Feasibility of Administering the Patient Reported Outcomes, Burdens and Experiences (PROBE) Questionnaire Through the Canadian Bleeding Disorders Registry (CBDR) and Comparison of Data From the Two Sources.

Introduction: The Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire can be used to measure quality of life in persons with haemophilia (PWH) and is integrated in the Canadian Bleeding Disorders Registry (CBDR). This offers the opportunity to compare the same data inputted by patients in PROBE and their treating team in CBDR.

Aim: Our objectives were to assess the feasibility of collecting PROBE data through CBDR and to compare the data collected from these two sources.

Association Between Operator Experience and Procedural Outcomes of Tracheal Intubation in the Emergency Department and ICU.

Study Objectives: Complications are common during emergency tracheal intubation. Although graduate medical education in emergency medicine and critical care mandate competency in this procedure, thresholds for proficiency are poorly defined. We evaluated the relationship between the operator performing intubation and complications of emergency tracheal intubation.

Machine Learning Models to Predict Risk of Maternal Morbidity and Mortality From Electronic Medical Record Data: Scoping Review.

Background: A majority (>80%) of maternal deaths in the United States are preventable. Using machine learning (ML) models that are generated from electronic medical records (EMRs) may be a promising approach to predict the risk of adverse maternal outcomes and enable proactive intervention to prevent maternal mortality. Current evidence syntheses of such ML approaches either focus only on specific maternal outcomes, aspects other than risk prediction, or do not consider the full pipeline of studies from the development to implementation in clinical practice.

Pathogenic Genomic Alterations in Circulating Tumor DNA Predict Overall Survival in Men with Metastatic Castrate-resistant Prostate Cancer.

Background And Objective: Although validated prognostic models exist for men with metastatic castration-resistant prostate cancer (mCRPC), current tools do not incorporate genomic biomarkers such as circulating tumor DNA (ctDNA) aneuploidy or pathogenic genetic alterations (PGAs). This study aimed to estimate the prevalence of PGAs in ctDNA, assess their correlation with ctDNA aneuploidy fraction, and evaluate their association with overall survival (OS). Additionally, we developed and validated a clinical-genetic (CG) model to predict OS.

The SHR/Akr Y chromosome reveals repeated turnover of the rat pseudoautosomal region.

Crossing-over between Chr X and Chr Y was first observed 90 years ago, in the brown rat, . However, the sequence of the rat pseudoautosomal region (PAR) has remained a mystery. We produced a near-complete sequence of Chr Y from the SHR strain, along with nearly a megabase of sequence from both telomeres of Chr X.

A Real-World Evaluation of Frontline Treatment for Acute Myeloid Leukemia With Azacitidine Plus Venetoclax.

Background: The combination of venetoclax + azacitidine (VenAza) has become the standard frontline treatment for older unfit AML patients.

Methods: We analyzed outcomes using VenAza for previously untreated unfit AML patients at a single center between 2020-2024.

Results: The overall response rate (ORR) was 69/105 (66%), was highest for patients with NPM1 (78%) and IDH1/2 (82%) mutations and lowest with TP53 mutations (40%).

Analysis of a mouse germ cell tumor model establishes pluripotency-associated miRNAs as conserved serum biomarkers for germ cell cancer detection.

Malignant testicular germ cells tumors (TGCTs) are the most common solid cancers in young men. Current TGCT diagnostics include conventional serum protein markers, but these lack the sensitivity and specificity to serve as accurate markers across all TGCT subtypes. MicroRNAs (miRNAs) are small non-coding regulatory RNAs and informative biomarkers for several diseases.

Parallel Functional Interrogations of Autism Risk Genes Reveal Drivers of Transcriptomic Convergence and the Female Protective Effect.

The surprising number and functional diversity of genes implicated in autism spectrum disorder (ASD) has made it challenging to identify core pathophysiological mechanisms or envision interventions with broad therapeutic potential. Here, parallel CRISPR-Cas13-based knockdown of 28 ASD genes and neighboring long non-coding RNAs reveals striking convergence on shared transcriptomic effects and neurodevelopmental phenotypes in human neural progenitor cells and cerebral organoids. Perturbations of single ASD genes caused the widespread dysregulation of other ASD genes, and reconstruction of gene regulatory networks uncovered the prominent autism risk gene as a critical driver of this transcriptomic convergence.

Case report: Potential physiological sources of the late response in epidural spinal recordings induced by spinal cord stimulation during intraoperative neuromonitoring.

Objective: This study aims to investigate the sources of later response in epidural spinal recordings (ESRs) obtained from implanted leads during spinal cord stimulation, a topic has not been widely studied in previous research.

Methods: Two patients with lower back and lower extremity pain underwent SCS implantation with intraoperative neuromonitoring (IONM). The timing of extracted peaks in ESRs and intramuscular electromyography (EMG) recordings were analyzed and compared to a Monte Carlo simulation for synchronization analysis.

Video vs Direct Laryngoscopy for Tracheal Intubation After Cardiac Arrest: A Secondary Analysis of the Direct vs Video Laryngoscope Trial.

Background: Airway management is a critical component of the care of patients experiencing cardiac arrest, but data from randomized trials on the use of video vs direct laryngoscopy for intubation in the setting of cardiac arrest are limited. Current American Heart Association guidelines recommend placement of an endotracheal tube either during CPR or shortly after return of spontaneous circulation, but do not provide guidance around intubation methods, including the choice of laryngoscope.

Research Question: Does use of video laryngoscopy improve the incidence of successful intubation on the first attempt, compared with use of direct laryngoscopy, among adults undergoing tracheal intubation after experiencing cardiac arrest?

Study Design And Methods: This secondary analysis of the Direct vs Video Laryngoscope (DEVICE) trial compared video laryngoscopy vs direct laryngoscopy in the subgroup of patients who were intubated after cardiac arrest.

Post-transcriptional cross- and auto-regulation buffer expression of the human RNA helicases and .

The Y-linked gene and its X-linked homolog survived the evolution of the human sex chromosomes from ordinary autosomes. encodes a multifunctional RNA helicase, with mutations causing developmental disorders and cancers. We find that, among X-linked genes with surviving Y homologs, is extraordinarily dosage sensitive.

Diabetes Mellitus Is Not a Risk Factor for Difficult Intubation Among Critically Ill Adults: A Secondary Analysis of Multicenter Trials.

Objectives: Diabetes mellitus has been associated with greater difficulty of tracheal intubation in the operating room. This relationship has not been examined for tracheal intubation of critically ill adults. We examined whether diabetes mellitus was independently associated with the time from induction of anesthesia to intubation of the trachea among critically ill adults.

Independent effects of testosterone, estradiol, and sex chromosomes on gene expression in immune cells of trans- and cisgender individuals.

The origins of sex differences in human disease are elusive, in part because of difficulties in separating the effects of sex hormones and sex chromosomes. To separate these variables, we examined gene expression in four groups of trans- or cisgender individuals: XX individuals treated with exogenous testosterone (n=21), XY treated with exogenous estradiol (n=13), untreated XX (n=20), and untreated XY (n=15). We performed single-cell RNA-sequencing of 358,426 peripheral blood mononuclear cells.

Association Between Neuromuscular Blocking Agents and Outcomes of Emergency Tracheal Intubation: A Secondary Analysis of Randomized Trials.

Study Objective: To examine the association between the neuromuscular blocking agent received (succinylcholine versus rocuronium) and the incidences of successful intubation on the first attempt and severe complications during tracheal intubation of critically ill adults in an emergency department (ED) or ICU.

Methods: We performed a secondary analysis of data from 2 multicenter randomized trials in critically ill adults undergoing tracheal intubation in an ED or ICU. Using a generalized linear mixed-effects model with prespecified baseline covariates, we examined the association between the neuromuscular blocking agent received (succinylcholine versus rocuronium) and the incidences of successful intubation on the first attempt (primary outcome) and severe complications during tracheal intubation (secondary outcome).

Successful treatment of AML using non-intensive chemotherapy in Jehovah's Witness patients.

Acute myeloid leukemia (AML) patients undergoing induction chemotherapy receive transfusion support to manage severe cytopenias and associated sequelae. Jehovah's Witness (JW) patients typically decline transfusion of most or all blood products. This can lead to exclusion of JW patients from otherwise life-saving treatments due to safety concerns.

Stable and robust Xi and Y transcriptomes drive cell-type-specific autosomal and Xa responses in vivo and in vitro in four human cell types.

Recent in vitro studies of human sex chromosome aneuploidy showed that the Xi ("inactive" X) and Y chromosomes broadly modulate autosomal and Xa ("active" X) gene expression. We tested these findings in vivo. Linear modeling of CD4 T cells and monocytes from individuals with one to three X chromosomes and zero to two Y chromosomes revealed 82 sex-chromosomal and 344 autosomal genes whose expression changed significantly with Xi and/or Y dosage in vivo.

MPAC: a computational framework for inferring pathway activities from multi-omic data.

Fully capturing cellular state requires examining genomic, epigenomic, transcriptomic, proteomic, and other assays for a biological sample and comprehensive computational modeling to reason with the complex and sometimes conflicting measurements. Modeling these so-called multi-omic data is especially beneficial in disease analysis, where observations across omic data types may reveal unexpected patient groupings and inform clinical outcomes and treatments. We present Multi-omic Pathway Analysis of Cells (MPAC), a computational framework that interprets multi-omic data through prior knowledge from biological pathways.

The inactive X chromosome drives sex differences in microglial inflammatory activity in human glioblastoma.

Whether an individual is a biological female or male affects cancer risk, but the responsible mechanisms and cell types remain obscure. Glioblastoma multiforme (GBM) is a male-biased cancer that is highly aggressive, and resistant to treatment, with poor patient survival. Dismal prognoses in GBM are due in part to the specialized immune system of the brain, consisting largely of microglia, which regulate GBM development and progression.

Destabilization of mRNAs enhances competence to initiate meiosis in mouse spermatogenic cells.

The specialized cell cycle of meiosis transforms diploid germ cells into haploid gametes. In mammals, diploid spermatogenic cells acquire the competence to initiate meiosis in response to retinoic acid. Previous mouse studies revealed that MEIOC interacts with RNA-binding proteins YTHDC2 and RBM46 to repress mitotic genes and to promote robust meiotic gene expression in spermatogenic cells that have initiated meiosis.

Variety, growing conditions and processing method act on different structural and biochemical traits to modify viscosity in tomato puree.

The texture of tomato products can be modified by choice of variety, their growing conditions and/or processing method, but no clear explanation exists of the mechanisms that transform fruit tissue, how they act on texture, or whether genetics and processing impact the same physical parameters. We therefore conducted a study that processed 4 varieties produced under low/high nitrogen supply, into puree using both hot and cold break processes. No specific rheological signature allows discrimination between cultivar-induced or process-induced textural changes, but that they can be distinguished by sensory analysis.

Automated Family Histories Significantly Improve Risk Prediction in an EHR.

We recently demonstrated that electronically constructed family pedigrees (e-pedigrees) have great value in epidemiologic research using electronic health record (EHR) data. Prior to this work, it has been well accepted that family health history is a major predictor for a wide spectrum of diseases, reflecting shared effects of genetics, environment, and lifestyle. With the widespread digitalization of patient data via EHRs, there is an unprecedented opportunity to use machine learning algorithms to better predict disease risk.