| 641. |
- Harlid, Sophia, 1978-, et al.
(författare)
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Diabetes mellitus in relation to colorectal tumor molecular subtypes : a pooled analysis of more than 9000 cases
- 2022
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 151:3, s. 348-360
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes is an established risk factor for colorectal cancer. However, colorectal cancer is a heterogeneous disease and it is not well understood whether diabetes is more strongly associated with some tumor molecular subtypes than others. A better understanding of the association between diabetes and colorectal cancer according to molecular subtypes could provide important insights into the biology of this association. We used data on lifestyle and clinical characteristics from the Colorectal Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), including 9756 colorectal cancer cases (with tumor marker data) and 9985 controls, to evaluate associations between reported diabetes and risk of colorectal cancer according to molecular subtypes. Tumor markers included BRAF and KRAS mutations, microsatellite instability and CpG island methylator phenotype. In the multinomial logistic regression model, comparing colorectal cancer cases to cancer-free controls, diabetes was positively associated with colorectal cancer regardless of subtype. The highest OR estimate was found for BRAF-mutated colorectal cancer, n = 1086 (ORfully adj: 1.67, 95% confidence intervals [CI]: 1.36-2.05), with an attenuated association observed between diabetes and colorectal cancer without BRAF-mutations, n = 7959 (ORfully adj: 1.33, 95% CI: 1.19-1.48). In the case only analysis, BRAF-mutation was differentially associated with diabetes (Pdifference = .03). For the other markers, associations with diabetes were similar across tumor subtypes. In conclusion, our study confirms the established association between diabetes and colorectal cancer risk, and suggests that it particularly increases the risk of BRAF-mutated tumors.
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| 642. |
- Herrera-Rivero, Marisol, et al.
(författare)
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Exploring the genetics of lithium response in bipolar disorders.
- 2023
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Ingår i: Research square.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
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| 643. |
- Herrera-Rivero, Marisol, et al.
(författare)
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Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder.
- 2023
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Ingår i: Research square.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1×10- 4 values, including HAS3, CNTNAP5 and NFIB. Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3β. We also found various genes associated with BP's age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4, XKR4, NRXN1, NRG1/3 and GRK5. Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.
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| 644. |
- Hsu, B. Y., et al.
(författare)
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Maternally transferred thyroid hormones and life-history variation in birds
- 2022
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Ingår i: Journal of Animal Ecology. - : Wiley. - 0021-8790 .- 1365-2656. ; 91:7, s. 1489-1506
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Tidskriftsartikel (refereegranskat)abstract
- In vertebrates, thyroid hormones (THs) play an important role in the regulation of growth, development, metabolism, photoperiodic responses and migration. Maternally transferred THs are important for normal early phase embryonic development when embryos are not able to produce endogenous THs. Previous studies have shown that variation in maternal THs within the physiological range can influence offspring phenotype. Given the essential functions of maternal THs in development and metabolism, THs may be a mediator of life-history variation across species. We tested the hypothesis that differences in life histories are associated with differences in maternal TH transfer across species. Using birds as a model, we specifically tested whether maternally transferred yolk THs covary with migratory status, developmental mode and traits related to pace-of-life (e.g. basal metabolic rate, maximum life span). We collected un-incubated eggs (n = 1-21 eggs per species, median = 7) from 34 wild and captive bird species across 17 families and six orders to measure yolk THs [both triiodothyronine (T3) and thyroxine (T4)], compiled life-history trait data from the literature and used Bayesian phylogenetic mixed models to test our hypotheses. Our models indicated that both concentrations and total amounts of the two main forms of THs (T3 and T4) were higher in the eggs of migratory species compared to resident species, and total amounts were higher in the eggs of precocial species, which have longer prenatal developmental periods, than in those of altricial species. However, maternal yolk THs did not show clear associations with pace-of-life-related traits, such as fecundity, basal metabolic rate or maximum life span. We quantified interspecific variation in maternal yolk THs in birds, and our findings suggest higher maternal TH transfer is associated with the precocial mode of development and migratory status. Whether maternal THs represent a part of the mechanism underlying the evolution of precocial development and migration or a consequence of such life histories is currently unclear. We therefore encourage further studies to explore the physiological mechanisms and evolutionary processes underlying these patterns.
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| 645. |
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| 646. |
- Hsu, C. -P, et al.
(författare)
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Roughness-dependent clogging of particle suspensions flowing into a constriction
- 2021
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 17:31, s. 7252-7259
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Tidskriftsartikel (refereegranskat)abstract
- When concentrated particle suspensions flow into a constricting channel, the suspended particles may either smoothly flow through the constriction or jam and clog the channel. These clogging events are typically detrimental to technological processes, such as in the printing of dense pastes or in filtration, but can also be exploited in micro-separation applications. Many studies have to date focused on important parameters influencing the occurrence of clogs, such as flow velocity, particle concentration, and channel geometry. However, the investigation of the role played by the particle surface properties has surprisingly received little attention so far. Here, we study the effect of surface roughness on the clogging of suspensions of silica particles under pressure-driven flows along a microchannel presenting a constriction. We synthesize micron-sized particles with uniform surface chemistry and tunable roughness and determine the occurrence of clogging events as a function of velocity and volume fraction for a given surface topography. Our results show that there is a clear correlation between surface roughness and flow rate, indicating that rougher particles are more likely to jam at the constriction for slower flows. These findings identify surface roughness as an essential parameter to consider in the formulation of particulate suspensions for applications where clogging plays an important role.
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| 647. |
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| 648. |
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| 649. |
- Hsu, L. H., et al.
(författare)
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Design and Fabrication of 0/1-Level RF-Via Interconnect for RF-MEMS Packaging Applications
- 2010
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Ingår i: IEEE Transactions on Advanced Packaging. - 1521-3323. ; 33:1, s. 30-36
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the parametric study of RF-via (0-level) and flip-chip bump (1-level) transitions for applications of packaging coplanar RF-MEMS devices. The key parameters were found to be the bumps' and vias' positions and the overlap of the metal pads, which should be carefully considered in the entire two levels of packages. The length of the backside transmission line, determining the MEMS substrate area, showed minor influence on the interconnect performance. With the experimental results, the design rules have been developed and established. The optimized interconnect structure for the two levels of packages demonstrates the return loss beyond 15 dB and the insertion loss within 0.6 dB from dc to 60 GHz.
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| 650. |
- Hsu, L. H., et al.
(författare)
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Design, Fabrication, and Reliability of Low-Cost Flip-Chip-On-Board Package for Commercial Applications up to 50 GHz
- 2012
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Ingår i: IEEE Transactions on Components, Packaging and Manufacturing Technology. - 2156-3985 .- 2156-3950. ; 2:3, s. 402-409
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a flip-chip-on-board (FCOB) packaging technology using a Rogers RO3210 laminate for microwave applications. Compared to the conventional microwave packaging architecture, the proposed FCOB technology skips one level of the ceramic package and thus results in lower reflections and manufacturing costs. To fulfill the small dimension requirement on printed circuit boards, the coplanar waveguide (CPW) transmission line and flip-chip bump were fabricated on a high-k RO3210 board (epsilon(r) = 10.2) with photolithography and electroplating. The GaAs chip patterned with the CPW line was then flip-chip-mounted onto the RO3210 laminate board. This structure displayed excellent performance from dc to 50 GHz with a return loss S-11 greater than 18 dB and insertion loss S-21 less than 0.5 dB. Meanwhile, the flip-chip bonding of the in-house-fabricated In0.52Al0.As-48/In0.6Ga0.4As metamorphic high-electron-mobility transistor devices on RO3210 also displayed excellent gain performance with a small degradation of 1 dB from dc to 40 GHz, showing the potential of implementing microwave integrated circuits on RO3210. To enhance the mechanical reliability, an epoxy-based underfill was injected into the flip-chip assemblies. Thermal cycling tests were performed to test the interconnect reliability, and the results indicated that the samples passed the thermal cycling test at least up to 600 cycles, showing excellent reliability for commercial applications. To the best of the authors' knowledge, this is the first study that evaluates the use of the RO3210 laminate for microwave flip-chip in open literature.
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