| 1. |
- Ahmed, Shafique, et al.
(författare)
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Terahertz probing of low-temperature degradation in zirconia bioceramics
- 2022
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Ingår i: Journal of The American Ceramic Society. - : Wiley. - 0002-7820 .- 1551-2916. ; 105:2, s. 1106-1115
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Tidskriftsartikel (refereegranskat)abstract
- ZrO2-based ceramics are widely used in biomedical applications due to its color, biocompatibility, and excellent mechanical properties. However, low-temperature degradation (LTD) introduces a potential risk for long-term reliability of these materials. The development of innovative nondestructive techniques, which can explore LTD in zirconia-derived compounds, is strongly required. Yttria stabilized zirconia, 3Y-TZP, is one of the well-developed ZrO2-based ceramics with improved resistance to LTD for dental crown and implant applications. Here, 3Y-TZP ceramic powders were pressed and sintered to study the LTD phenomenon by phase transition behavior. The LTD-driven tetragonal-to-monoclinic phase transition was confirmed by XRD. XPS analysis demonstrated that induced LTD reduced the oxygen vacancies which supports these findings. It is proved that after the degradation, the 3Y-TZP ceramics show the decreased dielectric permittivity at terahertz frequencies due to the crystallographic phase transformation. Terahertz nondestructive probe is a promising method to investigate LTD in zirconia ceramics.
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| 2. |
- He, Qinglong, et al.
(författare)
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Additive manufacturing of dense zirconia ceramics by fused deposition modeling via screw extrusion
- 2021
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Ingår i: Journal of the European Ceramic Society. - : Elsevier BV. - 0955-2219 .- 1873-619X. ; 41:1, s. 1033-1040
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Tidskriftsartikel (refereegranskat)abstract
- A fused deposition modeling(FDM)system via screw extrusion suitable for feeding granular feedstocks with high solid loading was developed. Key parameters included aspect ratio of the screw, the compression ratio and pitch etc. In order to get constant extruded mass flow and wire diameter a processing window was determined by optimizing the barrel temperature, the nozzle diameter and the screwing speed. Microstructural characterization coupled with flexural strength measurement revealed that a higher printing temperature was beneficial to the inter layer bonding. The sintered zirconia ceramic samples with 99% of theoretical density of the 3 mol% yttria stabilized tetragonal zirconia polycrystal (3Y-TZP) and flexural strength of 890 +/- 60 MPa was obtained. A set of zirconia ceramic parts with complex geometries and controllable dimensional accuracy was also successfully prepared for demonstrating the potential of the technique.
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| 3. |
- Li, Ting, et al.
(författare)
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Total genetic contribution assessment across the human genome
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying the overall magnitude of every single locus' genetic effect on the widely measured human phenome is of great challenge. We introduce a unified modelling technique that can consistently provide a total genetic contribution assessment (TGCA) of a gene or genetic variant without thresholding genetic association signals. Genome-wide TGCA in five UK Biobank phenotype domains highlights loci such as the HLA locus for medical conditions, the bone mineral density locus WNT16 for physical measures, and the skin tanning locus MC1R and smoking behaviour locus CHRNA3 for lifestyle. Tissue-specificity investigation reveals several tissues associated with total genetic contributions, including the brain tissues for mental health. Such associations are driven by tissue-specific gene expressions, which share genetic basis with the total genetic contributions. TGCA can provide a genome-wide atlas for the overall genetic contributions in each particular domain of human complex traits. Quantifying the effects of individual loci on the human phenome is a challenging task. Here, the authors introduce a modelling technique, TGCA, that assesses total genetic contribution per locus and apply this to UK Biobank phenotype domains, revealing top loci and links to tissue-specific gene expression.
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| 4. |
- Repetto, Linda, et al.
(författare)
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Genetic mechanisms of 184 neuro-related proteins in human plasma.
- 2023
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the genetic basis of neuro-related proteins is essential for dissecting the disease etiology of neuropsychiatric disorders and other complex traits and diseases. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits as well as complex diseases such as hypertension, high cholesterol, immune-related disorders, and psychiatric disorders. Integrating with established drug information, we validated 13 combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets for diseases and comorbidities. This consortium effort provides a large-scale proteogenomic resource for biomedical research.
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| 5. |
- Repetto, Linda, et al.
(författare)
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Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders.
- 2023
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Ingår i: Nature Portfolio. - : Research Square Platform LLC.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioral traits and the disease etiology of neuropsychiatric disorders. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits such as sleeping, smoking, feelings, alcohol intake, mental health, and psychiatric disorders. Integrating with established drug information, we validated 13 out of 13 matched combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets. This consortium effort provides a large-scale proteogenomic resource for biomedical research on human behaviors and other neuro-related phenotypes.
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| 6. |
- Xie, Hehan, et al.
(författare)
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3D gel printing of alumina ceramics followed by efficient multi-step liquid desiccant drying
- 2021
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Ingår i: Journal of the European Ceramic Society. - : Elsevier BV. - 0955-2219 .- 1873-619X. ; 41:13, s. 6634-6640
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Tidskriftsartikel (refereegranskat)abstract
- Dense alumina ceramics were additively manufactured efficiently through a 3D gel printing process. Hydroxyethyl cellulose (HEC) was applied to ensure the printability and rigid of the gel made from boehmite. A multi-step liquid desiccant drying method was implemented to improve the drying efficiency. The results showed that the solid loading and HEC addition were two useful parameters for adjusting the rheology properties of the gel to make it suitable for 3D printing. With polyethylene glycol(PEG) added as liquid desiccants, the printed bodies with section size of 10 mm could be dried within 26 h during which the deformation and crack formation was avoided despite a high linear shrinkage of 45 % was encountered. The successful preparation of dense monolithic alumna ceramics parts with an average grain size of 1 μm, 99 % of the theoretical density and a flexural strength of 380 ± 45 MPa indicated the potential of this process.
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| 7. |
- Yang, Zhijian, et al.
(författare)
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Genetic Landscape of the ACE2 Coronavirus Receptor
- 2022
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 30:SUPPL 1, s. 36-36
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Tidskriftsartikel (refereegranskat)abstract
- Background: SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood.Methods: We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.Results: We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells.Conclusions: Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.
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| 8. |
- Yasar, Ozlen F., et al.
(författare)
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The Carbonate and Sodium Environments in Precipitated and Biomimetic Calcium Hydroxy-Carbonate Apatite Contrasted with Bone Mineral : Structural Insights from Solid-State NMR
- 2021
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 125:19, s. 10572-10592
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral consists of calcium hydroxy-carbonate apatite (HCA) that incorporates other minor cation substituents, primarily Na+ (0.5-0.8 wt %). We examine the carbonate species in various HCA specimens with variable CO32- contents (4-10 wt %), encompassing phases prepared by precipitation and a biomimetic specimen formed from a bioactive glass inside a simulated body fluid as well as bone tissue from beagle dog. Using magic-angle spinning (MAS) nuclear magnetic resonance (NMR) along with infrared spectroscopy experiments, we identified and quantified carbonate anions replacing either hydroxyl (A-type CO32-) or phosphate (B-type CO32-) anions in the HCA lattice, along with the carbonate species present in the amorphous surface layer present at all synthetic and biogenic nanocrystalline HCA particles. Advanced C-13-based NMR experimentation enabled the selective detection of the minor (CO32-)-C-13 population of intact bone monoliths, whose C-13 NMR signals are otherwise swamped by those from collagen, unless chemically invasive deproteination procedures are invoked. The CO32- species present in 4 week- and 8 month-old bone of the alveolar process from beagle dog revealed mainly B-type lattice sites and carbonates present in the amorphous surface layer. No tissue aging effects were observed in the local CO32- environments. Likewise, NMR revealed very similar Na-23(+) parameters in HCA, regardless of its synthetic or biogenic origin or degree of structural order. A combination of interatomic-distance-sensitive MAS NMR experiments allowed the identification of the local environments of the various carbonate, phosphate, hydroxyl, and water species present in both the interior and the surface layer of the synthetic HCA particles. We highlight the similarities/differences in the chemical speciation and the spatial distribution of CO32- anions present in carbonate-bearing amorphous calcium phosphate (ACP) relative to the ACP-like surface layer of HCA and discuss the C-13 NMR peak assignments of the up to four coexisting CO32- populations in the synthetic/biogenic HCA phases.
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| 9. |
- Zhai, Yinghong, et al.
(författare)
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Cardiovascular Toxicity of Carfilzomib : The Real-World Evidence Based on the Adverse Event Reporting System Database of the FDA, the United States
- 2021
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Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media S.A.. - 2297-055X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carfilzomib, an effective proteasome inhibitor agent for the therapy of relapsed and refractory multiple myeloma, has been related to a significant number of cardiovascular events. However, patterns of cardiovascular complications associated with this agent remain poorly characterized in real-world settings.Objective: To gain further insight into the frequency, spectrum, clinical features, timing, and outcomes of carfilzomib-related cardiovascular toxicities.Methods: This disproportionality (case/non-case) study was conducted leveraging records from FAERS database from 2014 to 2019. Cardiovascular events were defined and broadly categorized eight entities using narrow version of the Standardized MedDRA Queries (SMQs). Reporting odds ratios (ROR) and information component (IC) were calculated to measure disproportionality. Additionally, statistical shrinkage was applied to reduce false-positive signals.Results: The final number of records involved was 28,479,963, with 3,370 records submitted for carfilzomib related cardiovascular events. Significant disproportionality association between carfilzomib administration and cardiovascular events was captured (IC025/ROR025 = 0.85/1.95) when exploring in the entire database. Upon further analysis, all eight broad categories of cardiovascular toxicities were disproportionately associated with carfilzomib with varying frequencies, time-to-onset, and severities. Cardiomyopathy-related complications (N = 1,301, 38.61%), embolic and thrombotic events (N = 821, 24.36%), and cardiac failure (N = 765, 22.70%) largely comprised the reported problems. Notably, the strongest signal was detected for cardiac failure (IC025/ROR025 = 1.33/2.59), followed by pulmonary hypertension (IC025/ROR025 = 1.19/2.34). Median onset time of cardiovascular events was 41days (Q1-Q3: 9-114 days), with the shortest median time being 16 days (Q1-Q3: 4-85 days) for ischemic heart disease, with the longest time being 68 days (Q1-Q3: 21-139 days) for embolic and thrombotic events. Torsade de pointes/QT prolongation was identified as a new complication (IC025/ROR025 = 0.33/1.29) and was particularly noteworthy for highest death proportion (44.11%).Conclusions: Treatment with carfilzomib can lead to severe and versatile cardiovascular events. Early and intensive monitoring is important, particularly in the first 3 months after carfilzomib initiation. Maximizing the benefit while reducing potential cardiovascular harms of carfilzomib should become a priority.
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| 10. |
- Zhai, Yinghong, et al.
(författare)
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Updated Insights on Cardiac and Vascular Risks of Proton Pump Inhibitors : A Real-World Pharmacovigilance Study
- 2022
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Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media S.A.. - 2297-055X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Proton pump inhibitors (PPIs) are among the most widely prescribed medications in clinical practice. However, there are also concerns about the potential risks of long-term PPI use. The present study aimed to examine the safety of PPIs and summarize their potential cardiac and vascular risks in a real-world setting.Methods: This pharmacovigilance study extracted records between January 2015 and December 2019 from the FDA Adverse Event Reporting System (FAERS) database. The association of seven PPI medications with cardiac and vascular events (CVEs) were evaluated. Two established pharmacovigilance methods, reporting odds ratio (ROR) and information components (IC) based statistical shrinkage, were used to measure disproportionality.Results: In total 62,140 CVE records associated with PPI use were investigated. Women showed a higher proportion (54.37%) of PPI-associated CVEs. The median time from PPI initiation to CVE onset was 97 [interquartile range (IQR): 8-491] days, with the shortest median time of 42 days (IQR: 2-277 days) for esomeprazole, and the longest time of 389 days (IQR: 0-525 days) for dexlansoprazole. Although PPIs were not associated with elevated CVE risks compared those of the whole database (IC025/ROR025 = -0.39/0.74), various signals emerged. Despite some similarities exist between the PPIs, their cardiac and vascular safety profiles varied significantly. Pantoprazole showed the broadest spectrum of signals, from thrombotic thrombocytopenic purpura (IC025/ROR025 = 0.01/1.08) to renal haemangioma (IC025/ROR025 = 3.14/9.58). Esomeprazole showed the second-broadest spectrum of toxicities, ranging from duodenal ulcer hemorrhage (IC025/ROR025 = 0.07/1.28) to hypertensive nephropathy (IC025/ROR025 = 4.09/18.72). Vascular signals were more dominant than cardiac signals, suggesting that vascular function was more heavily affected. Hypertensive nephropathy, renal haemangioma, renal artery stenosis, and renal infarct had strong signals across most PPI regimens and merited further attention.Conclusions: PPIs may inflict various CVEs, particularly those involving the vascular system, on the users. Given the wide range of onset times and different toxicity profiles for various PPI medications, they should be prescribed with caution.
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