Superparamagnetic relaxometry (SPMR) exploits the unique magnetic properties of targeted superparamagnetic iron oxide nanoparticles (SPIOs) to detect small numbers of cancer cells. Reconstruction of ...the spatial distribution of cancer-bound nanoparticles requires solving an ill-posed inverse problem. The current method, multiple source analysis (MSA), uses a least-squares fit to determine the strength and location of a pre-determined number of magnetic dipoles. In this proof-of-concept study, we propose the application of a sparsity averaged reweighting algorithm (SARA) for volumetric reconstruction of immobilized nanoparticle distributions. We first calibrate the parameters that define the location of the sensors in the forward model of measurement physics. Using this optimized model, we evaluated the performance of the algorithms on various configurations of single and multiple point-source phantoms. We investigated the effect of the data fidelity parameter, voxel size, and iterative reweighting on the reconstruction produced by SARA. We found that the calibrated physics model can predict the detected field values within 5% of the measured data. When only a single source was present, both algorithms were able to detect as little as 0.5 µg of immobilized particles. However, when two sources were measured simultaneously, MSA failed to detect sources containing as much as 10 µg of particles, while SARA detected all of the sources containing at least 5 µg of particles. We show that a suitable data fidelity parameter can be selected objectively, and the total magnitude and location of a point source reconstructed by SARA is not sensitive to voxel size. Detection and localization of multiple small clusters of nanoparticles is a crucial step in SPMR-based diagnostic applications. Our algorithm overcomes the need to know the number of dipoles before reconstruction and improves the sensitivity of the reconstruction when multiple sources are present.
The persistent low contraceptive use and high fertility in Nigeria despite improvements in educational achievements calls for an examination of the role of factors, which may moderate the use of ...modern contraception. This article explores the influence of sexual autonomy on the use of modern contraceptive methods among women and its relative importance compared with other, more traditional, indicators of women's autonomy such as education and occupation.
Data from two Demographic and Health Surveys (DHS), 2008 and 2013, were used in this study. An index of sexual autonomy was constructed by combining related DHS variables, and its association with current use of modern contraception was examined at each time point as well as over time using multivariate regression analysis.
The observed prevalence for use of modern contraception was 2.8 and 2.6 times higher among women who had high sexual autonomy in 2008 and 2013, respectively. The corresponding figures for women with secondary or higher education were 8.2 and 11.8 times higher, respectively, compared with women with no education. But after controlling for wealth index, religion, place of residence, autonomy and experience of intimate partner violence (IPV), the likelihood of use of modern contraception was lowered to about 2.5 (from 8.2) and 2.8 (from 11.8) times during 2008 and 2013, respectively, among women with secondary or higher education. The likelihood of use of modern contraception lowered only to 1.6 (from 2.8) and 1.8 (from 2.6) times among women with high sexual autonomy after controlling for other covariates, respectively, during the same period.
Sexual autonomy seems to play an important role in women's use of modern contraceptive methods independent of education and a number of other factors related to women's status. Sexual autonomy needs to be simultaneously promoted alongside increasing educational opportunities to enhance women's ability to use modern contraception.
Janus-activated kinase-2 (JAK2) plays an important role in the activation of signal transducer and activation of transcription 3 (STAT3), which is over expressed in majority of ovarian tumors. We ...have reported previously that diindolylmethane (DIM) induces apoptosis in ovarian cancer cells by inhibiting STAT3. However, the role of JAK2 in our model was not yet understood and hence evaluated in this report. SKOV-3 human ovarian cancer cells were used to evaluate concentration and time dependent effects of DIM. Interleukin 3 (IL-3) and epidermal growth factor (EGF) were used to activate JAK2. Tumor xenograft studies were used to determine modulation of JAK2 in vivo. DIM treatment blocked the phosphorylation of JAK2 at Tyr-1007 in a concentration-dependent manner. In a time-dependent study, inhibition of JAK2 by DIM was as early as 1 h, which was followed by the inhibition of STAT3 and survivin. IL-3-induced phosphorylation of JAK2 and STAT3 was significantly blocked by DIM. IL-3 treatment blocked DIM-induced apoptosis. EGF treatment resulted in the activation of JAK2 and STAT3 but suppressed by DIM. These results indicate the involvement of cytokines and growth factors in the activation of JAK2/STAT3 and that DIM suppress their activation. Furthermore, DIM in combination with cisplatin drastically reduced the phosphorylation of JAK2 when compared to cisplatin alone. Western blot analysis of tumors from DIM treated mice showed significant inhibition of JAK2 activation as compared with controls. These findings provide a rationale for further clinical investigation of DIM for its potential use alone or in combination with chemotherapy of ovarian cancer.
Signal transducer and activator of transcription 3 (STAT3) is activated in majority of ovarian tumors and confers resistance to cisplatin treatment in patients with ovarian cancer. We have reported ...previously that diindolylmethane (DIM) inhibits the growth of ovarian cancer cells. However, to date the exact mechanism by which DIM induces growth suppressive effects has not been clear. In this report the mode of action of DIM is investigated.
Six human ovarian cancer cell lines and an ovarian tumor xenograft animal model were used to study the effect of diindolylmethane alone or in combination with cisplatin.
Diindolylmethane treatment induced apoptosis in all six ovarian cancer cell lines. Phosphorylation of STAT3 at Tyr-705 and Ser-727 was reduced by DIM in a concentration-dependent manner. In addition, diindolylmethane treatment inhibited nuclear translocation, DNA binding, and transcriptional activity of STAT3. Interleukin (IL)-6-induced phosphorylation of STAT3 at Tyr-705 was significantly blocked by DIM. Overexpression of STAT3 by gene transfection blocked DIM-induced apoptosis. In addition, DIM treatment reduced the levels of IL-6 in ovarian cancer cells and in the tumors. DIM treatment also inhibited cell invasion and angiogenesis by suppressing hypoxia-inducible factor 1α (HIF-1α) and vascular epithelial growth factor (VEGF). Importantly, diindolylmethane treatment potentiated the effects of cisplatin in SKOV-3 cells by targeting STAT3. Oral administration of 3 mg diindolylmethane per day and subsequent administration of cisplatin substantially inhibited in vivo tumor growth. Western blotting analysis of tumor lysates indicated increased apoptosis and reduced STAT3 activation.
These findings provide a rationale for further clinical investigation of DIM alone or in combination for chemoprevention and/or chemotherapy of ovarian cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Noise in quantum computers can result in biased estimates of physical observables. Accurate bias-free estimates can be obtained using probabilistic error cancellation, an error-mitigation technique ...that effectively inverts well-characterized noise channels. Learning correlated noise channels in large quantum circuits, however, has been a major challenge and has severely hampered experimental realizations. Our work presents a practical protocol for learning and inverting a sparse noise model that is able to capture correlated noise and scales to large quantum devices. These advances allow us to demonstrate probabilistic error cancellation on a superconducting quantum processor, thereby providing a way to measure noise-free observables at larger circuit volumes.Probabilistic error cancellation could improve the performance of quantum computers without the prohibitive overhead of fault-tolerant error correction. The method has now been demonstrated on a device with 20 qubits.
The authors examined sociodemographic, lifestyle, and comorbidity factors that could confound or mediate U-shaped associations between sleep duration and health in 6,472 United Kingdom adults from ...the Whitehall II Study (1997-1999) and 3,027 US adults from the Western New York Health Study (1996-2001). Cross-sectional associations between short (<6 hours) and long (>8 hours) durations of sleep across several correlates were calculated as multivariable odds ratios. For short sleep duration, there were significant, consistent associations in both samples for unmarried status (United Kingdom: adjusted odds ratio (AOR) = 1.49, 95% confidence interval (CI): 1.15, 1.94; United States: AOR = 1.49, 95% CI: 1.10, 2.02), body mass index (AORs were 1.04 (95% CI: 1.01, 1.07) and 1.02 (95% CI: 1.00, 1.05)), and Short Form-36 physical (AORs were 0.96 (95% CI: 0.95, 0.98) and 0.97 (95% CI: 0.96, 0.98)) and mental (AORs were 0.95 (95% CI: 0.94, 0.96) and 0.98 (95% CI: 0.96, 0.99)) scores. For long sleep duration, there were fewer significant associations: age among men (AORs were 1.08 (95% CI: 1.01, 1.14) and 1.05 (95% CI: 1.02, 1.08)), low physical activity (AORs were 1.75 (95% CI: 0.97, 3.14) and 1.60 (95% CI: 1.09, 2.34)), and Short Form-36 physical score (AORs were 0.96 (95% CI: 0.93, 0.99) and 0.97 (95% CI: 0.95, 0.99)). Being unmarried, being overweight, and having poor general health are associated with short sleep and may contribute to observed disease associations. Long sleep may represent an epiphenomenon of comorbidity.
Magnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions
...(for example, task functional MRI (fMRI)). Mental health research and care have yet to realize similar advances from MRI. A primary challenge has been replicating associations between inter-individual differences in brain structure or function and complex cognitive or mental health phenotypes (brain-wide association studies (BWAS)). Such BWAS have typically relied on sample sizes appropriate for classical brain mapping
(the median neuroimaging study sample size is about 25), but potentially too small for capturing reproducible brain-behavioural phenotype associations
. Here we used three of the largest neuroimaging datasets currently available-with a total sample size of around 50,000 individuals-to quantify BWAS effect sizes and reproducibility as a function of sample size. BWAS associations were smaller than previously thought, resulting in statistically underpowered studies, inflated effect sizes and replication failures at typical sample sizes. As sample sizes grew into the thousands, replication rates began to improve and effect size inflation decreased. More robust BWAS effects were detected for functional MRI (versus structural), cognitive tests (versus mental health questionnaires) and multivariate methods (versus univariate). Smaller than expected brain-phenotype associations and variability across population subsamples can explain widespread BWAS replication failures. In contrast to non-BWAS approaches with larger effects (for example, lesions, interventions and within-person), BWAS reproducibility requires samples with thousands of individuals.
We investigated the relationship between socio-economic status and child undernutrition in West Africa (WA), and further examined the mediating role of dietary practices (measured as minimum dietary ...diversity (MDD), minimum meal frequency (MMF) and minimum acceptable diet (MAD)) and household environmental quality (HEQ) in the observed relationship.
Thirteen countries were included in the study. We leveraged the most recent Demographic and Health Surveys datasets ranging from 2010 to 2019. Poisson regression model with robust standard errors was used to estimate prevalence ratios and their corresponding 95 % CI. Structural equation modelling was used to conduct the mediation analysis.
West Africa.
132 448 under-five children born within 5 years preceding the survey were included.
Overall, 32·5 %, 8·2 %, 20·1 % and 71·7 % of WA children were stunted, wasted, underweight and anaemic, respectively. Prevalence of undernutrition decreased with increasing maternal education and household wealth (Trend
-values < 0·001). Secondary or higher maternal education and residence in rich households were associated with statistically significant decrease in the prevalence of stunting, wasting, underweight and anaemia among children in WA. MAD was found to mediate the association of low maternal education and poor household wealth with childhood stunting and underweight by 35·9 % to 44·5 %. MDD, MMF and HEQ did not mediate the observed relationship.
The study findings enables an evaluation and improvement of existing intervention strategies through a socio-economic lens to help address the high burden of child undernutrition in WA and other developing regions.
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