Reconstructing Covert Consciousness: Neural Decoding as a Novel Consciousness Assessment.

Determining the level of consciousness in patients with brain injury-and more fundamentally, establishing what they can experience-is ethically and clinically impactful. Patient behaviors may unreliably reflect their level of consciousness: a subset of unresponsive patients demonstrate covert consciousness by willfully modulating their brain activity to commands through fMRI or EEG. However, current paradigms for assessing covert consciousness remain fundamentally limited because they are insensitive, rely on imperfect assumptions of functional neuroanatomy, and do not reflect the spectrum of conscious experience.

Characterization of Factors Associated With Death in Deceased Patients With Mitochondrial Disorders: A Multicenter Cross-Sectional Survey.

Background And Objectives: Mitochondrial disorders are multiorgan disorders resulting in significant morbidity and mortality. We aimed to characterize death-associated factors in an international cohort of deceased individuals with mitochondrial disorders.

Methods: This cross-sectional multicenter observational study used data provided by 26 mitochondrial disease centers from 8 countries from January 2022 to March 2023.

Current and Future Role of Circulating DNA in the Diagnosis and Management of Urothelial Carcinoma.

The growing sophistication of tumor molecular profiling has helped to slowly transition oncologic care toward a more personalized approach in different tumor types, including in bladder cancer. The National Comprehensive Cancer Network recommends that all patients with stage IVA and stage IVB urothelial carcinoma have molecular analysis that integrates at least testing to help facilitate the selection of future therapeutic options. Sequencing of tumor-derived tissue is the mainstay to obtain this genomic testing, but as in other cancers, there has been extensive research into the integration of liquid biopsies in longitudinal management.

Surrogate End Points for Overall Survival in Neoadjuvant Randomized Clinical Trials for Early Breast Cancer.

Purpose: To assess trial-level surrogacy value for overall survival (OS) of the pathologic complete response (pCR) and invasive disease-free survival (iDFS) in randomized clinical trials (RCTs) for early breast cancer (BC).

Methods: Individual patient data of neoadjuvant RCTs with available data on pCR, iDFS, and OS were included in the analysis. We used the coefficient of determination from weighted linear regression models to quantify the association between treatment effects on OS and on the surrogate end points.

Randomizing the human genome by engineering recombination between repeat elements.

We lack tools to edit DNA sequences at scales necessary to study 99% of the human genome that is noncoding. To address this gap, we applied CRISPR prime editing to insert recombination handles into repetitive sequences, up to 1697 per cell line, which enables generating large-scale deletions, inversions, translocations, and circular DNA. Recombinase induction produced more than 100 stochastic megabase-sized rearrangements in each cell.

Sox2 interacts with Atoh1 and Huwe1 Loci to regulate Atoh1 transcription and stability during hair cell differentiation.

Stem cell pluripotency gene Sox2 stimulates expression of proneural basic-helix-loop-helix transcription factor Atoh1. Sox2 is necessary for the development of cochlear hair cells and binds to the Atoh1 3' enhancer to stimulate Atoh1 expression. We show here that Sox2 deletion in late embryogenesis results in the formation of extra hair cells, in contrast to the absence of hair cell development obtained after Sox2 knockout early in gestation.

G3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration.

The subcellular localization of mRNAs plays a pivotal role in biological processes, including cell migration. For instance, β-actin mRNA and its associated RNA-binding protein (RBP), ZBP1/IGF2BP1, are recruited to focal adhesions (FAs) to support localized β-actin synthesis, crucial for cell migration. However, whether other mRNAs and RBPs also localize at FAs remains unclear.

Artificial intelligence for segmentation and classification in lumbar spinal stenosis: an overview of current methods.

Purpose: Lumbar spinal stenosis (LSS) is a frequently occurring condition defined by narrowing of the spinal or nerve root canal due to degenerative changes. Physicians use MRI scans to determine the severity of stenosis, occasionally complementing it with X-ray or CT scans during the diagnostic work-up. However, manual grading of stenosis is time-consuming and induces inter-reader variability as a standardized grading system is lacking.

Distinct Aggregation Behavior of -Terminally Truncated Aβ Over Aβ in the Presence of Zn(II).

The deposition of amyloid-β (Aβ) aggregates and metal ions within senile plaques is a hallmark of Alzheimer's disease (AD). Among the modifications observed in Aβ peptides, -terminal truncation at Phe4, yielding Aβ, is highly prevalent in AD-affected brains and significantly alters Aβ's metal-binding and aggregation profiles. Despite the abundance of Zn(II) in senile plaques, its impact on the aggregation and toxicity of Aβ remains unexplored.

Infection-Related Hospitalization and Incident Heart Failure: The Atherosclerosis Risk in Communities Study.

Background: The immune response to infections may become dysregulated and promote myocardial damage contributing to heart failure (HF). We examined the relationship between infection-related hospitalization (IRH) and HF, HF with preserved ejection fraction, and HF with reduced ejection fraction.

Methods And Results: We studied 14 468 adults aged 45 to 64 years in the ARIC (Atherosclerosis Risk in Communities) Study who were HF free at visit 1 (1987-1989).

Generalizability of Randomized Controlled Trials to Routine Clinical Care in Ulcerative Colitis.

Background: Historically, randomized controlled trials (RCTs) have been criticized for being poorly generalizable to patients with ulcerative colitis (UC) evaluated in routine care. We aimed to evaluate the proportion of patients with UC starting an advanced therapy who would be eligible to participate in phase 3 registrational UC RCTs.

Methods: We conducted a retrospective cohort analysis of UC patients starting vedolizumab, ustekinumab, or tofacitinib at 2 IBD clinics at the University of Calgary.

Ventral Rectopexy: An International Expert Panel Consensus and Review of Contemporary Literature.

Background: Ventral rectopexy has become increasingly utilized in the surgical management of rectal prolapse. There is a need for a contemporary evaluation of the role of the procedure and description of its use in clinical practice.

Objective: To create an international consensus on ventral rectopexy.

Validation of a Novel MRI Biomarker of Infarct Severity to Predict Functional Outcome After Endovascular Thrombectomy.

Endovascular thrombectomy (EVT) dramatically improves clinical outcomes, but the final infarct volume (FIV) on MRI only accounts for a minority of the treatment effect. An imaging biomarker that more strongly correlates with post-EVT functional outcome would be helpful for clinical prognosis and serve as a surrogate outcome measure in trials of EVT-adjuvant therapies. Here, we aimed to validate a novel MRI-based metric, infarct density, which leverages post-EVT apparent diffusion coefficient (ADC) as a marker of infarct severity.

Impaired Exercise Capacity in High-Risk Diabetic Cardiomyopathy: The ARISE-HF Cardiopulmonary Exercise Testing Subanalysis.

Background: Objective indices of functional capacity in patients with diabetic cardiomyopathy and stage B heart failure (HF) have not been comprehensively defined. We sought to characterize the cardiopulmonary exercise characteristics of individuals with diabetic cardiomyopathy at high risk for overt HF.

Methods: The relationships from cardiopulmonary exercise testing with clinical and laboratory characteristics of participants with diabetic cardiomyopathy were evaluated using baseline data from the ARISE-HF trial (Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure).

Impaired Resting State Functional Connectivity in CADASIL Mutant Mice.

Cerebral autosomal-dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL) is the most prevalent monogenic inherited cause of cerebral small-vessel disease. Despite its prevalence, there is currently no proven therapy to prevent or reverse the progression of the disease. This study aimed to characterize the functional integrity of long white matter tracts in CADASIL transgenic mice, both with and without focal white matter lesions in the corpus callosum added on, utilizing optical resting-state functional connectivity imaging alongside behavioral examinations.

Characterization of LTBP2 mutation causing mitral valve prolapse.

Aims: Mitral valve prolapse (MVP) is a common valvular disorder associated with significant morbidity and mortality, with a strong genetic basis. This study aimed to identify a mutation in a family with MVP and to characterize the valve phenotype in LTBP2 knockout (KO) mice.

Methods And Results: Exome sequencing and segregation analysis were performed on a large family with MVP.