| 1. |
|
|
| 2. |
|
|
| 3. |
- Uhlin, F., et al.
(författare)
-
Endopeptidase Cleavage of Anti-Glomerular Basement Membrane Antibodies in vivo in Severe Kidney Disease: An Open-Label Phase 2a Study
- 2022
-
Ingår i: Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1046-6673 .- 1533-3450. ; 33:4, s. 829-838
-
Tidskriftsartikel (refereegranskat)abstract
- Background The prognosis for kidney survival is poor in patients presenting with circulating anti-glomerular basement membrane (GBM) antibodies and severe kidney injury. It is unknown if treat-ment with an endopeptidase that cleaves circulating and kidney bound IgG can alter the prognosis.& nbsp;Methods An investigator-driven phase 2a one-arm study (EudraCT 2016-004082-39) was performed in 17 hospitals in five European countries. A single dose of 0.25 mg/kg of imlifidase was given to 15 adults with circulating anti-GBM antibodies and an eGFR < 15 ml/min per 1.73m(2). All patients received standard treatment with cyclophosphamide and corticosteroids, but plasma exchange only if autoantibodies rebounded. The primary outcomes were safety and dialysis independency at 6 months.& nbsp;Results At inclusion, ten patients were dialysis dependent and the other five had eGFR levels between 7 and 14 ml/min per 1.73m(2). The median age was 61 years (range 19-77), six were women, and six were also positive for anti-neutrophil cytoplasmic antibodies. Then 6 hours after imlifidase infusion, all patients had anti-GBM antibodies levels below the reference range of a prespecified assay. At 6 months 67% (ten out of 15) were dialysis independent. This is significantly higher compared with 18% (nine out of 50) in a historical control cohort (P < 0.001, Fisher's exact test). Eight serious adverse events (including one death) were reported, none assessed as probably or possibly related to the study drug.& nbsp;Conclusions In this pilot study, the use of imlifidase was associated with a better outcome compared with earlier publications, without major safety issues, but the findings need to be confirmed in a randomized controlled trial.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Orme, L. C., et al.
(författare)
-
Climatic impacts on an Arctic lake since 1300 AD : a multi-proxy lake sediment reconstruction from Prins Karls Forland, Svalbard
- 2023
-
Ingår i: Journal of Paleolimnology. - : Springer Science and Business Media LLC. - 0921-2728 .- 1573-0417. ; 69:3, s. 249-266
-
Tidskriftsartikel (refereegranskat)abstract
- On the remote Arctic archipelago of Svalbard, there is increasing evidence of environmental impacts from climate change. The analysis of lake sedimentary records can be used to assess how strongly these recent changes have altered lake ecosystems. Sediments deposited during the last millennium from Lake Blokkvatnet, Prins Karls Forland, were analysed using a multiproxy approach, including stable isotope and X-ray fluorescence analysis. The results were interpreted as reflecting variability of (1) soil organic matter inwash, and potentially catchment and lake primary production, and (2) catchment weathering and erosion. Organic content began increasing after 1920 AD to the present, likely in response to warming. Earlier peaks of a similar magnitude occurred on three occasions since 1300 AD, with evidence indicating that these may have coincided with multidecadal-scale periods with higher temperatures, reduced sea ice and negative phases of the North Atlantic Oscillation. Catchment weathering and fluvial erosion began to increase around 1800 AD and peaked during the early twentieth century, potentially due to rising temperatures in autumn and winter causing increased liquid water availability. The records suggest that similar levels of erosion and weathering occurred between approximately 1300 and 1600 AD, spanning the transition from the Medieval Climate Anomaly to the Little Ice Age.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Andersson, F, et al.
(författare)
-
Comparison of the cost-effectiveness of budesonide and sodium cromoglycate in the management of childhood asthma in everyday clinical practice
- 2001
-
Ingår i: Annals of Allergy, Asthma & Immunology. - 1081-1206 .- 1534-4436. ; 86:5, s. 537-544
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Budesonide and sodium cromoglycate are both recommended as maintenance therapy for childhood asthma. Objective: To compare the cost-effectiveness of these two treatment strategies in clinical practice, in an open-label, pharmacoeconomic clinical trial. Methods: Health economics were evaluated in 138 children. ages 5 to 11 years, with unstable asthma not previously treated with corticosteroids or cromones. The asthma was stabilized during 4 to 6 weeks with budesonide 200 to 400 mug twice daily. The children were then randomly allocated to one of the two treatment strategies aiming at maintaining asthma control for 12 months, budesonide 400 mug/day (N = 69) or sodium cromoglycate 60 mg/day (N = 69). If asthma control was judged unsatisfactory, the doses were increased or the children were switched to the alternate treatment. Results: In children continuing on the same treatment, the degree of asthma control was similar in the two groups at study end. To maintain asthma control, 42% of cromoglycate children switched to budesonide, and then experienced a 14% increase in symptom-free days. No budesonide patient had to switch therapy because of lack of asthma control. Although not statistically significant, total annual cost per patient was 24% (Swedish kronor 4195, US $487, Euro 485) lower in the budesonide than the cromoglycate group, mainly due to a lower cost for asthma medication. Conclusions: A budesonide strategy for continued maintenance treatment, after an initial period of stabilizing treatment with budesonide, resulted in lower costs and less drug switches than did a strategy with sodium cromoglycate.
|
|
| 14. |
- Collins, J.W., et al.
(författare)
-
Assessing intra-operative ergonomics and workload in robotic surgery using inertia measuring unit sensors and validated questionnaires
- 2016
-
Ingår i: European urology. Supplement. - : Elsevier BV. - 1569-9056 .- 1878-1500. ; 15:7, s. 247-247
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION & OBJECTIVES: Robotic approaches have revolutionized radical prostatectomy surgery. The 3D vision and 10 fold magnification provide surgeons improved anatomical vision and more precise instrument control compared to open or laparoscopic techniques. However, the potential benefits of robotic techniques may have trade-offs in increased mental and physical demands for the surgeons. The assisting surgeon, also has the added workload of maintaining working postures that do not impede the robotic arms. This study implemented an innovative motion tracking tool along with validated workload questionnaires to assess the ergonomics and workload for both assisting and console surgeons during robotic surgery. MATERIAL & METHODS: Ten individual surgeons (6 console surgeons and 4 assistant surgeons) performed 15 robotic prostatectomy cases while wearing inertia measurement units (IMUs) to track neck, shoulder, and torso motion during each case. Postoperatively, participants completed a validated workload questionnaire (NASA-TLX). Analysis of variance was performed on all response variables that do not violate the assumption of normality to identify the impact of surgeon role (Console vs Assistant). RESULTS: Twenty-six questionnaires were completed from 13 assisting and 13 console surgeons over the 15 cases. Selfreported mental demand was 41% higher for surgeons at the console than assisting (p<0.05), but physical demand was not statistically different. Post-operative pain was reported highest for the right shoulder and neck and this was more frequently seen in the console surgeons. On IMU readings, the assisting surgeon experienced high neck flexion (>10 degrees) duration over 42% of the procedure compared to only 24% in the console surgeon. In general, surgeons posture on the console was primarily static resulting in fewer movements compared to assisting surgeons. Table 1 summarizes posture movements and durations of static postures. CONCLUSIONS: Postures were more ergonomic during console tasks than assisting by the operating table. However, the console constrains postures leading to static postural loads that have been associated with musculoskeletal symptoms for the neck, torso and shoulders.
|
|
| 15. |
|
|
| 16. |
- Fan, X., et al.
(författare)
-
Surgeons’ physical workload in open surgery versus robot-assisted surgery and nonsurgical tasks
- 2022
-
Ingår i: Surgical Endoscopy. - : Springer Nature. - 0930-2794 .- 1432-2218. ; 36:11, s. 8178-8194
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Musculoskeletal disorders (MSDs) are common among surgeons, and its prevalence varies among surgical modalities. There are conflicting results concerning the correlation between adverse work exposures and MSD prevalence in different surgical modalities. The progress of rationalization in health care may lead to job intensification for surgeons, but the literature is scarce regarding to what extent such intensification influences the physical workload in surgery. The objectives of this study were to quantify the physical workload in open surgery and compare it to that in (1) nonsurgical tasks and (2) two surgeon roles in robot-assisted surgery (RAS). Methods: The physical workload of 22 surgeons (12 performing open surgery and 10 RAS) was measured during surgical workdays, which includes trapezius muscle activity from electromyography, and posture and movement of the head, upper arms and trunk from inertial measurement units. The physical workload of surgeons in open surgery was compared to that in nonsurgical tasks, and to the chief and assistant surgeons in RAS, and to the corresponding proposed action levels. Mixed-effects models were used to analyze the differences. Results: Open surgery constituted more than half of a surgical workday. It was associated with more awkward postures of the head and trunk than nonsurgical tasks. It was also associated with higher trapezius muscle activity levels, less muscle rest time and a higher proportion of sustained low muscle activity than nonsurgical tasks and the two roles in RAS. The head inclination and trapezius activity in open surgery exceeded the proposed action levels. Conclusions: The physical workload of surgeons in open surgery, which exceeded the proposed action levels, was higher than that in RAS and that in nonsurgical tasks. Demands of increased operation time may result in higher physical workload for open surgeons, which poses an increased risk of MSDs. Risk-reducing measures are, therefore, needed.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Fotouhi, Omid, et al.
(författare)
-
Proteomics identifies neddylation as a potential therapy target in small intestinal neuroendocrine tumors
- 2019
-
Ingår i: Oncogene. - : NATURE PUBLISHING GROUP. - 0950-9232 .- 1476-5594. ; 38:43, s. 6881-6897
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with small intestinal neuroendocrine tumors (SI-NETs) frequently develop spread disease; however, the underlying molecular mechanisms of disease progression are not known and effective preventive treatment strategies are lacking. Here, protein expression profiling was performed by HiRIEF-LC-MS in 14 primary SI-NETs from patients with and without liver metastases detected at the time of surgery and initial treatment. Among differentially expressed proteins, overexpression of the ubiquitin-like protein NEDD8 was identified in samples from patients with liver metastasis. Further, NEDD8 correlation analysis indicated co-expression with RBX1, a key component in cullin-RING ubiquitin ligases (CRLs). In vitro inhibition of neddylation with the therapeutic agent pevonedistat (MLN4924) resulted in a dramatic decrease of proliferation in SI-NET cell lines. Subsequent mass spectrometry-based proteomics analysis of pevonedistat effects and effects of the proteasome inhibitor bortezomib revealed stabilization of multiple targets of CRLs including p27, an established tumor suppressor in SI-NET. Silencing of NEDD8 and RBX1 using siRNA resulted in a stabilization of p27, suggesting that the cellular levels of NEDD8 and RBX1 affect CRL activity. Inhibition of CRL activity, by either NEDD8/RBX1 silencing or pevonedistat treatment of cells resulted in induction of apoptosis that could be partially rescued by siRNA-based silencing of p27. Differential expression of both p27 and NEDD8 was confirmed in a second cohort of SI-NET using immunohistochemistry. Collectively, these findings suggest a role for CRLs and the ubiquitin proteasome system in suppression of p27 in SI-NET, and inhibition of neddylation as a putative therapeutic strategy in SI-NET.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
- Höög, Anders, et al.
(författare)
-
Somatostatin Receptor Expression in Renal Cell Carcinoma-A New Front in the Diagnostics and Treatment of Renal Cell Carcinoma
- 2018
-
Ingår i: Clinical Genitourinary Cancer. - : CIG MEDIA GROUP, LP. - 1558-7673 .- 1938-0682. ; 16:3, s. E517-E520
-
Tidskriftsartikel (refereegranskat)abstract
- Clinical Practice PointsRenal cell carcinoma (RCC) has a poor prognosis and is difficult to treat because of its ability to spread asymptomatically and its resistance to chemotherapy.In this patient series, we report that RCC metastases can be identified using gallium-68 (68Ga)-edotreotide (DOTATOC) positron emission tomography/computed tomography (PET/CT).Immunostaining of tumor tissue from primary RCC tumors and their matched adrenal, pancreatic, and thyroid metastases showed that RCC cells express membranous somatostatin receptor 2.These findings indicate that 68Ga-DOTATOC PET/CT can be used as a new imaging modality in management of metastatic RCC and might contribute to the development of new somatostatin analogue-based methods for the treatment of metastatic RCC.
|
|
| 28. |
- Jordan, Stanley C, et al.
(författare)
-
IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation.
- 2017
-
Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 377:5, s. 442-453
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Donor-specific antibodies create an immunologic barrier to transplantation. Current therapies to modify donor-specific antibodies are limited and ineffective in the most highly HLA-sensitized patients. The IgG-degrading enzyme derived from Streptococcus pyogenes (IdeS), an endopeptidase, cleaves human IgG into F(ab')2 and Fc fragments inhibiting complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, which suggests that IdeS might be useful for desensitization. We report on the combined experience of two independently performed open-label, phase 1-2 trials (conducted in Sweden and the United States) that assessed the efficacy of IdeS with regard to desensitization and transplantation of a kidney from an HLA-incompatible donor.METHODS: We administered IdeS to 25 highly HLA-sensitized patients (11 patients in Uppsala or Stockholm, Sweden, and 14 in Los Angeles) before the transplantation of a kidney from an HLA-incompatible donor. Frequent monitoring for adverse events, outcomes, donor-specific antibodies, and renal function was performed, as were renal biopsies. Immunosuppression after transplantation consisted of tacrolimus, mycophenolate mofetil, and glucocorticoids. Patients in the U.S. study also received intravenous immune globulin and rituximab after transplantation to prevent antibody rebound.RESULTS: Recipients in the U.S. study had a significantly longer cold ischemia time (the time elapsed between procurement of the organ and transplantation), a significantly higher rate of delayed graft function, and significantly higher levels of class I donor-specific antibodies than those in the Swedish study. A total of 38 serious adverse events occurred in 15 patients (5 events were adjudicated as being possibly related to IdeS). At transplantation, total IgG and HLA antibodies were eliminated. A total of 24 of 25 patients had perfusion of allografts after transplantation. Antibody-mediated rejection occurred in 10 patients (7 patients in the U.S. study and 3 in the Swedish study) at 2 weeks to 5 months after transplantation; all these patients had a response to treatment. One graft loss, mediated by non-HLA IgM and IgA antibodies, occurred.CONCLUSIONS: IdeS reduced or eliminated donor-specific antibodies and permitted HLA-incompatible transplantation in 24 of 25 patients. (Funded by Hansa Medical; ClinicalTrials.gov numbers, NCT02224820 , NCT02426684 , and NCT02475551 .).
|
|
| 29. |
- Jordan, Stanley C., et al.
(författare)
-
Imlifidase desensitization in crossmatch-positive, highly-sensitized kidney transplant recipients : Results of an international phase 2 trial (Highdes)
- 2021
-
Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 105:8, s. 1808-1817
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Highly-HLA sensitized patients have limited access to life-saving kidney transplantation due to a paucity of immunologically suitable donors. Imlifidase is a cysteine protease that cleaves IgG leading to a rapid decrease in antibody level and inhibition of IgG-mediated injury. This study investigates the efficacy and safety of imlifidase in converting a positive crossmatch test to negative, allowing highly sensitized patients to be transplanted with a living or deceased donor kidney.METHODS: This open-label, single arm, phase 2 trial conducted at five transplant centers, evaluated the ability of imlifidase to create a negative crossmatch test within 24 hours. Secondary endpoints included post-imlifidase DSA levels compared to pre-dose levels, renal function, and pharmacokinetic/pharmacodynamic profiles. Safety endpoints included adverse events and immunogenicity profile.RESULTS: 89.5% of the transplanted patients demonstrated conversion of baseline positive crossmatch to negative within 24 hours after imlifidase treatment. DSA most often rebounded 3-14 days post-imlifidase dose, with substantial interpatient variability. Patient survival was 100% with graft survival of 88.9% at 6 months. 38.9% had early biopsy proven antibody mediated rejection with onset 2-19 days post-transplantation. Serum IgG levels began to normalize after ~3-7 days post-transplantation. Anti-drug antibody levels were consistent with previous studies. Seven adverse events in six patients were classified as possibly or probably related to treatment and were mild-moderate in severity.CONCLUSIONS: Imlifidase was well tolerated, converted positive crossmatches to negative, and enabled patients with a median cPRA of 99.83% to undergo kidney transplantation resulting in good kidney function and graft survival at 6 months.
|
|
| 30. |
- Järnum, S., et al.
(författare)
-
Effects of IdeS on HLA-SAB, C1q-SAB and CDC-XM
- 2018
-
Ingår i: American Journal of Transplantation. - : John Wiley & Sons. - 1600-6135 .- 1600-6143. ; 18:S4: Oral Abstracts, s. 370-371
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 31. |
- Kjellman, Christian, et al.
(författare)
-
Outcomes at 3 years posttransplant in imlifidase-desensitized kidney transplant patients
- 2021
-
Ingår i: American Journal of Transplantation. - : Elsevier. - 1600-6135 .- 1600-6143. ; 21:12, s. 3907-3918
-
Tidskriftsartikel (refereegranskat)abstract
- Imlifidase is a cysteine proteinase which specifically cleaves IgG, inhibiting Fc-mediated effector function within hours of administration. Imlifidase converts a positive crossmatch to a potential donor (T cell, B cell, or both), to negative, enabling transplantation to occur between previously HLA incompatible donor-recipient pairs. To date, 39 crossmatch positive patients received imlifidase prior to a kidney transplant in four single-arm, open-label, phase 2 studies. At 3 years, for patients who were AMR+ compared to AMR-, death-censored allograft survival was 93% vs 77%, patient survival was 85% vs 94%, and mean eGFR was 49 ml/min/1.73 m2 vs 61 ml/min/1.73 m2 , respectively. The incidence of AMR was 38% with most episodes occurring within the first month post-transplantation. Sub-analysis of patients deemed highly sensitized with cPRA ≥ 99.9%, and unlikely to be transplanted who received crossmatch-positive, deceased donor transplants had similar rates of patient survival, graft survival, and eGFR but a higher rate of AMR. These data demonstrate that outcomes and safety up to 3 years in recipients of imlifidase-enabled allografts is comparable to outcomes in other highly sensitized patients undergoing HLA-incompatible transplantation. Thus, imlifidase is a potent option to facilitate transplantation among patients who have a significant immunologic barrier to successful kidney transplantation.
|
|
| 32. |
- Kjellman, M., et al.
(författare)
-
A Plasma Protein Biomarker Strategy for Detection of Small Intestinal Neuroendocrine Tumors
- 2021
-
Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 111:9, s. 840-849
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Small intestinal neuroendocrine tumors (SI-NETs) are difficult to diagnose in the early stage of disease. Current blood biomarkers such as chromogranin A (CgA) and 5-hydroxyindolacetic acid have low sensitivity (SEN) and specificity (SPE). This is a first preplanned interim analysis (Nordic non-interventional, prospective, exploratory, EXPLAIN study [NCT02630654]). Its objective is to investigate if a plasma protein multi-biomarker strategy can improve diagnostic accuracy (ACC) in SI-NETs. Methods: At the time of diagnosis, before any disease-specific treatment was initiated, blood was collected from patients with advanced SI-NETs and 92 putative cancer-related plasma proteins from 135 patients were analyzed and compared with the results of age- and sex-matched controls (n = 143), using multiplex proximity extension assay and machine learning techniques. Results: Using a random forest model including 12 top ranked plasma proteins in patients with SI-NETs, the multi-biomarker strategy showed SEN and SPE of 89 and 91%, respectively, with negative predictive value (NPV) and positive predictive value (PPV) of 90 and 91%, respectively, to identify patients with regional or metastatic disease with an area under the receiver operator characteristic curve (AUROC) of 99%. In 30 patients with normal CgA concentrations, the model provided a diagnostic SPE of 98%, SEN of 56%, and NPV 90%, PPV of 90%, and AUROC 97%, regardless of proton pump inhibitor intake. Conclusion: This interim analysis demonstrates that a multi-biomarker/machine learning strategy improves diagnostic ACC of patients with SI-NET at the time of diagnosis, especially in patients with normal CgA levels. The results indicate that this multi-biomarker strategy can be useful for early detection of SI-NETs at presentation and conceivably detect recurrence after radical primary resection.
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
- Kjellman, P, et al.
(författare)
-
Predictors of outcome in patients with papillary thyroid carcinoma
- 2006
-
Ingår i: European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. - : Elsevier BV. - 0748-7983. ; 32:3, s. 345-352
-
Tidskriftsartikel (refereegranskat)
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
- Locock, Andrew J., et al.
(författare)
-
New mineral names
- 2006
-
Ingår i: American Mineralogist. - 0003-004X .- 1945-3027. ; 91:11-12, s. 1945-1954
-
Tidskriftsartikel (refereegranskat)
|
|
| 45. |
|
|
| 46. |
- McCracken, Joselle M., et al.
(författare)
-
3D-Printed Hydrogel Composites for Predictive Temporal (4D) Cellular Organizations and Patterned Biogenic Mineralization
- 2019
-
Ingår i: Advanced Healthcare Materials. - : WILEY. - 2192-2640 .- 2192-2659. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Materials chemistries for hydrogel scaffolds that are capable of programming temporal (4D) attributes of cellular decision-making in supported 3D microcultures are described. The scaffolds are fabricated using direct-ink writing (DIW)-a 3D-printing technique using extrusion to pattern scaffolds at biologically relevant diameters (<= 100 mu m). Herein, DIW is exploited to variously incorporate a rheological nanoclay, Laponite XLG (LAP), into 2-hydroxyethyl methacrylate (HEMA)-based hydrogels-printing the LAP-HEMA (LH) composites as functional modifiers within otherwise unmodified 2D and 3D HEMA microstructures. The nanoclay-modified domains, when tested as thin films, require no activating (e.g., protein) treatments to promote robust growth compliances that direct the spatial attachment of fibroblast (3T3) and preosteoblast (E1) cells, fostering for the latter a capacity to direct long-term osteodifferentiation. Cell-to-gel interfacial morphologies and cellular motility are analyzed with spatial light interference microscopy (SLIM). Through combination of HEMA and LH gels, high-resolution DIW of a nanocomposite ink (UniH) that translates organizationally dynamic attributes seen with 2D gels into dentition-mimetic 3D scaffolds is demonstrated. These analyses confirm that the underlying materials chemistry and geometry of hydrogel nanocomposites are capable of directing cellular attachment and temporal development within 3D microcultures-a useful material system for the 4D patterning of hydrogel scaffolds.
|
|
| 47. |
- McCracken, Joselle M., et al.
(författare)
-
Ionic Hydrogels with Biomimetic 4D-Printed Mechanical Gradients : Models for Soft-Bodied Aquatic Organisms
- 2019
-
Ingår i: Advanced Functional Materials. - : WILEY-V C H VERLAG GMBH. - 1616-301X .- 1616-3028. ; 29:28
-
Tidskriftsartikel (refereegranskat)abstract
- Direct-ink writing (DIW), a rapidly growing and advancing form of additive manufacturing, provides capacities for on-demand tailoring of materials to meet specific requirements for final designs. The penultimate challenge faced with the increasing demand of customization is to extend beyond modification of shape to create 4D structures, dynamic 3D structures that can respond to stimuli in the local environment. Patterning material gradients is foundational for assembly of 4D structures, however, there remains a general need for useful materials chemistries to generate gray scale gradients via DIW. Here, presented is a simple materials assembly paradigm using DIW to pattern ionotropic gradients in hydrogels. Using structures that architecturally mimic sea-jelly organisms, the capabilities of spatial patterning are highlighted as exemplified by selectively programming the valency of the ion-binding agents. Spatial gradients, when combined with geometry, allow for programming the flexibility and movement of iron oxide nanoparticle-loaded ionotropic hydrogels to generate 4D-printed structures that actuate in the presence of local magnetic fields. This work highlights approaches to 4D design complexity that exploits 3D-printed gray-scale/gradient mechanics.
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
- Myklebust, MP, et al.
(författare)
-
Serum miR371 in testicular germ cell cancer before and after orchiectomy, assessed by digital-droplet PCR in a prospective study
- 2021
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 15582-
-
Tidskriftsartikel (refereegranskat)abstract
- MicroRNA-371a-3p (miR371) has been suggested as a sensitive biomarker in testicular germ cell cancer (TGCC). We aimed to compare miR371 with the classical biomarkers α-fetoprotein (AFP) and β-human chorionic gonadotropin (hCGβ). Overall, 180 patients were prospectively enrolled in the study, with serum samples collected before and after orchiectomy. We compared the use of digital droplet PCR (RT-ddPCR) with the quantitative PCR used by others for detection of miR371. The novel RT-ddPCR protocol showed high performance in detection of miR371 in serum samples. In the study cohort, miR371 was measured using RT-ddPCR. MiR371 detected CS1 of the seminoma and the non-seminoma sub-types with a sensitivity of 87% and 89%, respectively. The total sensitivity was 89%. After orchiectomy, miR371 levels declined in 154 of 159 TGCC cases. The ratio of miR371 pre- and post-orchiectomy was 20.5 in CS1 compared to 6.5 in systemic disease. AFP and hCGβ had sensitivities of 52% and 51% in the non-seminomas. MiR371 is a sensitive marker that performs better than the classical markers in all sub-types and clinical stages. Especially for the seminomas CS1, the high sensitivity of miR371 in detecting TGCC cells may have clinical implications.
|
|
