| 1. |
- Beal, Jacob, et al.
(författare)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
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.
|
|
| 2. |
- Ali, Arwa, et al.
(författare)
-
Proinflammatory allogeneic dendritic cells enhance the therapeutic efficacy of systemic anti-4-1BB treatment
- 2023
-
Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- As an immune adjuvant, proinflammatory allogeneic dendritic cells (AlloDCs) have demonstrated promising immune-priming effects in several preclinical and clinical studies. The effector cells, including NK cells and T cells are widely acknowledged as pivotal factors in the effectiveness of cancer immunotherapy due to their ability to selectively identify and eradicate malignant cells. 4-1BB, as a costimulatory receptor, plays a significant role in the stimulation of effector cell activation. This study evaluated the anti-tumor effects when combining intratumoral administration of the immune-adjuvant AlloDCs with systemic a4-1BB treatment directly acting on effector cells. In both the CT-26 murine colon carcinoma model and B16 murine melanoma model, AlloDCs demonstrated a significant enhancement in the therapeutic efficacy of a4-1BB antibody. This enhancement was observed through the delayed growth of tumors and prolonged survival. Analysis of the tumor microenvironment (TME) in the combined-treatment group revealed an immune-inflamed TME characterized by increased infiltration of activated endogenous DCs and IFN?(+) CD8(+) T cells, showing reduced signs of exhaustion. Furthermore, there was an augmented presence of tissue-resident memory (T-RM) CD8(+) T cells (CD103(+)CD49a(+)CD69(+)). The combination treatment also led to increased infiltration of CD39(+)CD103(+) tumor-specific CD8(+) T cells and neoantigen-specific T cells into the tumor. Additionally, the combined treatment resulted in a less immunosuppressive TME, indicated by decreased infiltration of myeloid-derived suppressor cells and Tregs. These findings suggest that the combination of intratumoral AlloDCs administration with systemic agonistic a4-1BB treatment can generate a synergistic anti-tumor response, thereby warranting further investigation through clinical studies.
|
|
| 3. |
- Gao, Hongyuan, et al.
(författare)
-
Monostatic MIMO radar direction finding in impulse noise
- 2021
-
Ingår i: Digital Signal Processing: A Review Journal. - : Elsevier BV. - 1051-2004. ; 117
-
Tidskriftsartikel (refereegranskat)abstract
- This work considers direction-finding using a monostatic multiple-input multiple-output (MIMO) radar in the presence of impulsive noise. Employing a novel low-order covariance-based exponential kernel function, the proposed maximum likelihood (ML) formulation exploits an introduced quantum whale optimization algorithm (QWOA) to form the direction estimates. The resulting estimates are shown to be robust to the presence of impulsive noise, offering preferable performance as compared to recent related approaches, even in cases when the number of available snapshots is small.
|
|
| 4. |
- Gao, Menghan, et al.
(författare)
-
A qPCR-Based Method for Quantification of RCA Contaminants in Oncolytic Adenovirus Products
- 2022
-
Ingår i: Frontiers in Molecular Biosciences. - : Frontiers Media S.A.. - 2296-889X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Oncolytic adenovirus is one of the most promising treatments against cancer and is widely evaluated clinically. During high titer production, “Wild-type-” like replication-competent adenovirus (RCA) contaminants can be generated through recombination events due to the DNA sequence similarity between oncolytic virus and host cells. These RCA contaminants raise various safety concerns in clinics. Cell culture-based methods have been developed to detect RCA contaminants in replication-deficient adenovirus vectors. These methods were based on that only RCA contaminants, but not the vectors, are able to grow in and lyse the test cell line. However, these methods are not suitable for distinguishing RCA contaminants from the oncolytic adenovirus products because both can replicate in test cell lines. Herein, we reported a qPCR-based method to quantify RCA contaminants quickly and reliably in E1B-deleted oncolytic adenovirus products. This method is based on specific detection of the E1B gene, which can be acquired during production via recombination events between viral and host cell DNA. The assay is sensitive with the limit of detection at 10 VP of the RCA contaminants and the limit of quantification at 75 VP of the RCA contaminants in each 40 µL qPCR reaction. We have also validated the method on virus batches produced in the non-GMP and GMP conditions. Our results showed that this qPCR-based method was reliable and robust for detecting and quantifying RCA contaminants in oncolytic adenovirus products. The method may also be adapted for other oncolytic adenoviruses products by switching primer sets.
|
|
| 5. |
- Gao, Menghan, et al.
(författare)
-
Associations of perinatal characteristics with endometriosis : a nationwide birth cohort study
- 2020
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 1464-3685 .- 0300-5771. ; 49:2, s. 537-547
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Perinatal characteristics are associated with subsequent risk of several chronic diseases. Previous studies regarding endometriosis were based on small samples and retrospective data and were limited by unmeasured confounding bias, leading to conflicting and inconclusive findings. We investigated the associations of maternal and birth characteristics with risk of endometriosis among Swedish women of reproductive age. METHODS: This total-population register-based cohort study consisted of 628 312 singleton women born in Sweden between 1973 and 1987, who were followed for diagnosed endometriosis from age 15 years until the end of 2012. Multivariable Cox regression was applied to examine associations with perinatal characteristics. Residual unmeasured confounding was assessed through within-family and E-value analyses. RESULTS: During follow-up, 8262 women received an endometriosis diagnosis. There were clear dose-response/linear associations of endometriosis with lower maternal education, endometriosis in the mother [adjusted hazard ratio (aHR): 2.24, 95% confidence interval (CI): 2.04-2.46], maternal smoking during pregnancy (aHR: 1.18, 95% CI: 1.04-1.33 for moderate smoker and aHR: 1.36, 95% CI: 1.18-1.57 for heavy smoker vs non-smoker), lower birthweight, and lower birthweight-for-gestational age (aHR: 0.93 per standard deviation increase, 95% CI: 0.91-0.95). Within-family and E-value analyses suggested that these perinatal characteristics are robust predictors of the incidence of endometriosis. We also found that an estimated 26% of the association between maternal smoking and early-onset endometriosis could be explained by birthweight-for-gestational age. CONCLUSION: This study finds support for fetal origins of endometriosis, in that exposure to adverse environment or restricted development during the perinatal period may increase the risk. Further research is needed to provide an understanding of the underlying mechanisms.
|
|
| 6. |
- Gao, Menghan, et al.
(författare)
-
Developmental origins of endometriosis : a Swedish cohort study
- 2019
-
Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 73:4, s. 353-359
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Endometriosis is a chronic condition affecting women of reproductive age and is associated with multiple health burdens. Yet, findings regarding its 'developmental origins' are inconsistent. We aimed to investigate the associations of birth characteristics with endometriosis. We also explored potential mediation by adult social and reproductive factors.METHODS: This cohort study consisted of 3406 women born in Uppsala, Sweden, between 1933 and 1972. We used data from archived birth records and endometriosis diagnoses at ages 15-50 recorded in the national patient registers. Socioeconomic and reproductive characteristics were obtained from routine registers. HRs were estimated from Cox regression.RESULTS: During the follow-up, 111 women have been diagnosed with endometriosis, and most cases are external endometriosis (ie, outside the uterus, n=91). Lower standardised birth weight for gestational age was associated with increased rate of endometriosis (HR 1.35 per standard deviation decrease; 95% CI 1.08 to 1.67). This increased rate was also detected among women with fewer number of live births (HR 2.38; 95% CI 1.40 to 4.07 for one child vs ≥2 children; HR 6.09; 95% CI 3.88 to 9.57 for no child vs ≥2 children) and diagnosed infertility problem (HR 2.00; 95% CI 1.10 to 3.61) prior to endometriosis diagnosis. All the observed associations were stronger for external endometriosis. However, no evidence was found that number of births was the mediator of the inverse association between standardised birth weight and endometriosis.CONCLUSION: This study supports the developmental origins theory and suggests that exposure to growth restriction during the fetal period is associated with increased risk of endometriosis during reproductive years.
|
|
| 7. |
- Gao, Menghan, et al.
(författare)
-
Exposure to out-of-home care in childhood and adult all-cause mortality : a cohort study
- 2017
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 46:3, s. 1010-1017
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Children placed in out-of-home care (OHC) have exceedingly high rates of health problems. Their poor health tends to persist across adolescence and into young adulthood, resulting in increased risks of mortality. Yet, very little is known about this group’s mortality risks later in life. The aim of this study was to investigate whether OHC was associated with the risk of all-cause mortality across adulthood, and whether these risks varied across different placement characteristics. Moreover, the study addressed potential confounding by including two comparison groups with children who grew up under similarly adverse living conditions but did not experience placement.Methods: Data were derived from a 60-year follow-up of a Stockholm cohort born in 1953 (n = 15 048), of whom around 9% have had experiences of OHC. The associations between OHC and subsequent all-cause mortality were analysed by means of Cox’s proportional hazards regression models.Results: Individuals who were placed in OHC at any point during their formative years had increased mortality risks across ages 20 to 56 years. Elevated risk of mortality was particularly pronounced among those who were placed in adolescence and/or because of their own behaviours. Children who were exposed to OHC had increased risks of mortality also when compared with those who grew up under similar living conditions but did not experience placement.Conclusions: Children in OHC constitute a high-risk group for subsequent mortality. In order to narrow the mortality gap, interventions may need to monitor not only health aspects but also to target the cognitive and social development of these children.
|
|
| 8. |
- Gao, Menghan
(författare)
-
Life course determinants of women’s health : from reproductive age to menopause
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Over the past four decades, growing evidence has indicated that characteristics such as birth weight and length of gestation are not only key indicators for infant’s health, but also predictors of adult health and disease risk. These findings lend support to the developmental origins of health and disease theory. However, evidence remains inconclusive in terms of female hormone-related disorders, including endometriosis and perimenopausal disorders. Also, little is known about the social patterning of these female health burdens from population-based studies. Furthermore, the psychological health of women with endometriosis has not been adequately explored in longitudinal studies. Based on identified knowledge gaps and taking advantage of Swedish high-quality population-based registers, this thesis aims to study how factors operating during early life, such as parental and birth characteristics, adult socioeconomic and reproductive factors are associated with subsequent risks of endometriosis and perimenopausal disorders. Further, it explores whether women with endometriosis have higher risk of psychiatric comorbidity. Study I explored the associations of early life social and health characteristics with risk of endometriosis in a cohort of the second generation of women from the Uppsala Birth Cohort Multigenerational Study. Lower birth weight-for-gestational age, fewer births, and previous infertility disorder were found to be associated with an increased risk of endometriosis. Nevertheless, the inverse association between low birth weight-for-gestational age and endometriosis could not be explained by women’s lower number of live births in adulthood. Study II replicated the original findings in Study I in a nationwide population-based cohort of females born in Sweden between 1973 and 1987. This study confirmed the inverse association between fetal growth rate and risk of endometriosis, and expanded Study I by showing associations of maternal smoking during pregnancy and lower maternal education with endometriosis risk in early to mid-adulthood. The study also found a part of the association between maternal smoking and risk of early-onset of endometriosis was due to slow fetal growth. Study III focused on the psychological health of women with endometriosis by assessing the bi-directional associations of endometriosis with all psychiatric disorders, as well as the role of familial confounding, in a nationwide cohort of all women born in Sweden in 1973-1990. Statistically significant bi-directional associations were found for endometriosis with many different types of psychiatric disorders, including affective psychotic disorders, depressive, anxiety and stress-related disorders, eating disorders, alcohol/drug dependence, personality disorders, and attention-deficit hyperactivity disorder. These bi-directional associations observed at the population level largely remained in comparisons between exposed and unexposed sisters, suggesting that shared familial liability may not fully explain these associations. Study IV investigated the developmental origins of three subtypes of perimenopausal disorders using the same cohort as Study I. Positive association between birth weight and a clinical diagnosis of menopausal and climacteric states was found. Higher risk of being diagnosed with other perimenopausal disorders (e.g., atrophic vaginitis) was observed among women born with shorter gestational age. This study also documented that women with higher parental and own educational level in adulthood were more likely to be diagnosed with perimenopausal disorders. Taken together, this thesis supports the developmental origins of two important female hormone-related disorders during reproductive age and menopause, namely endometriosis and perimenopausal disorders. Our findings highlight the importance of intrauterine environment in shaping the developmental adaptations of metabolism and organ function. In addition to the developmental origins, these female health burdens were associated with a range of socioeconomic and reproductive factors as well as mental health in earlier life. It is therefore important to take a life-course perspective for a greater understanding of the etiology of hormone-related health outcomes and consider potential targeting of the high-risk groups for earlier public health intervention.
|
|
| 9. |
- Gao, Menghan, et al.
(författare)
-
Psychiatric comorbidity among women with endometriosis : nationwide cohort study in Sweden
- 2020
-
Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 223:3, s. 415.e1-415.e16
-
Tidskriftsartikel (refereegranskat)abstract
- Background Endometriosis is a common gynecologic condition affecting women of reproductive age. It has been linked with greater rates of depression and anxiety in small, cross-sectional, and clinical studies. Other studies have reported that women with endometriosis have increased risk of bipolar disorder. These reports suggest that psychiatric disorders might be more common among women with endometriosis, contributing to increased burden of mental ill-health in this population of women. However, this hypothesis has not been adequately studied.Objectives In this population-based study, we investigated the overall psychiatric comorbidity among women with endometriosis, and the role of familial liability.Study Design Several Swedish national registers were linked and used to follow all women born in Sweden in 1973–1990 for diagnosed psychiatric disorders and endometriosis from age 14 years until year 2016. Sibling comparison analyses were performed in a subsample of 173,650 families.Results After adjustment for birth characteristics and education, women with endometriosis had an increased risk of being later diagnosed with depressive-, anxiety and stress-related disorders, alcohol/drug dependence, and attention-deficit hyperactivity disorder compared with the general population and with their sisters without endometriosis. The adjusted hazard ratios ranged from 1.56 (95% confidence interval, 1.29–1.88) for depressive disorders to 1.98 (95% confidence interval, 1.34–2.93) for attention-deficit hyperactivity disorder in the sibling analysis. Also, women with previous affective psychotic disorders, depressive-, anxiety and stress-related disorders, eating disorders, personality disorders, and attention-deficit hyperactivity disorder were more likely to be later diagnosed with endometriosis. The adjusted hazard ratios ranged from 1.51 (95% confidence interval, 1.30–1.76) for depressive disorders to 1.93 (95% confidence interval, 1.47–2.52) for personality disorders.Conclusion These findings reveal a high degree of comorbidity between endometriosis and many psychiatric disorders that was not entirely explained by shared familial confounding. Clinical practice may consider psychosocial support to women with endometriosis and treating them from a multidisciplinary perspective.
|
|
| 10. |
- Gondek, Dawid, et al.
(författare)
-
Inequality in hospitalization due to non-communicable diseases in Sweden : Age-cohort analysis of the Uppsala Birth Cohort Multigenerational Study
- 2021
-
Ingår i: SSM - Population Health. - : Elsevier BV. - 2352-8273. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- We aimed to investigate cohort differences in age trajectories of hospitalization due to non-communicable conditions, and if these varied by paternal socioeconomic position. We used the Uppsala Birth Cohort Multigenerational Study-including virtually complete information on medical diagnoses. Our sample constituted 28,448 individuals (103,262 observations). The outcome was five-year prevalence of hospitalization due to major non-communicable conditions in 1989-2008. The exposures were age (19-91), year-of-birth (1915-1929; 1938-1972), gender (man vs woman), and parental socioeconomic position (low, medium, and high). We used multilevel logit models to examine associations between exposures and the hospitalization outcome. Younger cohorts had a higher prevalence of hospitalization at overlapping ages than those born earlier, with inter-cohort differences emerging from early-adulthood and increasing with age. For instance, at age 40 predicted probability of hospitalization increased across birth-cohorts-from 1.2% (born in 1948-52) to 2.0% (born in 1963-67)-whereas at age 50 it was 2.9% for those born in 1938-42 compared with 4.6% among participants born in 1953-57. Those with medium and low socioeconomic position had 13.0% and 20.0% higher odds of experiencing hospitalization during the observation period, respectively-when age, year-of-birth and gender were accounted for. We found that no progress was made in reducing the socioeconomic inequalities in hospitalization across cohorts born between 1915 and 1972. Hence, more effective policies and interventions are needed to reduce the overall burden of morbidity-particularly among the most vulnerable.
|
|
