Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review.

Cancer immunotherapy-including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)-has become a standard, potentially curative treatment for a subset of advanced solid and liquid tumors. However, most patients with cancer do not benefit from the rapidly evolving improvements in the understanding of principal mechanisms determining cancer immune responsiveness (CIR); including patient-specific genetically determined and acquired factors, as well as intrinsic cancer cell biology. Though CIR is multifactorial, fundamental concepts are emerging that should be considered for the design of novel therapeutic strategies and related clinical studies.

Finding a constrained number of predictor phenotypes for multiple outcome prediction.

Background: Prognostic models help aid medical decision-making. Various prognostic models are available via websites such as MDCalc, but these models typically predict one outcome, for example, stroke risk. Each model requires individual predictors, for example, age, lab results and comorbidities.

Discovery of STX-721, a Covalent, Potent, and Highly Mutant-Selective EGFR/HER2 Exon20 Insertion Inhibitor for the Treatment of Non-Small Cell Lung Cancer.

After L858R and ex19del epidermal growth factor receptor (EGFR) mutations, ex20ins mutations are the third most common class of driver-mutations in non-small cell lung cancer (NSCLC). Unfortunately, first-, second-, and third-generation EGFR tyrosine kinase inhibitors (TKIs) are generally ineffective for ex20ins patients due to insufficient mutant activity and selectivity over wild-type EGFR, leading to dose-limiting toxicities. While significant advances in recent years have been made toward identifying potent EGFR ex20ins mutant inhibitors, mutant vs wild-type EGFR selectivity remains a significant challenge.

Understanding the Etiology of Externalizing Problems in Young Children: The Roles of Callous-Unemotional Traits and Irritability.

Objective: Callous-unemotional traits (CU), characterized as a lack of guilt and empathy; and irritability, a tendency to show anger and frustration; are 2 risk factors for externalizing behavioral problems. Externalizing problems, CU and irritability are all heritable. However, there is a dearth of studies examining the genetic and environmental associations between the 3 domains.

Interferon Inhibitors Increase rAAV Production in HEK293 Cells.

Recombinant adeno-associated viruses (rAAVs) comprise a promising viral vector for therapeutic gene delivery to treat disease. However, the current manufacturing capability of rAAVs must be improved to meet commercial demand. Previously published omics studies indicate that rAAV production through transient transfection triggers antiviral responses and endoplasmic reticulum stress responses in the host cell.

Vascular Quality Initiative Assessment of Compliance with Society for Vascular Surgery Practice Guidelines for the Endovascular Management of Claudication.

Introduction: In 2015, Society for Vascular Surgery guidelines on claudication management were released spanning optimal medical management, procedural, and post-procedure recommendations. Uptake of guidelines and changes to clinical practice over time remain unknown. This study hypothesized that guideline aligned practice increased after guideline release.

Challenges Faced by Patients Undergoing Fecal Ostomy Surgery: A Qualitative Study of Colorectal Cancer Patient Perspectives.

Background: Ostomy education and support is instrumental in surgical recovery and adaptation. We aimed to evaluate 1) challenges faced by fecal ostomy patients with colorectal cancer and 2) resources necessary for recovery.

Methods: We recruited patients 21-90 days after scheduled fecal ostomy surgery for locally advanced or metastatic colorectal cancer from a single, tertiary academic center.

Understanding the Concept of Patient Safety Culture: Constitutive and Operational Definitions for Health Care Organizations.

Background: Patient safety culture is crucial for improving health care quality, however, there is no consensus on its definition.

Purpose: This study aimed to clarify and update the concept of patient safety culture.

Methods: We employed Norris' 6-step concept clarification method.

A biophysical basis for the spreading behavior and limited diffusion of Xist.

Xist RNA initiates X inactivation as it spreads in cis across the chromosome. Here, we reveal a biophysical basis for its cis-limited diffusion. Xist RNA and HNRNPK together drive a liquid-liquid phase separation (LLPS) that encapsulates the chromosome.

Characterization of a novel PET radioligand for mitochondrial complex I in nonhuman primate.

The role of mitochondrial complex I (MC-I) dysfunction is well-documented across a range of neurodegenerative disorders. Recently, a novel positron emission tomography (PET) radioligand, [F]CNL02, has been synthesized to target MC-I. In this paper, we provide a comprehensive characterization of [F]CNL02, using nonhuman primate as a model system.

Development and Evaluation of a Presenter Coaching Program at an Academic Surgical Conference.

Objective: Presenting at academic conferences is an important means of disseminating research, networking, and building a professional reputation, but the quality of presentations at conferences is often suboptimal. This project describes the design, implementation, and evaluation of a presentation coaching program offered by an academic surgical society to presenters at its annual meeting.

Design: Oral presenters were paired with a coach and encouraged to meet independently, yet coaching was unstructured.

Janus kinase inhibition prevents autoimmune diabetes in LEW.1WR1 rats.

Numerous studies highlight the essential role of type I interferon (IFN) responses in type 1 diabetes. The absence of type I IFN signaling is associated with a partial reduction of autoimmune diabetes incidence in LEW.1WR1 rats.

Clonal Hematopoiesis in Women With Breast Cancer.

Purpose: Clonal hematopoiesis (CH) has been associated with a variety of adverse outcomes, most notably hematologic malignancy and ischemic cardiovascular disease. A series of recent studies also suggest that CH may play a role in the outcomes of patients with solid tumors, including breast cancer. Here, we review the clinical and biological data that underlie potential connections between CH, inflammation, and breast cancer, with a focus on the prevalence and impact of clonal hematopoiesis of indeterminate potential in patients with breast cancer.

The nuclear localization signal of CPSF6 governs post-nuclear import steps of HIV-1 infection.

The early stages of HIV-1 infection include the trafficking of the viral core into the nucleus of infected cells. However, much remains to be understood about how HIV-1 accomplishes nuclear import and the consequences of the import pathways utilized on nuclear events. The host factor cleavage and polyadenylation specificity factor 6 (CPSF6) assists HIV-1 nuclear localization and post-entry integration targeting.

Affective, Behavioral, and Cognitive Symptoms Associated With Focal Impaired Awareness (Complex Partial) Seizures: Evaluation and Treatment.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.

Spontaneous oxycodone withdrawal disrupts sleep, diurnal, and electrophysiological dynamics in rats.

Opioid dependence is defined by an aversive withdrawal syndrome upon drug cessation that can motivate continued drug-taking, development of opioid use disorder, and precipitate relapse. An understudied but common opioid withdrawal symptom is disrupted sleep, reported as both insomnia and daytime sleepiness. Despite the prevalence and severity of sleep disturbances during opioid withdrawal, there is a gap in our understanding of their interactions.

H-Dots: Renal Clearable Zwitterionic Nanocarriers for Disease Diagnosis and Therapy.

Nanocarriers have shown significant promise in the diagnosis and treatment of various diseases, utilizing a wide range of biocompatible materials such as metals, inorganic substances, and organic components. Despite diverse design strategies, key physicochemical properties, including hydrodynamic diameter, shape, surface charge, and hydrophilicity/lipophilicity, are crucial for optimizing biodistribution, pharmacokinetics, and therapeutic efficacy. However, these properties are often influenced by drug payload, presenting an ongoing challenge in developing versatile platform technologies for theranostics.

Permeability Benchmarking: Guidelines for Comparing , , and Measurements.

Permeability is a measure of the degree to which cells can transport molecules across biological barriers. Units of permeability are distance per unit time (typically cm/s), where accurate measurements are needed to define drug delivery in homeostasis and to model dysfunction occurring during disease. This perspective offers a set of community-led guidelines to benchmark permeability data across multidisciplinary approaches and different biological contexts.

Morphogenesis of bacterial cables in polymeric environments.

Many bacteria live in polymeric fluids, such as mucus, environmental polysaccharides, and extracellular polymers in biofilms. However, laboratory studies typically focus on cells in polymer-free fluids. Here, we show that interactions with polymers shape a fundamental feature of bacterial life-how they proliferate in space in multicellular colonies.