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| 2. |
- Adhikari, Subash, et al.
(author)
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A high-stringency blueprint of the human proteome
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Research review (peer-reviewed)abstract
- The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP’s tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.
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| 3. |
- Clincke, Marie-Francoise, et al.
(author)
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Very high density of Chinese hamster ovary cells in perfusion by alternating tangential flow or tangential flow filtration in WAVE bioreactorpart II : Applications for antibody production and cryopreservation
- 2013
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In: Biotechnology progress (Print). - : Wiley-Blackwell. - 8756-7938 .- 1520-6033. ; 29:3, s. 768-777
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Journal article (peer-reviewed)abstract
- A high cell density perfusion process of monoclonal antibody (MAb) producing Chinese hamster ovary (CHO) cells was developed in disposable WAVE Bioreactor using external hollow fiber (HF) filter as cell separation device. Tangential flow filtration (TFF) and alternating tangential flow (ATF) systems were compared and process applications of high cell density perfusion were studied here: MAb production and cryopreservation. Operations by perfusion using microfiltration (MF) or ultrafiltration (UF) with ATF or TFF and by fed-batch were compared. Cell densities higher than 108 cells/mL were obtained using UF TFF or UF ATF. The cells produced comparable amounts of MAb in perfusion by ATF or TFF, MF or UF. MAbs were partially retained by the MF using ATF or TFF but more severely using TFF. Consequently, MAbs were lost when cell broth was discarded from the bioreactor in the daily bleeds. The MAb cell-specific productivity was comparable at cell densities up to 1.3 x 108 cells/mL in perfusion and was comparable or lower in fed-batch. After 12 days, six times more MAbs were harvested using perfusion by ATF or TFF with MF or UF, compared to fed-batch and 28x more in a 1-month perfusion at 108 cells/mL density. Pumping at a recirculation rate up to 2.75 L/min did not damage the cells with the present TFF settings with HF short circuited. Cell cryopreservation at 0.5 x 108 and 108 cells/mL was performed using cells from a perfusion run at 108 cells/mL density. Cell resuscitation was very successful, showing that this system was a reliable process for cell bank manufacturing.
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| 4. |
- Högberg, Johan, 1994, et al.
(author)
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Relationship between hamstring strength and hop performance at 8 and 12 months after ACL reconstruction with hamstring tendon autografts
- 2024
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In: BMC SPORTS SCIENCE MEDICINE AND REHABILITATION. - 2052-1847. ; 16:1
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Journal article (peer-reviewed)abstract
- Background The relationship between hamstring strength and hop performance after anterior cruciate ligament (ACL) reconstruction with hamstring tendon (HT) autografts has not been well elucidated. The aim was to investigate the relationship between eccentric hamstring strength, assessed with the NordBord, and concentric hamstring strength, assessed with the Biodex, with hop performance at 8 and 12 months after ACL reconstruction.Methods Registry study. Patients >= 16 years who had undergone primary ACL reconstruction with HT autograft, followed by muscle strength and hop tests at 8 and 12 months were included. Correlations of the relative hamstring strength (Nm/kg or N/kg) and limb symmetry index (LSI) with hop performance were analyzed. Pearson's correlation coefficient, and coefficient of determination (r2) were used for statistical analysis.Results A total of 90 patients were included, of which 48 (53%) were women. The mean age at ACL reconstruction was 27.0 +/- 8.0 years. Relative hamstring strength had significant positive correlations with hop performance, ranging from r = 0.25-0.66, whereas hamstring strength LSI had significant positive correlations which ranged from r = 0.22-0.37 at 8 and 12 months after ACL reconstruction. At 12 months, the relative hamstring strength in the Biodex explained 32.5-43.6% of the hop performance in vertical hop height, hop for distance relative to height, and the total number of side hops, whereas the relative hamstring strength in the NordBord explained 15.2-23.0% of the hop performance.Conclusion The relative hamstring strength in the Biodex test explained 32.5-43.6% of the hop performance, whereas the relative hamstring strength in the NordBord explained 15.2-23.0%. Thus, our findings suggest that relative hamstring strength, especially in the hip-flexed position may be a better indicator of hop performance at 8 and 12 months after ACL reconstruction in patients treated with HT autograft.
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| 5. |
- Lindskog, Eric, et al.
(author)
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Generalized Playback Bar for Interactive Branched Video
- 2019
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In: PROCEEDINGS OF THE 27TH ACM INTERNATIONAL CONFERENCE ON MULTIMEDIA (MM19). - New York, NY, USA : ASSOC COMPUTING MACHINERY. - 9781450368896 ; , s. 2369-2377
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Conference paper (peer-reviewed)abstract
- During viewing of interactive branched video, users are asked to make viewing choices that impact the storyline of the video playback. This type of video puts the users in control of their viewing experiences and provides content creators with great flexibility how to personalize the viewing experience of individual viewers. However, in contrast to with traditional video, where the use of a playback bar is default for most - if not all - players, there currently does not exist any generic playback bar for branched video that helps visualize the upcoming branch choices. Instead, most branched video implementations are typically custom-made on a per-video basis (e.g., see custom-made Netflix and BBC movies) and do not use a playback bar. As an important step towards addressing this void, we present the first branched video player with a generalized playback bar that visualizes the tree-like video structure and the buffer levels of the different branches. The player is implemented in dash.js and is made public with this publication, is the first of its kind, and allows both the playback bar and the presentation of branch choices to be customized with regards to visual appearance, functionality, and the content itself. Furthermore, the design is generic (making it applicable to any video) and allows content creators to easily create large numbers of branched movies using a simple metafile format. Finally, and most importantly, we perform a three-phase user study in which we evaluate the playback bar, compare with alternative designs, and other branch-related features. The user study highlights the value of a branched video playback bar, and provides interesting insights into how it and other design customization features may best be integrated into a player.
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| 6. |
- Lindskog, Eric, et al.
(author)
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REEFT-360: Real-time Emulation and Evaluation Framework for Tile-based 360 Streaming under Time-varying Conditions
- 2021
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In: Proc. ACM Multimedia Systems Conference (ACM MMSys) 2021. - New York, NY, USA : ACM Digital Library. - 9781450384346 ; , s. 307-313
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Conference paper (peer-reviewed)abstract
- With 360° video streaming, the user's field of view (a.k.a. viewport) is at all times determined by the user's current viewing direction. Since any two users are unlikely to look in the exact same direction as each other throughout the viewing of a video, the frame-by-frame video sequence displayed during a playback session is typically unique. This complicates the direct comparison of the perceived Quality of Experience (QoE) using popular metrics such as the Multiscale-Structural Similarity (MS-SSIM). Furthermore, there is an absence of light-weight emulation frameworks for tiled-based 360° video streaming that allow easy testing of different algorithm designs and tile sizes. To address these challenges, we present REEFT-360, which consists of (1) a real-time emulation framework that captures tile-quality adaptation under time-varying bandwidth conditions and (2) a multi-step evaluation process that allows the calculation of MS-SSIM scores and other frame-based metrics, while accounting for the user's head movements. Importantly, the framework allows speedy implementation and testing of alternative head-movement prediction and tile-based prefetching solutions, allows testing under a wide range of network conditions, and can be used either with a human user or head-movement traces. The developed software tool is shared with the paper. We also present proof-of-concept evaluation results that highlight the importance of including a human subject in the evaluation.
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| 7. |
- Lindskog, Jakob, et al.
(author)
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Lower rates of return to sport in patients with generalised joint hypermobility two years after ACL reconstruction: a prospective cohort study.
- 2023
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In: BMC sports science, medicine & rehabilitation. - 2052-1847. ; 15:1
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Journal article (peer-reviewed)abstract
- Generalised joint hypermobility (GJH) has been associated with an increased risk of suffering an anterior cruciate ligament (ACL) injury. Patients with GJH exhibit lower muscle strength and poorer scores for patient-reported outcomes after ACL reconstruction, compared with patients without GJH. The aim of this study was to examine differences in the percentages of patients who return to sport (RTS) or pre-injury level of activity (RTP), muscle function and patient-reported outcomes at the time of RTS or RTP, as well as the time of RTS or RTP in patients with GJH compared with patients without GJH in the first two years after ACL reconstruction.This prospective study used data from an ACL- and rehabilitation-specific register located in Gothenburg, Sweden. Patients aged between 16 and 50, who had a primary ACL injury treated with reconstruction, were included. Data up to two years after ACL reconstruction were used and consisted of achieving RTS and RTP, results from isokinetic muscle function tests for knee extension and flexion and patient-reported outcomes (Knee Self-Efficacy Scale, Knee injury and Osteoarthritis Outcome Score and ACL-Return to Sport after Injury scale) at the time of RTS, as well as the time of RTP. A Beighton Score of ≥5/9 was used to define GJH. A Tegner Activity Scale of ≥6 was used to define RTS, while a Tegner equal to or above pre-injury level was used to define RTP.A total of 1,198 patients (54.7% women) with a mean age of 28.5±8.6 years were included. A smaller proportion of patients with GJH achieved RTS compared with patients without GJH (49.2% vs. 57.3%, Odds ratio: 0.720, p=0.041). Furthermore, patients with GJH were marginally less symmetrical on the knee extension strength test, expressed as a Limb Symmetry Index, at the time of RTP compared with patients without GJH (87.3±13.5 vs. 91.7±14.3, Cohen's d=0.142, p=0.022). No further differences were found between groups regarding any muscle function tests or patient-reported outcomes.A smaller proportion of patients with GJH achieved RTS compared with patients without GJH. Patients with GJH displayed less symmetrical knee extension strength at the time of RTP compared with patients without GJH.
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| 8. |
- Lindskog, Stefan, et al.
(author)
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Phenotypic expression of a family with multiple endocrine neoplasia type 2A due to a RET mutation at codon 618
- 2004
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In: The British journal of surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 91:6, s. 713-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: Multiple endocrine neoplasia type 2A (MEN2A) is caused by missense mutations in the RET proto-oncogene on chromosome 10. This paper reports the phenotypic expression of a family with MEN2A, in which serine substitutes for cysteine at codon 618 in exon 10 of the RET gene. It was first claimed that medullary thyroid cancer (MTC) with this rare mutation led to mild disease; this has recently been updated to intermediate-high risk, based on stratified genetic information. METHODS: The family was mapped over six generations. In 1971 family members were invited to join a screening programme. Genetic testing was started in 1994. RESULTS: Twenty-two individuals with MTC were identified, 16 by the screening programme. One screened patient had a phaeochromocytoma and four had hyperparathyroidism. At surgery for MTC 12 patients had local tumour metastases and two young patients also had liver metastases. No screened patient died from MTC during a mean observation time of 19 years. Six other family members were diagnosed with MTC by signs and symptoms, five of whom died from MTC. CONCLUSION: Because of the great interindividual differences in tumour aggressiveness within the family it is impossible to predict whether an individual gene carrier will have an aggressive MTC or not. This unpredictability is an additional argument, besides those obtained in stratified genetic studies, for operating on gene carriers at young age.
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| 9. |
- Morin, Eric, et al.
(author)
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Perivascular Neuropilin-1 expression is an independent marker of improved survival in renal cell carcinoma
- 2020
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In: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 250:4, s. 387-396
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Journal article (peer-reviewed)abstract
- Renal cell carcinoma (RCC) treatment has improved in the last decade with the introduction of drugs targeting tumor angiogenesis. However, the 5-year survival of metastatic disease is still only 10–15%. Here, we explored the prognostic significance of compartment-specific expression of Neuropilin 1 (NRP1), a co-receptor for vascular endothelial growth factor (VEGF). NRP1 expression was analyzed in RCC tumor vessels, in perivascular tumor cells, and generally in the tumor cell compartment. Moreover, complex formation between NRP1 and the main VEGF receptor, VEGFR2, was determined. Two RCC tissue microarrays were used; a discovery cohort consisting of 64 patients and a validation cohort of 314 patients. VEGFR2/NRP1 complex formation in cis (on the same cell) and trans (between cells) configurations was determined by in situ proximity ligation assay (PLA), and NRP1 protein expression in three compartments (endothelial cells, perivascular tumor cells, and general tumor cell expression) was determined by immunofluorescent staining. Expression of NRP1 in perivascular tumor cells was explored as a marker for RCC survival in the two RCC cohorts. Results were further validated using a publicly available gene expression dataset of clear cell RCC (ccRCC). We found that VEGFR2/NRP1 trans complexes were detected in 75% of the patient samples. The presence of trans VEGFR2/NRP1 complexes or perivascular NRP1 expression was associated with a reduced tumor vessel density and size. When exploring NRP1 as a biomarker for RCC prognosis, perivascular NRP1 and general tumor cell NRP1 protein expression correlated with improved survival in the two independent cohorts, and significant results were obtained also at the mRNA level using the publicly available ccRCC gene expression dataset. Only perivascular NRP1 expression remained significant in multivariable analysis. Our work shows that perivascular NRP1 expression is an independent marker of improved survival in RCC patients, and reduces tumor vascularization by forming complexes in trans with VEGFR2 in the tumor endothelium.
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| 10. |
- Morin, Eric, et al.
(author)
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VEGF receptor-2/neuropilin 1 trans-complex formation between endothelial and tumor cells is an independent predictor of pancreatic cancer survival
- 2018
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In: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 246:3, s. 311-322
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Journal article (peer-reviewed)abstract
- Unstable and dysfunctional tumor vasculature promotes cancer progression and spread. Signal transduction by the pro-angiogenic vascular endothelial growth factor (VEGF) receptor-2 (VEGFR2) is modulated by VEGFA-dependent complex formation with neuropilin 1 (NRP1). NRP1 expressed on tumor cells can form VEGFR2/NRP1 trans-complexes between tumor cells and endothelial cells which arrests VEGFR2 on the endothelial surface, thus interfering with productive VEGFR2 signaling. In mouse fibrosarcoma, VEGFR2/NRP1 trans-complexes correlated with reduced tumor vessel branching and reduced tumor cell proliferation. Pancreatic ductal adenocarcinoma (PDAC) strongly expressed NRP1 on both tumor cells and endothelial cells, in contrast to other common cancer forms. Using proximity ligation assay, VEGFR2/NRP1 trans-complexes were identified in human PDAC tumor tissue, and its presence was associated with reduced tumor vessel branching, reduced tumor cell proliferation, and improved patient survival after adjusting for other known survival predictors. We conclude that VEGFR2/NRP1 trans-complex formation is an independent predictor of PDAC patient survival.
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