Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

The ADHD Assessment Quality Assurance Standard for Children and Teenagers (CAAQAS).

Around 5% of the children and teenagers worldwide are affected by Attention-Deficit/Hyperactivity Disorder [ADHD], making it a major public health concern. Recently, demand for assessments has substantially increased, putting strain on healthcare and waiting lists. There is concern that pressure to clear service bottlenecks is leading to variable quality and reliability of ADHD assessments in this population.

Penalizing underage alcohol use is associated with lower mortality for young drivers: Use/lose laws and their association with motor vehicle collision mortality.

Background: Motor vehicle collisions (MVC) continue to be a leading cause of mortality for youth in the United States. Since 2010, seven states have revoked mandatory laws that suspended licenses for underage alcohol use, also known as use/lose laws. This study analyzed whether each state's policy change was associated with increased youth MVC mortality.

Efficacy, Safety, and Recurrence in Older Thyroid Eye Disease Patients Undergoing Teprotumumab Treatment.

Increasing life expectancy and an aging population have preserved quality of life decisions into older adulthood, defined by some clinical standards as greater than 75 years of age. While teprotumumab may represent a breakthrough in the treatment of thyroid eye disease, the teprotumumab phase III trial included only 2 patients aged over 75. Four female patients between the ages of 78 and 86-of whom 3 completed 8 infusions and 1 completed 7 infusions before discontinuation-were included in our study with a mean initial Clinical Activity Score score of 5.

Covered Stent Correction for Sinus Venosus Atrial Septal Defects, an Emerging Alternative to Surgical Repair: Results of an International Registry.

Background: Covered stent correction for a sinus venosus atrial septal defect (SVASD) was first performed in 2009. This innovative approach was initially viewed as experimental and was reserved for highly selected patients with unusual anatomic variants. In 2016, increasing numbers of procedures began to be performed, and in several centers, it is now offered as a standard of care option alongside surgical repair.

Consensus Recommendations for Studies of Outflow Facility and Intraocular Pressure Regulation Using Ex Vivo Perfusion Approaches.

Intraocular pressure (IOP) elevation is the primary risk factor and currently the main treatable factor for progression of glaucomatous optic neuropathy. In addition to direct clinical and living animal in vivo studies, ex vivo perfusion of anterior segments and whole eyes is a key technique for studying conventional outflow function as it is responsible for IOP regulation. We present well-tested experimental details, protocols, considerations, advantages, and limitations of several ex vivo model systems for studying IOP regulation.

Balancing High Clinical Volumes and Non-RVU Generating Activities in Radiology, Part ll: Future Directions.

The Radiology Research Alliance (RRA) of the Association of Academic Radiology (AAR) creates task forces to study emerging trends shaping the future of radiology. This article highlights the findings of the AAR-RRA Task Force on Balancing High Clinical Volumes and non-relative value unit (Non-RVU)-Generating Activities. The Task Force's mission was to evaluate and emphasize the value of non-RVU-generating activities that academic radiologists perform.

Metabolically intact nuclei are fluidized by the activity of the chromatin remodeling motor BRG1.

The structure and dynamics of the nucleus regulate cellular functions, with shape changes impacting cell motility. Although the nucleus is generally seen as the stiffest organelle in the cell, cells can nevertheless deform the nucleus to large strains by small mechanical stresses. Here, we show that the mechanical response of the cell nucleus exhibits active fluidization that is driven by the BRG1 motor of the SWI/SNF/BAF chromatin remodeling complex.

EXCELLENT Registry: A Prospective, Multicenter, Global Registry of Endovascular Stroke Treatment With the EMBOTRAP Device.

Background: The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots.

Methods: EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee.

Results: After screening 3799 patients, a total of 997 subjects (mean age, 70.

Adjuvant Immune Checkpoint Inhibitors for Muscle-Invasive Urothelial Carcinoma: An Updated Systematic Review, Meta-analysis, and Network Meta-analysis.

Context: Adjuvant immune checkpoint inhibitors (ICIs) have recently emerged as guideline-recommended treatments of high-risk muscle-invasive urothelial carcinoma (MIUC). However, there is limited evidence regarding the optimal candidates and the differential efficacy of adjuvant ICI regimens.

Objective: To synthesize and compare the efficacy and safety of adjuvant ICIs for high-risk MIUC using updated data from phase III randomized controlled trials.

Transcatheter Mitral Valve Replacement Using Annular Reduction by Cinching With TEER in the Commissure (ARCTIC).

Background: Mitral annular calcification with valve dysfunction remains a challenging syndrome. Operative risk is high, and available transcatheter therapies are limited.

Methods: This study describes our initial experience with a novel procedure to address large mitral annuli when no surgical or trial-based transcatheter mitral valve replacement device is available.

A systematic review and meta-analysis comparing the severity of core symptoms of attention-deficit hyperactivity disorder in females and males.

In the past decade, there have been substantial changes in diagnostic nomenclature. This study investigated sex differences in attention-deficit/hyperactivity disorder (ADHD) symptom severity based on Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV, DSM-IV(TR), and DSM-5 criteria, separating rating scale and clinical interview data in children and adults with ADHD. PubMed, PsycINFO, and Scopus were searched for published studies (1996-2021) reporting severity of attention, and hyperactivity/impulsivity in males and females.

Spatiotemporal lineage tracing reveals the dynamic spatial architecture of tumor growth and metastasis.

Tumor progression is driven by dynamic interactions between cancer cells and their surrounding microenvironment. Investigating the spatiotemporal evolution of tumors can provide crucial insights into how intrinsic changes within cancer cells and extrinsic alterations in the microenvironment cooperate to drive different stages of tumor progression. Here, we integrate high-resolution spatial transcriptomics and evolving lineage tracing technologies to elucidate how tumor expansion, plasticity, and metastasis co-evolve with microenvironmental remodeling in a -driven mouse model of lung adenocarcinoma.

Targeting CLK3 with Covalent Inhibitors: A Novel Strategy for Malaria Treatment.

Malaria still causes over 600,000 deaths annually, with rising resistance to frontline drugs by increasing this number each year. New medicines with novel mechanisms of action are, therefore, urgently needed. In this work, we solved the cocrystal structure of the essential malarial kinase CLK3 with the reversible inhibitor TCMDC-135051 (), enabling the design of covalent inhibitors targeting a unique cysteine residue (Cys368) poorly conserved in the human kinome.

Using virtual reality technology to prevent substance misuse and violence among university students: A pilot and feasibility study.

New prevention approaches that use engaging and innovative technologies are needed to reduce high rates of substance use and violence among university students. The present study developed and pilot-tested virtual reality (VR) technology that presented university students with immersive environments where they practiced skills with virtual peers. After viewing e-learning modules with prevention content, students engaged with immersive VR module prototypes to practice cognitive-behavioral skills for preventing risk behaviors, including assertive communication, negotiation, compromise, conflict resolution, and bystander intervention strategies.

International Variation in Health Status Benefits in Patients Undergoing Initial Invasive Versus Conservative Management for Chronic Coronary Disease: Insights From the ISCHEMIA Trial.

Background: The ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) demonstrated greater health status benefits with an initial invasive strategy, as compared with a conservative one, for patients with chronic coronary disease and moderate or severe ischemia. Whether these benefits vary globally is important to understand to support global adoption of the results.

Methods: We analyzed participants' disease-specific health status using the validated 7-item Seattle Angina Questionnaire (SAQ: >5-point differences are clinically important) at baseline and over 1-year follow-up across 37 countries in 6 international regions.

The Imaging-Neuropathological Gap in Acute Large Vessel Occlusive Stroke.

While imaging has traditionally played a fundamental role in the selection of patients undergoing endovascular thrombectomy, recent thrombectomy trials involving patients with large ischemic strokes demonstrated a consistent benefit of endovascular thrombectomy across all imaging strata, suggesting that reperfusion benefit may exist independent of current imaging constructs. Although these findings attest to the uniformly beneficial effects of reperfusion, they also shed doubt on the accuracy and utility of our imaging modalities in defining reversible versus irreversible ischemia and challenge the premise of imaging-based selection. We aimed to review the histopathologic studies and clinical trials that have shaped our understanding of current imaging constructs aiming to outline the existing imaging-neuropathological gap that may be far wider than previously perceived.

Early Adversity and Socioeconomic Factors in Pediatric Multiple Sclerosis: A Case-Control Study.

Background And Objectives: Psychosocial adversity and stress, known to predispose adults to neurodegenerative and inflammatory immune disorders, are widespread among children who experience socioeconomic disadvantage, and the associated neurotoxicity and proinflammatory profile may predispose these children to multiple sclerosis (MS). We sought to determine associations of socioeconomic disadvantage and psychosocial adversity with odds of pediatric-onset MS (POMS), age at POMS onset, and POMS disease activity.

Methods: This case-control study used data collected across 17 sites in the United States by the Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis Study.