A bibliometric analysis of HER2-positive breast cancer: 1987-2024.

Aim: The overamplification of human epidermal growth factor (HER2) in breast cancer (BC) has been the subject of numerous research publications since its discovery in 1987. This is the first bibliometric analysis (BA) conducted on HER2-positive (HER2+) BC. The purpose of this BA is to analyze the published research on HER2+ BC from 1987 to 2024, highlighting the most significant scientific literature, as well as the main contributing authors and journals, and evaluating the impact of clinical and lab-based publications on HER2+ BC research. Methods: The Web of Science Core Collection (WoSCC) was searched using the terms "Breast cancer" OR "Breast carcinoma" OR "Breast tumor" AND "HER2 positive" OR "HER2+". The search was limited by publication year (1987-2024) and only full English articles were included. WoS returned 7,469 relevant results, and from this dataset, a bibliometric analysis was conducted using the "analyze results" and "journal citation report" functions in WoS and the VOSviewer 1.6.16 software to generate bibliographic coupling and co-citation analysis of authors. Results: The analysis encompassed a total of 7,469 publications, revealing a notable increase in the annual number of publications, particularly in recent years. The United States, China, Italy, Germany, and Spain were the top five most prolific countries. The top five significant institutions that published HER2+ research were the University of Texas System, Unicancer, UTMD Anderson Cancer Center, Harvard University, and University of California System. Breast Cancer Research and Treatment, Clinical Cancer Research, and Clinical Breast Cancer were the top three notable journals with the highest number of HER2+ BC publications. Dennis Slamon (Nc = 45,411, H-index = 51) and Jose Baselga (Nc = 32,592, H-index = 55) were the most prolific authors. Evolving research topics include anti-HER2 therapy in the neoadjuvant setting, treatment of metastatic HER2+ BC, and overcoming therapy resistance. Conclusion: This study provides an overview of HER2+ BC research published over the past three decades. It provides insight into the most cited papers and authors, and the core journals, and identifies new trends. These manuscripts have had the highest impact in the field and reflect the continued evolution of HER2 as a therapeutic target in BC.

Blimp-1 and c-Maf regulate immune gene networks to protect against distinct pathways of pathobiont-induced colitis.

Intestinal immune responses to microbes are controlled by the cytokine IL-10 to avoid immune pathology. Here, we use single-cell RNA sequencing of colon lamina propria leukocytes (LPLs) along with RNA-seq and ATAC-seq of purified CD4+ T cells to show that the transcription factors Blimp-1 (encoded by Prdm1) and c-Maf co-dominantly regulate Il10 while negatively regulating proinflammatory cytokines in effector T cells. Double-deficient Prdm1fl/flMaffl/flCd4Cre mice infected with Helicobacter hepaticus developed severe colitis with an increase in TH1/NK/ILC1 effector genes in LPLs, while Prdm1fl/flCd4Cre and Maffl/flCd4Cre mice exhibited moderate pathology and a less-marked type 1 effector response. LPLs from infected Maffl/flCd4Cre mice had increased type 17 responses with increased Il17a and Il22 expression and an increase in granulocytes and myeloid cell numbers, resulting in increased T cell-myeloid-neutrophil interactions. Genes over-expressed in human inflammatory bowel disease showed differential expression in LPLs from infected mice in the absence of Prdm1 or Maf, revealing potential mechanisms of human disease.

'Insulin is super dangerous if you don't know what you're doing': Situating the risks of insulin within the image and performance enhancing drug community.

INTRODUCTION: Insulin is an essential treatment within diabetes management; however, it takes on a role of enhancement within image and performance enhancing drug (IPED) communities due to its anabolic effects. This study sought to provide insight into how IPED users perceive and manage the risks linked to insulin. METHODS: We conducted semi-structured interviews with 10 individuals from Australia and United Kingdom who used insulin as part of their IPED protocols. The analysis followed an iterative categorisation approach and applied the lens of situated rationality theory. RESULTS: The decision to incorporate insulin was influenced by peers' experiences and preferences. Participants highlighted the risks and responsibilities associated with insulin use, emphasising the need for precise lifestyle habits. They recognised the potential dangers and called for comprehensive harm reduction strategies within IPED communities to respond to such concerns. Some participants expressed reluctance to discuss insulin openly, underlining the importance of education and awareness to mitigate health risks associated with underground and uninformed use. DISCUSSION AND CONCLUSIONS: While people who use IPEDs demonstrate awareness of the risks associated with insulin, their practices of routinisation moderate these risks within the context of IPED use. Silence as a risk-reduction strategy highlights vulnerabilities among certain prospective users, while the hierarchical structure of IPED use establishes expertise and status within the community. Reconsidering insulin risks entails reframing harm reduction messages to better match the social dynamics of IPED communities. Closer ties between IPED communities can enhance support accessibility, particularly through peers, who, with their firsthand knowledge, can offer tailored guidance.

PARP Inhibitors in Breast Cancer: a Short Communication.

PURPOSE OF REVIEW: In the last decade, poly (ADP-ribose) polymerase (PARP) inhibitors have been approved in the treatment of several cancers, such as breast and ovarian cancer. This article aims to discuss the current uses, limitations, and future directions for PARP inhibitors (PARPis) in the treatment of breast cancer. RECENT FINDINGS: Following the results of the OlympiAD and EMBRACA trials, PARPis were approved in HER2-negative breast cancer with a germline BRCA mutation. We reviewed this class of drugs' mechanism of action, efficacy, and limitations, as well as further studies that discussed resistance, impaired homologous recombination repair (HRR), and the combination of PARPis with other drugs. Improving understanding of HRR, increasing the ability to target resistance, and combining PARPis with other novel agents are continuing to increase the clinical utility of PARPis.

Across the spectrum of legality: The market activities of influencers specialized in steroids and other performance and image enhancing drugs.

BACKGROUND: Like many other goods and services, performance and image enhancing drugs (PIEDs), and particularly androgenic anabolic steroids (AAS), are increasingly discussed and promoted by social media influencers. Little, however, is known about the influencers specialized in PIEDs and which drugs and services they promote and sell. AIMS: Against this background, the study has been intended to identify prominent influencers specialized in PIEDs, examine the market activities they engage in, and assess the latter's legality. METHODS: We first searched the clean internet to identify prominent PIED influencers. Second, we conducted a six-month-long, non-reactive digital ethnography of the social media accounts of 20 influencers and, via a content analysis, identified the market activities they engage in. Third, we assessed the latter's legality, primarily using the EU legislation as a benchmark. FINDINGS: The selected influencers are all current or former bodybuilders, predominantly male and from the United States. Many of them have developed a considerable number of followers, in three cases exceeding one million. They engage in various market activities that span the whole spectrum of legality, from legal to illegal, with many activities having an uncertain, but often dubious, legal status. CONCLUSIONS: Though they may promote harm reduction for some users, PIED influencers also promote the public acceptance of PIED use beyond the bodybuilding community and enhance access to PIEDs for millions of people. Multifaceted policy interventions are required, aiming at preventing influencers from becoming a major source of information on, and route of access to, PIEDs.

Blimp-1 and c-Maf regulate Il10 and negatively regulate common and unique proinflammatory gene networks in IL-12 plus IL-27-driven T helper-1 cells.

Background: CD4 + Th1 cells producing IFN-γ are required to eradicate intracellular pathogens, however if uncontrolled these cells can cause immunopathology. The cytokine IL-10 is produced by multiple immune cells including Th1 cells during infection and regulates the immune response to minimise collateral host damage. In this study we aimed to elucidate the transcriptional network of genes controlling the expression of Il10 and proinflammatory cytokines, including Ifng in Th1 cells differentiated from mouse naive CD4 + T cells. Methods: We applied computational analysis of gene regulation derived from temporal profiling of gene expression clusters obtained from bulk RNA sequencing (RNA-seq) of flow cytometry sorted naïve CD4 + T cells from mouse spleens differentiated in vitro into Th1 effector cells with IL-12 and IL-27 to produce Ifng and Il10, compared to IL-27 alone which express Il10 only , or IL-12 alone which express Ifng and no Il10, or medium control driven-CD4 + T cells which do not express effector cytokines . Data were integrated with analysis of active genomic regions from these T cells using an assay for transposase-accessible chromatin with sequencing (ATAC)-seq, integrated with literature derived-Chromatin-immunoprecipitation (ChIP)-seq data and the RNA-seq data, to elucidate the transcriptional network of genes controlling expression of Il10 and pro-inflammatory effector genes in Th1 cells. The co-dominant role for the transcription factors, Prdm1 (encoding Blimp-1) and Maf (encoding c-Maf) , in cytokine gene regulation in Th1 cells, was confirmed using T cells obtained from mice with T-cell specific deletion of these transcription factors. Results: We show that the transcription factors Blimp-1 and c-Maf each have unique and common effects on cytokine gene regulation and not only co-operate to induce Il10 gene expression in IL-12 plus IL-27 differentiated mouse Th1 cells, but additionally directly negatively regulate key proinflammatory cytokines including Ifng, thus providing mechanisms for reinforcement of regulated Th1 cell responses. Conclusions: These data show that Blimp-1 and c-Maf positively and negatively regulate a network of both unique and common anti-inflammatory and pro-inflammatory genes to reinforce a Th1 response in mice that will eradicate pathogens with minimum immunopathology.

Big business: The private sector market for image and performance enhancing drug harm reduction in the UK.

This article draws on three mutually independent ethnographic studies to explore the private sector market for image and performance enhancing drug (IPED) harm reduction in the UK, specifically examining (1) steroid accessory supplements; (2) blood testing services; and (3) bloodletting services. After contextualising the work with a discussion of IPED use and harm reduction and the substantial growth of the global health and fitness industry, each private sector provision is critically interrogated with the following questions in mind: what is the role and utility of these services compared to public sector provision? Why has the private sector begun to deliver IPED harm reduction products and services in the UK? And how does this provision relate to the health and fitness industry more broadly? The paper concludes with some reflections about the future direction of IPED harm reduction, the importance of community-led services, and the need to think innovatively if we are to best protect users' health and wellbeing.

Dynamic patterning of microparticles with acoustic impulse control.

This paper describes the use of impulse control of an acoustic field to create complex and precise particle patterns and then dynamically manipulate them. We first demonstrate that the motion of a particle in an acoustic field depends on the applied impulse and three distinct regimes can be identified. The high impulse regime is the well established mode where particles travel to the force minima of an applied continuous acoustic field. In contrast acoustic field switching in the low impulse regime results in a force field experienced by the particle equal to the time weighted average of the constituent force fields. We demonstrate via simulation and experiment that operating in the low impulse regime facilitates an intuitive and modular route to forming complex patterns of particles. The intermediate impulse regime is shown to enable more localised manipulation of particles. In addition to patterning, we demonstrate a set of impulse control tools to clear away undesired particles to further increase the contrast of the pattern against background. We combine these tools to create high contrast patterns as well as moving and re-configuring them. These techniques have applications in areas such as tissue engineering where they will enable complex, high fidelity cell patterns.

Publisher Correction: c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4+ T cells.

In the version of this article initially published, the Supplementary Data file was an incorrect version. The correct version is now provided. The error has been corrected in the HTML and PDF version of the article.

c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4+ T cells.

The transcription factor c-Maf induces the anti-inflammatory cytokine IL-10 in CD4+ T cells in vitro. However, the global effects of c-Maf on diverse immune responses in vivo are unknown. Here we found that c-Maf regulated IL-10 production in CD4+ T cells in disease models involving the TH1 subset of helper T cells (malaria), TH2 cells (allergy) and TH17 cells (autoimmunity) in vivo. Although mice with c-Maf deficiency targeted to T cells showed greater pathology in TH1 and TH2 responses, TH17 cell-mediated pathology was reduced in this context, with an accompanying decrease in TH17 cells and increase in Foxp3+ regulatory T cells. Bivariate genomic footprinting elucidated the c-Maf transcription-factor network, including enhanced activity of NFAT; this led to the identification and validation of c-Maf as a negative regulator of IL-2. The decreased expression of the gene encoding the transcription factor RORγt (Rorc) that resulted from c-Maf deficiency was dependent on IL-2, which explained the in vivo observations. Thus, c-Maf is a positive and negative regulator of the expression of cytokine-encoding genes, with context-specific effects that allow each immune response to occur in a controlled yet effective manner.