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Unfavorable transcriptome profiles and social disadvantage in hematopoietic cell transplantation: a CIBMTR analysis

1 day 8 hours ago
Patient-reported outcomes (PROs) capture subjective social determinants of health (SDOH), which can affect health outcomes through the stress response pathway. The Conserved Transcriptional Response to Adversity (CTRA) is a stress-mediated pro-inflammatory transcriptomic pattern that has been linked to adverse hematopoietic cell transplant (HCT) outcomes. This study examined the association of pre-transplant CTRA with patient-reported SDOH in allogeneic HCT recipients. In this cross-sectional...
Mallory Taylor

Omicron variant neutralizing antibodies following BNT162b2 BA.4/5 versus mRNA-1273 BA.1 bivalent vaccination in patients with end-stage kidney disease

3 days 8 hours ago
Neutralization of Omicron subvariants by different bivalent vaccines has not been well evaluated. This study characterizes neutralization against Omicron subvariants in 98 individuals on dialysis or with a kidney transplant receiving the BNT162b2 (BA.4/BA.5) or mRNA-1273 (BA.1) bivalent COVID-19 vaccine. Neutralization against Omicron BA.1, BA.5, BQ.1.1, and XBB.1.5 increased by 8-fold one month following bivalent vaccination. In comparison to wild-type (D614G), neutralizing antibodies against...
Kevin Yau

CYP26B1-related disorder: expanding the ends of the spectrum through clinical and molecular evidence

3 days 8 hours ago
CYP26B1 metabolizes retinoic acid in the developing embryo to regulate its levels. A limited number of individuals with pathogenic variants in CYP26B1 have been documented with a varied phenotypic spectrum, spanning from a severe manifestation involving skull anomalies, craniosynostosis, encephalocele, radio-humeral fusion, oligodactyly, and a narrow thorax, to a milder presentation characterized by craniosynostosis, restricted radio-humeral joint mobility, hearing loss, and intellectual...
Karina C Silveira

Clinical implementation of MetaFusion for accurate cancer-driving fusion detection from RNA Sequencing

5 days 8 hours ago
Oncogenic fusion genes may be identified from next-generation sequencing data, typically RNA-Seq. However, in a clinical setting, identifying these alterations is challenging against a background of non-relevant fusion calls that reduce workflow precision and specificity. Furthermore, although numerous algorithms have been developed to detect fusions in RNA-Seq, there are variations in their individual sensitivities. Here this problem was addressed by introducing MetaFusion into clinical use....
Michael Apostolides

Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free): A Protocol for a Multi-centre Randomized Cluster Crossover Trial

5 days 8 hours ago
Delirium is common after cardiac surgery and is associated with adverse outcomes. Administration of benzodiazepines before and after cardiac surgery is associated with delirium; guidelines recommend minimizing their use. Benzodiazepine administration during cardiac surgery remains common because of its recognized benefits. The Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free) trial is a randomized cluster crossover trial evaluating whether an institutional...
Jessica Spence

Large-scale whole exome sequencing studies identify two genes,CTSL and APOE, associated with lung cancer

1 week 1 day ago
Common genetic variants associated with lung cancer have been well studied in the past decade. However, only 12.3% heritability has been explained by these variants. In this study, we investigate the contribution of rare variants (RVs) (minor allele frequency <0.01) to lung cancer through two large whole exome sequencing case-control studies. We first performed gene-based association tests using a novel Bayes Factor statistic in the International Lung Cancer Consortium, the discovery study...
Jingxiong Xu

Epigenetic reprogramming of a distal developmental enhancer cluster drives SOX2 overexpression in breast and lung adenocarcinoma

1 week 1 day ago
Enhancer reprogramming has been proposed as a key source of transcriptional dysregulation during tumorigenesis, but the molecular mechanisms underlying this process remain unclear. Here, we identify an enhancer cluster required for normal development that is aberrantly activated in breast and lung adenocarcinoma. Deletion of the SRR124-134 cluster disrupts expression of the SOX2 oncogene, dysregulates genome-wide transcription and chromatin accessibility and reduces the ability of cancer cells...
Luis E Abatti

The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of the transcription factor ERG

1 week 1 day ago
The ERG (ETS-related gene) transcription factor is linked to various types of cancer, including leukemia. However, the specific ERG domains and co-factors contributing to leukemogenesis are poorly understood. Drug targeting a transcription factor such as ERG is challenging. Our study reveals the critical role of a conserved amino acid, proline, at position 199, located at the 3' end of the PNT (pointed) domain, in ERG's ability to induce leukemia. P199 is necessary for ERG to promote...
Eitan Kugler

Systematically testing human HMBS missense variants to reveal mechanism and pathogenic variation

1 week 3 days ago
Defects in hydroxymethylbilane synthase (HMBS) can cause acute intermittent porphyria (AIP), an acute neurological disease. Although sequencing-based diagnosis can be definitive, ∼⅓ of clinical HMBS variants are missense variants, and most clinically reported HMBS missense variants are designated as "variants of uncertain significance" (VUSs). Using saturation mutagenesis, en masse selection, and sequencing, we applied a multiplexed validated assay to both the erythroid-specific and ubiquitous...
Warren van Loggerenberg

Hazard vs. exposure: Does it make a difference in identifying chemicals with persistence and mobility concerns?

1 week 6 days ago
Persistent and mobile (PM) chemicals are considered emerging threats to the environment and drinking water because they can be transported over long distances, penetrate natural and artificial barriers, and resist removal by traditional water treatment procedures. Current chemical regulatory frameworks raise concerns over PM chemicals due to their potential to cause high human exposure through drinking water contamination. However, the criteria used to screen and identify these chemicals often...
Zhizhen Zhang

A marginalized two-part joint model for a longitudinal biomarker and a terminal event with application to advanced head and neck cancers

1 week 6 days ago
The sum of the longest diameter (SLD) of the target lesions is a longitudinal biomarker used to assess tumor response in cancer clinical trials, which can inform about early treatment effect. This biomarker is semicontinuous, often characterized by an excess of zeros and right skewness. Conditional two-part joint models were introduced to account for the excess of zeros in the longitudinal biomarker distribution and link it to a time-to-event outcome. A limitation of the conditional two-part...
Denis Rustand

Laser capture microdissection transcriptome reveals spatiotemporal tissue gene expression patterns of M. truncatula roots responding to rhizobia

1 week 6 days ago
We report a public resource for examining the spatiotemporal RNA expression of 54,893 M. truncatula genes during the first 72 hours of response to rhizobial inoculation. Using a methodology that allows synchronous inoculation and growth of over 100 plants in a single media container, we harvested the same segment of each root responding to rhizobia in the initial inoculation over a time course, collected individual tissues from these segments with laser capture microdissection, and created and...
Elise Schnabel

A standardized workflow for long-term longitudinal actigraphy data processing using one year of continuous actigraphy from the CAN-BIND Wellness Monitoring Study

2 weeks 1 day ago
Monitoring sleep and activity through wearable devices such as wrist-worn actigraphs has the potential for long-term measurement in the individual's own environment. Long periods of data collection require a complex approach, including standardized pre-processing and data trimming, and robust algorithms to address non-wear and missing data. In this study, we used a data-driven approach to quality control, pre-processing and analysis of longitudinal actigraphy data collected over the course of 1...
Anastasiya Slyepchenko

TRAPPC6B biallelic variants cause a neurodevelopmental disorder with TRAPP II and trafficking disruptions

2 weeks 1 day ago
Highly conserved transport protein particle (TRAPP) complexes regulate subcellular trafficking pathways. Accurate protein trafficking has been increasingly recognized to be critically important for normal development, particularly in the nervous system. Variants in most TRAPP complex subunits have been found to lead to neurodevelopmental disorders with diverse but overlapping phenotypes. We expand on limited prior reports on TRAPPC6B with detailed clinical and neuroradiologic assessments, and...
Hashem Almousa

Persistent organic pollutants in global surface soils: Distributions and fractionations

2 weeks 1 day ago
The distribution and fractionation of persistent organic pollutants (POPs) in different matrices refer to how these pollutants are dispersed and separated within various environmental compartments. This is a significant study area as it helps us understand the transport efficiencies and long-range transport potentials of POPs to enter remote areas, particularly polar regions. This study provides a comprehensive review of the progress in understanding the distribution and fractionation of POPs....
Yi-Fan Li

Inferring single-cell transcriptomic dynamics with structured latent gene expression dynamics

2 weeks 2 days ago
Gene expression dynamics provide directional information for trajectory inference from single-cell RNA sequencing data. Traditional approaches compute RNA velocity using strict modeling assumptions about transcription and splicing of RNA. This can fail in scenarios where multiple lineages have distinct gene dynamics or where rates of transcription and splicing are time dependent. We present "LatentVelo," an approach to compute a low-dimensional representation of gene dynamics with deep learning....
Spencer Farrell