Engineered Cellular Therapies for the Treatment of Thoracic Cancers.

Thoracic malignancies (lung cancers and malignant pleural mesothelioma) are prevalent worldwide and are associated with high morbidity and mortality. Effective treatments are needed for patients with advanced disease. Cell therapies are a promising approach to the treatment of advanced cancers that make use of immune effector cells that have the ability to mediate antitumor immune responses.

Electronic health record data analysis on the impact of rescue-triggered inhaled corticosteroids on controller therapy in Black and Latinx individuals from a pragmatic, open-label, patient-level randomised trial.

Objective: The Person Empowered Asthma Relief (PREPARE) study found that as-needed inhaled corticosteroid (ICS) supplementation combined with participants' usual controller and rescue therapy reduced asthma exacerbations for Black and Hispanic/Latinx individuals. We aimed to determine whether treatment assignment to the intervention group (Patient Activated Reliever-Triggered ICS (PARTICS)) versus the control group (usual care) influenced controller therapy based on clinicians' written prescriptions.

Design: Secondary data analysis of electronic health record data of a pragmatic, open-label, patient-level randomised trial.

Myeloid activation clears ascites and reveals IL27-dependent regression of metastatic ovarian cancer.

Patients with metastatic ovarian cancer (OvCa) have a 5-year survival rate of <30% due to the persisting dissemination of chemoresistant cells in the peritoneal fluid and the immunosuppressive microenvironment in the peritoneal cavity. Here, we report that intraperitoneal administration of β-glucan and IFNγ (BI) induced robust tumor regression in clinically relevant models of metastatic OvCa. BI induced tumor regression by controlling fluid tumor burden and activating localized antitumor immunity.

Clinician-Reported Barriers and Needs for Implementation of Continuous Glucose Monitoring.

Background: Continuous glucose monitoring (CGM) for patients with type 1 and type 2 diabetes is associated with improved clinical, behavioral, and psychosocial patient health outcomes and is part of the American Diabetes Association's Standards of Medical Care. CGM prescription often takes place in endocrinology practices, yet 50% of adults with type 1 diabetes and 90% of all people with type 2 diabetes receive their diabetes care in primary care settings. This study examined primary care clinicians' perceptions of barriers and resources needed to support CGM use in primary care.

Leveraging mixed-effects location scale models to assess the ERP mismatch negativity's psychometric properties and trial-by-trial neural variability in toddler-mother dyads.

Trial-by-trial neural variability, a measure of neural response stability, has been examined in relation to behavioral indicators using summary measures, but these methods do not characterize meaningful processes underlying variability. Mixed-effects location scale models (MELSMs) overcome these limitations by accounting for predictors and covariates of variability but have been rarely used in developmental studies. Here, we applied MELSMs to the ERP auditory mismatch negativity (MMN), a neural measure often related to language and psychopathology.

The Odyssey of HOMER: Comparative Effectiveness Research on Medication for Opioid Use Disorder During the COVID-19 Pandemic.

The usual challenges of conducting primary care research, including randomized trials, have been exacerbated, and new ones identified, during the COVID-19 pandemic. HOMER (Home versus Office for Medication Enhanced Recovery; subsequently, Comparing Home, Office, and Telehealth Induction for Medication Enhanced Recovery) is a pragmatic, comparative-effectiveness research trial that aims to answer a key question from patients and clinicians: What is the best setting in which to start treatment with buprenorphine for opioid use disorder for this patient at this time? In this article, we describe the difficult journey to find the answer. The HOMER study began as a randomized trial comparing treatment outcomes in patients starting treatment with buprenorphine via induction at home (unobserved) vs in the office (observed, synchronous).

Intraperitoneal activation of myeloid cells clears ascites and reveals IL27-dependent regression of metastatic ovarian cancer.

Patients with metastatic ovarian cancer (OvCa) have a 5-year survival rate of less than 30% due to persisting dissemination of chemoresistant cells in the peritoneal fluid and the immunosuppressive microenvironment in the peritoneal cavity. Here, we report that intraperitoneal administration of β-glucan and IFNγ (BI) induced robust tumor regression in clinically relevant models of metastatic OvCa. BI induced tumor regression by controlling fluid tumor burden and activating localized antitumor immunity.

A randomised, placebo-controlled, double blind, crossover trial on the effect of a 20:1 cannabidiol: Δ9-tetrahydrocannabinol medical cannabis product on neurocognition, attention, and mood.

As cannabinoid-based medications gain popularity in the treatment of refractory medical conditions, it is crucial to examine the neurocognitive effects of commonly prescribed products to ensure associated safety profiles. The present study aims to investigate the acute effects of a standard 1 mL sublingual dose of CannEpil®, a medicinal cannabis oil containing 100 mg cannabidiol (CBD) and 5 mg Δ9-tetrahydrocannabinol (THC) on neurocognition, attention, and mood. A randomised, double-blind, placebo-controlled, within-subjects design assessed 31 healthy participants (16 female, 15 male), aged between 21 and 58 years, over a two-week experimental protocol.

Growth Signaling Networks Orchestrate Cancer Metabolic Networks.

Normal cells grow and divide only when instructed to by signaling pathways stimulated by exogenous growth factors. A nearly ubiquitous feature of cancer cells is their capacity to grow independent of such signals, in an uncontrolled, cell-intrinsic manner. This property arises due to the frequent oncogenic activation of core growth factor signaling pathway components, including receptor tyrosine kinases, PI3K-AKT, RAS-RAF, mTORC1, and MYC, leading to the aberrant propagation of pro-growth signals independent of exogenous growth factors.

A semi-naturalistic open-label study examining the effect of prescribed medical cannabis use on simulated driving performance.

Background: Despite increasing medical cannabis use, research has yet to establish whether and to what extent products containing delta-9-tetrahydrocannabinol (THC) impact driving performance among patients. Stable doses of prescribed cannabinoid products during long-term treatment may alleviate clinical symptoms affecting cognitive and psychomotor performance.

Aim: To examine the effects of open-label prescribed medical cannabis use on simulated driving performance among patients.

Demonstrating Agreement between Radio and Fluorescence Measurements of the Depth of Maximum of Extensive Air Showers at the Pierre Auger Observatory.

We show, for the first time, radio measurements of the depth of shower maximum (X_{max}) of air showers induced by cosmic rays that are compared to measurements of the established fluorescence method at the same location. Using measurements at the Pierre Auger Observatory we show full compatibility between our radio and the previously published fluorescence dataset, and between a subset of air showers observed simultaneously with both radio and fluorescence techniques, a measurement setup unique to the Pierre Auger Observatory. Furthermore, we show radio X_{max} resolution as a function of energy and demonstrate the ability to make competitive high-resolution X_{max} measurements with even a sparse radio array.

A systematic review of oculomotor deficits associated with acute and chronic cannabis use.

Driving is a critical everyday task necessitating the rapid and seamless integration of dynamic visually derived information to guide neurobehaviour. Biological markers are frequently employed to detect Δ9-tetrahydrocannabinol (THC) consumption among drivers during roadside tests, despite not necessarily indicating impairment. Characterising THC-specific alterations to oculomotor behaviour may offer a more sensitive measure for indexing drug-related impairment, necessitating discrimination between acute THC effects, chronic use and potential tolerance effects.

FLT3 tyrosine kinase inhibition modulates PRC2 and promotes differentiation in acute myeloid leukemia.

Internal tandem duplication mutations in fms-like tyrosine kinase 3 (FLT3-ITD) are recurrent in acute myeloid leukemia (AML) and increase the risk of relapse. Clinical responses to FLT3 inhibitors (FLT3i) include myeloid differentiation of the FLT3-ITD clone in nearly half of patients through an unknown mechanism. We identified enhancer of zeste homolog 2 (EZH2), a component of polycomb repressive complex 2 (PRC2), as a mediator of this effect using a proteomic-based screen.

A Semi-Naturalistic, Open-Label Trial Examining the Effect of Prescribed Medical Cannabis on Neurocognitive Performance.

Background And Objectives: Medical cannabis use is increasing in Australia and other jurisdictions, yet little is known about the effects of medical cannabis on cognitive function. Findings from studies of non-medical ('recreational') cannabis may not be applicable to patients using prescribed medical cannabis to manage a health condition.

Methods: In this semi-naturalistic, open-label trial, patients with various health conditions attended a single laboratory session in which they self-administered a standard dose of prescribed medical cannabis as per instructions on the pharmacy label.

Implementation of a Stepped Care Program to Address Emotional Recovery among Traumatic Injury Patients.

Background: Annually, over 600,000 adults served in US trauma centers (≥20%) develop posttraumatic stress disorder (PTSD) and/or depression in the first year after injury. American College of Surgeons guidelines include screening and addressing mental health recovery in trauma centers. Yet, many trauma centers do not monitor and address mental health recovery, and it is a priority to learn how to implement evidence-informed mental health programs in trauma centers.

Preference for and impact of telehealth vs in-person asthma visits among Black and Latinx adults.

Background: Black and Latinx adults experience disproportionate asthma-related morbidity and limited specialty care access. The severe acute respiratory syndrome coronavirus 2 pandemic expanded telehealth use.

Objective: To evaluate visit type (telehealth [TH] vs in-person [IP]) preferences and the impact of visit type on asthma outcomes among Black and Latinx adults with moderate-to-severe asthma.

Effect of CannEpil on simulated driving performance and co-monitoring of ocular activity: A randomised controlled trial.

Background: Medicinal cannabis products containing Δ9-tetrahydrocannabinol (THC) are increasingly accessible. Yet, policy guidelines regarding fitness to drive are lacking, and cannabinoid-specific indexations of impairment are underdeveloped.

Aims: To determine the impact of a standardised 1 mL sublingual dose of CannEpil, a medicinal cannabis oil containing 100 mg cannabidiol (CBD) and 5 mg THC on simulated driving performance, relative to placebo and whether variations in vehicle control can be indexed by ocular activity.

Real-Time, Multiplexed SHERLOCK for in Vitro Diagnostics.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the need for simple, low-cost, and scalable diagnostics that can be widely deployed for rapid testing. Clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostics have emerged as a promising technology, but its implementation in clinical laboratories has been limited by the requirement of a separate amplification step prior to CRISPR-associated (Cas) enzyme-based detection. This article reports the discovery of two novel Cas12 enzymes (SLK9 and SLK5-2) that exhibit enzymatic activity at 60°C, which, when combined with loop-mediated isothermal amplification (LAMP), enable a real-time, single-step nucleic acid detection method [real-time SHERLOCK (real-time SLK)].