CDC40 suppression induces CDCA5 splicing defects and anti-proliferative effects in lung cancer cells.

High mortality and low response rates in lung cancer patients call for novel therapeutic targets. Data mining of whole-genome genetic dependency screens suggest Cell Division Cycle 40 (CDC40) to be an essential protein for lung cancer cell survival. We characterized CDC40 knockdown effects in multiple lung cancer cell lines, revealing induced cell cycle defects that resulted in strong growth inhibition and activation of apoptosis.

The role of identity exploration in student leadership training.

Identity exploration is a pivotal component in shaping effective student leadership trainers. This article examines identity exploration in student leadership training, highlighting the role of self-awareness, reflection on positionality, and the intricate interplay of power and privilege within identity development. By delving into the nuances of identity, trainers can not only enhance their own understanding but also foster inclusive and empowering environments for emerging student leaders.

Impact of an Education Module on the Knowledge and Attitudes of EM Physicians Towards Prescribing Buprenorphine/Naloxone for Opioid Use Disorder.

Background: Opioid overdose continues to be a major cause of morbidity and mortality. Buprenorphine is an important treatment for patients with opioid-use disorder (OUD) and initiation in the emergency department (ED) has been shown to improve outcomes for these patients.

Purpose/hypothesis: Our objective was to assess the impact of a three-pronged education package on the knowledge and attitudes of emergency physicians towards using buprenorphine for treatment of OUD.

Decolonizing leadership knowledge: Context, culture, and complexity.

Leadership knowledge is viewed as an essential aspect of overall leadership learning, yet questions abound as to who decides what forms of knowledge are recognized as legitimate. This article reviews existing frames of leadership knowledge along with prior attempts to codify leadership knowledge. We then examine the function of leadership knowledge within the leadership learning framework (LLF) and explore how it connects to and illuminates other facets of the LLF model.

Leadership identity development.

This article examines various applications of the leadership identity development (LID) grounded theory and model and explores the process used to apply LID to the construction of collegiate student leadership development experiences. Featured programs include those that use LID as a design element of the program, but do not explicitly teach it; those that explicitly teach the content of the LID theory and model in leadership programs and curricula; and those that use LID at the institutional level to inform university-wide leadership programming. The article concludes with critiques and considerations for leadership educators interested in applying LID in their leadership education and development programs.

Discovery of a Novel DCAF1 Ligand Using a Drug-Target Interaction Prediction Model: Generalizing Machine Learning to New Drug Targets.

DCAF1 functions as a substrate recruitment subunit for the RING-type CRL4 and the HECT family EDVP E3 ubiquitin ligases. The WDR domain of DCAF1 serves as a binding platform for substrate proteins and is also targeted by HIV and SIV lentiviral adaptors to induce the ubiquitination and proteasomal degradation of antiviral host factors. It is therefore attractive both as a potential therapeutic target for the development of chemical inhibitors and as an E3 ligase that could be recruited by novel PROTACs for targeted protein degradation.

Exploring the utility, limitations, and possibilities of the leadership identity development (LID) model.

The article summarizes a conversation with early career scholars who utilize the LID theory and model in their scholarship and practice. Authors offer thoughts as to which aspects of leader and leadership identity development remain most useful to leadership education and development, as well as ways this body of scholarship might also be incomplete and insufficient. They reflect on how leader and leadership identity development theorizing is related to identity, equity, and power.

Deepening leadership identity development.

After decrying the lack of attention paid to identity, equity, and power in leadership education, this article delineates key concepts such as identity, identity development, and leader/leadership identity development. It explores areas of concordance and distinction across leader and leadership identity development models and suggests increasing convergence across these bodies of scholarship and adding criticality for deeper leadership identity development.

Impact on stakeholders of a cultural adaptation of a social and emotional well-being intervention in an Aboriginal community.

Purpose: Australian Indigenous people conceptualise health broadly as situated within a social and emotional well-being (SEWB) framework. A consultation process with an Aboriginal community revealed that the fundamental principles of the population wide, community-based Act-Belong-Commit mental health promotion Campaign were consistent with Aboriginal people's understanding of SEWB and that a cultural adaptation of the Campaign would be welcomed in the community. The purpose of this paper is to present key stakeholders' feedback on the Campaign adaptation.

In pursuit of inter-specialty consensus on excited delirium syndrome: a scoping literature review.

Excited delirium syndrome (ExDS) is a controversial and disputed diagnosis involving altered mentation, agitation, and, frequently, substance abuse. Recently, it has become a common pre-hospital diagnosis, serving as justification for use of force, restraint, and/or medication administration. To conduct a scoping review across three databases to describe the most frequently reported diagnostic criteria for ExDS, as well as to explore its use as a diagnosis for deaths of individuals in the custody of law enforcement.

Indigenous Cultural Identity of Research Authors Standard: research and reconciliation with Indigenous Peoples in rural health journals.

The Indigenous Cultural Identity of Research Authors Standard (ICIRAS) is based on a gap in research publishing practice where Indigenous peoples' identity is not systematically and rigorously recognised in rural health research publications. There are widespread reforms, in different research areas, to counter the reputation of scientific research as a vehicle of racism and discrimination. Reflecting on these broader movements, the editorial teams of three rural health journals - Rural and Remote Health, the Australian Journal of Rural Health, and the Canadian Journal of Rural Medicine - adopted a policy of 'Nothing about Indigenous Peoples, without Indigenous Peoples'.

Sex Differences in the Brain Transcriptome Related to Alcohol Effects and Alcohol Use Disorder.

There is compelling evidence that sex and gender have crucial roles in excessive alcohol (ethanol) consumption. Here, we review some of the data from the perspective of brain transcriptional differences between males and females, focusing on rodent animal models. A key emerging transcriptional feature is the role of neuroimmune processes.

Responding to the Psychological Needs of Health-Care Workers During the COVID-19 Pandemic: Case Study from the Medical College of Wisconsin.

With the advent of the novel coronavirus (COVID-19) pandemic, health-care workers have been faced with an inordinately high level of trauma as frontline providers. The Medical College of Wisconsin (MCW) partnered with affiliate hospitals and community partners to mobilize a matrix of available support and interventions to deliver psychological services to reach all levels of health-care providers in timely, accessible formats. While virtual peer support groups were the most utilized resource among the support group options, other opportunities also provided unique benefits to learners whose education had been disrupted by the pandemic.

Hidden costs and commitments: Leadership, social class, and experiential learning.

As leadership can be developed and practiced in multiple on- and off-campus contexts, this chapter offers ways to make experiential opportunities more accessible to poor and working-class students. Aiding students in leveraging leadership learning experiences they already have through family and community roles are explored.

Proteomics of REPLICANT perfusate detects changes in the metastatic lymph node microenvironment.

In breast cancer (BC), detecting low volumes of axillary lymph node (ALN) metastasis pre-operatively is difficult and novel biomarkers are needed. We recently showed that patient-derived ALNs can be sustained ex-vivo using normothermic perfusion. We now compare reactive (tumour-free; n = 5) and macrometastatic (containing tumour deposits >2 mm; n = 4) ALNs by combining whole section multiplex immunofluorescence with TMT-labelled LC-MS/MS of the circulating perfusate.

Cancer-associated hypersialylated MUC1 drives the differentiation of human monocytes into macrophages with a pathogenic phenotype.

The tumour microenvironment plays a crucial role in the growth and progression of cancer, and the presence of tumour-associated macrophages (TAMs) is associated with poor prognosis. Recent studies have demonstrated that TAMs display transcriptomic, phenotypic, functional and geographical diversity. Here we show that a sialylated tumour-associated glycoform of the mucin MUC1, MUC1-ST, through the engagement of Siglec-9 can specifically and independently induce the differentiation of monocytes into TAMs with a unique phenotype that to the best of our knowledge has not previously been described.

Leveraging an Open Science Drug Discovery Model to Develop CNS-Penetrant ALK2 Inhibitors for the Treatment of Diffuse Intrinsic Pontine Glioma.

There are currently no effective chemotherapeutic drugs approved for the treatment of diffuse intrinsic pontine glioma (DIPG), an aggressive pediatric cancer resident in the pons region of the brainstem. Radiation therapy is beneficial but not curative, with the condition being uniformly fatal. Analysis of the genomic landscape surrounding DIPG has revealed that activin receptor-like kinase-2 (ALK2) constitutes a potential target for therapeutic intervention given its dysregulation in the disease.

Real-time ex vivo perfusion of human lymph nodes invaded by cancer (REPLICANT): a feasibility study.

Understanding how breast cancer (BC) grows in axillary lymph nodes (ALNs), and refining how therapies might halt that process, is clinically important. However, modelling the complex ALN microenvironment is difficult, and no human models exist at present. We harvested ALNs from ten BC patients, and perfused them at 37 °C ex vivo for up to 24 h.

An innate-like Vδ1 γδ T cell compartment in the human breast is associated with remission in triple-negative breast cancer.

Innate-like tissue-resident γδ T cell compartments capable of protecting against carcinogenesis are well established in mice. Conversely, the degree to which they exist in humans, their potential properties, and their contributions to host benefit are mostly unresolved. Here, we demonstrate that healthy human breast harbors a distinct γδ T cell compartment, primarily expressing T cell receptor (TCR) Vδ1 chains, by comparison to Vδ2 chains that predominate in peripheral blood.

Integrin-Mediated Macrophage Adhesion Promotes Lymphovascular Dissemination in Breast Cancer.

Lymphatic vasculature is crucial for metastasis in triple-negative breast cancer (TNBC); however, cellular and molecular drivers controlling lymphovascular metastasis are poorly understood. We define a macrophage-dependent signaling cascade that facilitates metastasis through lymphovascular remodeling. TNBC cells instigate mRNA changes in macrophages, resulting in β4 integrin-dependent adhesion to the lymphovasculature.

Arguments for the Adoption of a Nystagmus Care Pathway.

Pathological nystagmus is a spontaneous oscillation of the eyes. It is a complex problem with many subtypes and causes ranging from the acute neurological emergency to chronic visual disorders. There is considerable variability in clinical management and patient experience across the UK.