The histone H3.3 K27M mutation suppresses Ser31phosphorylation and mitotic fidelity, which can directly drive gliomagenesis.

Serine 31 is a phospho-site unique to the histone H3.3 variant; mitotic phospho-Ser31 is restricted to pericentromeric heterochromatin, and disruption of phospho-Ser31 results in chromosome segregation defects and loss of p53-dependant G cell-cycle arrest. Ser31 is proximal to the H3.

Showcasing diversity, equity, and inclusion in neurological surgery: a comparative analysis of neurological surgery residency program websites in the United States.

Residency websites can often be crucial for influencing neurosurgery applicants' first impressions of programs. This study explores the representation of diversity on neurological surgery residency program websites and evaluates the impact of Diversity, Equity, and Inclusion (DEI) statements. The websites of 117 neurological surgery residency programs were evaluated for the presence of 12 diversity and inclusion elements.

Transcatheter Aortic-Valve Replacement for Asymptomatic Severe Aortic Stenosis.

Background: For patients with asymptomatic severe aortic stenosis and preserved left ventricular ejection fraction, current guidelines recommend routine clinical surveillance every 6 to 12 months. Data from randomized trials examining whether early intervention with transcatheter aortic-valve replacement (TAVR) will improve outcomes in these patients are lacking.

Methods: At 75 centers in the United States and Canada, we randomly assigned, in a 1:1 ratio, patients with asymptomatic severe aortic stenosis to undergo early TAVR with transfemoral placement of a balloon-expandable valve or clinical surveillance.

Structure-Activity Relationship of Potent, Selective, and Orally Bioavailable Molecular Glue Degraders of CK1α.

The original molecular glue degraders (thalidomide, lenalidomide, and pomalidomide) are known to bind to cereblon (CRBN) and alter its surface to induce recruitment, ubiquitination, and degradation of therapeutically valuable neosubstrates (IKZF1, IKZF3, and CK1α). With the aim of understanding and modulating neosubstrate specificity, we recently reported the discovery of SJ3149 (), a selective and potent molecular glue degrader of CK1α, that is active in multiple cancer cell lines. Herein, we describe the medicinal chemistry efforts that resulted in the discovery of SJ3149 as well as other potent and selective CK1α degraders.

When adults with speech-language impairment meet law enforcement: A qualitative analysis of client experiences.

Introduction: Members of law enforcement and the general public who have limited knowledge of persons with communication impairments (PCI) may misinterpret their communication behaviors. Few studies exist about communication between PCI and law enforcement, and data are lacking about the factors that may influence their interactions. Considering this need, we addressed the following research questions: How will PCI describe their attitudes and experiences related to interacting with law enforcement? What individual characteristics may influence these attitudes and experiences?

Methods: In individual semi-structured interviews, we asked 10 adults with speech-language differences (aphasia, dysarthria, or stuttering) to describe their experiences of interacting with members of law enforcement, the communication strategies they would use when interacting with law enforcement, and what they would like members of law enforcement to know about their communication needs.

Commitment to cytokinetic furrowing requires the coordinate activity of microtubules and Plk1.

At anaphase, spindle microtubules (MTs) position the cleavage furrow and trigger actomyosin assembly by localizing the small GTPase RhoA and the scaffolding protein anillin to a narrow band along the equatorial cortex [1-6]. Using vertebrate somatic cells we examined the temporal control of furrow assembly. Although its positioning commences at anaphase onset, furrow maturation is not complete until ∼10-11 min later.

Altered vocal communication in adult vasopressin-deficient Brattleboro rats.

The neuropeptide, arginine vasopressin (AVP), has been implicated in social communication across a diverse array of species. Many rodents communicate basic behavioral states with negative versus positive valence through high-pitched vocalizations above the human hearing range (ultrasonic vocalizations; USVs). Previous studies have found that Brattleboro (Bratt) rats, which have a mutation in the Avp gene, exhibit deficits in their USVs from the early postnatal period through adolescence, but the magnitude of this effect appears to decrease from the juvenile to adolescent phase.

Bullying Involvement and Subtypes of Disabilities: Who is Likely to be Affected by What?

The current study uses latent class analysis (LCA) and binary logistic regression analysis to explore profiles of bullying and how they might be associated with the types of disabilities. LCA was used to determine a categorization of involvement in bullying among youth with various types of disabilities. Binary logistic regression analysis was conducted to explore how profiles of bullying involvement might be associated with types of disabilities.

Identifying Barriers to Timely Follow-up After Elevated PSA Screening: A Retrospective Analysis of a Large Healthcare System.

Objective: To examine elevated PSA follow-up within our system and identify areas for improvement in the timely diagnosis of prostate cancer.

Methods: We queried the Mass General Brigham's Enterprise Data Warehouse from 2018-2021, identifying patients with elevated PSA and documented time to follow-up. Timely follow-up was defined as having a urologist appointment, prostate biopsy, or prostate magnetic resonance imaging within 6 months from diagnosis.

BRD-810 is a highly selective MCL1 inhibitor with optimized in vivo clearance and robust efficacy in solid and hematological tumor models.

The MCL1 gene is frequently amplified in cancer and codes for the antiapoptotic protein myeloid cell leukemia 1 (MCL1), which confers resistance to the current standard of care. Therefore, MCL1 is an attractive anticancer target. Here we describe BRD-810 as a potent and selective MCL1 inhibitor and its key design principle of rapid systemic clearance to potentially minimize area under the curve-driven toxicities associated with MCL1 inhibition.

Machine Learning Identification of Modifiable Predictors of Patient Outcomes After Transcatheter Aortic Valve Replacement.

Background: Transcatheter aortic valve replacement (TAVR) is an important treatment option for patients with severe symptomatic aortic stenosis. It is important to identify predictors of excellent outcomes (good clinical outcomes, more time spent at home) after TAVR that are potentially amenable to improvement.

Objectives: The purpose of the study was to use machine learning to identify potentially modifiable predictors of clinically relevant patient-centered outcomes after TAVR.

Ultrasound Guidance to Replicate Transuterine BioGlue Injection in the Fetal Hydrocephalus Sheep Model.

Introduction: Congenital hydrocephalus often results in irreversible and severe damage to the brain despite postnatal interventions. The potential for prenatal intervention to mitigate these deleterious effects underscores the importance of a suitable animal model. We aimed assess the results of an ultrasound-guided transuterine approach to replicate the BioGlue injection fetal hydrocephalus model.

A Review of Respiratory Syncytial Virus Epidemiology Among Children: Linking Effective Prevention to Vulnerable Populations.

Respiratory syncytial virus (RSV) is the greatest contributor to lower respiratory tract infections (LRTI) in children less than 5 years of age and the leading cause for infant hospitalizations in the United States (US). The burden of severe disease disproportionately impacts racial and ethnic minority groups, highlighting the need for interventions that promote health equity. Recent advancements in effective prophylactic agents have the potential to drastically alter the landscape of RSV disease among all young children.

H3K27-Altered Diffuse Midline Glioma of the Brainstem: From Molecular Mechanisms to Targeted Interventions.

Pediatric high-grade gliomas are a devastating subset of brain tumors, characterized by their aggressive pathophysiology and limited treatment options. Among them, H3 K27-altered diffuse midline gliomas (DMG) of the brainstem stand out due to their distinct molecular features and dismal prognosis. Recent advances in molecular profiling techniques have unveiled the critical role of H3 K27 alterations, particularly a lysine-to-methionine mutation on position 27 (K27M) of the histone H3 tail, in the pathogenesis of DMG.

The Risk for Readmission to Juvenile Detention: The Role of Trauma Exposure and Trauma-related Mental Health Disorders.

The purpose of this study was to examine the impact of childhood trauma exposure, posttraumatic stress disorder, and trauma-related comorbid diagnoses on the risk for readmission to juvenile detention among youth in a large metropolitan area ( = 1282). The following research questions were addressed: 1) Does a greater number of childhood traumas increase the risk for readmission to detention following release? 2) Does the risk for readmission differ by type of trauma? 3) Do PTSD and other co-morbid diagnoses increase the risk for readmission? and 4) What role do demographic factors play in the relationship between trauma-related variables and risk for readmission? This study utilized the screening results of 1282 youth who were voluntarily screened for PTSD, depressive symptoms and substance use during their initial intake to detention. More than half of the sample was readmitted during the three-year study period, with readmissions most likely to occur within one year of release.

Climate change, microplastics, and male infertility.

Purpose Of Review: Semen quality is on the decline. While the etiology is unknown, recent literature suggests there may be a relationship between climate change, environmental toxins and male fertility. This review relays new information regarding associations between our environment and male infertility.

Diversity of Research Participant Gender, Race, and Ethnicity in Communication Sciences and Disorders: A Systematic Review and Quantitative Synthesis of American Speech-Language-Hearing Association Publications in 2020.

Purpose: One manifestation of systemic inequities in communication sciences and disorders (CSD) is the chronic underreporting and underrepresentation of sex, gender, race, and ethnicity in research. The present study characterized recent demographic reporting practices and representation of participants across CSD research.

Methods: We systematically reviewed and extracted key reporting and participant data from empirical studies conducted in the United States (US) with human participants published in the year 2020 in journals by the American Speech-Language-Hearing Association (ASHA; = 407 articles comprising a total = 80,058 research participants, search completed November 2021).

Application of induced proximity for therapeutic discovery.

In this Voices piece, the Cell Chemical Biology editors ask researchers from a range of backgrounds: what are some exciting discoveries in the induced proximity field and the next frontier for therapeutic development?

Production, Isolation, and Detection of Poly IC in Extracellular Vesicles from U937 Cells.

Double-stranded RNA is produced by viruses during their replicative cycle. It is a potent immune modulator and indicator of viral infection within the body. Extracellular vesicles (EVs) are lipid-bound particles released from cells homeostatically.

Fluid transitions.

Water is critical for survival and thirst is a powerful way of ensuring that fluid levels remain in balance. Overconsumption, however, can have deleterious effects, therefore optimization requires a need to balance the drive for water with the satiation of that water drive. This review will highlight our current understanding of how thirst is both generated and quenched, with particular focus on the roles of angiotensin II, glucagon like-peptide 1, and estradiol in turning on and off the thirst drive.

Estimating the impact of enhanced care at minority-serving hospitals on disparities in the treatment of breast, prostate, lung, and colon cancers.

Background: The objective of this study was to quantify disparities in cancer treatment delivery between minority-serving hospitals (MSHs) and non-MSHs for breast, prostate, nonsmall cell lung, and colon cancers from 2010 to 2019 and to estimate the impact of improving care at MSHs on national disparities.

Methods: Data from the National Cancer Database (2010-2019) identified patients who were eligible for definitive treatments for the specified cancers. Hospitals in the top decile by minority patient proportion were classified as MSHs.