The Evolution of the Hive Educator Role.

The evolution of a digitally focused clinical educator in Adult Critical Care Units at Manchester Foundation Trust (MFT), has been pivotal to the success and support of Nursing staff. The role has grown beyond what was initially managed to support services widely.

Frontoparietal functional connectivity moderates the link between time spent on social media and subsequent negative affect in daily life.

Evidence on the harms and benefits of social media use is mixed, in part because the effects of social media on well-being depend on a variety of individual difference moderators. Here, we explored potential neural moderators of the link between time spent on social media and subsequent negative affect. We specifically focused on the strength of correlation among brain regions within the frontoparietal system, previously associated with the top-down cognitive control of attention and emotion.

Psychological distance intervention reminders reduce alcohol consumption frequency in daily life.

Modifying behaviors, such as alcohol consumption, is difficult. Creating psychological distance between unhealthy triggers and one's present experience can encourage change. Using two multisite, randomized experiments, we examine whether theory-driven strategies to create psychological distance-mindfulness and perspective-taking-can change drinking behaviors among young adults without alcohol dependence via a 28-day smartphone intervention (Study 1, N = 108 participants, 5492 observations; Study 2, N = 218 participants, 9994 observations).

The persistent homology of genealogical networks.

Genealogical networks (i.e. family trees) are of growing interest, with the largest known data sets now including well over one billion individuals.

Dense Sampling Approaches for Psychiatry Research: Combining Scanners and Smartphones.

Together, data from brain scanners and smartphones have sufficient coverage of biology, psychology, and environment to articulate between-person differences in the interplay within and across biological, psychological, and environmental systems thought to underlie psychopathology. An important next step is to develop frameworks that combine these two modalities in ways that leverage their coverage across layers of human experience to have maximum impact on our understanding and treatment of psychopathology. We review literature published in the last 3 years highlighting how scanners and smartphones have been combined to date, outline and discuss the strengths and weaknesses of existing approaches, and sketch a network science framework heretofore underrepresented in work combining scanners and smartphones that can push forward our understanding of health and disease.

Within-Person Temporal Associations Among Self-Reported Physical Activity, Sleep, and Well-Being in College Students.

Objective: A holistic understanding of the naturalistic dynamics among physical activity, sleep, emotions, and purpose in life as part of a system reflecting wellness is key to promoting well-being. The main aim of this study was to examine the day-to-day dynamics within this wellness system.

Methods: Using self-reported emotions (happiness, sadness, anger, anxiousness) and physical activity periods collected twice per day, and daily reports of sleep and purpose in life via smartphone experience sampling, more than 28 days as college students ( n = 226 young adults; mean [standard deviation] = 20.

Analyses of PD-L1 and Inflammatory Gene Expression Association with Efficacy of Nivolumab ± Ipilimumab in Gastric Cancer/Gastroesophageal Junction Cancer.

Purpose: In advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC), there is a need to identify biomarkers of response to therapies, such as immune checkpoint inhibitors.

Patients And Methods: In exploratory analyses from CheckMate 032 (GC/GEJC cohort), we evaluated associations between nivolumab ± ipilimumab (NIVO ± IPI) efficacy and programmed death ligand 1 (PD-L1) expression, defined by tumor cells (% TC) or combined positive score (CPS; sum of PD-L1-staining TCs + immune cells, divided by total viable TCs, × 100) using the Dako PD-L1 IHC 28-8 pharmDx assay, or inflammatory gene expression.

Results: There was a trend toward increased efficacy (objective response and overall survival) when PD-L1 expression was determined by CPS compared with % TC at higher cutoffs of ≥5 and ≥10 in the pooled analysis of all treatment regimens.

Association of inflammatory biomarkers with clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma.

Background & Aims: Nivolumab, a programmed death (PD)-1 (PD-1) inhibitor, led to durable responses, manageable safety, and increased survival in patients with advanced hepatocellular carcinoma (HCC). In our retrospective analysis, we studied the immunobiology and potential associations between biomarkers and outcomes with nivolumab in HCC.

Methods: Fresh and archival tumour samples from dose-escalation and dose-expansion phases of the CheckMate 040 trial were analysed by immunohistochemistry and RNA sequencing to assess several inflammatory gene expression signatures, including CD274 (PD-ligand 1 [PD-L1]), CD8A, LAG3, and STAT1.

Simultaneous motion monitoring and truth-in-delivery analysis imaging framework for MR-guided radiotherapy.

Intrafraction motion (i.e. motion occurring during a treatment session) can play a pivotal role in the success of abdominal and thoracic radiation therapy.

Differential regulation of PD-L1 expression by immune and tumor cells in NSCLC and the response to treatment with atezolizumab (anti-PD-L1).

Programmed death-ligand 1 (PD-L1) expression on tumor cells (TCs) by immunohistochemistry is rapidly gaining importance as a diagnostic for the selection or stratification of patients with non-small cell lung cancer (NSCLC) most likely to respond to single-agent checkpoint inhibitors. However, at least two distinct patterns of PD-L1 expression have been observed with potential biological and clinical relevance in NSCLC: expression on TC or on tumor-infiltrating immune cells (ICs). We investigated the molecular and cellular characteristics associated with PD-L1 expression in these distinct cell compartments in 4,549 cases of NSCLC.

Development of a PD-L1 Complementary Diagnostic Immunohistochemistry Assay (SP142) for Atezolizumab.

Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non-small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry, to identify patients who will derive the most benefit from treatment with atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity, sensitivity, and the ability to stain both tumor cells (TC) and tumor-infiltrating immune cells (IC), in NSCLC and UC tissues.

Current Status of Companion and Complementary Diagnostics: Strategic Considerations for Development and Launch.

US Food and Drug Administration (FDA)-approved diagnostic assays play an increasingly common role in managing patients to prolong lifespan while also enhancing quality of life. Diagnostic assays can be essential for the safe and effective use of therapeutics (companion diagnostic), or may inform on improving the benefit/risk ratio without restricting drug access (complementary diagnostic). This tutorial reviews strategic considerations for drug and assay development resulting in FDA-approved companion or complementary diagnostic status.

Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial.

Background: First-line chemotherapy for patients with cisplatin-ineligible locally advanced or metastatic urothelial carcinoma is associated with short response duration, poor survival, and high toxicity. This study assessed atezolizumab (anti-programmed death-ligand 1 [PD-L1]) as treatment for metastatic urothelial cancer in cisplatin-ineligible patients.

Methods: For this single-arm, multicentre, phase 2 study, in 47 academic medical centres and community oncology practices in seven countries in North America and Europe, we recruited previously untreated patients with locally advanced or metastatic urothelial cancer who were cisplatin ineligible.

MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer.

There have been no major advances for the treatment of metastatic urothelial bladder cancer (UBC) in the last 30 years. Chemotherapy is still the standard of care. Patient outcomes, especially for those in whom chemotherapy is not effective or is poorly tolerated, remain poor.

Developing a center for nursing research: an influence on nursing education and research through mentorship.

Nursing research, education, and mentoring are effective strategies to enhance and generate nursing knowledge. In order to explore new opportunities using an international and interdisciplinary approach, a Center for Nursing Research (CNR) was developed at Kean University a public institution for higher education in the United States. At the CNR, nursing professionals and students collaborate in all aspects of nursing education and the research process from a global perspective and across disciplines.

Human-canine interaction: exploring stress indicator response patterns of salivary cortisol and immunoglobulin A.

A repeated measures design was used to analyze the effect of a canine interaction on salivary cortisol and immunoglobulin A (IgA) in 33 adults; 16 were pet owners and 17 were non-pet owners. Cortisol and IgA levels before and after a canine interaction (experimental) or viewing a canine movie (control) were measured by enzyme-linked immunosorbent assay and spectrophotometer. Data show a significant interaction effect for salivary cortisol in non-pet owners (p = 0.

miR-221/222 targeting of trichorhinophalangeal 1 (TRPS1) promotes epithelial-to-mesenchymal transition in breast cancer.

Compared with the luminal subtype, the basal-like subtype of breast cancer has an aggressive clinical behavior, but the reasons for this difference between the two subtypes are poorly understood. We identified microRNAs (miRNAs) miR-221 and miR-222 (miR-221/222) as basal-like subtype-specific miRNAs that decrease expression of epithelial-specific genes and increase expression of mesenchymal-specific genes. In addition, expression of these miRNAs increased cell migration and invasion, which collectively are characteristics of the epithelial-to-mesenchymal transition (EMT).

TRPS1 targeting by miR-221/222 promotes the epithelial-to-mesenchymal transition in breast cancer.

The basal-like subtype of breast cancer has an aggressive clinical behavior compared to that of the luminal subtype. We identified the microRNAs (miRNAs) miR-221 and miR-222 (miR-221/222) as basal-like subtype-specific miRNAs and showed that expression of miR-221/222 decreased expression of epithelial-specific genes and increased expression of mesenchymal-specific genes, and increased cell migration and invasion in a manner characteristic of the epithelial-to-mesenchymal transition (EMT). The transcription factor FOSL1 (also known as Fra-1), which is found in basal-like breast cancers but not in the luminal subtype, stimulated the transcription of miR-221/222, and the abundance of these miRNAs decreased with inhibition of the epidermal growth factor receptor (EGFR) or MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase), placing miR-221/222 downstream of the RAS pathway.

Raccoon roundworm encephalitis.

Raccoon roundworm encephalitis is a rare but devastating infection characterized by progressive neurological decline despite attempted therapy. Patients present with deteriorating neurological function, eosinophilia, and history of pica or geophagia resulting in ingestion of the parasite. Neuroimaging studies demonstrate nonspecific findings of progressive white matter inflammation and cortical atrophy.

In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models.

Purpose: The pathways underlying basal-like breast cancer are poorly understood, and as yet, there is no approved targeted therapy for this disease. We investigated the role of mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) inhibitors as targeted therapies for basal-like breast cancer.

Experimental Design: We used pharmacogenomic analysis of a large panel of breast cancer cell lines with detailed accompanying molecular information to identify molecular predictors of response to a potent and selective inhibitor of MEK and also to define molecular mechanisms underlying combined MEK and PI3K targeting in basal-like breast cancer.

A tumor sorting protocol that enables enrichment of pancreatic adenocarcinoma cells and facilitation of genetic analyses.

Molecular profiling of human cancer is complicated by both stromal contamination and cellular heterogeneity within samples from tumor biopsies. In this study, we developed a tissue-processing protocol using mechanical dissociation and flow cytometric sorting that resulted in the respective enrichment of stromal and tumor fractions from frozen pancreatic adenocarcinoma samples. Molecular profiling of DNA from the sorted populations using high-density single nucleotide polymorphism arrays revealed widespread chromosomal loss of heterozygosity in tumor fractions but not in either the stromal fraction or unsorted tissue specimens from the same sample.

Pediatric salivary gland imaging.

A variety of lesions occur in the pediatric salivary glands. With modern imaging techniques such as Doppler sonography, helical CT, and MRI, identification of a specific etiology is often possible. Knowledge of clinical information, normal anatomy, and imaging characteristics of salivary gland pathology are essential for appropriate radiologic evaluation.

Proteomic analysis of breast cancer molecular subtypes and biomarkers of response to targeted kinase inhibitors using reverse-phase protein microarrays.

Although breast cancer molecular subtypes have been extensively defined by means of gene expression profiling over the past decade, little is known, at the proteomic level, as to how signaling pathways are differentially activated and serve to control proliferation in different breast cancer subtypes. We used reverse-phase protein arrays to examine phosphorylation status of 100 proteins in a panel of 30 breast cancer cell lines and showed distinct pathway activation differences between different subtypes that are not obvious from previous gene expression studies. We also show that basal levels of phosphorylation of key signaling nodes may have diagnostic utility in predicting response to selective inhibitors of phosphatidylinositol 3-kinase and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase.

Transcriptional control of human T-BET expression: the role of Sp1.

Murine T-bet (T-box expressed in T cells) is a master regulator of IFN-gamma gene expression in NK and T cells. T-bet also plays a critical role in autoimmunity, asthma and other diseases. However, cis elements or trans factors responsible for regulating T-bet expression remain largely unknown.