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Omicron BA.4/5 neutralization and T-cell responses in organ transplant recipients after Booster mRNA vaccine: a Multicenter Cohort Study

1 day 12 hours ago
CONCLUSION: In summary, a booster significantly increases BA.4/5-specific neutralization and polyfunctional CD4+ T-cell responses, suggesting protection from severe disease even with new Omicron variants. However, SOT recipients that are older, on mycophenolate and prednisone need further preventative strategies.
Victor H Ferreira

Neurotrophin signaling is a central mechanism of salivary dysfunction after irradiation that disrupts myoepithelial cells

4 days 12 hours ago
The mechanisms that prevent regeneration of irradiated (IR) salivary glands remain elusive. Bulk RNAseq of IR versus non-IR human salivary glands showed that neurotrophin signaling is highly disrupted post-radiation. Neurotrophin receptors (NTRs) were significantly upregulated in myoepithelial cells (MECs) post-IR, and single cell RNAseq revealed that MECs pericytes, and duct cells are the main sources of neurotrophin ligands. Using two ex vivo models, we show that nerve growth factor (NGF)...
Alejandro M Chibly

Penalized maximum likelihood inference under the mixture cure model in sparse data

4 days 12 hours ago
INTRODUCTION: When a study sample includes a large proportion of long-term survivors, mixture cure (MC) models that separately assess biomarker associations with long-term recurrence-free survival and time to disease recurrence are preferred to proportional-hazards models. However, in samples with few recurrences, standard maximum likelihood can be biased.
Changchang Xu

Improving RNA Fusion Call Confidence and Reliability in Molecular Diagnostic Testing

6 days 12 hours ago
Next-generation sequencing is a superior method for detecting known and novel RNA fusions in formalin-fixed, paraffin-embedded tissue over fluorescence in situ hybridization and RT-PCR. However, confidence in fusion calling and true negatives may be compromised by poor RNA quality. Using a commercial panel of 507 genes and the recommended 3-million read threshold to accept results, two cases yielded false negatives while exceeding this recommendation during clinical validation. To develop a...
Mariusz Shrestha

Determining the Longitudinal Serologic Response to COVID-19 Vaccination in the Chronic Kidney Disease Population: A Clinical Research Protocol

6 days 12 hours ago
CONCLUSIONS: This large multicenter serologic study of participants living with kidney disease will generate data on the kinetics of SARS-CoV-2 immune response to vaccination across the spectrum of CKD, providing insights into the amplitude and duration of immunity conferred by COVID-19 vaccination and allowing for characterization of factors associated with immune response. The results of this study may be used to inform immunization guidelines and public health recommendations for the 4...
Kevin Yau

Great expectations: patients' preferences for clinically significant results from genomic sequencing

1 week 1 day ago
We aimed to describe patient preferences for a broad range of secondary findings (SF) from genomic sequencing (GS) and factors driving preferences. We assessed preference data within a trial of the Genomics ADvISER, (SF decision aid) among adult cancer patients. Participants could choose from five categories of SF: (1) medically actionable; (2) polygenic risks; (3) rare diseases; (4) early-onset neurological diseases; and (5) carrier status. We analyzed preferences using descriptive statistics...
Salma Shickh

Gas-Dependent Active Sites on Cu/ZnO Clusters for CH<sub>3</sub>OH Synthesis

1 week 1 day ago
This study describes an instantaneously gas-induced dynamic transition of an industrial Cu/ZnO/Al(2)O(3) catalyst. Cu/ZnO clusters become "alive" and lead to a promotion in reaction rate by almost one magnitude, in response to the variation of the reactant components. The promotional changes are functions of either CO(2)-to-CO or H(2)O-to-H(2) ratio which determines the oxygen chemical potential thus drives Cu/ZnO clusters to undergo reconstruction and allows the maximum formation of Cu-Zn^(2+)...
Weifeng Tu

The hidden factor: accounting for covariate effects in power and sample size computation for a binary trait

1 week 1 day ago
MOTIVATION: Accurate power and sample size estimation is crucial to the design and analysis of genetic association studies. When analyzing a binary trait via logistic regression, important covariates such as age and sex are typically included in the model. However, their effects are rarely properly considered in power or sample size computation during study planning. Unlike when analyzing a continuous trait, the power of association testing between a binary trait and a genetic variant depends,...
Ziang Zhang

Educational exposures associated with preclinical medical student interest in pursuing surgical residency: Longitudinal mixed-methods study with narrative evaluation

1 week 2 days ago
CONCLUSIONS: Shadowing and mentorship were important factors for students in the decision-making process in pursuing surgery. Identifying high-yield educational experiences-for students to determine if one wants to pursue a surgical specialty is important for educators in curriculum design for resource allocation.
Adree Khondker

Single substitution in H3.3G34 alters DNMT3A recruitment to cause progressive neurodegeneration

1 week 5 days ago
Germline histone H3.3 amino acid substitutions, including H3.3G34R/V, cause severe neurodevelopmental syndromes. To understand how these mutations impact brain development, we generated H3.3G34R/V/W knock-in mice and identified strikingly distinct developmental defects for each mutation. H3.3G34R-mutants exhibited progressive microcephaly and neurodegeneration, with abnormal accumulation of disease-associated microglia and concurrent neuronal depletion. G34R severely decreased H3K36me2 on the...
Sima Khazaei

A central chaperone-like role for 14-3-3 proteins in human cells

1 week 5 days ago
14-3-3 proteins are highly conserved regulatory proteins that interact with hundreds of structurally diverse clients and act as central hubs of signaling networks. However, how 14-3-3 paralogs differ in specificity and how they regulate client protein function are not known for most clients. Here, we map the interactomes of all human 14-3-3 paralogs and systematically characterize the effect of disrupting these interactions on client localization. The loss of 14-3-3 binding leads to the...
Dmitri Segal

A contractile injection system is required for developmentally regulated cell death in Streptomyces coelicolor

1 week 5 days ago
Diverse bacterial species produce extracellular contractile injection systems (eCISs). Although closely related to contractile phage tails, eCISs can inject toxic proteins into eukaryotic cells. Thus, these systems are commonly viewed as cytotoxic defense mechanisms that are not central to other aspects of bacterial biology. Here, we provide evidence that eCISs appear to participate in the complex developmental process of the bacterium Streptomyces coelicolor. In particular, we show that S....
Maria Vladimirov

Excessive transcription-replication conflicts are a vulnerability of BRCA1-mutant cancers

1 week 5 days ago
BRCA1 mutations are associated with increased breast and ovarian cancer risk. BRCA1-mutant tumors are high-grade, recurrent, and often become resistant to standard therapies. Herein, we performed a targeted CRISPR-Cas9 screen and identified MEPCE, a methylphosphate capping enzyme, as a synthetic lethal interactor of BRCA1. Mechanistically, we demonstrate that depletion of MEPCE in a BRCA1-deficient setting led to dysregulated RNA polymerase II (RNAPII) promoter-proximal pausing, R-loop...
Parasvi S Patel

The spatial and temporal distribution of SARS-CoV-2 from the built environment of COVID-19 patient rooms: A multicentre prospective study

2 weeks 2 days ago
CONCLUSIONS: We were able to detect SARS-CoV-2 on the floors in rooms of patients with COVID-19. The viral burden did not vary over time or by distance from the patient's bed. These results suggest floor swabbing for the detection of SARS-CoV-2 in a built environment such as a hospital room is both accurate and robust to variation in sampling location and duration of occupancy.
Michael Fralick