Current clinical trials for craniopharyngiomas: what's on the horizon?

Craniopharyngiomas are histologically low-grade tumors in the sellar/suprasellar region that grow close to critical structures including the hypothalamus, pituitary gland, and optic chiasm. Due to this challenging location, many patients face long-term complications including neuroendocrine, neurologic, and visual deficits. As a result, there is interest in developing risk-optimized treatments that minimize damage to adjacent normal tissue and limit chronic complications patients face.

Spatiotemporal binding of cyclophilin A and CPSF6 to capsid regulates HIV-1 nuclear entry and integration.

Unlabelled: Human immunodeficiency virus type 1 (HIV-1) capsid, which is the target of the antiviral lenacapavir, protects the viral genome and binds multiple host proteins to influence intracellular trafficking, nuclear import, and integration. Previously, we showed that capsid binding to cleavage and polyadenylation specificity factor 6 (CPSF6) in the cytoplasm is competitively inhibited by cyclophilin A (CypA) binding and regulates capsid trafficking, nuclear import, and infection. Here, we determined that a capsid mutant with increased CypA binding affinity had significantly reduced nuclear entry and mislocalized integration.

Sleep Timing, Sleep Timing Regularity, and Cognitive Performance in Women Entering Late Adulthood: The Study of Women's Health Across the Nation (SWAN).

Study Objectives: This study examined whether sleep timing and its regularity are associated with cognitive performance in older women and whether associations vary based on cardiometabolic risk factors.

Methods: The cross-sectional analysis included 1,177 community-dwelling females (mean age 65 years) from the observational Study of Women's Health Across the Nation (SWAN) annual visit 15. Sleep timing (mean midpoint from sleep onset to wake-up) and its regularity (standard deviation of midpoint ) were assessed using actigraphy.

Genetic ancestry superpopulations show distinct prevalence and outcomes across pediatric central nervous system tumors from the PBTA and PNOC.

Background: Central nervous system (CNS) tumors lead to cancer-related mortality in children. Genetic ancestry-associated cancer prevalence and outcomes have been studied, but is limited.

Methods: We performed genetic ancestry prediction in 1,452 pediatric patients with paired normal and tumor whole genome sequencing from the Open Pediatric Cancer (OpenPedCan) project to evaluate the influence of reported race and ethnicity and ancestry-based genetic superpopulations on tumor histology, molecular subtype, survival, and treatment.

Sleep macro-architecture and dementia risk in adults: Meta-analysis of 5 cohorts from the Sleep and Dementia Consortium.

Study Objectives: Poor sleep may play a role in the risk of dementia. However, few studies have investigated the association between polysomnography (PSG)-derived sleep architecture and dementia incidence. We examined the relationship between sleep macro-architecture and dementia incidence across five US-based cohort studies from the Sleep and Dementia Consortium (SDC).

The effect of replacing prolonged sitting with intermittent standing during a simulated workday on the subsequent night's sleep.

A bout of leisure-time physical activity improves sleep on the subsequent night. However, whether breaking up sedentary time during the workday improves sleep is unknown. The purpose of this study was to examine whether breaking up prolonged sitting by standing during the workday leads to better sleep the following night.

Engagement in moderate-intensity physical activity supports overnight memory retention in older adults.

Preserving the ability to vividly recall emotionally rich experiences contributes to quality of life in older adulthood. While prior works suggest that moderate-intensity physical activity (MPA) may bolster memory, it is unclear whether this extends to emotionally salient memories consolidated during sleep. In the current study, older adults (mean age = 72.

Patterns of physical activity, sedentary behavior, and sleep across pregnancy before and during two COVID pandemic years.

Background: Physical activity is recommended during pregnancy, and high sedentary behavior and poor sleep may increase the risk of pregnancy complications. Activity patterns and sleep were negatively impacted by the COVID pandemic in many segments of the population, but the impact of the pandemic on pregnant people is understudied. We aimed to compare patterns of physical activity, sedentary time, and sleep during pregnancy between a pre-COVID and a COVID-era cohort.

Radiographic and visual response to the type II RAF inhibitor tovorafenib in children with relapsed/refractory optic pathway glioma in the FIREFLY-1 trial.

Background: Due to their anatomical locations, optic pathway gliomas (OPGs) can rarely be cured by resection. Given the importance of preserving visual function, we analyzed radiological and visual acuity (VA) outcomes for the type II RAF inhibitor tovorafenib in the OPG subgroup of the phase 2 FIREFLY-1 trial.

Methods: FIREFLY-1 investigated the efficacy (arm 1, n=77), safety, and tolerability (arms 1/2) of tovorafenib (420 mg/m2 once weekly; 600 mg maximum) in patients with BRAF-altered relapsed/refractory pediatric low-grade glioma (pLGG).

Omnigene-Gut ensures fecal microbiome stability in the pediatric population.

Increasing evidence exists that the gut microbiome influences toxicity as well as outcomes in a variety of cancers. To investigate the role of the gut microbiome in pediatric neuro-oncology, microbiome analysis has been included in multiple prospective pediatric neuro-oncology clinical trials (NCT05009992, NCT04732065, NCT04775485). In these trials, the OMNIgene-GUT preservation tubes are used for the collection of the feces.

Phagolysosomes break down the membrane of a non-apoptotic corpse independent of macroautophagy.

Cell corpses must be cleared in an efficient manner to maintain tissue homeostasis and regulate immune responses. Ubiquitin-like Atg8/LC3 family proteins promote the degradation of membranes and internal cargo during both macroautophagy and corpse clearance, raising the question how macroautophagy contributes to corpse clearance. Studying the clearance of non-apoptotic dying polar bodies in Caenorhabditis elegans embryos, we show that the LC3 ortholog LGG-2 is enriched inside the polar body phagolysosome independent of autophagosome formation.

Atypical Sensory Loss Pattern in an Isolated Thalamic Stroke: A Case Report.

This case report discusses a 51-year-old male who presented to the emergency department (ED) with left-sided hemiparesthesia and left leg incoordination. The initial brain computed tomography (CT) scan was negative, and the follow-up brain CT three days after the onset of symptoms was also negative. Although sensitivity and specificity are not 100%, CT remains the first-line diagnostic test for detecting a cerebrovascular accident (CVA).

Retrospective Comparison of Targeted Anticancer Drugs Predicted by the CNS-TAP Tool Versus Those Selected by a Molecularly Driven Tumor Board in Children With DIPG.

The recent trial Pediatric Neuro-Oncology Consortium 003 (PNOC003) utilized a molecular tumor board to recommend personalized treatment regimens based on tumor sequencing results in children with DIPG. We separately developed the Central Nervous System Targeted Agent Prediction (CNS-TAP) tool, which numerically scores targeted anticancer agents using preclinical, clinical, and patient-specific data. We hypothesized that highly scored agents from CNS-TAP would overlap with the PNOC003 tumor board's recommendations.

Multilevel challenges to equitable inclusion of children in trials when parents use languages other than English: A qualitative report from Children's Oncology Group's Diversity and Health Disparities Committee Language Equity Working Group.

Background: Increasing representation in clinical trials is a priority for the National Cancer Institute and Children's Oncology Group (COG). Our survey of COG-affiliated institutions revealed that many sites have insufficient processes and resources to enroll children whose parents use languages other than English (LOE). We describe reported barriers and facilitators to enrolling children in clinical trials when parents use LOE and propose opportunities for improvement.

Quantitative Approach to Quality Review of Prenatal Ultrasound Examinations: Fetal Biometry.

: To evaluate the quality of an ultrasound practice, both large-scale and focused audits are recommended by professional organizations, but such audits can be time-consuming, inefficient, and expensive. Our objective was to develop a time-efficient, quantitative, objective, large-scale method to evaluate fetal biometry measurements for an entire practice, combined with a process for focused image review for personnel whose measurements are outliers. : Ultrasound exam data for a full year are exported from commercial ultrasound reporting software to a statistical package.

Recurrent adamantinomatous craniopharyngiomas show MAPK pathway activation, clonal evolution and rare TP53-loss-mediated malignant progression.

The two types of craniopharyngioma, adamantinomatous (ACP) and papillary (PCP), are clinically relevant tumours in children and adults. Although the biology of primary craniopharyngioma is starting to be unravelled, little is known about the biology of recurrence. To fill this gap in knowledge, we have analysed through methylation array, RNA sequencing and pERK1/2 immunohistochemistry a cohort of paired primary and recurrent samples (32 samples from 14 cases of ACP and 4 cases of PCP).

An adapted transdiagnostic sleep and circadian intervention for adults with excess weight and suboptimal sleep health: pilot study results.

Study Objectives: This single-arm, mixed-methods, pilot study examined the feasibility and preliminary efficacy of an adapted version of the transdiagnostic intervention for sleep and circadian dysfunction (TranS-C) on multidimensional sleep health (MDSH) in a sample of adults with excess weight and suboptimal sleep health.

Methods: Participants received up to eight, weekly, remotely delivered, tailored TranS-C sessions. At pre- and post-intervention, the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and 7 days of Fitbit data were used to evaluate changes in sleep dimensions (regularity, alertness, timing, satisfaction, duration, and efficiency) and the composite MDSH score.

Phagolysosomes break down the membrane of a non-apoptotic corpse independent of macroautophagy.

Cell corpses must be cleared in an efficient manner to maintain tissue homeostasis and regulate immune responses. Ubiquitin-like Atg8/LC3 family proteins promote the degradation of membranes and internal cargo during both macroautophagy and corpse clearance, raising the question how macroautophagy contributes to corpse clearance. Studying the clearance of non-apoptotic dying polar bodies in embryos, we show that the LC3 ortholog LGG-2 is enriched in the polar body phagolysosome independent of membrane association or autophagosome formation.

Clinical trial recruitment of people who speak languages other than English: a Children's Oncology Group report.

Background: Persons who speak languages other than English are underrepresented in clinical trials, likely in part because of inadequate multilevel resources. We conducted a survey of institutions affiliated with the Children's Oncology Group (COG) to characterize current research recruitment practices and resources regarding translation and interpretation services.

Methods: In October 2022, a 20-item survey was distributed electronically to institutions affiliated with COG to assess consent practices and resources for recruiting participants who speak languages other than English to COG trials.