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Exploration of PET and MRI radiomic features for decoding breast cancer phenotypes and prognosis.
Radiomics is an emerging technology for imaging biomarker discovery and disease-specific personalized treatment management. This paper aims to determine the benefit of using multi-modality radiomics data from PET and MR images in the characterization breast cancer phenotype and prognosis. Eighty-four features were extracted from PET and MR images of 113 breast cancer patients. Unsupervised clustering based on PET and MRI radiomic features created three subgroups. These derived subgroups were statistically significantly associated with tumor grade (pβ=β2.0βΓβ10-6), tumor overall stage (pβ=β0.037), breast cancer subtypes (pβ=β0.0085), and disease recurrence status (pβ=β0.0053). The PET-derived first-order statistics and gray level co-occurrence matrix (GLCM) textural features were discriminative of breast cancer tumor grade, which was confirmed by the results of L2-regularization logistic regression (with repeated nested cross-validation) with an estimated area under the receiver operating characteristic curve (AUC) of 0.76 (95% confidence interval (CI)β=β[0.62, 0.83]). The results of ElasticNet logistic regression indicated that PET and MR radiomics distinguished recurrence-free survival, with a mean AUC of 0.75 (95% CIβ=β[0.62, 0.88]) and 0.68 (95% CIβ=β[0.58, 0.81]) for 1 and 2 years, respectively. The MRI-derived GLCM inverse difference moment normalized (IDMN) and the PET-derived GLCM cluster prominence were among the key features in the predictive models for recurrence-free survival. In conclusion, radiomic features from PET and MR images could be helpful in deciphering breast cancer phenotypes and may have potential as imaging biomarkers for prediction of breast cancer recurrence-free survival
The MOSDEF Survey: Kinematic and Structural Evolution of Star-Forming Galaxies at
We present ionized gas kinematics for 681 galaxies at from
the MOSFIRE Deep Evolution Field survey, measured using models which account
for random galaxy-slit misalignments together with structural parameters
derived from CANDELS Hubble Space Telescope (HST) imaging. Kinematics and sizes
are used to derive dynamical masses. Baryonic masses are estimated from stellar
masses and inferred gas masses from dust-corrected star formation rates (SFRs)
and the Kennicutt-Schmidt relation. We measure resolved rotation for 105
galaxies. For the remaining 576 galaxies we use models based on HST imaging
structural parameters together with integrated velocity dispersions and
baryonic masses to statistically constrain the median ratio of intrinsic
ordered to disordered motion, . We find that
increases with increasing stellar mass and decreasing specific SFR (sSFR).
These trends may reflect marginal disk stability, where systems with higher gas
fractions have thicker disks. For galaxies with detected rotation we assess
trends between their kinematics and mass, sSFR, and baryon surface density
(). Intrinsic dispersion correlates most with
and velocity correlates most with mass. By comparing
dynamical and baryonic masses, we find that galaxies at are
baryon dominated within their effective radii (), with Mdyn/Mbaryon
increasing over time. The inferred baryon fractions within ,
, decrease over time, even at fixed mass, size, or surface
density. At fixed redshift, does not appear to vary with
stellar mass but increases with decreasing and increasing
. For galaxies at , the median inferred baryon
fractions generally exceed 100%. We discuss possible explanations and future
avenues to resolve this tension.Comment: Accepted to ApJ. Added Figure 9, corrected sample size (main results
unchanged). 28 pages, 13 figure
Embodied Knowledge: Writing Researchersβ Bodies Into Qualitative Health Research
After more than a decade of postpositivist health care research and an increase in narrative writing practices, social scientific, qualitative health research remains largely disembodied. The erasure of researchersβ bodies from conventional accounts of research obscures the complexities of knowledge production and yields deceptively tidy accounts of research. Qualitative health research could benefit significantly from embodied writing that explores the discursive relationship between the body and the self and the semantic challenges of writing the body by incorporating bodily details and experiences into research accounts. Researchers can represent their bodies by incorporating autoethnographic narratives, drawing on all of their senses, interrogating the connections between their bodily signifiers and research processes, and experimenting with the semantics of self and body. The author illustrates opportunities for embodiment with excerpts from an ethnography of a geriatric oncology team and explores implications of embodied writing for the practice of qualitative health research
Analysis of thrombogenicity under flow reveals new insights into the prothrombotic state of patients with post-COVID syndrome
Background: Post-COVID syndrome (PCS) affects millions of people worldwide, causing a multitude of symptoms and impairing quality of life months or even years after acute COVID-19. A prothrombotic state has been suggested; however, underlying mechanisms remain to be elucidated. /
Objectives: To investigate thrombogenicity in PCS using a microfluidic assay, linking microthrombi, thrombin generation, and the von Willebrand factor (VWF):a Disintegrin and Metalloproteinase with a Thrombospondin Type 1 motif, member 13 (ADAMTS13) axis. /
Methods: Citrated blood was perfused through microfluidic channels coated with collagen or an antibody against the VWF A3 domain, and thrombogenicity was monitored in real time. Thrombin generation assays were performed and Ξ±(2)-antiplasmin, VWF, and ADAMTS13 activity levels were also measured. /
Results: We investigated thrombogenicity in a cohort of 21 patients with PCS with a median time following symptoms onset of 23 months using a dynamic microfluidic assay. Our data show a significant increase in platelet binding on both collagen and anti-VWF A3 in patients with PCS compared with that in controls, which positively correlated with VWF antigen (Ag) levels, the VWF(Ag):ADAMTS13 ratio (on anti-VWF A3), and inversely correlated with ADAMTS13 activity (on collagen). Thrombi forming on collagen presented different geometries in patients with PCS vs controls, with significantly increased thrombi area mainly attributable to thrombi length in the patient group. Thrombi length positively correlated with VWF(Ag):ADAMTS13 ratio and thrombin generation assay results, which were increased in 55.5% of patients. Ξ±(2)-Antiplasmin levels were normal in 89.5% of patients. /
Conclusion: Together, these data present a dynamic assay to investigate the prothrombotic state in PCS, which may help unravel the mechanisms involved and/or establish new therapeutic strategies for this condition
Ξ<sup>9</sup>-tetrahydrocannabinol and 2-AG decreases neurite outgrowth and differentially affects ERK1/2 and Akt signaling in hiPSC-derived cortical neurons
Endocannabinoids regulate different aspects of neurodevelopment. In utero exposure to the exogenous psychoactive cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC), has been linked with abnormal cortical development in animal models. However, much less is known about the actions of endocannabinoids in human neurons. Here we investigated the effect of the endocannabinoid 2-arachidonoyl glycerol (2AG) and Δ9-THC on the development of neuronal morphology and activation of signaling kinases, in cortical neurons derived from human induced pluripotent stem cells (hiPSCs). Our data indicate that the cannabinoid type 1 receptor (CB1R), but not the cannabinoid 2 receptor (CB2R), GPR55 or TRPV1 receptors, is expressed in young, immature hiPSC-derived cortical neurons. Consistent with previous reports, 2AG and Δ9-THC negatively regulated neurite outgrowth. Interestingly, acute exposure to both 2AG and Δ9-THC inhibited phosphorylation of serine/threonine kinase extracellular signal-regulated protein kinases (ERK1/2), whereas Δ9-THC also reduced phosphorylation of Akt (aka PKB). Moreover, the CB1R inverse agonist SR 141716A attenuated the decrease in neurite outgrowth and ERK1/2 phosphorylation induced by 2AG and Δ9-THC. Taken together, our data suggest that hiPSC-derived cortical neurons express CB1Rs and are responsive to exogenous cannabinoids. Thus, hiPSC-neurons may represent a good cellular model for investigating the role of the endocannabinoid system in regulating cellular processes in developing human neurons
Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity
TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5Ξ± but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations
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