Utility of Parent and Teacher Behavior Ratings for Self-Regulatory Outcomes of Preschool Children: A Multi-Study Examination.

Despite frequent reliance on teacher and parent ratings of children's behavior for multi-informant assessment, agreement between teachers' and parents' ratings is low. This study examined the predictive utility of teacher and parent ratings for children's self-regulatory outcomes (i.e.

Tuft cells transdifferentiate to neural-like progenitor cells in the progression of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is partly initiated through the transdifferentiation of acinar cells to metaplasia, which progresses to neoplasia and cancer. Tuft cells (TCs) are chemosensory cells not found in the normal pancreas but arise in cancer precursor lesions and diminish during progression to carcinoma. These metaplastic TCs (mTCs) suppress tumor progression through communication with the tumor microenvironment, but their fate during progression is unknown.

Potent antitumor activity of a designed interleukin-21 mimic.

Long-standing goals of cancer immunotherapy are to activate cytotoxic antitumor T cells across a broad range of affinities while dampening suppressive regulatory T (Treg) cell responses, but current approaches achieve these goals with limited success. Here, we report a IL-21 mimic, 21h10, designed to have augmented stability and high signaling potency in both humans and mice. In multiple animal models and in human melanoma patient derived organotypic tumor spheroids (PDOTS), 21h10 showed robust antitumor activity.

Guiding Students to Think Critically about Reproductive Development and Public Conversations on Sex and Gender.

Developmental Biology is intricately connected to current issues of societal and political importance. Bringing these connections into the classroom makes the biology topics relevant to our students and, when students find classroom topics relevant, they are more likely to think critically about the material. In addition, this type of engagement encourages students to remain in science majors and pursue careers in biological and biomedical fields.

Bivalent target-binding bioPROTACs induce potent degradation of oncogenic SHP2.

Targeted protein degradation is an emergent and rapidly evolving therapeutic strategy. In particular, biologics-based targeted degradation modalities (bioPROTACs) are relatively under explored compared to small molecules. Here, we investigate how target affinity, cellular localization, and valency of bioPROTACs impact efficacy of targeted degradation of the oncogenic phosphatase src-homology 2 containing protein tyrosine phosphatase-2 (SHP2).

Strategies to promote language inclusion at 17 CTSA hubs.

The prioritization of English language in clinical research is a barrier to translational science. We explored promising practices to advance the inclusion of people who speak languages other than English in research conducted within and supported by NIH Clinical Translational Science Award (CTSA) hubs. Key informant interviews were conducted with representatives ( = 24) from CTSA hubs ( = 17).

A Novel Gain-of-Signal Assay to Detect Targeted Protein Degradation.

Targeted protein degradation offers a promising avenue for expanding therapeutic development to previously inaccessible proteins of interest by regulating the target abundance rather than activity. However, current methods to screen for effective degraders serve as major bottlenecks for the development of degrader therapies. Here, we develop a novel assay platform for identification and characterization of macromolecules capable of inducing targeted degradation of oncogenic phosphatase SHP2.

DGKα/ζ inhibition lowers the TCR affinity threshold and potentiates antitumor immunity.

Diacylglycerol kinases (DGKs) attenuate diacylglycerol (DAG) signaling by converting DAG to phosphatidic acid, thereby suppressing pathways downstream of T cell receptor signaling. Using a dual DGKα/ζ inhibitor (DGKi), tumor-specific CD8 T cells with different affinities (TRP1 and TRP1), and altered peptide ligands, we demonstrate that inhibition of DGKα/ζ can lower the signaling threshold for T cell priming. TRP1 and TRP1 CD8 T cells produced more effector cytokines in the presence of cognate antigen and DGKi.

Risk Factors for Surgical Site Complications After Outpatient Lumbar Spine Surgery.

With the recent increase of minor lumbar spine surgeries being performed in the outpatient setting, there is a need for information on factors that contribute to post-operative complications for these surgeries. This was a prospective observational study examining risk factors for self-reported post-operative drainage in patients who underwent lumbar spine surgery. Patient surveys and the hospital's electronic medical records were used to collect data on patient demographic, patient lifestyle, and surgical variables.

Pancreatic Neoplasms Are Frighteningly Common: A Role for Immune Surveillance?

Carpenter and colleagues analyze organ donors to find that pancreatic intraepithelial neoplasia (PanIN), the precursor lesions of pancreatic ductal adenocarcinoma, are highly prevalent in the average healthy adult starting from a young age. Why these precursor lesions do not progress to cancer in most people is a mystery. See related article by Carpenter et al.

Transforming Growth Factor-β Blockade in Pancreatic Cancer Enhances Sensitivity to Combination Chemotherapy.

Background & Aims: Transforming growth factor-b (TGFb) plays pleiotropic roles in pancreatic cancer, including promoting metastasis, attenuating CD8 T-cell activation, and enhancing myofibroblast differentiation and deposition of extracellular matrix. However, single-agent TGFb inhibition has shown limited efficacy against pancreatic cancer in mice or humans.

Methods: We evaluated the TGFβ-blocking antibody NIS793 in combination with gemcitabine/nanoparticle (albumin-bound)-paclitaxel or FOLFIRINOX (folinic acid [FOL], 5-fluorouracil [F], irinotecan [IRI] and oxaliplatin [OX]) in orthotopic pancreatic cancer models.

CE: Febrile Neutropenia in the Chemotherapy Patient.

Febrile neutropenia is a serious complication of chemotherapy treatment and may present as the only clinical sign of infection. If not addressed in a timely manner, it may progress to multisystem organ failure and may be fatal. Initial assessment of fever in those receiving chemotherapy requires prompt administration of antibiotics, ideally within one hour of presentation.

Ornithine aminotransferase supports polyamine synthesis in pancreatic cancer.

There is a need to develop effective therapies for pancreatic ductal adenocarcinoma (PDA), a highly lethal malignancy with increasing incidence and poor prognosis. Although targeting tumour metabolism has been the focus of intense investigation for more than a decade, tumour metabolic plasticity and high risk of toxicity have limited this anticancer strategy. Here we use genetic and pharmacological approaches in human and mouse in vitro and in vivo models to show that PDA has a distinct dependence on de novo ornithine synthesis from glutamine.

cIAP1/2 Antagonism Induces Antigen-Specific T Cell-Dependent Immunity.

Checkpoint blockade immunotherapy has failed in pancreatic cancer and other poorly responsive tumor types in part due to inadequate T cell priming. Naive T cells can receive costimulation not only via CD28 but also through TNF superfamily receptors that signal via NF-κB. Antagonists of the ubiquitin ligases cellular inhibitor of apoptosis protein (cIAP)1/2, also called second mitochondria-derived activator of caspases (SMAC) mimetics, induce degradation of cIAP1/2 proteins, allowing for the accumulation of NIK and constitutive, ligand-independent activation of alternate NF-κB signaling that mimics costimulation in T cells.

Demonstrating the Value of the Clinical Nurse Specialist: A "How-to" Guide.

Purpose/objectives: The purpose of this article is to provide a guide to identifying measurements of value and how to calculate different types of return on investment (ROI). Exemplars of clinical nurse specialist (CNS) work efforts with ROI will be presented.

Description Of The Project/problem: The CNS is the oldest advanced practice role; however, the role can be vague, making it difficult to articulate the value of the CNS in the organization.

Implementation of an Evidence-Based Practice Change Removing Heparin From Implanted Vascular Access Devices.

The objective of this article was to describe the implementation and outcomes of an evidence-based practice change to remove heparin from implanted vascular access device (IVAD) management. An extensive search of the literature was performed, and articles were appraised and synthesized to determine the best practice. A common theme emerged from the literature, showing that 0.

Gamma-induction in frontotemporal dementia (GIFTeD) randomized placebo-controlled trial: Rationale, noninvasive brain stimulation protocol, and study design.

Introduction: Frontotemporal dementia (FTD) is a neurodegenerative disorder for which there is no effective pharmacological treatment. Recently, interneuron activity responsible for fast oscillatory brain activity has been found to be impaired in a mouse model of FTD with consequent cognitive and behavioral alterations. In this study, we aim to investigate the safety, tolerability, and efficacy of a novel promising therapeutic intervention for FTD based on 40 Hz transcranial alternating current stimulation (tACS), a form of non-invasive brain stimulation thought to engage neural activity in a frequency-specific manner and thus suited to restore altered brain oscillatory patterns.

Elimination of Routine Urinalysis before Elective Orthopaedic Surgery Reduces Antibiotic Utilization without Impacting Catheter-associated Urinary Tract Infection or Surgical Site Infection Rates.

Purpose: Routine preoperative urinalysis has been the standard of care for the orthopedic population for decades, regardless of symptoms. Studies have demonstrated antibiotic overuse and low concordance between bacteria cultured from the surgical wound and the urine. Testing and treatment of asymptomatic urinary tract colonization before total joint arthroplasty (TJA) is unnecessary and increases patient risk.

Inhibition of Hedgehog Signaling Alters Fibroblast Composition in Pancreatic Cancer.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease characterized by an extensive fibroinflammatory stroma, which includes abundant cancer-associated fibroblast (CAF) populations. PDAC CAFs are heterogeneous, but the nature of this heterogeneity is incompletely understood. The Hedgehog pathway functions in PDAC in a paracrine manner, with ligands secreted by cancer cells signaling to stromal cells in the microenvironment.