LMD-18. Detection and serial monitoring of CSF ctDNA in breast cancer leptomeningeal disease (BCLM)

Background CSF cytology is the gold standard diagnostic test for BCLM, but is hampered by a low sensitivity, often necessitating repeated lumbar puncture to confirm or refute the diagnosis. Furthermore, during the treatment of BCLM, there is no robust quantitative response tool to guide treatment decisions. Material and Methods cfDNA was obtained from CSF and plasma in patients with breast cancer undergoing investigation for BCLM (n = 28) and during subsequent intrathecal treatment (n = 13). Ultra low pass whole genome sequencing (ulpWGS) and estimation of the ctDNA fraction was performed. Results were validated by mutation-specific digital droplet PCR (ddPCR). Results 22/28 cases had confirmed BCLM by positive MRI and/or CSF cytology. The remaining 6/28 had suspected but non-confirmed BCLM, and at median 20 months follow up, these patients were BCLM-free. CSF ctDNA fraction was significantly elevated (median 57.5, IQR 38.3 - 84.9%) in confirmed BCLM compared to 6 non-confirmed BCLM (median 5.0, IQR 0.0 - 6.7%) (p <0.0001). ctDNA fraction was detected in BCLM confirmed cases regardless of negative cytology or MRI. Plasma ctDNA fraction was only detected in extra-cranial disease progression. ctDNA fraction was concordant with mutant allele fraction measured by ddPCR (n = 118 samples). Serial CSF ctDNA fraction during intrathecal treatment showed dynamic changes, while CSF cytology and MRI were often unchanged or equivocal. Early reduction in CSF ctDNA fraction was associated with longer responses to intrathecal therapy. Further, rising ctDNA fraction during intrathecal chemotherapy could be detected up to 6 weeks before relapse in neurological symptoms, cytology or MRI. Conclusion Measuring CSF ctDNA fraction is a sensitive diagnostic test for BCLM and could lead to more timely and accurate diagnosis. During intrathecal chemotherapy, CSF ctDNA also provides a quantitative response biomarker to help guide clinical management in this difficult treatment scenario.

VISCOSITY OF GLUCOSE SOLUTIONS PREPARED IN WATER SUBJECTED TO AN ELECTROMAGNETIC FIELD

The paper presents the results of a study of the rheological properties of glucose solutions prepared using water exposed to an electromagnetic field with a frequency of 30 to 200 MHz. The studies were carried out with solutions with a concentration of 20%, the shear rate varied in the range of 100–1000 s-1. As a result of the study, a distinct influence of the influence of the electromagnetic field was found, while the quantitative response depends on the shear rate, frequency of the electromagnetic field and the time of exposure of water from the moment of field exposure to preparation of the solution. In the overwhelming majority of cases, there is a decrease in the viscosity of solutions at a shear rate of 1000 s-1 as a result of exposure to an electromagnetic field. A quantitative correlation between the change in viscosity and the frequency and time of post-field exposure was not found. In some cases (shear rate 200 and 500 s-1), there is a multidirectional change in viscosity versus exposure time. The results are compared with those previously obtained for agar solutions. A unidirectional change in the viscosity of glucose and agar solutions was found as a result of the action of an electromagnetic field on the solvent, which can serve as evidence of its structural reorganization. An explanation for the observed dependences is proposed, which is based on a change in the hydration interactions of glucose molecules in solution and, as a consequence, a change in the force and energy characteristics under shear stresses.

Can we put Humpty Dumpty back together again? What does protein quantification mean in bottom-up proteomics?

Bottom-up proteomics provides peptide measurements and has been invaluable for moving proteomics into large-scale analyses. In bottom-up proteomics, protein parsimony and protein inference derived from these measured peptides are important for determining which protein coding genes are present. However, given the complexity of RNA splicing processes, and how proteins can be modified post-translationally, it is overly simplistic to assume that all peptides that map to a singular protein coding gene will demonstrate the same quantitative response. Accordingly, by assuming all peptides from a protein coding sequence are representative of the same protein we may be missing out on detecting important biological differences. To better account for the complexity of the proteome we need to think of new or better ways of handling peptide data.

Quantitative response to nitrite from field-induced decomposition of the chloride adduct of RDX by reactive stage tandem ion mobility spectrometry

An additional dimension of selectivity for the determination of RDX by ion mobility spectrometry (IMS) was introduced through field-induced decomposition of RDX·Cl− to NO2− on a spectral baseline free of interfering peaks.

Regression models

This chapter evaluates regression models, focusing on the normal linear regression model. The normal linear regression model establishes a relationship between a quantitative response (also called outcome or dependent) variable, assumed to be normally distributed, and one or more explanatory (also called regression, predictor, or independent) variables about which no distributional assumptions are made. The model is usually referred to as 'the general linear model'. The chapter then differentiates between simple linear regression and multiple regression. The term 'simple linear regression' covers the regression model where there is one response variable and one explanatory variable, assuming a linear relationship between the two. The chapter also discusses the model formulae in R; generalized linear models; collinearity and aliasing; and logarithmic transformations.

Release Characteristics of Enoxaparin Sodium Loaded Polymethylmethacrylate Bone Cement

Background: This study aimed to prepare the polymethylmethacrylate (PMMA) bone cement release system with different concentrations of enoxaparin sodium (ES) and to investigate the release characteristics of ES after loading into the PMMA bone cement. Methods: In the experimental group, 40g Palacos®R PMMA bone cement was loaded with various amount of ES 4000, 8000, 12000, 16000, 20000, and 24000 AXaIU, respectively. The control group was not loaded with ES. Scanning electron microscopy (SEM) was used to observe the surface microstructure of the bone cement in the two groups. In the experiment group, the mold was extracted continuously with pH7.4 Tris-HCL buffer for 10 days. The extract solution was collected every day and the anti-FXa potency was measured. The experiment design and statistical analysis were conducted using a quantitative response parallel line method. Results: Under the SEM, it was observed that ES was filled in the pores of PMMA bone cement polymer structure and released from the pores after extraction. There was a burst effect of the release. The release amount of ES on the first day was 0.415, 0.858, 1.110, 1.564, 1.952 and 2.513 respectively from the six groups with various ES loading amount of 4000, 8000, 12000, 16000, 20000 and 24000 AXaIU, all reaching the peak of release on the first day. The release decreased rapidly on the next day and entered the plateau phase on the fourth day. Conclusion: PMMA bone cement can be used as a carrier to effectively release enoxaparin sodium within a short term.

Comparative Studies of Reproductive Diapause in North American Populations of Three Hippodamia Species (Coleoptera: Coccinellidae)

Quantifying responses of three congeneric species of lady beetles, Hippodamia parenthesis (Say), Hippodamia convergens (Guerin), and Hippodamia variegata (Goeze) (Coleoptera: Coccinellidae), to abiotic factors that influence their seasonal biology provides an understanding of the phenology of these species in North America. The developmental response and the induction and duration of adult hibernal diapause in four North American populations of H. parenthesis, collected between 40° N and 44° N latitude, was determined when beetles were reared at four photoperiods (L:D 16:8, 14:10, 12;12, and 10:14) at 22°C. Preimaginal development of the four H. parenthesis populations reared at the photoperiods was affected by population, photoperiod, and the interaction between population and photoperiod. Fifteen to 19% of H. parenthesis females reared at L:D 16:8 entered diapause, whereas shorter photoperiods (L:D 12:12 and 10:14) induced diapause in all females. Variation in response to L:D 14:10 was observed among the four populations of H. parenthesis, similar to the response observed in H. convergens and H. variegata. In contrast to the response of H. parenthesis females, in which four individuals oviposited at L:D 12:12 or 10:14 within 120 d, the duration of reproductive diapause in H. convergens and H. variegata females at L:D 12:12 and 10:14 showed a prolonged quantitative response to photoperiod. Comparisons of the responses (days to first oviposition) to photoperiod of H. parenthesis and H. variegata from the same collection sites showed significant differences at most photoperiods. Similarly, responses at all photoperiods varied between H. parenthesis and H. convergens from similar latitudes in Iowa.