PurposeNeoadjuvant chemotherapy (NAC) has a well-established role in locally advanced or chemoresponsive breast cancers (BC). Chemotherapic regimens are effective when patients receive the optimal doses. Toxicities are common in overweight/obese patients but may occur also in normal weight counterparts. This leads to delays, reductions, or discontinuation of treatment, with impact on outcomes. Current dosing is based on body weight and predicted Body Surface Area (BSA). These parameters do not take into consideration the individual variations of fat mass (FM) and fat-free mass (FFM) that affect pharmacokinetics. Assessment of body composition (BoCo), rather than Body Mass Index (BMI), could help to better plan chemotherapy and reduce drug-related toxicities. Our aim was to analyze the correlations between body weight, anthropometric measures, BoCO, and toxicities related to NAC in non-metastatic BC patients.MethodsThis is a retrospective observational cohort study that includes 120 consecutive BC patients undergoing NAC, enrolled between May 2018 and December 2020. All patients received an evaluation of anthropometric parameters (height, weight, waist and hip circumference, BMI) and an assessment of BoCo using Segmental Multi-Frequency-Bioelectrical Impedance Analysis.ResultsA logistic regression models confirmed that a higher FM was associated with a higher rate of neurological and hematologic toxicities in protocols containing Platinum. Moreover, patients with a low FFM% have a higher risk for hematologic toxicity in protocols containing Platinum.ConclusionA routine assessment of BoCo, in addition to evaluation of anthropometric measures and BMI, could allow to personalize chemotherapy doses, in order to reduce chemotherapy-related toxicities.
Background: Invasive lobular carcinoma (ILC) of the breast is the second most common histologic subtype of breast cancer. Specifically due to the lack of e-caderine, ILC has the tendency to be multifocal/multicentric and bilateral with a diffuse growth pattern. Moreover, one of the main challenges is obtain clear margins despite the under/overestimation of the lesions on mammography and US, while breast MRI has been widely recognized as the most reliable imaging method for surgical planning. Data about best surgical treatment remains conflicting for ILC and mastectomy has traditionally been chosen as the safest treatment. The aim of this retrospective study is to affirm that level I and II oncoplastic surgery (OPS) is a safe and effective treatment in patients with ILC accurately studied with MRI.
Determining the surface on which a vehicle is moving is vital information for improving active safety systems. Performing the surface classification or estimating adherence through tire slippage can lead to late action in possible risk situations. Currently, approaches based on image, sound, and vibration analysis are emerging as a viable alternatives, though sometimes complex. This work proposes a methodology based on the use of low-cost accelerometers combined with Deep Learning techniques to achieve continuous surface estimation. The performance of the proposed system is evaluated with real tests, where high percentages of accuracy are obtained in the classification task.
Paget's disease (PD) represents 1-3% of all breast cancers and mostly occurs in postmenopausal women. Multiple studies have certified that breast conserving surgery (BCS) followed by radiotherapy is a feasible option for patients with in situ or invasive PD, ensuring local control and survival rates similar to those achieved with mastectomy. We retrospectively analyzed 115 patients (111 women, 4 men) affected by PD treated in our Institution between January 2000 and May 2021. Median age at diagnosis was 60 years and median follow-up 82 months (range 2 - 230); 69 patients were treated with breast conserving surgery (BCS) and 46 with modified radical mastectomy or skin sparing mastectomy. Sentinel lymph node biopsy (SLNB) was performed in all cases of underlying invasive carcinoma and in high-risk patients with 32 cases with positive node status. All patients treated with BCS underwent to radiation therapy; 35 patients received adjuvant chemotherapy. At histological examination 59 patients (51%) had an underlying invasive carcinoma; in 11 patients (9%), only PD was found. In 45 patients (40%) was found a non-invasive cancer alone. Nine patients (7,8%) developed a local recurrence, 7 patients (6%) are alive with distant metastasis and 10 patients (8,6%) died. In our series no statistically differences were shown between PD alone, PD associated with in situ or PD with invasive cancer, regardless of the surgical procedure. BCS followed by radiotherapy was confirmed as effective and safe for selected patients affected by PD. According to our search in the Literature, this is one of the largest series of PD at a single center, even though the retrospective analysis presents obvious limitations and more than half of the patients were operated between 2015 and 2021, thus requiring longer periods of observation. Paget's Disease is a rare form of breast cancer and in half of cases is associated with an invasive carcinoma. Separating our sample into three subgroups based on tumor histology there were no significant differences in term of LC, DFS and OS rate in patients treated with different type of surgery. The correct treatment strategies and the prognosis depend on staging and pathological features of the underlying disease.
Introduction: Granular cell tumor is a rare neoplasm of soft tissue and only in 1% of cases, it can shows a malignant behaviour. It is presumed to be a tumor originating from perineural or putative Schwann cells of peripheral nerves. Materials and Methods: We reviewed five patients affected by Granular cell tumor of the breast treated between January 2011 and January 2021 at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS of Rome, Italy. Results: All of the granular cell tumors presented as solitary, painless and firm lump, highly suggestive of malignancy. The radiological findings were heterogeneous and non-specific. All lesions presented as masses, more clearly evident on ultrasound as hypoechoic lesions, with irregular shape, blurred contours and borderline features. The tumors were composed of large polygonal cells with abundant eosinophilic granular cytoplasm and small, central nuclei, being immunohistochemically positive for S100, Vimentin (with variable staining), CD56; negative for HMB45, MelanA, AE1/AE3, EMA, and Desmin. Conclusion: Granular cell tumor is a rare, usually benign breast disease that can have very similar characteristics to breast cancer both clinically and radiologically. Treatment of choice consists in wide resection or lumpectomy with margin assessment (no ink on tumor).
Abstract We previously studied synchronous ductal carcinomas in situ (DCIS) and invasive ductal carcinomas (IDC) using our novel approach of multiplex interphase Fluorescence in situ Hybridization (miFISH) that allows simultaneous enumeration of copy numbers of up to 20 gene loci per single cell, providing new insights into tumor clonality and intratumor heterogeneity (ITH). A high degree of chromosomal instability was present in DCIS, and we frequently observed a direct clonal evolution from DCIS to IDC. We now ask whether this degree of instability is also present in even earlier potential precursor lesions like atypical ductal hyperplasias (ADH). We are therefore conducting a retrospective study analyzing ADH lesions from patients without synchronous DCIS or IDC (pure ADH) and from patients with ADH adjacent to higher-grade lesions. Using our miFISH assay, we simultaneously assess copy number changes of six oncogenes (COX2 (1q), PIK3CA (3q), MET (7q), MYC (8q), CCND1 (11q), HER2 (17q), ZNF217 (20q)) and six tumor suppressor genes (FHIT (3p), DBC2 (8p), RB1 (13q), CDH1 (16q), TP53 (17q), NF2 (22q), typical for breast tumorigenesis. So far, we have analyzed fifteen pure ADH and five ADH with synchronous DCIS or IDC. The miFISH analysis showed that the majority of all pure ADH displayed a stable diploid genome without any copy number changes observed for the genes tested while only 3/15 (20%) showed changes, namely (i) a COX2 and HER2 gain in a diploid genome, (ii) a CDH1and MET loss in a tetraploid genome and (iii) a COX2 gain in a diploid genome. In the group of ADH with adjacent higher-grade lesions (n=5), all DCIS and IDC lesions analyzed displayed breast cancer specific copy number changes corroborating our previous results. Of note, two of the ADH lesions adjacent to these aberrant DCIS or IDC lesions had normal diploid genomes. Of the remaining three synchronous ADH lesions, one showed a complex gain and loss pattern similar to its adjacent DCIS, the second one was characterized by a simple COX2 gain which was maintained in the adjacent DCIS in addition to a DBC2 loss and MYC gain. The third ADH displayed a tetraploid clone without any gains or losses, while the adjacent IDC revealed a complex gain and loss pattern in its tetraploid genome. Our preliminary data indicate that the majority of pure ADH does not harbor copy number changes. However, there is a small subset of pure ADH revealing gain and loss patterns typical for DCIS and IDC often involving COX2 gain indicating it as an early event. Of note, ADH lesions adjacent to DCIS or IDC tend to display similar changes as their adjacent higher-grade lesions suggesting them as direct precursor lesions. We are currently analyzing more ADH samples and plan to add material from an ADH patient cohort with long-term follow-up to explore whether miFISH can stratify ADH patients into different risk groups. Citation Format: Kiara Whitaker, Jausheng Tzeng, Daniela Hirsch, Irianna Torres, Steven Brower, Gert Auer, Miguel Sanchez, Thomas Ried, Kerstin Heselmeyer-Haddad. miFISH single cell analysis as a potential tool to stratify the progression risk in patients with Atypical Ductal Hyperplasia (ADH) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2498.
Abstract Our previous studies of synchronous Ductal Carcinomas in Situ (DCIS) and Invasive Ductal Carcinomas (IDC) often showed a high degree of chromosomal instability already in DCIS, and frequently a direct clonal evolution from DCIS to IDC. We now asked the question whether this degree of instability is also present in DCIS that did not progress to IDC. In collaboration with Englewood Hospital and Medical Center, we are therefore conducting a retrospective study analyzing FFPE material from 20 DCIS patients with low-grade or high-grade DCIS who did not present with invasive breast carcinoma during their follow-up (5-10 years) and compared the findings to 10 DCIS patients who presented with synchronous IDC. Using our novel multiplex interphase FISH (miFISH) assay, we are able to determine copy number changes of five oncogenes (COX2, MYC, CCND1, HER2, ZNF217) and three tumor suppressor genes (DBC2, CDH1, TP53) and assessed intratumor heterogeneity (ITH) and clonal evolution during disease progression. The miFISH analysis showed that low-grade DCIS displayed mostly stable patterns of gene copy numbers in a diploid genome, while high-grade DCIS frequently had increased nuclear DNA content (ploidy) associated with a higher degree of ITH. However, some low-grade DCIS exhibited complex and unstable patterns with higher ploidy. Also, a few high-grade DCIS were defined by few copy number changes, e.g., the gain of a whole chromosome 8 (DBC and MYC), resulting in a clonal population with a low instability index. DCIS and their synchronous IDC often displayed very similar miFISH patterns indicating direct expansion of dominant clones. Of note, the DCIS cells of one case were defined by the well described 1q gain/16q loss pattern and acquired subsequently a chromosome 8 gain in the IDC, confirming our previous observation that the gain of MYC is a pivotal step in breast cancer progression. Our data also show that DCIS with or without synchronous IDC exhibited similar patterns. This could indicate that DCIS in general, regardless of grading, should be treated as lesions with progressive potential. Phylogenetic tree modeling with our custom FISHtrees software will further elucidate the dynamics of DCIS lesions. In summary, miFISH analysis and phylogenetic tree modeling allow an in-depth characterization of precursor lesions and their evolutionary trajectory. We anticipate that this approach will ultimately help to stratify progression risk in patients with DCIS. Citation Format: Irianna Marie Torres, Leanora Hernandez, Jausheng Tzeng, Russell Schwartz, Alejandro Schaffer, Edward Michael Gertz, Daniela Hirsch, Steven Brower, Miguel Sanchez, Gert Auer, Kerstin Heselmeyer-Haddad, Thomas Ried. Genomic dynamics in breast cancer progression analyzed by miFISH analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2189.
Zircon sand plays an important role in the ceramic industry. The presence of the long-lived radionuclides of uranium and thorium in the zircon sand means this material should be considered as NORM and therefore it is necessary to determine the makeup of the radionuclides present and their activity concentration. In this paper, a simple method of total sample dissolution has been set up for its subsequent measurement by alpha-particle spectrometry. Gamma spectrometry and alpha-particle spectrometry have been jointly used to determine the radionuclide content and also to check the condition of radioactive equilibrium among the radionuclides, commonly used in gamma spectrometry.
Abstract We previously studied synchronous Ductal Carcinomas in Situ (DCIS) and Invasive Ductal Carcinomas (IDC) using a novel approach of multiplexing FISH probes that allows us to simultaneously assess the copy numbers of up to 20 loci within intact nuclei providing new insights into tumor clonality and heterogeneity. A high degree of chromosomal instability already in DCIS, and frequently, but not always, a direct clonal evolution from DCIS to IDC was detected. We now ask whether this degree of instability is also present in DCIS that did not progress to IDC and are therefore analyzing FFPE material from 20 patients with either low-grade and high-grade DCIS who did not present with invasive breast carcinoma during their follow-up (5-10 years), in addition to 10 patients who presented with synchronous IDC. The multiplex FISH assay used targets five oncogenes (COX2, MYC, CCND1, HER2, ZNF217) and three tumor suppressor genes (DBC2, CDH1, TP53) frequently altered in breast carcinomas. To date, we have analyzed two paired cases of synchronous DCIS and IDC, DCIS-IDC 3 and 4, and three cases of DCIS without IDC, OP-DCIS 1, 4 and 5. The paired cases exhibited very similar aberration patterns for synchronous DCIS and IDC indicating the invasive carcinoma is closely related to the DCIS lesion. Specifically, the major clones in DCIS 3 (low-grade) and IDC 3 showed a diploid tumor cell population with a gain of COX2, and losses of DBC2, MYC, TP53, and HER2. Of note, the only difference observed was a gain of ZNF217 in the DCIS which was not seen in the major clone of the invasive carcinoma. The other paired case, DCIS 4 (high-grade) and IDC 4, showed major clones of triploid tumor cell populations with gains of COX2, CCND1 and MYC and losses of DBC2, CDH1, TP53 and ZNF217. The three DCIS cases without synchronous or subsequent IDC exhibited varying degrees of aberration and complexity patterns in their clonal populations. Case OP-DCIS 1, a high-grade DCIS, revealed a tetraploid cell population which showed a major clone with an amplification of CCND1 and a MYC gain combined with losses of DBC2, CDH1, TP53 and HER2. A low-grade DCIS, OP-DCIS 4, exhibited a diploid cell population with a major clone showing loss of CDH1 as the only aberration. The third case OP-DCIS 5 (low-grade DCIS) exhibited a diploid cell population with one major clone showing losses of CDH1, MYC, DBC2, TP53, HER2 and CCND1. Our preliminary observations show a tendency of diploid lesions with a predominance of loss patterns for low-grade DCIS, while high-grade DCIS seem to reveal higher ploidy with more complex gain and loss patterns. However, also low-grade DCIS with mainly loss patterns progress to invasive cancers as seen in case DCIS-IDC3. We expect that the analysis of the remaining cases will further elucidate the dynamics of DCIS lesions which will hopefully help to assess and stratify progression risk in patients with DCIS. Citation Format: Irianna Marie Torres, Leanora Hernandez, Jausheng Tzeng, Russell Schwartz, Alejandro Schaffer, Edward Gertz, Stephen Brower, Miguel Sanchez, Gert Auer, Kerstin Heselmeyer-Haddad, Ried Thomas. Single-cell genetic analysis of ductal carcinoma in situ with and without synchronous invasive breast cancer by multiplex FISH delineates specific patterns of tumor clonality and heterogeneity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2908. doi:10.1158/1538-7445.AM2017-2908
SummaryGM crops are the most studied crops in history. Approximately 5% of the safety studies on them show adverse effects that are a cause for concern and tend to be featured in media reports. Although these reports are based on just a handful of GM events, they are used to cast doubt on all GM crops. Furthermore, they tend to come from just a few laboratories and are published in less important journals. Importantly, a close examination of these reports invariably shows methodological flaws that invalidate any conclusions of adverse effects. Twenty years after commercial cultivation of GM crops began, a bona fide report of an adverse health effect due to a commercialized modification in a crop has yet to be reported.
The potential impact of genetically modified (GM) crops on biodiversity is one of the main concerns in an environmental risk assessment (ERA). The likelihood of outcrossing and pollen-mediated gene flow from GM crops and non-GM crops are explained by the same principles and depend primarily on the biology of the species. We conducted a national-scale study of the likelihood of outcrossing between 11 GM crops and vascular plants in Chile by use of a systematized database that included cultivated, introduced and native plant species in Chile. The database included geographical distributions and key biological and agronomical characteristics for 3505 introduced, 4993 native and 257 cultivated (of which 11 were native and 246 were introduced) plant species. Out of the considered GM crops (cotton, soya bean, maize, grape, wheat, rice, sugar beet, alfalfa, canola, tomato and potato), only potato and tomato presented native relatives (66 species total). Introduced relative species showed that three GM groups were formed having: a) up to one introduced relative (cotton and soya bean), b) up to two (rice, grape, maize and wheat) and c) from two to seven (sugar beet, alfalfa, canola, tomato and potato). In particular, GM crops presenting introduced noncultivated relative species were canola (1 relative species), alfalfa (up to 4), rice (1), tomato (up to 2) and potato (up to 2). The outcrossing potential between species [OP; scaled from very low' (1) to very high' (5)] was developed, showing medium OPs (3) for GM-native relative interactions when they occurred, low (2) for GMs and introduced noncultivated and high (4) for the grape-Vitis vinifera GM-introduced cultivated interaction. This analytical tool might be useful for future ERA for unconfined GM crop release in Chile.
With the inclusion of ubiquitous computing in education, it is intended that the student is an active agent in its formation process and interacts with its context. This paper presents the design and implementation of architecture for ubiquitous learning environments in which they integrate physical spaces with applications which are then executed by users. The system supports objects augmented with RFID tags, NFC and QR Code. Each tag contains data that uniquely identifies the resource. To validate the proposed architecture is developed experimentally tested a prototype at the end of it is done to verify that the proposed architecture improves the academic performance of students.
Background: Songbirds are a preeminent animal model for understanding the neural basis underlying the development and evolution of a complex learned behavior, bird song. However, only a few quantitative methods exist to analyze these species-specific sequential behaviors in multiple species using the same calculation method.New method: We report a method of analysis that focuses on calculating the frequency of characteristic syllable transitions in songs. This method comprises two steps: The first step involves forming correlation matrices of syllable similarity scores, named syllable similarity matrices (SSMs); these are obtained by calculating the round-robin comparison of all the syllables in two songs, while maintaining the sequential order of syllables in the songs. In the second step, each occurrence rate of three patterns of binarized "2 rows x 2 columns" cells in the SSMs is calculated to extract information on the characteristic syllable transitions.Results: The SSM analysis method allowed obtaining species-specific features of song patterns and intraspecies individual variability simultaneously. Furthermore, it enabled quantitative tracking of the developmental trajectory of the syllable sequence patterns.Comparison with existing method: This method enables us to extract the species-specific song patterns and dissect the regulation of song syntax development without human-biased procedures for syllable identification. This method can be adapted to study the acoustic communication systems in several animal species, such as insects and mammals.Conclusions: This present method provides a comprehensive qualitative approach for understanding the regulation of species specificity and its development in vocal learning. (C) 2016 Elsevier B.V. All rights reserved.
With the inclusion of ubiquitous computing in education, it is intended that the student is an active agent in its formation process and interacts with its context. This paper presents the design and implementation of architecture for ubiquitous learning environments in which they integrate physical spaces with applications which are then executed by users. The system supports objects augmented with RFID tags, NFC and QR Code. Each tag contains data that uniquely identifies the resource. To validate the proposed architecture is developed experimentally tested a prototype at the end of it is done to verify that the proposed architecture improves the academic performance of students.
To the Editor: A survey published in your pages several years ago1 and a more recent review published elsewhere2 indicate that there are >32,000 papers in the literature relating to genetically modified (GM) crops food and feed. Of those papers, only a subset relate specifically to human and environmental health risks.… Download references
In this study, granular activated carbon, GAC, was modified by oxidation with HO and NaClO aqueous solutions and heat treatment at 900 ° C. The N adsorption isotherms at − 196 ° C and SEM and FTIR results were used to characterize the properties of the prepared ACs. Textural parameters such as BET surface area and pore volumes were assessed by gas adsorption. The BET surface area values of solids were between 687 and 876 m 2 g -1 . Additionally, immersion enthalpies of activated carbons in benzene, water, hydrochloric acid and sodium hydroxide solutions and Ni(II) and Cd(II) solutions of 500 mgL were determined, with values between 32 and 145 Jg -1 . Ni(II) and Cd(II) adsorption isotherms were determined at pH 6 on activated carbons and competitive adsorption tests were realized between the two ions. The results show that in the tests carried out, the adsorption capacity decreased when the content of chemical groups on the surface also decreased. Finally, the experimental results of adsorption from the solution were adjusted to the Langmuir and Freundlich models and the first model was found to be better. With maximum adsorption capacities, the values for Ni(II) were between 3.99 and 64.9 mgg -1 and for Cd(II) were between 2.61 and 55.2 mgg -1 . The values of the competitive adsorption ions present in the solution, Ni(II) and Cd(II), in the activated carbons, decreased compared to those obtained in the simple adsorption, indicating the effect of the an ion competitive presence in adsorption another.
One of the promising routes for hydrogen production consists of the dissociation of the water molecule through two-step thermochemical cycles based on iron oxides, i.e., ferrites. In a previous work, our group evaluated the activity of five commercial ferrites for this purpose, being Ni ferrite the one that exhibits the highest hydrogen production. In this work, the results obtained after a more exhaustive study of the thermochemical cycle based on a commercially available Ni ferrite are presented. Structural characterization of NiFe2O4 after each step of the thermochemical cycle is shown, as well as oxygen and hydrogen production over several cycles. In addition, kinetic parameters of this cycle are also studied, fitting the experimental data obtained under isothermal conditions to the most appropriate model among those ascribed to gas–solid non-catalytic multistep reaction systems.