In vitro anti-leukemia, antioxidant, and anti-inflammatory properties of Lantana camara.

It has been demonstrated that Lantana camara possesses several therapeutic properties that can be used to treat various human diseases, including dermatological and gastrointestinal conditions, tetanus, malaria, and tumours. In this investigation, every collected part of L. camara was extracted with absolute methanol to examine its antioxidant capacity using the DPPH assay and its anti-leukemia activity on two AML cell lines, MOLM-13 and MV4-11. In addition, anti-inflammatory effectiveness was evaluated. The results show that extracts from various sections of L. camara have a significant ability to neutralize free radicals, as indicated by their EC50 values. Most of the extracts had values less than 100 µg/ml, with the flower extract having an even lower value of less than 50 µg/ml. Experiments on two AML cell lines showed that the anti-leukemia effects of the extracts were remarkable, with the most potent impact belonging to the root extract (IC50 was 9.78 ± 0.61 and 12.48 ± 1.69 for MOLM-13 and MV4-11 cell lines). The antitumor effect of the extracts was determined to be time- and dose-dependent and did not correlate with antioxidant capacity. Furthermore, when BJ cells were exposed to L. camara root and leaf extracts, their migratory potential was dramatically reduced compared to untreated cells. The extracts demonstrated potential anti-inflammatory capabilities by lowering NO production in LPS-induced BJ cells.

Clinical implementation of artificial-intelligence-assisted detection of breast cancer metastases in sentinel lymph nodes: the CONFIDENT-B single-center, non-randomized clinical trial.

Pathologists' assessment of sentinel lymph nodes (SNs) for breast cancer (BC) metastases is a treatment-guiding yet labor-intensive and costly task because of the performance of immunohistochemistry (IHC) in morphologically negative cases. This non-randomized, single-center clinical trial (International Standard Randomized Controlled Trial Number:14323711) assessed the efficacy of an artificial intelligence (AI)-assisted workflow for detecting BC metastases in SNs while maintaining diagnostic safety standards. From September 2022 to May 2023, 190 SN specimens were consecutively enrolled and allocated biweekly to the intervention arm (n = 100) or control arm (n = 90). In both arms, digital whole-slide images of hematoxylin-eosin sections of SN specimens were assessed by an expert pathologist, who was assisted by the 'Metastasis Detection' app (Visiopharm) in the intervention arm. Our primary endpoint showed a significantly reduced adjusted relative risk of IHC use (0.680, 95% confidence interval: 0.347-0.878) for AI-assisted pathologists, with subsequent cost savings of ~3,000 €. Secondary endpoints showed significant time reductions and up to 30% improved sensitivity for AI-assisted pathologists. This trial demonstrates the safety and potential for cost and time savings of AI assistance.

Phenotyping Down syndrome: discovery and predictive modelling with electronic medical records.

BACKGROUND: Individuals with Down syndrome (DS) have a heightened risk for various co-occurring health conditions, including congenital heart disease (CHD). In this two-part study, electronic medical records (EMRs) were leveraged to examine co-occurring health conditions among individuals with DS (Study 1) and to investigate health conditions linked to surgical intervention among DS cases with CHD (Study 2). METHODS: De-identified EMRs were acquired from Vanderbilt University Medical Center and facilitated creating a cohort of N = 2282 DS cases (55% females), along with comparison groups for each study. In Study 1, DS cases were one-by-two sex and age matched with samples of case-controls and of individuals with other intellectual and developmental difficulties (IDDs). The phenome-disease association study (PheDAS) strategy was employed to reveal co-occurring health conditions in DS versus comparison groups, which were then ranked for how often they are discussed in relation to DS using the PubMed database and Novelty Finding Index. In Study 2, a subset of DS individuals with CHD [N = 1098 (48%)] were identified to create longitudinal data for N = 204 cases with surgical intervention (19%) versus 204 case-controls. Data were included in predictive models and assessed which model-based health conditions, when more prevalent, would increase the likelihood of surgical intervention. RESULTS: In Study 1, relative to case-controls and those with other IDDs, co-occurring health conditions among individuals with DS were confirmed to include heart failure, pulmonary heart disease, atrioventricular block, heart transplant/surgery and primary pulmonary hypertension (circulatory); hypothyroidism (endocrine/metabolic); and speech and language disorder and Alzheimer's disease (neurological/mental). Findings also revealed more versus less prevalent co-occurring health conditions in individuals with DS when comparing with those with other IDDs. Findings with high Novelty Finding Index were abnormal electrocardiogram, non-rheumatic aortic valve disorders and heart failure (circulatory); acid-base balance disorder (endocrine/metabolism); and abnormal blood chemistry (symptoms). In Study 2, the predictive models revealed that among individuals with DS and CHD, presence of health conditions such as congestive heart failure (circulatory), valvular heart disease and cardiac shunt (congenital), and pleural effusion and pulmonary collapse (respiratory) were associated with increased likelihood of surgical intervention. CONCLUSIONS: Research efforts using EMRs and rigorous statistical methods could shed light on the complexity in health profile among individuals with DS and other IDDs and motivate precision-care development.

The Relationship Between the Microbiome and Antimicrobial Resistance.

Antibiotics have benefitted human health since their introduction nearly a century ago. However, the rise of antibiotic resistance may portend the dawn of the "post-antibiotic age." With the narrow pipeline for novel antimicrobials, we need new approaches to deal with the rise of multidrug resistant organisms. In the last 2 decades, the role of the intestinal microbiota in human health has been acknowledged and studied widely. Of the various activities carried out by the gut microbiota, colonization resistance is a key function that helps maintain homeostasis. Therefore, re-establishing a healthy microbiota is a novel strategy for treating drug resistance organisms. Preliminary studies suggest that this is a viable approach. However, the extent of their success still needs to be examined. Herein, we will review work in this area and suggest where future studies can further investigate this method for dealing with the threat of antibiotic resistance.

Analysis-Specific Fast Simulation at the LHC with Deep Learning.

We present a fast-simulation application based on a deep neural network, designed to create large analysis-specific datasets. Taking as an example the generation of W + jet events produced in s =  13 TeV proton-proton collisions, we train a neural network to model detector resolution effects as a transfer function acting on an analysis-specific set of relevant features, computed at generation level, i.e., in absence of detector effects. Based on this model, we propose a novel fast-simulation workflow that starts from a large amount of generator-level events to deliver large analysis-specific samples. The adoption of this approach would result in about an order-of-magnitude reduction in computing and storage requirements for the collision simulation workflow. This strategy could help the high energy physics community to face the computing challenges of the future High-Luminosity LHC.

Defining the variety of cell types in developing and adult human kidneys by single-cell RNA sequencing.

The kidney is among the most complex organs in terms of the variety of cell types. The cellular complexity of human kidneys is not fully unraveled and this challenge is further complicated by the existence of multiple progenitor pools and differentiation pathways. Researchers disagree on the variety of renal cell types due to a lack of research providing a comprehensive picture and the challenge to translate findings between species. To find an answer to the number of human renal cell types, we discuss research that used single-cell RNA sequencing on developing and adult human kidney tissue and compares these findings to the literature of the pre-single-cell RNA sequencing era. We find that these publications show major steps towards the discovery of novel cell types and intermediate cell stages as well as complex molecular signatures and lineage pathways throughout development. The variety of cell types remains variable in the single-cell literature, which is due to the limitations of the technique. Nevertheless, our analysis approaches an accumulated number of 41 identified cell populations of renal lineage and 32 of non-renal lineage in the adult kidney, and there is certainly much more to discover. There is still a need for a consensus on a variety of definitions and standards in single-cell RNA sequencing research, such as the definition of what is a cell type. Nevertheless, this early-stage research already proves to be of significant impact for both clinical and regenerative medicine, and shows potential to enhance the generation of sophisticated in vitro kidney tissue.

Alkaline pH Increases Swimming Speed and Facilitates Mucus Penetration for Vibrio cholerae.

Intestinal mucus is the first line of defense against intestinal pathogens. It acts as a physical barrier between epithelial tissues and the lumen that enteropathogens must overcome to establish a successful infection. We investigated the motile behavior of two Vibrio cholerae strains (El Tor C6706 and Classical O395) in mucus using single-cell tracking in unprocessed porcine intestinal mucus. We determined that V. cholerae can penetrate mucus using flagellar motility and that alkaline pH increases swimming speed and, consequently, improves mucus penetration. Microrheological measurements indicate that changes in pH between 6 and 8 (the physiological range for the human small intestine) had little effect on the viscoelastic properties of mucus. Finally, we determined that acidic pH promotes surface attachment by activating the mannose-sensitive hemagglutinin (MshA) pilus in V. cholerae El Tor C6706 without a measurable change in the total cellular concentration of the secondary messenger cyclic dimeric GMP (c-di-GMP). Overall, our results support the hypothesis that pH is an important factor affecting the motile behavior of V. cholerae and its ability to penetrate mucus. Therefore, changes in pH along the human small intestine may play a role in determining the preferred site for V. cholerae during infection.IMPORTANCE The diarrheal disease cholera is still a burden for populations in developing countries with poor sanitation. To develop effective vaccines and prevention strategies against Vibrio cholerae, we must understand the initial steps of infection leading to the colonization of the small intestine. To infect the host and deliver the cholera toxin, V. cholerae has to penetrate the mucus layer protecting the intestinal tissues. However, the interaction of V. cholerae with intestinal mucus has not been extensively investigated. In this report, we demonstrated using single-cell tracking that V. cholerae can penetrate intestinal mucus using flagellar motility. In addition, we observed that alkaline pH improves the ability of V. cholerae to penetrate mucus. This finding has important implications for understanding the dynamics of infection, because pH varies significantly along the small intestine, between individuals, and between species. Blocking mucus penetration by interfering with flagellar motility in V. cholerae, reinforcing the mucosa, controlling intestinal pH, or manipulating the intestinal microbiome will offer new strategies to fight cholera.

Vibrio cholerae adapts to sessile and motile lifestyles by cyclic di-GMP regulation of cell shape.

The cell morphology of rod-shaped bacteria is determined by the rigid net of peptidoglycan forming the cell wall. Alterations to the rod shape, such as the curved rod, occur through manipulating the process of cell wall synthesis. The human pathogen Vibrio cholerae typically exists as a curved rod, but straight rods have been observed under certain conditions. While this appears to be a regulated process, the regulatory pathways controlling cell shape transitions in V. cholerae and the benefits of switching between rod and curved shape have not been determined. We demonstrate that cell shape in V. cholerae is regulated by the bacterial second messenger cyclic dimeric guanosine monophosphate (c-di-GMP) by posttranscriptionally repressing expression of crvA, a gene encoding an intermediate filament-like protein necessary for curvature formation in V. cholerae. This regulation is mediated by the transcriptional cascade that also induces production of biofilm matrix components, indicating that cell shape is coregulated with V. cholerae's induction of sessility. During microcolony formation, wild-type V. cholerae cells tended to exist as straight rods, while genetically engineering cells to maintain high curvature reduced microcolony formation and biofilm density. Conversely, straight V. cholerae mutants have reduced swimming speed when using flagellar motility in liquid. Our results demonstrate regulation of cell shape in bacteria is a mechanism to increase fitness in planktonic and biofilm lifestyles.

Renal transplant patient survives a donor-derived abdominal invasive mucormycosis (Lichtheimia ramos a).

Mucormycosis is a life-threatening invasive fungal infection, most commonly described in severely immunocompromised patients. It is characterized by rapid invasive growth of the fungus and often with fatal outcome. We report a case of a renal transplant recipient diagnosed with a donor-derived invasive mucormycosis. In this patient, we used a step-wise approach of withdrawal of immunosuppressants, antifungal induction therapy, extensive surgical debridement of all (potentially) infected tissue, abdominal irrigation of liposomal amphotericin B and interferon gamma. Due to rapid diagnosis and intensive therapy the patient survived.

An untargeted metabolomic approach for the putative characterization of metabolites from Scenedesmus obliquus in response to cadmium stress.

Cadmium (Cd) is a widespread contaminant in aquatic systems and has a variety of toxicological implications on freshwater microorganisms. In this study, the green algae Scenedesmus obliquus was exposed to increasing Cd concentrations that inhibited growth by 20% (12.6 µmol L-1), 30% (39.8 µmol L-1) and 40% (83.2 µmol L-1) and the metabolite profiles of released and cellular biomolecules were explored using an untargeted direct infusion high resolution Fourier transform ion cyclotron resonance mass spectrometry approach. In Cd untreated cultures, intrinsic differences in composition existed between released biomolecules and freeze-dried cells. Based on putatively characterized compound groups, a greater proportion of Cys-GSH isomers and carboxyamides were present in exudates whereas sugar isomers and phosphonic acids comprised most cellular metabolites. In cultures exposed to 83.2 µmol L-1 Cd, an overall shift in metabolomic response across both released biomolecules and cellular components resulted in an increase of lipid-based esters, and Cys-GSH isomers. These two important metabolites are used in antioxidant defense mechanisms and reactive oxygen species prevention during cellular stress. The diversity of metabolites also decreased as Cd concentrations increased when compared to untreated cultures, suggesting that overall metabolites specialize upon metal stress. We show systemic shifts from sugar and carboxylic isomers to specialized proteins and lipid isomers to help S. obliquus cope with stress. These findings highlight the potential use of this green algae as a potential biosorbent and sheds light into the metabolomics of Cd toxicology and insights into microbial metal adaptation.

Tumble Suppression Is a Conserved Feature of Swarming Motility.

Many bacteria use flagellum-driven motility to swarm or move collectively over a surface terrain. Bacterial adaptations for swarming can include cell elongation, hyperflagellation, recruitment of special stator proteins, and surfactant secretion, among others. We recently demonstrated another swarming adaptation in Escherichia coli, wherein the chemotaxis pathway is remodeled to decrease tumble bias (increase run durations), with running speeds increased as well. We show here that the modification of motility parameters during swarming is not unique to E. coli but is shared by a diverse group of bacteria we examined-Proteus mirabilis, Serratia marcescens, Salmonella enterica, Bacillus subtilis, and Pseudomonas aeruginosa-suggesting that increasing run durations and speeds are a cornerstone of swarming.IMPORTANCE Bacteria within a swarm move characteristically in packs, displaying an intricate swirling motion in which hundreds of dynamic rafts continuously form and dissociate as the swarm colonizes an increasing expanse of territory. The demonstrated property of E. coli to reduce its tumble bias and hence increase its run duration during swarming is expected to maintain and promote side-by-side alignment and cohesion within the bacterial packs. In this study, we observed a similar low tumble bias in five different bacterial species, both Gram positive and Gram negative, each inhabiting a unique habitat and posing unique problems to our health. The unanimous display of an altered run-tumble bias in swarms of all species examined in this investigation suggests that this behavioral adaptation is crucial for swarming.

Monoclonal gammopathy of renal significance (MGRS) histopathologic classification, diagnostic workup, and therapeutic options.

Monoclonal gammopathy of renal significance (MGRS) includes all kidney disorders caused by a monoclonal protein (M-protein) secreted by a small plasma cell clone or other B-cell clones in patients who do not meet the diagnostic criteria for multiple myeloma or other B-cell malignancies. The underlying disorder in patients with MGRS is generally consistent with monoclonal gammopathy of undetermined significance (MGUS). MGRS-associated kidney disorders are various and the list is still expanding. The kidney disorders can manifest as glomerular diseases, tubulopathies, and vascular involvement with varying clinical presentations. Diagnosis is often challenging because of the wide spectrum of MGRS, and it is difficult to establish a pathogenic link between the presence of the M-protein or serum free light chains and kidney diseases; further complicating accurate diagnosis is the high incidence of MGUS and/or kidney disorders, independent of MGRS, in elderly patients. However, MGRS can significantly impair kidney function. Because treatment can stop and also reverse kidney disease, early recognition is of great importance. A combined haematologic and nephrologic approach is crucial to establish the causative role of the M-protein in the pathogenesis of kidney disease. Clone-directed therapy, which may include autologous stem cell transplantation in eligible patients, often results in improved outcomes. In this review, we discuss the histopathologic classification of MGRS lesions, provide a renal and haematologic diagnostic workup, discuss treatment options for MGRS, and introduce a Benelux MGRS Working Group.

Smoke-free environment policy in Vietnam: what did people see and how did they react when they visited various public places?

INTRODUCTION: Since Vietnam has signed WHO framework on tobacco control (FCTC) in 2003 and has issued tobacco control law in 2013, there has been little research concerning about what impacts smoke-free regulations have had on public compliance. The objective of this study was to assess public exposure to secondhand smoke and reaction toward smoke-free policy regulations in Vietnam and the associated factor. METHODS: Using the design of GATS (Global Adult Tobacco Survey), a nationally representative sample of 8,996 adults were approached for data collection. Logistic regression was used to examine the associated factor. RESULTS: The study revealed that the prevalence of respondents exposed to secondhand smoke was much higher in bars/café/tea shops (90.07%) and restaurants (81.81%) than in any other public places, universities (36.70%), government buildings (31.12%), public transport (20.04%), healthcare facilities (17.85%) and schools (15.84%). 13.23% of respondents saw smokers violate smoke-free regulations. Among those who saw them violate smoke-free regulations, just one-third cautioned them to stop smoking. Strikingly, a higher rate of cautioning smokers to stop smoking was observed among the older, married, and better educated respondents. Respondents who were married, better educated and in lower economic status were more likely to remind smokers to stop smoking. CONCLUSIONS: The study has called for strengthening two of the six MPOWER (Monitor, Protect, Offer, Warn, Enforce and Raise) components of the tobacco free initiative introduced by WHO, Monitoring tobacco use and prevention policies and Protecting people from tobacco smoke.

Escherichia coli Remodels the Chemotaxis Pathway for Swarming.

Many flagellated bacteria "swarm" over a solid surface as a dense consortium. In different bacteria, swarming is facilitated by several alterations such as those corresponding to increased flagellum numbers, special stator proteins, or secreted surfactants. We report here a change in the chemosensory physiology of swarming Escherichia coli which alters its normal "run tumble" bias. E. coli bacteria taken from a swarm exhibit more highly extended runs (low tumble bias) and higher speeds than E. coli bacteria swimming individually in a liquid medium. The stability of the signaling protein CheZ is higher in swarmers, consistent with the observed elevation of CheZ levels and with the low tumble bias. We show that the tumble bias displayed by wild-type swarmers is the optimal bias for maximizing swarm expansion. In assays performed in liquid, swarm cells have reduced chemotactic performance. This behavior is specific to swarming, is not specific to growth on surfaces, and persists for a generation. Therefore, the chemotaxis signaling pathway is reprogrammed for swarming.IMPORTANCE The fundamental motile behavior of E. coli is a random walk, where straight "runs" are punctuated by "tumbles." This behavior, conferred by the chemotaxis signaling system, is used to track chemical gradients in liquid. Our study results show that when migrating collectively on surfaces, E. coli modifies its chemosensory physiology to decrease its tumble bias (and hence to increase run durations) by post-transcriptional changes that alter the levels of a key signaling protein. We speculate that the low tumble bias may contribute to the observed Lévy walk (LW) trajectories within the swarm, where run durations have a power law distribution. In animals, LW patterns are hypothesized to maximize searches in unpredictable environments. Swarming bacteria face several challenges while moving collectively over a surface-maintaining cohesion, overcoming constraints imposed by a physical substrate, searching for nutrients as a group, and surviving lethal levels of antimicrobials. The altered chemosensory behavior that we describe in this report may help with these challenges.

Occurrence of 1153 organic micropollutants in the aquatic environment of Vietnam.

The rapid increase in the number and volume of chemical substances being used in modern society has been accompanied by a large number of potentially hazardous chemicals being found in environmental samples. In Vietnam, the monitoring of chemical substances is mainly limited to a small number of known pollutants in spite of rapid economic growth and urbanization, and there is an urgent need to examine a large number of chemicals to prevent impacts from expanding environmental pollution. However, it is difficult to analyze a large number of chemicals using existing methods, because they are time consuming and expensive. In the present study, we determined 1153 substances to grasp a pollution picture of microcontaminants in the aquatic environment. To achieve this objective, we have used two comprehensive analytical methods: (1) solid-phase extraction (SPE) and LC-TOF-MS analysis, and (2) SPE and GC-MS analysis. We collected 42 samples from northern (the Red River and Hanoi), central (Hue and Danang), and southern (Ho Chi Minh City and Saigon-Dongnai River) Vietnam. One hundred and sixty-five compounds were detected at least once. The compounds detected most frequently (>40 % samples) at µg/L concentrations were sterols (cholesterol, beta-sitosterol, stigmasterol, coprostanol), phthalates (bis(2-ethylhexyl) phthalate and di-n-butyl phthalate), and pharmaceutical and personal care products (caffeine, metformin). These contaminants were detected at almost the same detection frequency as in developed countries. The results reveal that surface waters in Vietnam, particularly in the center of large cities, are polluted by a large number of organic micropollutants, with households and business activities as the major sources. In addition, risk quotients (MEC/PNEC values) for nonylphenol, sulfamethoxazole, ampicillin, acetaminophen, erythromycin and clarithromycin were higher than 1, which indicates a possibility of adverse effects on aquatic ecosystems.

Cellular senescence in the aging and diseased kidney.

The program of cellular senescence is involved in both the G1 and G2 phase of the cell cycle, limiting G1/S and G2/M progression respectively, and resulting in prolonged cell cycle arrest. Cellular senescence is involved in normal wound healing. However, multiple organs display increased senescent cell numbers both during natural aging and after injury, suggesting that senescent cells can have beneficial as well as detrimental effects in organismal aging and disease. Also in the kidney, senescent cells accumulate in various compartments with advancing age and renal disease. In experimental studies, forced apoptosis induction through the clearance of senescent cells leads to better preservation of kidney function during aging. Recent groundbreaking studies demonstrate that senescent cell depletion through INK-ATTAC transgene-mediated or cell-penetrating FOXO4-DRI peptide induced forced apoptosis, reduced age-associated damage and dysfunction in multiple organs, in particular the kidney, and increased performance and lifespan. Senescence is also involved in oncology and therapeutic depletion of senescent cells by senolytic drugs has been studied in experimental and human cancers. Although studies with senolytic drugs in models of kidney injury are lacking, their dose limiting side effects on other organs suggest that targeted delivery might be needed for successful application of senolytic drugs for treatment of kidney disease. In this review, we discuss (i) current understanding of the mechanisms and associated pathways of senescence, (ii) evidence of senescence occurrence and causality with organ injury, and (iii) therapeutic strategies for senescence depletion (senotherapy) including targeting, all in the context of renal aging and disease.

The effect of resveratrol on the developmental competence of porcine oocytes vitrified at germinal vesicle stage.

We tested the effects of resveratrol both as a pre-treatment and as a recovery treatment after warming during in vitro maturation (IVM) on the viability and developmental competence of porcine oocytes vitrified at the germinal vesicle stage. Pre-treatment before vitrification of oocytes for 3 hr with 2 µM resveratrol did not affect survival, oocyte maturation and embryo developmental competence to the blastocyst stage after parthenogenetic activation. However, supplementation of the medium with resveratrol during subsequent IVM after vitrification and warming significantly improved the ability of surviving oocytes to develop to the blastocyst stage, and this effect was observed only on vitrified, but not on non-vitrified oocytes. The intracellular levels of glutathione and hydrogen peroxide in oocytes were not affected by vitrification and resveratrol treatment. Also, there was no significant difference in the occurrence of apoptosis measured by annexin V binding between vitrified and non-vitrified oocytes, regardless of the resveratrol treatment. In conclusion, resveratrol did not prevent the cellular damages in immature porcine oocytes during vitrification; however, when added to the IVM medium, it specifically improved the developmental competence of vitrified oocytes. Further research will be necessary to clarify the mechanisms of action of resveratrol on the recovery of vitrified oocytes from vitrification-related damages.

Evaluating feasibility of an automated 3-dimensional scanner using Raman spectroscopy for intraoperative breast margin assessment.

Breast conserving surgery is the preferred treatment for women diagnosed with early stage invasive breast cancer. To ensure successful breast conserving surgeries, efficient tumour margin resection is required for minimizing tumour recurrence. Currently surgeons rely on touch preparation cytology or frozen section analysis to assess tumour margin status intraoperatively. These techniques have suboptimal accuracy and are time-consuming. Tumour margin status is eventually confirmed using postoperative histopathology that takes several days. Thus, there is a need for a real-time, accurate, automated guidance tool that can be used during tumour resection intraoperatively to assure complete tumour removal in a single procedure. In this paper, we evaluate feasibility of a 3-dimensional scanner that relies on Raman Spectroscopy to assess the entire margins of a resected specimen within clinically feasible time. We initially tested this device on a phantom sample that simulated positive tumour margins. This device first scans the margins of the sample and then depicts the margin status in relation to an automatically reconstructed image of the phantom sample. The device was further investigated on breast tissues excised from prophylactic mastectomy specimens. Our findings demonstrate immense potential of this device for automated breast tumour margin assessment to minimise repeat invasive surgeries.