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Introduction: The recent ACOSOG Z11102 trial demonstrated low recurrence rates with breast conserving surgery (BCS) in women with multiple ipsilateral breast cancers (MIBC). Questions remain regarding the oncologic safety of BCS in women with MIBC receiving neoadjuvant chemotherapy (NAC)., Methods: We conducted a retrospective cohort study of adult patients who underwent BCS following NAC for stage I-III breast cancer from 2012 to 2021 at two academic centers. Descriptive statistics were used to summarize the data and the Kaplan-Meier method was used to provide estimates for recurrence and survival outcomes. MIBC was defined as ≥2 foci of malignancy., Results: A total of 544 patients were included; 29.4% (n = 160) ER+/HER2-, 17.7% (n = 96) ER+/HER2+, 18.2% (n = 99) ER-/HER2+, and 34.7% (n = 189) with ER-/HER2-disease. Overall, 80.5% (n = 438) had unifocal breast cancer while 19.5% (n = 106) had MIBC. Of patients with MIBC, 90.6% (n = 96) had multifocal and 9.4% (n = 10) had multicentric disease. Pathologic complete response was achieved in 41.1% of patients with MIBC versus 41.5% of patients with unifocal disease (p = 0.94). At a median follow-up of 55 months (IQR 32-83); 4.8% of patients in the unifocal group and 4.7% of patients in the MIBC group had had a local recurrence (p = 0.97). There was no difference in 5-year local recurrence-free survival (p = 0.92), recurrence-free survival (p = 0.06), or overall survival (p = 0.07) between the groups., Conclusion: In this large cohort of women undergoing BCS post-NAC, there was no significant difference in in breast tumor recurrence or survival outcomes between patients with unifocal disease and those with MIBC., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ipshita Prakash reports a relationship with F Hoffmann-La Roche Ltd that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Introduction: The impact of timing of genetic testing on uptake of risk reducing mastectomy (RRM) in affected female BRCA1/2 or PALB2 carriers remains an area of evolving interest, particularly with the introduction of mainstream genetic testing initiatives., Methods: Women with stage I-III breast cancer and a confirmed germline pathogenic variant in BRCA1/2 or PALB2 between 2000 and 2023 were identified from an institutional genetics database. Uptake of RRM was evaluated according to disclosure of genetic testing results before or after index surgery for a first diagnosis of breast cancer., Results: The cohort included 287 female BRCA1/2 or PALB2 carriers with a median age of 44 years (IQR, 36-52). Overall, 155 (54 %) carriers received genetic testing results before and 132 (46 %) after index breast surgery. Receipt of genetic testing results before surgery was associated with a higher rate of index bilateral mastectomy (58.7 % vs. 7.6 %, p < 0.001) and a commensurate decrease in adjuvant radiation (41.9 % vs. 74.2 %, p < 0.001). At a median follow up of 4.4 years after genetic testing, 219 (76.3 %) affected carriers had undergone bilateral RRM, including 83.9 % with preoperative knowledge and 67.4 % of patients with postoperative knowledge of their germline pathogenic variant (log rank, p < 0.001). On multivariate regression, disclosure of genetic testing results before index breast surgery was independently associated with long-term uptake of bilateral mastectomy (HR 1.69, 95 % CI 1.21-2.38)., Conclusion: Genetic testing results delivered prior to index breast surgery increase uptake of bilateral RRM in affected BRCA1/2 and PALB2 carriers. Efforts to mainstream genetic testing would help optimize surgical decision-making., Competing Interests: Declaration of competing interest Jean-Francois Boileau reports honoraria from Roche, Novartis, Genomic Health, Pfizer, Allergan, and Merck; personal fees from Roche, Genomic Health, NanoString Technologies, Pfizer, Eli Lilly, Novartis, and Merck; and travel support from Roche, GlaxoSmithKline, Novartis, Pfizer, and Lifecell outside the submitted work., (© 2024 Elsevier Ltd, BASO ∼ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The purpose of this study is to evaluate preoperative predictors of nodal metastases in patients with early-stage, HER2-positive (HER2+) breast cancer., Methods: The SEER Database was queried to identify women with a first diagnosis of stage I-II (T1-T2) HER2-positive breast cancer treated with upfront surgery in 2018. Multivariable logistic regression was used to identify clinical characteristics independently associated with nodal involvement., Results: Overall, 3333 women with stage I-II HER2+ breast cancer met inclusion criteria and were included in the study. The median age at diagnosis was 59 years (IQR, 51-69 years). Most patients underwent breast-conserving surgery (60.9%), with a median of 3 (IQR 2-4) axillary lymph nodes removed. On final pathology, 762 (22.9%) of T1-T2 HER2+ patients were node positive; 2.7% pN0[i+], 3.7% pN1mi, 15.1% pN1, and 1.4% pN2. Women less than 40 years and those between 40 and 49 years showed the highest proportion of axillary lymph node metastasis, in 33.7% and 30.7% respectively, and declining with age (p < 0.001). Patients with triple-positive breast cancer had the highest rates of nodal involvement (24.8%), compared to 20.7% ER+/PR-/HER2+ and 19.6% of HER2-enriched patients (p = 0.006). On adjusted analysis, age, biologic subtype, tumour size, and type of surgery remained independent predictors of nodal involvement. On subgroup analysis, women under age 50 with T1c HER2-enriched or triple-positive breast cancer had a 33% and 35% incidence of nodal involvement, which declined with age., Conclusions: The likelihood of pathologic nodal involvement in early-stage HER2+ breast cancer is contingent on age, ER/PR status, and tumour size., Competing Interests: Declaration of competing interest Jean-Francois Boileau reports honoraria from Roche, Novartis, Genomic Health, Pfizer, Allergan, and Merck; personal fees from Roche, Genomic Health, NanoString Technologies, Pfizer, Eli Lilly, Novartis, and Merck; and travel support from Roche, GlaxoSmithKline, Novartis, Pfizer, and Lifecell outside the submitted work. The remaining authors have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier Ltd.)

Specialty coffee can be developed by the application of explicit microorganisms or starters to obtain desired fermentation. In the present study, natural fermentation (NF) of Arabica coffee was carried out spontaneously, the other set was inoculated with Pichia kudriavzevii (Y) starter culture (isolated, identified and mass cultured). The effect of microbial fermentation, metagenomics, production of functional metabolites, volatiles and their sensorial aspects were studied. The bioprocess illustrated cohesive interface of coffee nutrients and microbial communities like Mycobacterium, Acinetobacter, Gordonia, etc., in NF, Lactobacillus and Leuconostoc were prevailing in Y. The Pichia and Rhodotorula dominated in both the groups. The bioactivity of bacteria and fungi induced complex changes in physicochemical features like pH (4.2-5.2), Brix° (9.5-3.0), and metabolic transition in sugar (3.0-0.7%), alcohol (1.4-2.7%), organic acids modulating flavour precursors and organoleptics in the final brew. In the roasted bean, Y exhibited higher sugar (42%), protein (25%), polyphenol (3.5%), CGA (2.5%), caffeine (17.2%), and trigonelline (2.8%) than NF. The volatile profile exhibited increased flavour molecules like furans, ketones, and pyrazines in Y, besides lactone complexes. The organoleptics in Y were highlighted with honey, malt and berry notes. P. kudriavzevii coffee fermentation could be beneficial in specialty coffee production and enhancement of distinct characteristic flavours., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this study, we developed Different Artificial Intelligence (AI) models namely Artificial Neural Network (ANN), Adaptive Network based Fuzzy Inference System (ANFIS) and Support Vector Machine (SVM) for the prediction of Compression Coefficient of soil (Cc) which is one of the most important geotechnical parameters. A Monte Carlo approach was used for the sensitivity analysis of the AI models and input parameters. For the construction and validation of the models, 189 soft clayey soil samples were analyzed. In the models study, 13 input parameters: depth of sample, bulk density, plasticity index, moisture content, clay content, specific gravity, void ratio, liquid limit, dry density, porosity, plastic limit, degree of saturation, and liquidity index were used to obtain one output parameter "Cc". Validation of the models was done using statistical methods such as Mean Absolute Error (MAE), Root Mean Square Error (RMSE), and Coefficient of determination (R 2 ). Results of the model validation indicate that though performance of all the three models is good but SVM model is the best in the prediction of Cc. The Monte Carlo method based sensitivity analysis results show that out of the 13 input parameters considered for the models study, four parameters namely clay, degree of saturation, specific gravity and depth of sample are the most relevant in the prediction of Cc, and other parameters (bulk density, dry density, void ratio and porosity) are the most insignificant parameters for the prediction of Cc. Removal of these insignificant parameters helped to reduce the dimension of the input space and also model running time, and improved significantly the performance of the AI models. The results of this study might help in selecting the suitable AI models and input parameters for better and quick prediction of the Cc of soil., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Groundwater vulnerability assessment is a measure of potential groundwater contamination for areas of interest. The main objective of this study is to modify original DRASTIC model using four objective methods, Weights-of-Evidence (WOE), Shannon Entropy (SE), Logistic Model Tree (LMT), and Bootstrap Aggregating (BA) to create a map of groundwater vulnerability for the Sari-Behshahr plain, Iran. The study also investigated impact of addition of eight additional factors (distance to fault, fault density, distance to river, river density, land-use, soil order, geological time scale, and altitude) to improve groundwater vulnerability assessment. A total of 109 nitrate concentration data points were used for modeling and validation purposes. The efficacy of the four methods was evaluated quantitatively using the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC). AUC value for original DRASTIC model without any modification of weights and rates was 0.50. Modification of weights and rates resulted in better performance with AUC values of 0.64, 0.65, 0.75, and 0.81 for BA, SE, LMT, and WOE methods, respectively. This indicates that performance of WOE is the best in assessing groundwater vulnerability for DRASTIC model with 7 factors. The results also show more improvement in predictability of the WOE model by introducing 8 additional factors to the DRASTIC as AUC value increased to 0.91. The most effective contributing factor for ground water vulnerability in the study area is the net recharge. The least effective factors are the impact of vadose zone and hydraulic conductivity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Floods are one of the most damaging natural hazards causing huge loss of property, infrastructure and lives. Prediction of occurrence of flash flood locations is very difficult due to sudden change in climatic condition and manmade factors. However, prior identification of flood susceptible areas can be done with the help of machine learning techniques for proper timely management of flood hazards. In this study, we tested four decision trees based machine learning models namely Logistic Model Trees (LMT), Reduced Error Pruning Trees (REPT), Naïve Bayes Trees (NBT), and Alternating Decision Trees (ADT) for flash flood susceptibility mapping at the Haraz Watershed in the northern part of Iran. For this, a spatial database was constructed with 201 present and past flood locations and eleven flood-influencing factors namely ground slope, altitude, curvature, Stream Power Index (SPI), Topographic Wetness Index (TWI), land use, rainfall, river density, distance from river, lithology, and Normalized Difference Vegetation Index (NDVI). Statistical evaluation measures, the Receiver Operating Characteristic (ROC) curve, and Freidman and Wilcoxon signed-rank tests were used to validate and compare the prediction capability of the models. Results show that the ADT model has the highest prediction capability for flash flood susceptibility assessment, followed by the NBT, the LMT, and the REPT, respectively. These techniques have proven successful in quickly determining flood susceptible areas., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The safety of steviol glycosides is based on data available on several individual steviol glycosides and on the terminal absorbed metabolite, steviol. Many more steviol glycosides have been identified, but are not yet included in regulatory assessments. Demonstration that these glycosides share the same metabolic fate would indicate applicability of the same regulatory paradigm. In vitro incubation assays with pooled human fecal homogenates, using rebaudiosides A, B, C, D, E, F and M, as well as steviolbioside and dulcoside A, at two concentrations over 24-48 h, were conducted to assess the metabolic fate of various steviol glycoside classes and to demonstrate that likely all steviol glycosides are metabolized to steviol. The data show that glycosidic side chains containing glucose, rhamnose, xylose, fructose and deoxy-glucose, including combinations of α(1-2), β-1, β(1-2), β(1-3), and β(1-6) linkages, were degraded to steviol mostly within 24 h. Given a common metabolite structure and a shared metabolic fate, safety data available for individual steviol glycosides can be used to support safety of purified steviol glycosides in general. Therefore, steviol glycosides specifications adopted by the regulatory authorities should include all steviol glycosides belonging to the five groups of steviol glycosides and a group acceptable daily intake established., (Copyright © 2016 Elsevier Inc. All rights reserved.)

From the commercial extract of the leaves of Stevia rebaudiana, two new minor diterpene glycosides having α-glucosyl linkage were isolated besides the known steviol glycosides including stevioside, steviolbioside, rebaudiosides A-F, rubusoside and dulcoside A. The structures of the two compounds were identified as 13-[(2-O-(3-α-O-d-glucopyranosyl)-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid β-d-glucopyranosyl ester (1), and 13-[(2-O-β-d-glucopyranosyl-3-O-(4-O-α-d-glucopyranosyl)-β-d-glucopyranosyl-β-d-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid β-d-glucopyranosyl ester (2), on the basis of extensive NMR and MS spectral data as well as chemical studies., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

From the commercial extract of the leaves of Stevia rebaudiana, two new diterpenoid glycosides were isolated besides the known steviol glycosides including stevioside, rebaudiosides A-F, rubusoside, and dulcoside A. The structures of the two new compounds were identified as 13-[(2-O-6-deoxy-β-d-glucopyranosyl-β-d-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid β-d-glucopyranosyl ester (1), and 13-[(2-O-6-deoxy-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid β-d-glucopyranosyl ester (2), on the basis of extensive NMR and MS spectral data as well as chemical studies., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Although most drugs are formulated in the crystalline state, amorphous or other crystalline forms are often generated during the formulation process. The presence of other forms can dramatically affect the physical and chemical stability of the drug. The identification and quantitation of different forms of a drug is a significant analytical challenge, especially in a formulated product. The ability of solid-state 13C NMR spectroscopy with cross polarization (CP) and magic-angle spinning (MAS) to quantify the amounts of three of the multiple crystalline and amorphous forms of the artificial sweetener neotame is described. It was possible to quantify, in a mixture of two anhydrous polymorphic forms of neotame, the amount of each polymorph within 1-2%. In mixtures of amorphous and crystalline forms of neotame, the amorphous content could be determined within 5%. It was found that the crystalline standards that were used to prepare the mixtures were not pure crystalline forms, but rather a mixture of crystalline and amorphous forms. The effect of amorphous content in the crystalline standards on the overall quantitation of the two crystalline polymorphic forms is discussed. The importance of differences in relaxation parameters and CP efficiencies on quantifying mixtures of different forms using solid-state NMR spectroscopy is also addressed., ((c) 2005 Wiley-Liss, Inc.)

The conformational flexibility and the molecular packing patterns of the neotame molecule in its various crystal forms, including neotame monohydrate, methanol solvate, ethanol solvate, benzene solvate, and anhydrate polymorph G, are analyzed in this work. The Cerius2 molecular modeling program with the Dreiding 2.21 force field was employed to calculate the most stable conformations of neotame molecules in the gaseous state and to analyze the conformations of the neotame molecule in its various crystal forms. Using graph set analysis, the hydrogen bond patterns of these crystal forms were compared. The neotame molecule takes different conformations in its crystal forms and in the free gaseous state. Cerius2 found 10 conformers with lower conformational energies than those in the actual crystal structures, which represent an energetic compromise. The relatively large differences between the energies of the conformers indicate the necessity for rewriting or customizing the force field for neotame. The hydrogen bonding patterns of the neotame methanol and ethanol solvates are identical, but different from those of the other three forms, which also differ from each other. The neotame molecule in its various crystal forms takes different conformations that differ from those in the gaseous state because of the influence of crystal packing. The intramolecular ring, S5, is present in all the crystal forms. The following hydrogen bonding patterns occur in some of the crystal forms: diad, D; intramolecular rings, S(6) and S(7); chains, C(5) and C(6); and an intermolecular ring, R2(2)(12)., (Copyright 2002 Wiley-Liss, Inc.)

The dehydration of neotame monohydrate was monitored at various temperatures by differential scanning calorimetry (DSC), thermogravimetry (TGA), hot-stage microscopy (HSM), powder X-ray diffractometry (PXRD), and (13)C solid-state nuclear magnetic resonance (SSNMR) spectroscopy. This work emphasizes kinetic analysis of isothermal TGA data by fitting to various solid-state reaction models and by model-free kinetic treatment. The dehydration of neotame monohydrate follows the kinetics of a two-dimensional phase boundary reaction (R2) at 40-50 degrees C with an activation energy of 75 +/- 9 kJ/mol, agreeing well with 60-80 kJ/mol from model-free kinetics. At a low heating rate in DSC and TGA, neotame monohydrate undergoes dehydration to produce anhydrate Form E, which then converts to anhydrate Form A, followed by the melting of A. Neotame monohydrate under dry nitrogen purge at 50 mL/min undergoes partial isothermal dehydration at 50 degrees C to produce neotame anhydrate Form A. When neotame monohydrate is heated very slowly from 50 to 65-70 degrees C over 24 h, pure Form A is obtained., (Copyright 2002 Wiley-Liss, Inc.)

A series of L,L- (42, 44, 46, and 60) and D,D- (43, 45, 47, and 61) dipeptide derivatives composed of phenylglycine, phenylalanine, homophenylalanine, and valine and containing a 2-chloroethylamino group at the C-terminus and an N'-(2-chloroethyl)-N'-nitroso-aminocarbonyl group at the N-terminus of the dipeptides were prepared. The dipeptide derivatives (42-47, 60, and 61) were first evaluated in vivo for their anticancer activities against the murine lymphocytic leukemia P388. Compounds 42, 44, 46, and 60 possessed activities ranging from 46 to 111 percent increase in life span (%ILS), whereas 43 was marginal (%ILS = 31) and 45, 47, and 61 were inactive. In general, the L,L-series exhibited low to good activity (%ILS = 46-111), whereas the corresponding D, D-series, except for 43 (%ILS = 31), was devoid of activity. The analogously structured monoamino acid derivatives of L-alanine (74), L-phenylalanine (75), and L-aspartic acid (76) exhibited higher activity against P388 than the dipeptide derivatives (i.e., 481, 297, and 481 %ILS, respectively). The more active representatives of dipeptides (i.e., 42, 44, and 60) and the amino acids derivatives 74-76 were then tested in vivo against the murine lymphoid leukemia L1210. Compounds 42, 44, and 60 exhibited either low or marginal activity (i.e., the %ILS values were 46, 31, and 26, respectively). Compounds 74, 75, and 76 possessed low to moderate activity, as evidenced by the %ILS values of 56, 48, and 64, respectively. The %ILS parameters obtained against the P388 and L1210 tumor lines were correlated with the corresponding lipophilicities, and there is a trend towards higher activity with concomitant decrease in hydrophobicity.