Correction: del Molino del Barrio et al. Breast Cancer: An Examination of the Potential of ACKR3 to Modify the Response of CXCR4 to CXCL12. Int. J. Mol. Sci. 2018, 19, 3592.

The authors and Editorial Office were made aware of an error in a figure within the original publication [...].

Scoping the Priorities and Concerns of Parents: Infodemiology Study of Posts on Mumsnet and Reddit.

BACKGROUND: Health technology innovation is increasingly supported by a bottom-up approach to priority setting, aiming to better reflect the concerns of its intended beneficiaries. Web-based forums provide parents with an outlet to share concerns, advice, and information related to parenting and the health and well-being of their children. They provide a rich source of data on parenting concerns and priorities that could inform future child health research and innovation. OBJECTIVE: The aim of the study is to identify common concerns expressed on 2 major web-based forums and cluster these to identify potential family health concern topics as indicative priority areas for future research and innovation. METHODS: We text-mined the r/Parenting subreddit (69,846 posts) and the parenting section of Mumsnet (99,848 posts) to create a large corpus of posts. A generative statistical model (latent Dirichlet allocation) was used to identify the most discussed topics in the corpus, and content analysis was applied to identify the parenting concerns found in a subset of posts. RESULTS: A model with 25 topics produced the highest coherence and a wide range of meaningful parenting concern topics. The most frequently expressed parenting concerns are related to their child's sleep, self-care, eating (and food), behavior, childcare context, and the parental context including parental conflict. Topics directly associated with infants, such as potty training and bottle feeding, were more common on Mumsnet, while parental context and screen time were more common on r/Parenting. CONCLUSIONS: Latent Dirichlet allocation topic modeling can be applied to gain a rapid, yet meaningful overview of parent concerns expressed on a large and diverse set of social media posts and used to complement traditional insight gathering methods. Parents framed their concerns in terms of children's everyday health concerns, generating topics that overlap significantly with established family health concern topics. We provide evidence of the range of family health concerns found at these sources and hope this can be used to generate material for use alongside traditional insight gathering methods.

Dissecting the Therapeutic Mechanisms of Sphingosine-1-Phosphate Receptor Agonism during Ischaemia and Reperfusion.

Sphingosine 1-phosphate (S1P) and S1P receptors (S1PR) regulate many cellular processes, including lymphocyte migration and endothelial barrier function. As neutrophils are major mediators of inflammation, their transendothelial migration may be the target of therapeutic approaches to inflammatory conditions such as ischaemia-reperfusion injury (IRI). The aim of this project was to assess whether these therapeutic effects are mediated by S1P acting on neutrophils directly or indirectly through the endothelial cells. First, our murine model of peritoneum cell recruitment demonstrated the ability of S1P to reduce CXCL8-mediated neutrophil recruitment. Mechanistic in vitro studies revealed that S1P signals in neutrophils mainly through the S1PR1 and 4 receptors and induces phosphorylation of ERK1/2; however, this had no effect on neutrophil transmigration and adhesion. S1P treatment of endothelial cells significantly reduced TNF-α-induced neutrophil adhesion under flow (p < 0.01) and transendothelial migration towards CXCL8 during in vitro chemotaxis assays (p < 0.05). S1PR1 agonist CYM5442 treatment of endothelial cells also reduced neutrophil transmigration (p < 0.01) and endothelial permeability (p < 0.005), as shown using in vitro permeability assays. S1PR3 agonist had no effects on chemotaxis or permeability. In an in vivo mouse model of renal IRI, S1PR agonism with CYM5442 reduced endothelial permeability as shown by reduced Evan's Blue dye extravasation. Western blot was used to assess phosphorylation at different sites on vascular endothelial (VE)-cadherin and showed that CYM5442 reduced VEGF-mediated phosphorylation. Taken together, the results of this study suggest that reductions in neutrophil infiltration during IRI in response to S1P are mediated primarily by S1PR1 signalling on endothelial cells, possibly by altering phosphorylation of VE-cadherin. The results also demonstrate the therapeutic potential of S1PR1 agonist during IRI.

A pipeline analysis of advanced therapy medicinal products.

Advanced therapy medicinal products (ATMPs) are innovative biological products categorised as either gene, somatic cell, tissue-engineered or combined therapies. As of March 2022, 12 ATMPs are marketed in the EU and UK. We identified 482 unique ATMPs within 616 technology records from the National Institute for Health and Care Research Innovation Observatory database, 4 of which are currently marketed. These 482 ATMPs were identified in 583 clinical trials. Of the 616 records, 57.1% were for gene therapies and 1.6% were for combined therapies. Records covered various indications, including 130 haematological malignancies and 60 genetic disorders. Marketing authorisation intelligence was included in 14% of records.

ScanMedicine: An online search system for medical innovation.

ScanMedicine is a novel searching system dedicated to providing health care professionals, patients, carers, the public, decision- and policy-makers, and researchers with open access to the development pipeline underpinning health technology innovations. In the first phase of developing ScanMedicine, we have focused on capturing and consolidating clinical trial records hosted on national and international clinical trials registries and medical device approval data from the FDA. ScanMedicine has been developed based on microservice architecture allowing the system to be constantly improved in a flexible and scalable manner. ScanMedicine offers users a convenient and effective single search interface with interactive visualisation features that can provide an overview of the health technology innovation landscape.

Using Natural Language Processing to Explore Mental Health Insights From UK Tweets During the COVID-19 Pandemic: Infodemiology Study.

Background: There is need to consider the value of soft intelligence, leveraged using accessible natural language processing (NLP) tools, as a source of analyzed evidence to support public health research outputs and decision-making. Objective: The aim of this study was to explore the value of soft intelligence analyzed using NLP. As a case study, we selected and used a commercially available NLP platform to identify, collect, and interrogate a large collection of UK tweets relating to mental health during the COVID-19 pandemic. Methods: A search strategy comprised of a list of terms related to mental health, COVID-19, and lockdown restrictions was developed to prospectively collate relevant tweets via Twitter's advanced search application programming interface over a 24-week period. We deployed a readily and commercially available NLP platform to explore tweet frequency and sentiment across the United Kingdom and identify key topics of discussion. A series of keyword filters were used to clean the initial data retrieved and also set up to track specific mental health problems. All collated tweets were anonymized. Results: We identified and analyzed 286,902 tweets posted from UK user accounts from July 23, 2020 to January 6, 2021. The average sentiment score was 50%, suggesting overall neutral sentiment across all tweets over the study period. Major fluctuations in volume (between 12,622 and 51,340) and sentiment (between 25% and 49%) appeared to coincide with key changes to any local and/or national social distancing measures. Tweets around mental health were polarizing, discussed with both positive and negative sentiment. Key topics of consistent discussion over the study period included the impact of the pandemic on people's mental health (both positively and negatively), fear and anxiety over lockdowns, and anger and mistrust toward the government. Conclusions: Using an NLP platform, we were able to rapidly mine and analyze emerging health-related insights from UK tweets into how the pandemic may be impacting people's mental health and well-being. This type of real-time analyzed evidence could act as a useful intelligence source that agencies, local leaders, and health care decision makers can potentially draw from, particularly during a health crisis.

Novel delivery of cellular therapy to reduce ischemia reperfusion injury in kidney transplantation.

Ex vivo normothermic machine perfusion (NMP) of donor kidneys prior to transplantation provides a platform for direct delivery of cellular therapeutics to optimize organ quality prior to transplantation. Multipotent Adult Progenitor Cells (MAPC® ) possess potent immunomodulatory properties that could minimize ischemia reperfusion injury. We investigated the potential capability of MAPC cells in kidney NMP. Pairs (5) of human kidneys, from the same donor, were simultaneously perfused for 7 hours. Kidneys were randomly allocated to receive MAPC treatment or control. Serial samples of perfusate, urine, and tissue biopsies were taken for comparison. MAPC-treated kidneys demonstrated improved urine output (P = .009), decreased expression of injury biomarker NGAL (P = .012), improved microvascular perfusion on contrast-enhanced ultrasound (cortex P = .019, medulla P = .001), downregulation of interleukin (IL)-1ß (P = .050), and upregulation of IL-10 (P < .047) and Indolamine-2, 3-dioxygenase (P = .050). A chemotaxis model demonstrated decreased neutrophil recruitment when stimulated with perfusate from MAPC-treated kidneys (P < .001). Immunofluorescence revealed prelabeled MAPC cells in the perivascular space of kidneys during NMP. We report the first successful delivery of cellular therapy to a human kidney during NMP. Kidneys treated with MAPC cells demonstrate improvement in clinically relevant parameters and injury biomarkers. This novel method of cell therapy delivery provides an exciting opportunity to recondition organs prior to transplantation.

Breast Cancer: An Examination of the Potential of ACKR3 to Modify the Response of CXCR4 to CXCL12.

Upon binding with the chemokine CXCL12, the chemokine receptor CXCR4 has been shown to promote breast cancer progression. This process, however, can be affected by the expression of the atypical chemokine receptor ACKR3. Given ACKR3's ability to form heterodimers with CXCR4, we investigated how dual expression of both receptors differed from their lone expression in terms of their signalling pathways. We created single and double CXCR4 and/or ACKR3 Chinese hamster ovary (CHO) cell transfectants. ERK and Akt phosphorylation after CXCL12 stimulation was assessed and correlated with receptor internalization. Functional consequences in cell migration and proliferation were determined through wound healing assays and calcium flux. Initial experiments showed that CXCR4 and ACKR3 were upregulated in primary breast cancer and that CXCR4 and ACKR3 could form heterodimers in transfected CHO cells. This co-expression modified CXCR4's Akt activation after CXCL12's stimulation but not ERK phosphorylation (p < 0.05). To assess this signalling disparity, receptor internalization was assessed and it was observed that ACKR3 was recycled to the surface whilst CXCR4 was degraded (p < 0.01), a process that could be partially inhibited with a proteasome inhibitor (p < 0.01). Internalization was also assessed with the ACKR3 agonist VUF11207, which caused both CXCR4 and ACKR3 to be degraded after internalization (p < 0.05 and p < 0.001), highlighting its potential as a dual targeting drug. Interestingly, we observed that CXCR4 but not ACKR3, activated calcium flux after CXCL12 stimulation (p < 0.05) and its co-expression could increase cellular migration (p < 0.01). These findings suggest that both receptors can signal through ERK and Akt pathways but co-expression can alter their kinetics and internalization pathways.

Colloidal system to explore structural and dynamical transitions in rod networks, gels, and glasses.

We introduce a model system consisting of self-assembled polyamide anisotropic colloids suspended in an aqueous surfactant solution for studies of the dynamics of rod networks, gels, and glasses. The colloidal particles are formed by recrystallization of a polyamide from an aqueous surfactant phase at temperatures from 59 to 100 degrees C. The aspect ratio increases monotonically with temperature from T=59 degrees C to T=100 degrees C and rods with an aspect ratio r=8+/-1 to r=306+/-14 form. We show by confocal laser scanning microscopy and dynamic light scattering a structural transition from dilute rod behavior with diffusive dynamics to a homogeneous network structure with increasingly slow dynamics as the volume fraction is increased. Furthermore, increasing the aspect ratio of rods induces a similar structural transition from dilute rod behavior to a network structure, although at a lower volume fraction. Finally, we vary the pair potential between the rods by a polymer-induced depletion interaction and thereby observe an unexpected network-to-bundle transition. The bundles are several rod diameters wide and 1-2 rod lengths long. The rods appear to be ordered nematically within each bundle. The bundling transition leads to an order of magnitude decrease in the storage modulus of the suspensions. The results can be applied to develop strategies for complex fluid stabilization as well as for fundamental studies of rod gelation and vitrification.