| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
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| 3. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 4. |
- Axfors, Cathrine, et al.
(författare)
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Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I-2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
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| 5. |
- Lin, Yi-Ting, et al.
(författare)
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Differences in the Microbial Composition of Hemodialysis Patients Treated with and without β-Blockers
- 2021
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Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- β-blockers are commonly prescribed to treat cardiovascular disease in hemodialysis patients. Beyond the pharmacological effects, β-blockers have potential impacts on gut microbiota, but no study has investigated the effect in hemodialysis patients. Hence, we aim to investigate the gut microbiota composition difference between β-blocker users and nonusers in hemodialysis patients. Fecal samples collected from hemodialysis patients (83 β-blocker users and 110 nonusers) were determined by 16S ribosomal RNA amplification sequencing. Propensity score (PS) matching was performed to control confounders. The microbial composition differences were analyzed by the linear discriminant analysis effect size, random forest, and zero-inflated Gaussian fit model. The α-diversity (Simpson index) was greater in β-blocker users with a distinct β-diversity (Bray–Curtis Index) compared to nonusers in both full and PS-matched cohorts. There was a significant enrichment in the genus Flavonifractor in β-blocker users compared to nonusers in full and PS-matched cohorts. A similar finding was demonstrated in random forest analysis. In conclusion, hemodialysis patients using β-blockers had a different gut microbiota composition compared to nonusers. In particular, the Flavonifractor genus was increased with β-blocker treatment. Our findings highlight the impact of β-blockers on the gut microbiota in hemodialysis patients.
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| 6. |
- Dong, Yi, et al.
(författare)
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Anosmia, mild cognitive impairment, and biomarkers of brain aging in older adults
- 2023
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:2, s. 589-601
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Tidskriftsartikel (refereegranskat)abstract
- Olfactory impairment is a potential marker for prodromal dementia, but the underlying mechanisms are poorly understood. This population-based study included 4214 dementia-free participants (age ≥65 years). Olfaction was assessed using the 16-item Sniffin’ Sticks identification test. In the subsamples, we measured plasma amyloid beta (Aβ)40, Aβ42, total tau, and neurofilament light chain (NfL; n = 1054); and quantified hippocampal, entorhinal cortex, and white matter hyperintensity (WMH) volumes, and Alzheimer's disease (AD)-signature cortical thickness (n = 917). Data were analyzed with logistic and linear regression models. In the total sample, mild cognitive impairment (MCI) was diagnosed in 1102 persons (26.2%; amnestic MCI, n = 931; non-amnestic MCI, n = 171). Olfactory impairment was significantly associated with increased likelihoods of MCI, amnestic MCI, and non-amnestic MCI. In the subsamples, anosmia was significantly associated with higher plasma total tau and NfL concentrations, smaller hippocampal and entorhinal cortex volumes, and greater WMH volume, and marginally with lower AD-signature cortical thickness. These results suggest that cerebral neurodegenerative and microvascular lesions are common neuropathologies linking anosmia with MCI in older adults.
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| 7. |
- Han, Xiaolei, et al.
(författare)
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Accelerometer-measured sedentary behavior patterns, brain structure, and cognitive function in dementia-free older adults : a population-based study
- 2023
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 96:2, s. 657-668
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sedentary behavior is associated with cognitive impairment, but the neuropathological mechanisms underlying their associations are poorly understood.Objective: To investigate the associations of accelerometer-measured sedentary behavior patterns with brain structure and cognition, and further to explore the potential mechanisms.Methods: This community-based study included 2,019 older adults (age≥60 years, 59% women) without dementia derived from participants in the baseline examination of MIND-China (2018-2020). We assessed sedentary parameters using an accelerometer and cognitive function using a neuropsychological test battery. Structural brain markers were assessed on the structural brain MRI scans in a subsample (n = 1,009). Data were analyzed using the general linear, isotemporal substitution, and mediation models.Results: In the total sample (n = 2,019), adjusting for multiple covariates and moderate-to-vigorous-intensity physical activity, longer mean sedentary bout duration was linearly related with lower z-scores of global cognition, verbal fluency, and memory (ptrend < 0.05), whereas greater total sedentary time was linearly associated with lower z-scores of global cognition, verbal fluency, and memory only among individuals with long sedentary time (>10 h/day) (ptrend < 0.05); Breaking up sedentary time with same amount of light-intensity physical activity was significantly associated with higher verbal fluency and memory z-scores (p < 0.05). In the MRI subsample (n = 1,009), separately entering structural brain MRI markers into the mediation models substantially attenuated the associations of mean sedentary bout duration with global cognition, verbal fluency, and memory z-scores.Conclusion: Prolonged uninterrupted sedentary time is associated with poor global cognition, memory, and verbal fluency among rural older adults, and structural brain markers could partially mediate the association.
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| 8. |
- Hsu, Yu-Hsuan, et al.
(författare)
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epsilon-Ga2O3 Grown on c-Plane Sapphire by MOCVD with a Multistep Growth Process
- 2022
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Ingår i: Crystal Growth & Design. - : AMER CHEMICAL SOC. - 1528-7483 .- 1528-7505. ; 22:3
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Tidskriftsartikel (refereegranskat)abstract
- Gallium oxide (Ga2O3) has especially become popular because of its established applications in semiconductors. Of five polymorphs, monoclinic beta-Ga2O3 is the most thermodynamically stable phase. However, orthorhombic Ga2O3 (also known as epsilon-Ga2O3 or kappa-Ga2O3) is gaining increasing interest due to its high lattice symmetry and peculiar ferroelectricity. Although the structural approach for estimating Ga2O3 has been studied both theoretically and experimentally, epsilon-Ga2O3 and kappa-Ga2O3 are still confused. In this study, epsilon-Ga2O3 epilayers are grown on c-plane sapphire by metal-organic chemical vapor deposition with a multistep growth process. A thin annealed epsilon-Ga2O3 buffer layer is grown in the first step. The sequent growth steps with slow, fast, or combination of slow then fast growth rate significantly influence the quality of epilayers compared with that of directly grown Ga2O3. Through a detailed transmission electron microscopy (TEM) characterization of these Ga2O3 epilayers, the structural relationship between orthorhombic kappa-Ga2O3 and hexagonal epsilon-Ga2O3 is elucidated. A series of first-principles density functional theory calculations are also carried out to confirm the argument.
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| 9. |
- Huang, Jih-Kai, et al.
(författare)
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Decreased levels of perfluoroalkyl substances in patients receiving hemodialysis treatment
- 2023
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 896
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Tidskriftsartikel (refereegranskat)abstract
- Perfluoroalkyl substances (PFAS) have been reported to be harmful to multiple organs in the human body. Based on a previous study suggesting that hemodialysis (HD) may be a means of eliminating PFAS from the human body, we aimed to compare the serum PFAS concentrations of patients undergoing regular HD, patients with chronic kidney disease (CKD) and controls. Additionally, we also investigated the correlation between PFAS and biochemical data, as well as concurrent comorbidities. We recruited 301 participants who had been on maintenance dialysis for >90 days, 20 participants with stage 5 non-dialysis CKD, and 55 control participants who did not have a diagnosis of kidney disease, with a mean creatinine level of 0.77 mg/dl. Eight different PFAS, namely perfluorooctanoic acid (PFOA), total and linear perfluorooctanesulfonic acid (PFOS), perfluoroheptanoic acid (PFHpA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Spearman correlation and multivariable linear regression with 5 % false discovery rate were used to evaluate the relationships between PFAS and clinical parameters in HD patients and controls. Circulating concentrations of seven PFAS, including total and linear PFOS (T-PFOS and L-PFOS) PFDA, PFNA, PFHxS, PFOA, and PFUnDA, were significantly lower in the HD group compared to the CKD and control group. For the interplay between biochemical data and PFAS, all of the studied PFAS were positively correlated with aspartate aminotransferase, alanine aminotransferase, glucose, blood urea nitrogen, ferritin, and vitamin D in the controls, while in HD patients, the PFAS were all positively correlated with albumin, uric acid, iron, and vitamin D. These findings may offer valuable insights for future studies seeking to eliminate PFAS.
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| 10. |
- Huang, Wen-Yi, et al.
(författare)
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Effectiveness of using calligraphic activity to treat people with schizophrenia : a randomized controlled trial in Southern Taiwan
- 2022
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Ingår i: THERAPEUTIC ADVANCES IN CHRONIC DISEASE. - : Sage Publications. - 2040-6223 .- 2040-6231. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prior research has shown preliminary evidence that calligraphy activity improves various body functions and decreases severity of psychotic symptoms in individuals with schizophrenia. However, major limitations of earlier studies include small and heterogeneous samples. The current large-scale randomized controlled trial examined effects of calligraphy activity on cognition (including attention), emotions, psychotic symptoms, quality of life, and mood in people with schizophrenia. Methods: One-hundred-and-fifty patients with schizophrenia were randomly allocated to the treatment group (receiving calligraphy activity) or the control group (receiving general activity), both of which lasted for 24weeks (70 minutes per session; one session per week). Assessments were conducted at pretest, posttest, and three-month follow-up. The Montreal Cognitive Assessment, Chu's Attention Test, Depression, Anxiety, and Stress Scale, Positive and Negative Syndrome Scale, World Health Questionnaire on the Quality of Life-Brief Form, and Visual Analogue Scale were used. Results: Improved cognition and attention were found in both groups, although no group effects were shown. The treatment group appeared to show lower severity of positive symptoms at follow-up than posttest, whereas the control group appeared to show the opposite pattern. Improved mood was found in the treatment group. Conclusion: This study provides evidence regarding effects of calligraphy activity on increasing cognition and potentially decreasing severity of positive symptoms in patients with schizophrenia. Calligraphy activity can be incorporated in clinical occupational therapy and may be provided to supplement medication treatment.
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