| 1. |
- Brasko, Csilla, et al.
(författare)
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Intelligent image-based in situ single-cell isolation
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying heterogeneities within cell populations is important for many fields including cancer research and neurobiology; however, techniques to isolate individual cells are limited. Here, we describe a high-throughput, non-disruptive, and cost-effective isolation method that is capable of capturing individually targeted cells using widely available techniques. Using high-resolution microscopy, laser microcapture microscopy, image analysis, and machine learning, our technology enables scalable molecular genetic analysis of single cells, targetable by morphology or location within the sample.
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| 2. |
- Albshesh, Ahmad, et al.
(författare)
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Effectiveness of Third-Class Biologic Treatment in Crohn's Disease : A Multi-Center Retrospective Cohort Study
- 2021
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 10:13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn's disease (CD) failing anti- Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described.Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD.Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16-22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5).Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.
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| 3. |
- Chaparro, Maria, et al.
(författare)
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Surgery due to Inflammatory Bowel Disease During Pregnancy: Mothers and Offspring Outcomes From an ECCO Confer Multicentre Case Series [Scar Study]
- 2022
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Ingår i: Journal of Crohn's & Colitis. - Oxford, United Kingdom : Oxford University Press. - 1873-9946 .- 1876-4479. ; 16:9, s. 1428-1435
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Tidskriftsartikel (refereegranskat)abstract
- Aims: i] To evaluate the evolution of pregnancies and offspring after inflammatory bowel disease [IBD] surgery during pregnancy; and ii] to describe the indications, the surgical techniques, and the frequency of caesarean section concomitant with surgery.Methods: Patients operated on due to IBD during pregnancy after 1998 were included. Participating clinicians were asked to review their databases to identify cases. Data on patients demographics, IBD characteristics, medical treatments, IBD activity, pregnancy outcomes, surgery, delivery, and foetal and maternal outcomes, were recorded.Results: In all, 44 IBD patients were included, of whom 75% had Crohns disease; 18% of the surgeries were performed in the first trimester, 55% in the second, and 27% in the third trimester. One patient had complications during surgery, and 27% had postsurgical complications. No patient died. Of deliveries, 70% were carried out by caesarean section. There were 40 newborns alive. There were four miscarriages/stillbirths [one in the first, two in the second, and one in the third trimester]; two occurred during surgery, and another two occurred 2 weeks after surgery; 14% of the surgeries during the second trimester and 64% of those in the third trimester ended up with a simultaneous caesarean section or vaginal delivery. Of the 40 newborns, 61% were premature and 47% had low birth weight; 42% of newborns needed hospitalisation [25% in the intensive care unit].Conclusions: IBD surgery during pregnancy remains an extremely serious situation. Therefore, surgical management should be performed in a multidisciplinary team, involving gastroenterologists, colorectal surgeons, obstetricians, and neonatal specialists.
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| 4. |
- Hunashal, Yamanappa, et al.
(författare)
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Approaching Protein Aggregation and Structural Dynamics by Equilibrium and Nonequilibrium Paramagnetic Perturbation
- 2022
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 94:31, s. 10949-10958
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Tidskriftsartikel (refereegranskat)abstract
- PENELOP (Paramagnetic Equilibrium vs Nonequilibrium magnetization Enhancement or LOss Perturbation) is the presented nuclear magnetic resonance (NMR) approach to identify at once the location of proteins' exposed surface, hindered accessibility, and exchange processes occurring on a mu s-ms time scale. In addition to mapping the protein surface accessibility, the application of this method under specific conditions makes it possible to distinguish conformational mobility and chemical exchange processes, thereby providing an alternative to characterization by more demanding techniques (transverse relaxation dispersion, saturation transfer, and high-pressure NMR). Moreover, its high sensitivity enables studying samples at low, physiologically more relevant concentrations. Association, dynamics, and oligomerization are addressed by PENELOP for a component of SARS-CoV-2 replication transcription complex and an amyloidogenic protein.
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| 5. |
- Kiss, Anita, et al.
(författare)
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Synthesis of novel 17-triazolyl-androst-5-en-3-ol epimers via Cu(I)-catalyzed azide-alkyne cycloaddition and their inhibitory effect on 17 alpha-hydroxylase/ C-17,C-20-lyase
- 2018
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Ingår i: Steroids. - : Elsevier BV. - 0039-128X .- 1878-5867. ; 135, s. 79-91
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Tidskriftsartikel (refereegranskat)abstract
- The regioselective Cu(I)-catalyzed 1,3-dipolar cycloaddition of 17 alpha- and 17 beta-azidoandrost-5-en-3 beta-ol epimers (3b and 5b) with different terminal alkynes afforded novel 1,4-substituted triazolyl derivatives (8a-k and 9a-k). For the preparation of 5'-iodo-l',2',3'-triazoles (8m-n and 9m-n), an improved method was developed, directly from steroidal azides and terminal alkynes, in reaction mediated by Cul and IC1 as iodinating agents. Acetolysis and subsequent hydrolysis of 8n and 9n yielded 5'-hydroxy-l',2',3'-triazoles 8o and 9o. The inhibitory effect of 8a-o, 9a-o, 3, and 5 on rat testicular C-17,C-20-lyase was investigated by means of an in vitro radioincubation technique. The results revealed that the C-17 epimers of steroidal triazoles influence the C-17,C-20-lyase effect. Inhibitors were found only in the 17 alpha-triazolyl series (8a-o), whereas in the C-17 azide pair the 17 beta compound (5b) was more potent.
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| 6. |
- Molnár, Tamás, et al.
(författare)
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Comparison of complexes formed by a crustacean and a vertebrate trypsin with bovine pancreatic trypsin inhibitor - the key to achieving extreme stability?
- 2013
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Ingår i: The FEBS journal. - : Wiley. - 1742-4658 .- 1742-464X. ; 280:22, s. 5750-5763
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Tidskriftsartikel (refereegranskat)abstract
- This paper provides evidence for the extremely high resistance of a complex of crayfish trypsin (CFT) and bovine pancreatic trypsin inhibitor (BPTI) against heating and chemical denaturing agents such as sodium dodecyl sulfate (SDS) and urea. To dissociate this complex, 15min boiling in SDS was necessary, compared to a complex of bovine trypsin (BT) (EC 3.4.21.4) and BPTI, which dissociates in SDS without boiling. The CFT-BPTI complex remained stable even in 9m urea, while the BT-BPTI complex started to dissociate at concentrations of approximately 4m urea. The melting temperatures of the BT-BPTI and CFT-BPTI complexes, as determined by differential scanning calorimetry, were found to be 79.6 and 100.1°C, respectively. The behaviour of the apo-enzymes - CFT was found to have a less stable structure compared to BT - did not provide a definite indication regarding the differential effects on their stabilities. To explore the structural features responsible for this extreme stability, we crystallized CFT in complex with BPTI, and identified extended contacts compared to the BT-BPTI complex. Comparison of the B-factors of similar trypsin-trypsin inhibitor complexes suggests that molecular flexibility of the components is also required for the strong protein-protein interaction. Although the structural reason for the extreme stability of the CFT-BPTI complex is not yet fully understood, our study may be a starting point for the development of new protein complexes with enhanced stability.
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| 7. |
- Peyrin-Biroulet, Laurent, et al.
(författare)
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I-CARE, a European prospective cohort study assessing safety and effectiveness of biologics in inflammatory bowel disease
- 2023
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 21:3, s. 771-788.e10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with for anti-tumor necrosis factor and other biologics monotherapy as well as in combination with immunomodulators.METHODS: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study, to include patients with a diagnosis of Crohn's disease, ulcerative colitis or IBD unclassified established at least 3 months prior to enrollment.RESULTS: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6,169 (60.4%) patients with Crohn's disease, 3,853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving AZA/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one quarter of patients (26.8%) underwent prior IBD related surgery. Sixty-six % of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion, and 1.1% had a history of colonic, esophageal or uterine cervix high-grade dysplasia.CONCLUSION: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients.
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| 8. |
- Phillips, Frank, et al.
(författare)
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Orofacial Granulomatosis associated with Crohn's Disease : a multi-centre case series
- 2022
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Ingår i: Journal of Crohn's & Colitis. - : Elsevier. - 1873-9946 .- 1876-4479. ; 16:3, s. 430-435
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Orofacial granulomatosis (OFG) is a rare syndrome that may be associated with Crohn's disease (CD). We aimed to characterise this relationship and the management options in the biologic era.METHODS: This multicentre case series was supported by the European Crohn's and Colitis Organisation (ECCO), and performed as part of the Collaborative Network of Exceptionally Rare case reports (CONFER) project. Clinical data were recorded in a standardised collection form.RESULTS: This report includes 28 patients with OFG associated with CD: 14 males (mean age of 32 years, ±12.4 SD) and 14 females (40.3 years, ±21.0 SD). Non-oral upper gastrointestinal tract involvement was seen in 6 cases and perianal disease in 11. The diagnosis of OFG was made prior to CD diagnosis in 2 patients, concurrently in 8 and after CD diagnosis in 18. The distribution of OFG involved the lips in 16 cases and buccal mucosa in 18. Pain was present in 25 cases, with impaired swallowing or speaking in 6. Remission was achieved in 23 patients, notably with the use of anti-TNFs in 9 patients, vedolizumab in 1, ustekinumab in 1 and thalidomide in 2. A further 5 cases were resistant to therapies including anti-TNFs.CONCLUSION: OFG associated with CD may occur before, concurrently or after the diagnosis of CD. Perianal and UGI disease are common associations and there is a significant symptom burden in many. Remission can be obtained with a variety of immunosuppressive treatments, including several CD approved biologicals.
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| 9. |
- Piccinini, Filippo, et al.
(författare)
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Advanced Cell Classifier : User-Friendly Machine-Learning-Based Software for Discovering Phenotypes in High-Content Imaging Data
- 2017
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Ingår i: CELL SYSTEMS. - : CELL PRESS. - 2405-4712. ; 4:6, s. 651-
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Tidskriftsartikel (refereegranskat)abstract
- High-content, imaging-based screens now routinely generate data on a scale that precludes manual verification and interrogation. Software applying machine learning has become an essential tool to automate analysis, but these methods require annotated examples to learn from. Efficiently exploring large datasets to find relevant examples remains a challenging bottleneck. Here, we present Advanced Cell Classifier (ACC), a graphical software package for phenotypic analysis that addresses these difficulties. ACC applies machine-learning and image-analysis methods to high-content data generated by large-scale, cell-based experiments. It features methods to mine microscopic image data, discover new phenotypes, and improve recognition performance. We demonstrate that these features substantially expedite the training process, successfully uncover rare phenotypes, and improve the accuracy of the analysis. ACC is extensively documented, designed to be user-friendly for researchers without machine-learning expertise, and distributed as a free open-source tool at www.cellclassifier.org.
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