Impact of Vein-to-vein Time in Patients With R/R LBCL Treated With Axicabtagene Ciloleucel.

Chimeric antigen receptor (CAR) T-cell products axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel) are approved for relapsed/refractory large B-cell lymphoma (R/R LBCL). Emerging evidence indicates that delayed CAR T-cell infusion, including prolonged time from leukapheresis to infusion, known as vein-to-vein time (V2Vt), may adversely impact clinical outcomes. We conducted a systematic literature review (SLR) and meta-analysis to identify differences in V2Vt in patients with R/R LBCL treated with axi-cel, tisa-cel, or liso-cel.

Geosocial Media's Early Warning Capabilities Across US County-Level Political Clusters: Observational Study.

Background: The novel coronavirus disease (COVID-19) sparked significant health concerns worldwide, prompting policy makers and health care experts to implement nonpharmaceutical public health interventions, such as stay-at-home orders and mask mandates, to slow the spread of the virus. While these interventions proved essential in controlling transmission, they also caused substantial economic and societal costs and should therefore be used strategically, particularly when disease activity is on the rise. In this context, geosocial media posts (posts with an explicit georeference) have been shown to provide a promising tool for anticipating moments of potential health care crises.

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.

Forecasting Asparaginase Need and Cost for Childhood Cancer Using ACCESS FORxECAST.

Purpose: Asparaginase (ASN) is a critical component of pediatric ALL protocols. Until recently, ASN was available in three formulations: native Escherichia coli, PEGylated E. coli (PEG), and Erwinase, with native E.

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.

Errors are robustly tamed in cumulative knowledge processes.

As knowledge accumulates in science and society in a distributed fashion, erroneous derivations can be introduced into the corpus of knowledge. Such derivations can compromise the validity of any units of knowledge that rely on them in the future. Can societal knowledge maintain some level of integrity given simple distributed error-checking mechanisms? In this paper, we investigate the following formulation of the question: assuming that a constant fraction of the new derivations is wrong, is it possible for simple error-checking mechanisms that apply when a new unit of knowledge is derived to maintain the integrity of the corpus of knowledge? This question was introduced by Ben-Eliezer et al.

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.

Systematic bias in malaria parasite relatedness estimation.

Genetic studies of Plasmodium parasites increasingly feature relatedness estimates. However, various aspects of malaria parasite relatedness estimation are not fully understood. For example, relatedness estimates based on whole-genome-sequence (WGS) data often exceed those based on sparser data types.

Characterization of cognitive decline in long-duration type 1 diabetes by cognitive, neuroimaging and pathological examinations.

Background: We aimed to characterize factors associated with the under-studied complication of cognitive decline in aging people with long-duration type 1 diabetes (T1D).

Methods: Joslin "Medalists" (n = 222; T1D ≥ 50 years) underwent cognitive testing. Medalists (n = 52) and age-matched non-diabetic controls (n = 20) underwent neuro- and retinal imaging.

Graph contrastive learning of subcellular-resolution spatial transcriptomics improves cell type annotation and reveals critical molecular pathways.

Imaging-based spatial transcriptomics (iST), such as MERFISH, CosMx SMI, and Xenium, quantify gene expression level across cells in space, but more importantly, they directly reveal the subcellular distribution of RNA transcripts at the single-molecule resolution. The subcellular localization of RNA molecules plays a crucial role in the compartmentalization-dependent regulation of genes within individual cells. Understanding the intracellular spatial distribution of RNA for a particular cell type thus not only improves the characterization of cell identity but also is of paramount importance in elucidating unique subcellular regulatory mechanisms specific to the cell type.

Revised Process for ACNS Guidelines Development.

The development of clinical practice guidelines is an evolving field. In response to the need for consistent, evidence-based medical practice, the American Clinical Neurophysiology Society identified the need to update the Society's guideline development process. The American Clinical Neurophysiology Society Guidelines Committee created an action plan with the goal of improving transparency and rigor for future guidelines and bringing existing guidelines to current standards.

Adjuvant Atezolizumab for Early Triple-Negative Breast Cancer: The ALEXANDRA/IMpassion030 Randomized Clinical Trial.

Importance: Triple-negative breast cancer is an aggressive subtype with a high incidence in young patients, a high incidence in non-Hispanic Black women, and a high risk of progression to metastatic cancer, a devastating sequela with a 12- to 18-month life expectancy. Until recently, one strategy for treating early-stage triple-negative breast cancer was chemotherapy after surgery. However, it was not known whether the addition of immune therapy to postsurgery chemotherapy would be beneficial.

Point-counterpoint: should sedation be used for image-guided biopsies?

Cross-sectional interventional radiology procedures can be performed using a range of techniques with approaches varying across institutions. One area in which practices for these procedures may differ is in the use of moderate sedation. This perspective discusses the pros and cons of using moderate sedation for deep organ biopsies commonly experienced in radiology departments.

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.

[Catheter ablation in patients with heart failure-who benefits?].

Atrial fibrillation (AF) ablation is associated with a lower likelihood of death and surgical heart failure (HF) interventions in patients with HF. This effect is mainly driven by reduced all cause and cardiovascular death following ablation. Ablation also results in improved left ventricular (LV) function, decreased AF burden and AF regression.

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).