Mammographic Image Denoising and Enhancement Using the Anscombe Transformation, Adaptive Wiener Filtering, and the Modulation Transfer Function

A new restoration methodology is proposed to enhance mammographic images through the improvement of contrast features and the simultaneous suppression of noise. Denoising is performed in the first step using the Anscombe transformation to convert the signal-dependent quantum noise into an approximately signal-independent Gaussian additive noise. In the Anscombe domain, noise is filtered through an adaptive Wiener filter, whose parameters are obtained by considering local image statistics. In the second step, a filter based on the modulation transfer function of the imaging system in the whole radiation field is applied for image enhancement. This methodology can be used as a preprocessing module for computer-aided detection (CAD) systems to improve the performance of breast cancer screening. A preliminary assessment of the restoration algorithm was performed using synthetic images with different levels of quantum noise. Afterward, we evaluated the effect of the preprocessing on the performance of a previously developed CAD system for clustered microcalcification detection in mammographic images. The results from the synthetic images showed an increase of up to 11.5 dB (p = 0.002) in the peak signal-to-noise ratio. Moreover, the mean structural similarity index increased up to 8.3 % (p < 0.001). Regarding CAD performance, the results suggested that the preprocessing increased the detectability of microcalcifications in mammographic images without increasing the false-positive rates. Receiver operating characteristic analysis revealed an average increase of 14.1 % (p = 0.01) in overall CAD performance when restored image sets were used.     

Mechanistic QSAR of aromatic amines: new models for discriminating between homocyclic mutagens and nonmutagens, and validation of models for carcinogens

Because of its environmental and industrial importance, the aromatic amines are the single chemical class most studied for its ability to induce mutations and cancer. The large database of mutagenicity and carcinogenicity results has been studied with Quantitative Structure-Activity Relationship (QSAR) approaches by several authors, leading to models for the following: (a) the mutagenic potency in Salmonella thyphimurium; (b) the carcinogenic potency in rodents; and (c) the discrimination between rodent carcinogens and noncarcinogens. However, satisfactory models for the discrimination between mutagens and nonmutagens are lacking. The present work provides new QSARs for mutagenic/nonmutagenic homocyclic aromatic amines in S. typhimurium strains TA98 and TA100. The two new models are validated by checking their ability to predict the mutagenicity of further aromatic amines not included in the training set, and not used to generate the QSAR models. In addition, we also validated previous QSAR models for the carcinogenicity/noncarcinogenicity of the aromatic amines with external data. The mechanistic implications of the models are discussed in light of the other QSARs for the aromatic amines. The results of the analysis point to two QSAR models (one for mutagenicity and one for rodent carcinogenicity) as reliable tools for the in silico characterization of the risk posed by the aromatic amines.     

Prospective Study Testing a Simplified Paclitaxel Premedication Regimen in Patients with Early Breast Cancer

Background

In early trials, hypersensitivity reactions (HSRs) to paclitaxel were common, thus prompting the administration of antihistamines and corticosteroids before every paclitaxel dose. We tested the safety of omitting corticosteroids after cycle 2 during the paclitaxel portion of the dose-dense (DD) doxorubicin-cyclophosphamide (AC)–paclitaxel regimen.

Patients, Materials, and Methods

In this prospective, single-arm study, patients who completed four cycles of DD-AC for stage I–III breast cancer received paclitaxel 175 mg/m² every 2 weeks for four cycles. Patients received a standard premedication protocol containing dexamethasone, diphenhydramine, and a histamine H2 blocker prior to the first two paclitaxel cycles. Dexamethasone was omitted in cycles three and four if there were no HSRs in previous cycles. We estimated the rate of grade 3–4 HSRs.

Results

Among 127 patients enrolled, 125 received more than one dose of protocol therapy and are included in the analysis. Fourteen (11.2%; 90% confidence interval, 6.9%–20.0%) patients had any-grade HSRs, for a total of 22 (4.5%; 3.1%–6.4%) HSRs over 486 paclitaxel cycles. Any-grade HSRs occurred in 1.6% (0.3%–5.0%), 6.5% (3.3%–11.3%), 7.4% (3.9%–12.5%), and 2.6% (0.7%–6.6%) of patients after paclitaxel cycles 1, 2, 3, and 4, respectively. Dexamethasone use was decreased by 92.8% in cycles 3 and 4. Only one patient experienced grade 3 HSR in cycles 3 or 4, for a rate of grade 3/4 HSR 0.4% (0.02%–2.0%) (1/237 paclitaxel infusions). That patient had grade 2 HSR during cycle 2, and the subsequent grade 3 event occurred despite usual dexamethasone premedication. A sensitivity analysis restricted to patients not known to have received dexamethasone in cycles 3 and 4 found that any-grade HSRs occurred in 2.7% (3/111; 0.7%–6.8%) and 0.9% (1/109; 0.05%–4.3%) of patients in cycle 3 and 4, respectively.

Conclusion

Corticosteroid premedication can be safely omitted in cycles 3 and 4 of dose-dense paclitaxel if HSRs are not observed during cycles 1 and 2.

Implications for Practice

Because of the potential for hypersensitivity reactions (HSRs) to paclitaxel, corticosteroids are routinely prescribed prior to each dose, on an indefinite basis. This prospective study, including 125 patients treated with 486 paclitaxel cycles, demonstrates that corticosteroids can be safely omitted in future cycles if HSRs did not occur during cycles 1 and 2 of paclitaxel and that this strategy reduces the use of corticosteroids in cycles 3 and 4 by 92.8% relative to current standard of care.

     

Changes in skeletal muscle oxygenation during incremental exercise measured with near infrared spectroscopy

To determine the change in muscle oxygenation in response to progressively increasing work rate exercise, muscle oxyhemoglobin + oxymyoglobin saturation was measured transcutaneously with near infrared spectroscopy in the vastus lateralis muscle during cycle ergometry. Studies were done in 11 subjects while gas exchange was measured breath-by-breath. As work rate was increased, tissue oxygenation initially either remained constant near resting levels or, more usually, decreased. Near the work rate and metabolic rate where significant lactic acidosis was detected by excess CO₂ production (lactic acidosis threshold, LAT), muscle oxygenation decreased more steeply. As maximum oxygen uptake ( ) was approached, the rate of desaturation slowed. In 8 of the 11 subjects, tissue O₂ saturation reached a minimum which was sustained for 1–3 min before was reached. The LAT correlated with both the (r = 0.95,P < 0.0001) and the work rate (r = 0.94,P < 0.0001) at which the rate of tissue O₂ desaturation accelerated. These results describe a consistent pattern in the rate of decrease in muscle oxygenation, slowly decreasing over the lower work rate range, decreasing more rapidly in the work rate range of the LAT and then slowing at about 80% of , approaching or reaching a minimum saturation at .     

Transformation of Old Concepts for a New Era of Cancer Immunotherapy: Cytokine Therapy and Cancer Vaccines as Combination Partners of PD1/PD-L1 Inhibitors

Purpose of Review

Immune checkpoint inhibitors (ICI) are only effective in a subset of patients. Here, we will review the rationale and data supporting the combination of PD-1 pathway inhibition with recombinant cytokines and neoantigen-based cancer vaccines that can potentially increase the number of patients who will benefit from immunotherapy.

Recent Findings

The safety and tolerability of new interleukin(IL)-2 formulations, IL-15 super agonist, and PEGylated IL-10 have been evaluated in early phase clinical trials with promising efficacy data, both as monotherapy and in combination with ICI. Larger studies focusing on the efficacy of these combinations are ongoing. Personalized neoantigen-based cancer vaccines, enabled by improvements in sequencing computational capabilities, have been proven to be feasible, safe, and able to trigger a consistent vaccine-specific immune response in cancer patients.

Summary

New pharmacologically modified recombinant cytokines and personalized neoantigen-based vaccines may turn these approaches into powerful tools for effective combination immunotherapy.

     

Complex yessotoxins profile in Protoceratium reticulatum from north-western Adriatic sea revealed by LC-MS analysis.

While the occurrence of yessotoxin (YTX) has been reported worldwide from Protoceratium reticulatum, the biogenetic origin of some YTX analogues is still unknown, thus raising an issue whether they are metabolites of YTX formed in mussels or true products of different dinoflagellate species. Findings reported herein suggest that P. reticulatum from the north-western Adriatic sea is responsible for production, together with YTX (1), of homoYTX (2), 45-OHYTX (3), carboxyYTX (5), and noroxoYTX (7). YTX and its analogues have been determined by high performance liquid chromatography coupled with electrospray ion trap mass spectrometry (HPLC-MS and HPLC-MSn experiments). The result is the first to confirm production of these YTX analogues from this species and indicate it as a producing organism of homoYTX, 45-OHYTX, carboxyYTX, and noroxoYTX found in shellfish.     

Volatile organic compounds (VOCs) and air mutagenicity: Results of one year monitoring at an urban site

The concentrations of four volatile organic compounds (VOCs: benzene, toluene, ethylbenzene and xylenes) and the levels of inhalable (< 10 μm) airborne particles were monitored during 1 year at a site with intense vehicular traffic in the city of Rome. VOCs as well as airborne particulate matter were sampled every alternate day and pooled in fortnightly samples representative of the first and second half of each month. Some meteorological parameters (mean temperature, heliophany, air pressure and relative humidity) were concurrently recorded. Air particulate extracts were tested for mutagenicity in the Salmonella reversion system with tester strain TA98. Air mutagenicity levels were compared to air concentrations of benzene and alkylbenzenes, putative indicators of vehicular traffic, in order to elucidate their interrelationships. The results of multivariate statistical analyses show that seasonal variations in air mutagenicity are mainly dependent on the increased content of organic matter in airborne particles, possibly resulting from the increased deposition rate of semivolatile compounds with low ambient temperature. A weaker association was observed between air mutagenicity level and VOCs concentrations.