A comprehensive investigation of gluten free bread dough rheology, proving and baking performance and bread qualities by response surface design and principal component analysis

Contribution of methylcellulose (MC), psyllium seed husk powder (PSY), and water addition level to gluten free bread quality and correlations between dough rheological properties and bread qualities were investigated by response surface design and principal component analysis. The generalised Maxwell model was applied to estimate the relaxation frequency of gluten free doughs. The addition of PSY has a complex influence on pasting viscosity at high temperature and an additional peak was observed. MC significantly influenced dough extensibility and work of adhesion, which are good predictors of bread volume and textural properties. Other rheological responses are less significantly correlated to specific volume, but they are sensitive to formulation variations, reflect dough structures and stability, related to proving behaviours, and correlated to loaf concavity. An inappropriate combination of water and hydrocolloids might lead to problems such as low stability of doughs, overexpansion, and weak crumb structure at high water addition levels, or, in contrast, high rigidity of dough, a trap of excessive air during mixing, and restrained gas cell expansion with high hydrocolloid addition and low water addition

Non-destructive characterisation of mesenchymal stem cell differentiation using LC-MS-based metabolite footprinting

Bone regeneration is a complex biological process where major cellular changes take place to support the osteogenic differentiation of mesenchymal bone progenitors. To characterise these biological changes and better understand the pathways regulating the formation of mature bone cells, the metabolic profile of mesenchymal stem cell (MSC) differentiation in vitro has been assessed non-invasively during osteogenic (OS) treatment using a footprinting technique. Liquid chromatography (LC)-mass spectrometry (MS)-based metabolite profiling of the culture medium was carried out in parallel to mineral deposition and alkaline phosphatase activity which are two hallmarks of osteogenesis in vitro. Metabolic profiles of spent culture media with a combination of univariate and multivariate analyses investigated concentration changes of extracellular metabolites and nutrients linked to the presence of MSCs in culture media. This non-invasive LC-MS-based analytical approach revealed significant metabolic changes between the media from control and OS-treated cells showing distinct effects of MSC differentiation on the environmental footprint of the cells in different conditions (control vs. OS treatment). A subset of compounds was directly linked to the osteogenic time-course of differentiation, and represent interesting metabolite candidates as non-invasive biomarkers for characterising the differentiation of MSCs in a culture medium

Evaluation of nipple aspirate fluid as a diagnostic tool for early detection of breast cancer

YesThere has been tremendous progress in detection of breast cancer in postmenopausal women, resulting in two-thirds of women surviving more than 20 years after treatment. However, breast cancer remains the leading cause of cancerrelated deaths in premenopausal women. Breast cancer is increasing in younger women due to changes in life-style as well as those at high risk as carriers of mutations in high-penetrance genes. Premenopausal women with breast cancer are more likely to be diagnosed with aggressive tumours and therefore have a lower survival rate. Mammography plays an important role in detecting breast cancer in postmenopausal women, but is considerably less sensitive in younger women. Imaging techniques, such as contrast-enhanced MRI improve sensitivity, but as with all imaging approaches, cannot differentiate between benign and malignant growths. Hence, current well-established detection methods are falling short of providing adequate safety, convenience, sensitivity and specificity for premenopausal women on a global level, necessitating the exploration of new methods. In order to detect and prevent the disease in high risk women as early as possible, methods that require more frequent monitoring need to be developed. The emergence of “omics” strategies over the last 20 years, enabling the characterisation and understanding of breast cancer at the molecular level, are providing the potential for long term, longitudinal monitoring of the disease. Tissue and serum biomarkers for breast cancer stratification, diagnosis and predictive outcome have emerged, but have not successfully translated into clinical screening for early detection of the disease. The use of breast-specific liquid biopsies, such as nipple aspirate fluid (NAF), a natural secretion produced by breast epithelial cells, can be collected non-invasively for biomarker profiling. As we move towards an age of active surveillance, home-based liquid biopsy collection kits are increasingly being applied and these could provide a paradigm shift where NAF biomarker profiling is used for routine breast health monitoring. The current status of established and newly emerging imaging techniques for early detection of breast cancer and the potential for alternative biomarker screening of liquid biopsies, particularly those applied to high-risk, premenopausal women, will be reviewed.Proteomics research was supported by Yorkshire Cancer Research projects, BPP047 and B381PA, and co-funded by the European Regional Development Fund and the Republic of Cyprus through the Research Promotion Foundation projects ΥΓΕΙΑ/ΒΙΟΣ/0311(ΒΙΕ/07) and NEKYP/0311/17

Biobanking and consenting to research: a qualitative thematic analysis of young people’s perspectives in the North East of England

Background: Biobanking biospecimens and consent are common practice in paediatric research. We need to explore children and young people’s (CYP) knowledge and perspectives around the use of and consent to biobanking. This will ensure meaningful informed consent can be obtained and improve current consent procedures. Methods: We designed a survey, in co-production with CYP, collecting demographic data, views on biobanking, and consent using three scenarios: 1) prospective consent, 2) deferred consent, and 3) reconsent and assent at age of capacity. The survey was disseminated via the Young Person’s Advisory Group North England (YPAGne) and participating CYP’s secondary schools. Data were analysed using a qualitative thematic approach by three independent reviewers (including CYP) to identify common themes. Data triangulation occurred independently by a fourth reviewer. Results: One hundred two CYP completed the survey. Most were between 16–18 years (63.7%, N = 65) and female (66.7%, N = 68). 72.3% had no prior knowledge of biobanking (N = 73). Acceptability of prospective consent for biobanking was high (91.2%, N = 93) with common themes: ‘altruism’, ‘potential benefits outweigh individual risk’, 'frugality', and ‘(in)convenience’. Deferred consent was also deemed acceptable in the large majority (84.3%, N = 86), with common themes: ‘altruism’, ‘body integrity’ and ‘sample frugality’. 76.5% preferred to reconsent when cognitively mature enough to give assent (N = 78), even if parental consent was previously in place. 79.2% wanted to be informed if their biobanked biospecimen is reused (N = 80). Conclusion: Prospective and deferred consent acceptability for biobanking is high among CYP in the UK. Altruism, frugality, body integrity, and privacy are the most important themes. Clear communication and justification are paramount to obtain consent. Any CYP with capacity should be part of the consenting procedure, if possible

Identification of Stage-Specific Breast Markers using Quantitative Proteomics

YesMatched healthy and diseased tissues from breast cancer patients were analyzed by quantitative proteomics. By comparing proteomic profiles of fibroadenoma (benign tumors, three patients), DCIS (noninvasive cancer, three patients), and invasive ductal carcinoma (four patients), we identified protein alterations that correlated with breast cancer progression. Three 8-plex iTRAQ experiments generated an average of 826 protein identifications, of which 402 were common. After excluding those originating from blood, 59 proteins were significantly changed in tumor compared with normal tissues, with the majority associated with invasive carcinomas. Bioinformatics analysis identified relationships between proteins in this subset including roles in redox regulation, lipid transport, protein folding, and proteasomal degradation, with a substantial number increased in expression due to Myc oncogene activation. Three target proteins, cofilin-1 and p23 (increased in invasive carcinoma) and membrane copper amine oxidase 3 (decreased in invasive carcinoma), were subjected to further validation. All three were observed in phenotype-specific breast cancer cell lines, normal (nontransformed) breast cell lines, and primary breast epithelial cells by Western blotting, but only cofilin-1 and p23 were detected by multiple reaction monitoring mass spectrometry analysis. All three proteins were detected by both analytical approaches in matched tissue biopsies emulating the response observed with proteomics analysis. Tissue microarray analysis (361 patients) indicated cofilin-1 staining positively correlating with tumor grade and p23 staining with ER positive status; both therefore merit further investigation as potential biomarkers.Cyprus Research Promotion Foundation, Yorkshire Cancer Researc

Current practice and surgical outcomes of neoadjuvant chemotherapy for early breast cancer : UK NeST study

Funding Information: This work was funded by a grant from the Association of Breast SurgeryPeer reviewedPublisher PD

Variation in the provision and practice of implant-based breast reconstruction in the UK: Results from the iBRA national practice questionnaire

Introduction The introduction of biological and synthetic meshes has revolutionised the practice of implant-based breast reconstruction (IBBR) but evidence for effectiveness is lacking. The iBRA (implant Breast Reconstruction evAluation) study is a national trainee-led project that aims to explore the practice and outcomes of IBBR to inform the design of a future trial. We report the results of the iBRA National Practice Questionnaire (NPQ) which aimed to comprehensively describe the provision and practice of IBBR across the UK. Methods A questionnaire investigating local practice and service provision of IBBR developed by the iBRA Steering Group was completed by trainee and consultant leads at breast and plastic surgical units across the UK. Summary data for each survey item were calculated and variation between centres and overall provision of care examined. Results 81 units within 79 NHS-hospitals completed the questionnaire. Units offered a range of reconstructive techniques, with IBBR accounting for 70% (IQR:50–80%) of participating units' immediate procedures. Units on average were staffed by 2.5 breast surgeons (IQR:2.0–3.0) and 2.0 plastic surgeons (IQR:1.0–3.0) performing 35 IBBR cases per year (IQR:20-50). Variation was demonstrated in the provision of novel different techniques for IBBR especially the use of biological (n = 62) and synthetic (n = 25) meshes and in patient selection for these procedures. Conclusions The iBRA-NPQ has demonstrated marked variation in the provision and practice of IBBR in the UK. The prospective audit phase of the iBRA study will determine the safety and effectiveness of different approaches to IBBR and allow evidence-based best practice to be explored

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences