcome. For the theoretical clinical case, it is observed that the gamma(+) index varies for different treatment parameters (e.g. dose per fraction). The dose area histogram (DAH) from the plan and film dose distributions are associated with P+ values of 50.8% and 49.0%, for a (D) over bar to the target of 54.0 Gy and 53.3 Gy, respectively. Conclusion: The gamma(+) index shows advantageous properties in the quantitative evaluation of dose delivery and quality control of IMRT treatments because it includes information about the expected responses and radiobiological doses of the individual tissues.
|
|
| 9. |
- Su, Fan-Chi, et al.
(författare)
-
A graphic user interface toolkit for specification, report and comparison of dose-response relations and treatment plans using the biologically effective uniform dose
- 2010
-
Ingår i: Computer Methods and Programs in Biomedicine. - : Elsevier BV. - 0169-2607 .- 1872-7565. ; 100:1, s. 69-78
-
Tidskriftsartikel (refereegranskat)abstract
- A toolkit (BEUDcal) has been developed for evaluating the effectiveness and for predicting the outcome of treatment plans by calculating the biologically effective uniform dose (BEUD) and complication-free tumor control probability. The input for the BEUDcal is the differential dose-volume histograms of organs exported from the treatment planning system. A clinical database is built for the dose-response parameters of different tumors and normal tissues. Dose-response probabilities of all the examined organs are illustrated together with the corresponding BEUDs and the P+ values. Furthermore, BEUDcal is able to generate a report that simultaneously presents the radiobiological evaluation together with the physical dose indices, showing the complementary relation between the physical and radiobiological treatment plan analysis performed by BEUDcal. Comparisons between treatment plans for helical tomotherapy and multileaf collimator-based intensity modulated radiotherapy of a lung patient were demonstrated to show the versatility of BEUDcal in the assessment and report of dose-response relations.
|
|
