Small-angle scattering of complex fluids in flow.

Complex fluids encompass a significant proportion of the materials that we use today from feedstocks such as cellulose fibre dispersions, materials undergoing processing or formulation, through to consumer end products such as shampoo. Such systems exhibit intricate behaviour due to their composition and microstructure, particularly when analysing their texture and response to flow (rheology). In particular, these fluids when flowing may undergo transitions in their nano- to microstructure, potentially aligning with flow fields, breaking and reassembling or reforming, or entirely changing phase. This manifests as macroscopic changes in material properties, such as core-annular flow of concentrated emulsions in pipelines or the favourable texture of liquid soaps. Small-angle scattering provides a unique method for probing underlying changes in fluid nano- to microstructure, from a few angströms to several microns, of complex fluids under flow. In particular, the alignment of rigid components or shape changes of soft components can be explored, along with local inter-particle ordering and global alignment with macroscopic flow fields. This review highlights recent important developments in the study of such complex fluid systems that couple flow or shear conditions with small-angle scattering measurements, and highlights the physical insight obtained by these experiments. Recent results from neutron scattering measurements made using a simple flow cell are presented, offering a facile method to explore alignment of complex fluids in an easily accessible geometry, and contextualised within existing and potential future research questions.

Synergetic Effects of Aloe Vera Extract with Trimethylglycine for Targeted Aquaporin 3 Regulation and Long-Term Skin Hydration.

Aquaporin 3 (AQP3) channels are tetrameric membrane-bound channels that facilitate the transport of water and other small solutes across cell membranes in the skin. Decreased AQP3 expression is associated with skin dryness, skin aging, psoriasis, and delayed wound healing. Thus, our study focused on a novel combination based on Aloe barbadensis leaf extract and trimethylglycine for targeted AQP3 regulation in skin keratinocytes and deep skin moisturization. Firstly, a dose-finding cytotoxicity assay of the selected substances was performed with a 2,5-diphenyl-2H-tetrazolium bromide (MTT) indicator on HaCaT cells. The substances' ability to increase the amount of AQP3 in keratinocytes was evaluated in a keratinocyte cell culture by means of ELISA. Additionally, the deep skin hydration effect was confirmed in clinical research with healthy volunteers. According to the results, the maximum tolerated doses providing viability at 70% (MTDs) values for Aloe barbadensis leaf extract and trimethylglycine were 24.50% and 39.00%, respectively. Following the research and development, a complex based on Aloe barbadensis leaf extract and trimethylglycine in a 1:1 mass ratio exhibited a good cytotoxicity profile, with an MTDs value of 37.90%. Furthermore, it was shown that the combination had a clear synergetic effect and significantly increased AQP3 by up to 380% compared to the negative control and glyceryl glucoside (p < 0.001). It was clinically confirmed that the developed shower gel containing Aloe barbadensis leaf extract and trimethylglycine safely improved skin hydration after one use and over 28 days. Thus, this novel plant-based combination has promising potential for AQP3 regulation in the skin epidermis and a role in the development of dermatological drugs for the treatment of skin xerosis and atopic-related conditions.

The Effects of Benralizumab on Lung Volumes and Airway Resistance in Severe Eosinophilic Asthma: A Real-World Study.

INTRODUCTION: Add-on biological monoclonal antibodies such as benralizumab (anti-IL-5Ra) are recommended by international guidelines to reduce exacerbations in severe eosinophilic asthma (SEA). However, few studies have assessed the impact of these therapies on lung function-related outcomes. Our goal was to evaluate the effectiveness of benralizumab on lung function, including lung volumes and airway resistance, in SEA patients in Portugal. METHODS: This was a real-world, observational, prospective, multicentric study including adult patients diagnosed with SEA (January-June 2023). Spirometry and plethysmography were performed at baseline (T0) and after six months of treatment (T6) with benralizumab to assess: total lung capacity (TLC), residual volume (RV), forced expiratory volume in one second (FEV1), forced vital capacity (FVC), mean forced expiratory flow between 25% and 75% of FVC (mFEF-25/75), intrathoracic gas volume (ITGV), and respiratory airway resistance (Raw). Descriptive statistics (with categorical variables described as frequencies and continuous values as mean and standard deviation (SD)) and paired t-test and Cohen's d effect size were calculated (analyses performed in StataCorp v.15.1; StataCorp LLC, TX, USA). RESULTS: Overall, 30 SEA patients were evaluated, mostly women (n=18, 60.0%), with atopy (n=22, 73.3%), a mean age of 58.4 years (SD 11.7), and assisted by pulmonology (n=19, 63.3%) or immunology-allergology (n=11, 36.7%) services. Mean eosinophilia at baseline was 1103.57 cells/mcL (SD 604.88; minimum-maximum 460-2400); after the use of benralizumab, the count dropped to zero. After six months of treatment, a significant increase (p<0.0001) in FVC (15.3%), FEV1 (22.6%), and mFEF-25/75 (17.7%) were observed from baseline (Cohen's d between 0.78 and 1.11). ITGV, RV, RV/TLC, and Raw significantly decreased (p<0.0001) during the study period (-17.3%, -29.7%, -8.9%, and -100.6%, respectively) (Cohen's d between -0.79 and -1.06). No differences in TLC were obtained (p=0.173). No differences between sexes were observed for any measure. Patients with more significant eosinophilia (>900 cells/mcL count; n=15) presented better responses in FEV1 (p=0.001) and mFEF-25/75 (p=0.007). CONCLUSIONS: A notable eosinophil depletion with add-on benralizumab led to significant improvements in SEA patients' respiratory function (static lung volumes and airway resistance) in real-world settings after six months. The significant deflating effect of benralizumab on patients' hyperinflated lungs led to enhanced expiratory flow (increased FEV1 and mFEF-25/75) and air trapping (decreased RV/TLC), suggesting this antibody improves bronchial obstruction, lung hyperinflation, and airway resistance. Further studies in a larger population are required to confirm these findings.

Phase transition and gelation in cellulose nanocrystal-based aqueous suspensions studied by SANS.

HYPOTHESIS: Aqueous suspensions of cellulose nanocrystals (CNC) form a re-entrant liquid crystal (LC) phase with increasing salinity. Phase separation occurs in this LC state leading to a biphasic gel with a flow programmable structure that can be used to form anisotropic soft materials. We term this state a Liquid Crystal Hydroglass (LCH). Defining the mechanisms by which the LCH forms requires detailed structural analysis at the mesoscopic length scale. EXPERIMENTS: By utilising Small Angle Neutron Scattering (SANS), we investigated the microstructure transitions in CNC suspensions, with a particular focus on the unique LC re-entrancy and gelation into the biphasic LCH. FINDINGS: Scattering from LCH gels comprises contributions from a dispersed liquid state and static heterogeneity, characterised using a Lorentzian-Gaussian model of inhomogeneity. This conceptually supports a gelation mechanism (spinodal decomposition) in CNC suspensions towards a biphasic structure of the LCH. It also demonstrates that, with increasing salinity, the non-monotonic variation in effective volume fraction of CNC rods fundamentally causes the LC re-entrancy. This work provides the first experimental characterisation of the LC-re-entrancy and formation of an anisotropic LCH gel. The proposed mechanism can be extended to understanding the general behaviour of anisotropic colloids.

Influence of Surfactant Structure on Polydisperse Formulations of Alkyl Ether Sulfates and Alkyl Amidopropyl Betaines.

Surfactants provide detergency, foaming, and texture in personal care formulations, yet the micellization of typical industrial primary and cosurfactants is not well understood, particularly in light of the polydisperse nature of commercial surfactants. Synergistic interactions are hypothesized to drive the formation of elongated wormlike self-assemblies in these mixed surfactant systems. Small-angle neutron scattering, rheology, and pendant drop tensiometry are used to examine surface adsorption, viscoelasticity, and self-assembly structure for wormlike micellar formulations comprising cocoamidopropyl betaine, and its two major components laurylamidopropyl betaine and oleylamidopropyl betaine, with sodium alkyl ethoxy sulfates. The tail length of sodium alkyl ethoxy sulfates was related to their ability to form wormlike micelles in electrolyte solutions, indicating that a tail length greater than 10 carbons is required to form wormlike micelles in NaCl solutions, with the decyl homologue unable to form elongated micelles and maintaining a low viscosity even at 20 wt % surfactant loading with 4 wt % NaCl present. For these systems, the incorporation of a disperse ethoxylate linker does not enable shorter chain surfactants to elongate into wormlike micelles for single-component systems; however, it could increase the interactions between surfactants in mixed surfactant systems. For synergy in surfactant mixing, the nonideal regular solution theory is used to study the sulfate/betaine mixtures. Tail mismatch appears to drive lower critical micelle concentrations, although tail matching improves synergy with larger relative reductions in critical micelle concentrations and greater micelle elongation, as seen by both tensiometric and scattering measurements.

Colloidal Nafion Particles: Are Cylinders Ubiquitous?

Colloidal Nafion morphology plays a critical role in determining the performance of fuel cells and electrolyzers. While small-angle neutron scattering (SANS) studies previously described Nafion in liquid media as dispersed cylinders, the analysis remains nonunique with multiple possible morphological descriptions of the data. Here, using SANS and all-atomistic molecular dynamics, we confirm that Nafion morphology in liquid media differs substantially depending on dispersing agent and dispersion method. H+ Nafion dispersed in N-methyl pyrrolidone forms swollen cluster particles with physically cross-linked ionic groups. Scattering profiles from dispersed Nafion membrane have a large structure factor feature not observed for redispersed Nafion D-521. H+ Nafion dispersed in water has a highly elongated cylindrical morphology (radius = 10 ± 1.5 Å, height = 358 ± 4.7 Å) with fully dissociated and solvated sulfonic acid groups on the particle wall. These results highlight an important discrepancy between the methods of preparing Nafion dispersions and the use of simplified analysis techniques to describe Nafion morphology.

Shear influence on colloidal cluster growth: a SANS and USANS study.

This study examines the time evolution of silica/water clusters where the formation of a gel network from unitary silica particles is interrupted by a simple Couette shear field. The aim is to enable the general understanding of this simple system by examining the microscopic basis for the changes in viscosity by providing structural inputs from small-angle scattering for a simple theoretical model. The experimental system is an 8.3 nm particle silica solution (Ludox) where the gelation has been initiated by lowering the pH in a Couette cell providing a constant shear rate of 250 s-1. A unified small-angle neutron scattering (SANS) and ultra-small-angle neutron scattering (USANS) procedure is described to measure the scattered intensity in a wavevector range of 3 × 10-4 ≤ q (nm-1) ≤ 3.1 × 10-1, probing structural changes over a broad range of length scales from the nanometre to the micrometre. Scattering data provide a new means of better understanding the behaviour of colloidal clusters when subjected to an external applied shear over a continuous time sequence after gel initiation; a fit of the time-dependent scattered intensity leads to an estimation of the cluster's effective volume fraction and size as a function of time. A reductionist theoretical basis is described to predict the time-dependent viscosity behaviour of the sheared colloidal suspension gel-initiated cluster growth from the volume fraction of the clusters.

Cystic lesions of the retrorectal space.

Cysts of the retrorectal space comprise a heterogeneous group of rare lesions. Most develop from embryological remnants and include tailgut cysts, dermoid cysts, rectal duplication cysts, anal canal duplication cysts, sacrococcygeal teratomas and anterior meningocoele. Tailgut cyst is the most common cyst of developmental origin, usually presenting as a multilocular cystic mass with mucoid content and lined by multiple epithelial types. Compared with tailgut cysts, rectal duplication cysts display all layers of the large bowel wall including a well-defined muscularis propria. Retrorectal cysts of non-developmental origin are far less common and represent lesions that either infrequently involve the retrorectal space or undergo extensive cystic change. This review provides an overview of the various histological types of cystic lesions of the retrorectal space, divided into cysts of developmental origin and those of non-developmental origin. A practical pathological and multidisciplinary approach to diagnosing these lesions is presented.

Structure-Performance Relationships for Tail Substituted Zwitterionic Betaine-Azobenzene Surfactants.

Azobenzene-containing surfactants (azo-surfactants) have garnered significant attention for their use in generating photoresponsive foams, interfaces, and colloidal systems. The photoresponsive behavior of azo-surfactants is driven by the conformational and electronic changes that occur when the azobenzene chromophore undergoes light-induced trans ⇌ cis isomerization. Effective design of surfactants and targeting of their properties requires a robust understanding of how the azobenzene functionality interacts with surfactant structure and influences overall surfactant behavior. Herein, a library of tail substituted azo-surfactants were synthesized and studied to better understand how surfactant structure can be tailored to exploit the azobenzene photoswitch. This work shows that tail group structure (length and branching) has a profound influence on the critical micelle concentration of azo-surfactants and their properties once adsorbed to an air-water interface. Neutron scattering studies revealed the unique role that intermolecular π-π azobenzene interactions have on the self-assembly of azo-surfactants, and how the influence of these interactions can be tuned using tail group structure to target specific aqueous aggregate morphologies.

Hepatic small vessel neoplasm - A systematic review.

BACKGROUND: Hepatic small vessel neoplasm (HSVN) is a recently described vascular neoplasm of the liver that can mimic hepatic angiosarcoma (AS) because of its infiltrative nature but is considered biologically less aggressive. We carried out a systematic review of the literature after previously coming across a case of HSVN [1] to guide our surveillance. METHODS: We conducted a systematic review for all cases using PubMed, EMBASE, Cochrane Central Register of Controlled Trials, case report journals and Google Scholar according to the PRISMA guidelines using the terms "hepatic small vessel neoplasm" or "hepatic small vessel neoplasia" with no language restrictions. The review was registered with Research Registry (UIN: reviewregistry1127) [2]. RESULTS: We identified 69 articles, of which 6 articles were eligible after screening. A total of 23 cases were identified. Median age was 58 (range 24-83 years) with a male preponderance (17 M:6F). Mean tumour size was 2.8 cm (range 0.2-15.9 cm). Mean follow-up was 7 months (range 1-24 months) with no reported evidence of recurrence in both patient groups with no residual disease or with positive margins after resection. DISCUSSION: HSVN appears to demonstrate a benign clinical course with no reported recurrences or metastatic disease. Long-term follow-up data will further supplement our understanding of these tumours and guide future management.

Silent EEG-Speech Recognition Using Convolutional and Recurrent Neural Network with 85% Accuracy of 9 Words Classification.

In this work, we focus on silent speech recognition in electroencephalography (EEG) data of healthy individuals to advance brain-computer interface (BCI) development to include people with neurodegeneration and movement and communication difficulties in society. Our dataset was recorded from 270 healthy subjects during silent speech of eight different Russia words (commands): 'forward', 'backward', 'up', 'down', 'help', 'take', 'stop', and 'release', and one pseudoword. We began by demonstrating that silent word distributions can be very close statistically and that there are words describing directed movements that share similar patterns of brain activity. However, after training one individual, we achieved 85% accuracy performing 9 words (including pseudoword) classification and 88% accuracy on binary classification on average. We show that a smaller dataset collected on one participant allows for building a more accurate classifier for a given subject than a larger dataset collected on a group of people. At the same time, we show that the learning outcomes on a limited sample of EEG-data are transferable to the general population. Thus, we demonstrate the possibility of using selected command-words to create an EEG-based input device for people on whom the neural network classifier has not been trained, which is particularly important for people with disabilities.

Design and synthesis of an azobenzene-betaine surfactant for photo-rheological fluids.

HYPOTHESIS: Morphology of surfactant self-assemblies are governed by the intermolecular interactions and packing constraints of the constituent molecules. Therefore, rational design of surfactant structure should allow targeting of the specific self-assembly modes, such as wormlike micelles (WLMs). By inclusion of an appropriate photo-responsive functionality to a surfactant molecule, light-based control of formulation properties without the need for additives can be achieved. EXPERIMENTS: A novel azobenzene-containing surfactant was synthesised with the intention of producing photo-responsive wormlike micelles. Aggregation of the molecule in its cis and trans isomers, and its concomitant flow properties, were characterised using UV-vis spectroscopy, small-angle neutron scattering, and rheological measurements. Finally, the fluids capacity for mediating particle diffusion was assessed using dynamic light scattering. FINDINGS: The trans isomer of the novel azo-surfactant was found to form a viscoelastic WLM network, which transitioned to inviscid ellipsoidal aggregates upon photo-switching to the cis isomer. This was accompanied by changes in zero-shear viscosity up to 16,000×. UV-vis spectroscopic and rheo-SANS analysis revealed π-π interactions of the trans azobenzene chromophore within the micelles, influencing aggregate structure and contributing to micellar rigidity. Particles dispersed in a 1 wt% surfactant solution showed a fivefold increase in apparent diffusion coefficient after UV-irradiation of the mixture.

Hepatic small vessel neoplasm case report: A surveillance conundrum.

INTRODUCTION: Hepatic small vessel neoplasm (HSVN) is a recently described vascular neoplasm of the liver that can mimic hepatic angiosarcoma (AS) because of its infiltrative nature but is considered benign or, at most, low-grade. HSVN appears to demonstrate a benign clinical course with no reported recurrences or metastatic disease, although its long-term malignant potential is uncertain. CASE PRESENTATION: We present a 57-year-old man with an incidentally growing segment VII lesion that displayed features concerning for a neoplasm. He underwent a posterior sectionectomy and final histopathology confirmed a 27 mm HSVN. As the long-term malignant potential of HSVN is uncertain, he will be followed up with serial MRI scans over the next 5 years. DISCUSSION: HSVN is a recently described entity, it is uncertain what the long-term malignant potential of HSVN can be. Reported cases have not shown any evidence of disease progression. CONCLUSION: There are no clear guidelines established on the duration of the follow-up of HSVN. More research needs to be done to determine further the natural history of these tumours and possible radiological criteria.

The 2019 World Health Organization Classification of appendiceal, colorectal and anal canal tumours: an update and critical assessment.

The recently published 5th edition 2019 World Health Organization (WHO) Classification of Tumours of the Digestive System brings significant changes from the 2010 4th edition. An emphasis on uniformity in nomenclature and grading for tumours across all organ systems is a particular feature of the 5th edition blue book series that is reflected in the gastrointestinal tract (GIT) classification. For example, simplified two tiered grading is reinforced for preinvasive lesions throughout the GIT, with dysplasia at all sites now being considered either low or high grade. Similarly, a uniform approach to classification and grading of GIT neuroendocrine neoplasms has been consolidated, with an emphasis on distinguishing grade 3 neuroendocrine tumours from neuroendocrine carcinomas. In this review, we discuss and critically assess the important and sometimes controversial changes made to the classification of tumours of the lower GIT, comprising the colorectum, vermiform appendix and anal canal. The particularly controversial decision to endorse the term 'sessile serrated lesion' for lesions previously termed 'sessile serrated polyp/adenoma' is explored. The morphological, molecular, and clinical insights behind the substitution of the term 'goblet cell adenocarcinoma' for 'goblet cell carcinoid' are assessed. The evolution of the classification of appendiceal mucinous neoplasms is considered. Inflammatory bowel disease related dysplasia and its evolving subtypes, with major implications for pathologists in routine practice, is explained.

Molecular Exchange Kinetics in Complex Coacervate Core Micelles: Role of Associative Interaction.

Molecular exchange dynamics between spherical complex coacervate core micelles (C3Ms) are documented using time-resolved small-angle neutron scattering measurements (TR-SANS), and the effects of salt concentration, type of charges, and core block polydispersity to the chain exchange are quantified. Isotopically labeled block copolyelectrolytes were prepared by postpolymerization modification of two nearly identical poly(ethylene oxide-b-allyl glycidyl ether), one with normal and the other with deuterated PEO blocks (i.e., hPEO-PAGE and dPEO-PAGE). The observed rates at multiple salt concentrations are consolidated using time-salt superposition shift factors representing chain exchange rates and analyzed. Our comprehensive analytical relaxation function based on the sticky-Rouse model and the thermodynamic barrier for core block extraction successfully describes the molecular exchange kinetics between the isotopically labeled C3Ms. We believe this work provides fundamental design criteria for C3Ms with engineered chain exchange dynamics.

Lobular carcinoma in situ: diagnostic criteria and molecular correlates.

Lobular neoplasia (LN) is an atypical proliferation of small, dyscohesive epithelial cells within the terminal duct lobular unit (TDLU), with or without pagetoid extension and encompasses both lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH). LN is a non-obligate precursor of invasive breast carcinoma and the diagnosis of LN confers an increased risk of invasive carcinoma development, compared to the general population. Diagnostic challenges arise in the accurate classification of LCIS into classic, pleomorphic and florid subtypes, in distinguishing between LCIS and ductal carcinoma in situ (DCIS) and in the appropriate use and interpretation of E-cadherin immunohistochemistry. Due to the paucity of robust data on the natural history of LCIS, and hence its clinical significance, the management is often pragmatic rather than entirely evidence-based and requires a multidisciplinary approach. In this review, we discuss the clinicopathologic and molecular features of LCIS and address the key challenges that arise in the diagnosis and management of LCIS.

Reducing oral corticosteroids in severe asthma (ROSA Project): a nationwide Portuguese consensus.

INTRODUCTION AND OBJECTIVES: We aimed to build a national consensus to optimize the use of oral corticosteroids (OCS) in severe asthma in Portugal. MATERIAL AND METHODS: A modified 3-round Delphi including 65 statements (topics on chronic systemic corticotherapy, therapeutic schemes, asthma safety and monitoring) was performed via online platform (October-November 2019). A five-point Likert-type scale was used (1-'strongly disagree'; 5-'strongly agree'). Consensus threshold was established as a percentage of agreement among participants ≥90% in the 1st round and ≥85% in the 2nd and 3rd rounds. The level of consensus achieved by the panel was discussed with the participants (face-to-face meeting). RESULTS: Forty-eight expert physicians in severe asthma (specialists in allergology and pulmonology) participated in the study. Almost half of the statements (28/65; 43.1%) obtained positive consensus by the end of round one. By the end of the exercise, 12 (18.5%) statements did not achieve consensus. Overall, 87% of physicians agree that further actions for OCS cumulative risk assessment in acute asthma exacerbations are needed. The vast majority (91.7%) demonstrated a favorable perception for using biological agents whenever patients are eligible. Most participants (95.8%) are more willing to accept some degree of lung function deterioration compared to other outcomes (worsening of symptoms, quality of life) when reducing OCS dose. Monitoring patients' comorbidities was rated as imperative by all experts. CONCLUSIONS: These results can guide an update on asthma management in Portugal and should be supplemented by studies on therapy access, patients' adherence, and costs.

Phenotypic drift in metastatic progression of breast cancer: A case report with histologically heterogeneous lesions that are clonally related.

Breast cancer metastasis to the stomach is rare; invasive lobular carcinoma has a predilection to spread to the gastrointestinal system and is morphologically similar to primary diffuse gastric carcinoma. This case highlights heterogeneous metastatic progression and that documentation of heterogeneity is important for informing future treatment strategies and prognostication.

In Situ Nanostructural Analysis of Concentrated Wormlike Micellar Fluids Comprising Sodium Laureth Sulfate and Cocamidopropyl Betaine Using Small-Angle Neutron Scattering.

Concentrated wormlike micellar fluids form the basis for a vast array of formulated products, from liquid soaps and shampoos to drag reduction and drilling fluids. Typically, these systems are analyzed using bulk rheological measurements to determine their flow properties and cryo-microscopy to detect their nanostructure. Small-angle neutron scattering provides an opportunity to directly and nonperturbatively analyze nanostructure in situ but is complicated for concentrated systems by correlations from interparticle volume exclusion. Here, we use small-angle and ultra-small-angle neutron scattering to probe directly for the first time the nanostructure of concentrated wormlike micellar fluids composed of the widely used surfactant pair sodium laureth sulfate and cocamidopropyl betaine in aqueous electrolytes. Obtained data are analyzed using different approaches to determine scattering contributions from the wormlike particles themselves and interactions between them. It is found that approximating worms as locally rigid cylinders offers some insight into their aggregation dimensions at short length scales, and both volume exclusion and screened Coulombic interaction potentials describe interactions reasonably well. Using the semi-empirical polymer reference interaction site model (PRISM) gives excellent agreement with observed scattering, and physical insight obtained using this approach is discussed in detail. A drawback of this method is the significant complexity in coding the model in order to fit data, so to facilitate this for future researchers, we provide with this paper a fully operational, open-source code to utilize this model.

Metaplastic breast cancers frequently express immune checkpoint markers FOXP3 and PD-L1.

BACKGROUND: Metaplastic breast carcinoma encompasses a heterogeneous group of tumours with differentiation into squamous and/or spindle, chondroid, osseous or rhabdoid mesenchymal-looking elements. Emerging immunotherapies targeting Programmed Death Ligand 1 (PD-L1) and immune-suppressing T cells (Tregs) may benefit metaplastic breast cancer patients, which are typically chemo-resistant and do not express hormone therapy targets. METHODS: We evaluated the immunohistochemical expression of PD-L1 and FOXP3, and the extent of tumour infiltrating lymphocytes (TILs) in a large cohort of metaplastic breast cancers, with survival data. RESULTS: Metaplastic breast cancers were significantly enriched for PD-L1 positive tumour cells, compared to triple-negative ductal breast cancers (P < 0.0001), while there was no significant difference in PD-L1 positive TILs. Metaplastic breast cancers were also significantly enriched for TILs expressing FOXP3, with FOXP3 positive intra-tumoural TILs (iTILs) associated with an adverse prognostic outcome (P = 0.0226). Multivariate analysis identified FOXP3 iTILs expression status as an important independent prognostic factor for patient survival. CONCLUSIONS: Our findings indicate the clinical significance and prognostic value of FOXP3, PD-1/PD-L1 checkpoint and TILs in metaplastic breast cancer and confirm that a subset of metaplastics may benefit from immune-based therapies.