Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer's disease.

Background: PSEN1, PSEN2, and APP mutations cause Alzheimer's disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earlier AAO; however, certain PSEN1 mutations cause a later AAO, similar to those observed in PSEN2 and APP.

Methods: We examined whether common disease endotypes exist across these mutations with a later AAO (~ 55 years) using hiPSC-derived neurons from familial Alzheimer's disease (FAD) patients harboring mutations in PSEN1, PSEN2, and APP and mechanistically characterized by integrating RNA-seq and ATAC-seq.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Experimental investigation and finite element analysis on the durability of root-filled teeth treated with multisonic irrigation.

Objective: This study compared the fracture load, stress distribution, and survival probability under cyclic loading of extensively restored teeth treated with multisonic irrigation with those treated with conventional instrumentation, with or without a post.

Methods: Mesial-occlusal-distal cavities were prepared in 30 human mandibular premolars. The teeth were randomly divided into 3 groups of 10 based on the endodontic and restorative procedures: (1) Root canal treatment (RCT) followed by resin composite restoration (control group), (2) RCT followed by a glass fiber post restoration (conventional group), and (3) minimal instrumentation plus multisonic irrigation followed by resin composite restoration (GW group).

Nuclear Cardiology Surrogate Biomarkers in Clinical Trials.

Nuclear cardiology offers a diverse range of imaging tools that provide valuable insights into myocardial perfusion, inflammation, metabolism, neuroregulation, thrombosis, and microcalcification. These techniques are crucial not only for diagnosing and managing cardiovascular conditions but also for gaining pathophysiologic insights. Surrogate biomarkers in nuclear cardiology, represented by detectable imaging changes, correlate with disease processes or therapeutic responses and can serve as endpoints in clinical trials when they demonstrate a clear link with these processes.

Pan-phylum genomes of hornworts reveal conserved autosomes but dynamic accessory and sex chromosomes.

Hornworts, one of the three bryophyte phyla, show some of the deepest divergences in extant land plants, with some families separated by more than 300 million years. Previous hornwort genomes represented only one genus, limiting the ability to infer evolution within hornworts and their early land plant ancestors. Here we report ten new chromosome-scale genomes representing all hornwort families and most of the genera.

Generating distant analogies increases metaphor production.

Although a large body of work has explored the mechanisms underlying metaphor comprehension, less research has focused on spontaneous metaphor production. Previous research suggests that reasoning about analogies can induce a relational mindset, which causes a greater focus on underlying abstract similarities. We explored how inducing a relational mindset may increase the tendency to use metaphors to describe topics.

Statistical principles in neurointervention part 1: basic principles, descriptive statistics and univariable analysis.

Neurointervention has seen significant advancements in recent decades with the adoption of myriad new technologies and techniques. Initially reliant on case reports and small case series, we now benefit from multicenter studies and randomized trials that can provide robust practice-changing evidencea and often employ sophisticated statistical methods. This two-part series on statistical principles in neurointervention aims to equip neurointerventionalists with essential statistical knowledge for critically reviewing literature and conducting methodologically sound research.

US state minimum wages and rates of maltreatment-related death among children.

Background: The number of U.S. deaths due to child maltreatment (abuse and neglect) has been increasing over several years.

Recruitment of Young Gay, Bisexual, and Other Men Who Have Sex With Men for a Web-Based Human Papillomavirus Vaccination Intervention: Differences in Participant Characteristics and Study Engagement by Recruitment Source in a Randomized Controlled Trial.

Background: Young gay, bisexual, and other men who have sex with men have been referred to as a "hard-to-reach" or "hidden" community in terms of recruiting for research studies. With widespread internet use among this group and young adults in general, web-based avenues represent an important approach for reaching and recruiting members of this community. However, little is known about how participants recruited from various web-based sources may differ from one another.

Improved Patient-Reported Outcomes With Post-Transplant Cyclophosphamide: A Quality-of-Life Evaluation and 2-Year Outcomes of BMT CTN 1703.

The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant.

Epstein-Barr Virus-Associated Frosted Branch Angiitis: A Case Report and Brief Review.

Purpose: To report the clinical presentation, treatment course, and outcome of a case of bilateral frosted branch angiitis (FBA) and neuroretinitis associated with acute Epstein-Barr virus (EBV) infection in a pediatric patient with Turner Syndrome.

Methods: Case report with multimodal ocular imaging and extensive systemic workup.

Results: A 16-year-old female with Turner syndrome presented with acute bilateral vision loss, hearing loss, and ataxia.

Systems-level liquid biopsy in advanced prostate cancer.

Treatment for castration-resistant prostate cancer (CRPC) primarily involves the suppression of androgen receptor (AR) activity using androgen receptor signaling inhibitors (ARSIs). While ARSIs have extended patient survival, resistance inevitably develops. Mechanisms of resistance include genomic aberrations at the AR locus that reactivate AR signaling, or lineage plasticity that drives emergence of AR-independent phenotypes.

The Role of Cytonemes and Diffusive Transport in the Establishment of Morphogen Gradients.

Spatial distributions of morphogens provide positional information in developing systems, but how the distributions are established and maintained remains an open problem. Transport by diffusion has been the traditional mechanism, but recent experimental work has shown that cells can also communicate by filopodia-like structures called cytonemes that make direct cell-to-cell contacts. Here we investigate the roles each may play individually in a complex tissue and how they can jointly establish a reliable spatial distribution of a morphogen.

Basic Science and Pathogenesis.

Background: With the emerging role of the blood biomarkers in Alzheimer's Disease (AD) clinical practice and trials, it is crucial to identify and address factors influencing the concentrations of these biomarkers in circulation for enhanced clinical utility. We aim to assess the impact of lung function on plasma AD biomarker levels and elucidate the relationship between lung function and Alzheimer's Disease and Related Dementias (ADRD).

Method: We used the Peak Expiratory Flow (PEF), plasma biomarkers of AD (Amyloid beta 42/40 (Aβ42/40) ratio, phosphorylated-tau181 (p-tau181), Neurofilament light chain (NfL) and Glial fibrillary acidic protein (GFAP)) measured in the Health and Retirement Study (HRS) 2016 survey participants (n = 3801) and incident dementia (n = 142) over 4 years.

Clinical Manifestations.

Background: Prior longitudinal studies among older adults have documented associations between hearing loss and changes in brain morphology. Whether interventions involving hearing aids can reduce age-related atrophy is unknown. A substudy within the Aging and Cognitive Health Evaluation in Elders (ACHIEVE, Clinicaltrials.

Beverage-Induced Surface Changes in Biomimetic Dental Resin Composite: AFM and Bacterial Analysis.

Objective:  Continuous advancements in composite resin materials have revolutionized and expanded its clinical use, improving its physical and mechanical properties. Attaining and retaining surface texture and gloss are crucial for the long-term durability of the composite resin material. This study investigated the supra-nanospherical filler composite material compared with different composite resin materials immersed in different beverages.

Clinical Manifestations.

Background: Subjective Cognitive Decline (SCD) is a prevalent condition impacting 11.7% of older adults, which increases the risk for mild cognitive impairment and dementia. The transition to SCD and dementia is often accompanied by an increase in affective symptoms (i.

Clinical Manifestations.

Background: Traditional cognitive and daily functioning measures that utilize episodic assessment schedules are less sensitive to subtle within-person change in those at risk for Alzheimer's disease (AD). This study aimed to evaluate whether longitudinal trajectories of high frequency cognitive assessments (HFA) and passively assessed higher order instrumental activities of daily living (IADLs) differ between those with intact cognition (CN, n = 59) and mild cognitive impairment (MCI, n = 45). An exploratory aim evaluated whether the use of person-specific distributions would detect differences in longitudinal trajectories not captured by traditional between-group analyses.

INCREASED CITRULLINATED HISTONE H3 LEVELS AND ACCELERATED THROMBIN KINETICS IN TRAUMA PATIENTS WHO DEVELOP VENOUS THROMBOEMBOLISM.

Background: Neutrophil extracellular traps (NETs), and its formation and release, known as NETosis, may play a role in the initiation of thrombin generation (TG) in trauma. The objective of this study was to assess whether trauma patients, who develop symptomatic venous thromboembolism (VTE), have increased levels of plasma citrullinated histone H3 (CitH3) and accelerated TG kinetics.

Methods: Patients presenting to a Level I Trauma Center as trauma activations had samples collected within 12 hours of time of injury (TOI), alongside healthy volunteers (HV).

Craniofacial Pain Locations and Outcomes After Endoscopic Sinus Surgery for Unilateral Sphenoid Sinusitis: A Multi-Institutional Study.

Introduction: Unilateral sphenoid sinus opacification on computed tomography is caused by a variety of pathologies including inflammatory and infectious sinusitis, benign and malignant tumors, and encephaloceles. The purpose of this study was to report craniofacial pain locations and outcomes in inflammatory unilateral sphenoid sinusitis (USS) patients who underwent endoscopic sinus surgery (ESS).

Methods: A multi-institutional retrospective cohort study was conducted on all adult patients who had ESS for USS from 2015 to 2022.

Postoperative Implementation of Virtual Reality and Wearable Devices: Opportunities and Challenges.

Objective: To examine implementation of virtual reality (VR) and Fitbit wearable activity devices in postoperative recovery.

Methods: This was a prospective, 4-arm, randomized controlled trial of patients undergoing inpatient head and neck surgery at a tertiary academic center from November 2021 to July 2022. Patients were randomized to Control, VR, Fitbit, or combined VR + Fitbit groups.

International Consensus Guidance for the Management of Glucocorticoid Related Complications in Neuromuscular Disease.

Introduction/aims: Glucocorticoid (GC)-related adverse reactions and risks are commonly seen during the treatment of immune-mediated and inflammatory neuromuscular disorders. There is wide variation in the management of associated complications. The aim of this study is to develop international consensus guidance on the management of GC-related complications in neuromuscular disorders.

Racial, Socioeconomic, and Geographic Disparities in Preamputation Vascular Care for Patients With Chronic Limb-Threatening Ischemia.

Background: Black patients, those with low socioeconomic status (SES), and those living in rural areas have elevated rates of major lower extremity amputation, which may be related to a lack of subspecialty chronic limb-threatening ischemia care. We evaluated the association between race, rurality, SES, and preamputation vascular care.

Methods: Among patients aged 66 to 86 years with fee-for-service Medicare who underwent major lower extremity amputation for chronic limb-threatening ischemia from July 2010 to December 2019, we compared the proportion who received vascular care in the 12 months before amputation by race (Black versus White), rurality, and SES (dual eligibility for Medicaid versus no dual eligibility) using multivariable logistic regression adjusting for clinical and demographic covariates.