Kinematic signature of high risk labored breathing revealed by novel signal analysis.

Breathing patterns (respiratory kinematics) contain vital prognostic information. This dimension of physiology is not captured by conventional vital signs. We sought to determine the feasibility and utility of quantifying respiratory kinematics.

The potential of HBV cure: an overview of CRISPR-mediated HBV gene disruption.

Hepatitis B virus (HBV) infection is a common cause of liver disease worldwide. The current antiviral treatment using nucleotide analogues (NAs) can only suppress HBV replication but cannot eliminate chronic HBV infection due to the persistence of covalently closed circular (ccc) DNA that sustains viral replication. The CRISPR/Cas9 system is a novel genome-editing tool that enables precise gene disruption and inactivation.

The application of radionuclide therapy for breast cancer.

Radionuclide-mediated diagnosis and therapy have emerged as effective and low-risk approaches to treating breast cancer. Compared to traditional anatomic imaging techniques, diagnostic radionuclide-based molecular imaging systems exhibit much greater sensitivity and ability to precisely illustrate the biodistribution and metabolic processes from a functional perspective in breast cancer; this transitions diagnosis from an invasive visualization to a noninvasive visualization, potentially ensuring earlier diagnosis and on-time treatment. Radionuclide therapy is a newly developed modality for the treatment of breast cancer in which radionuclides are delivered to tumors and/or tumor-associated targets either directly or using delivery vehicles.

Age prediction from 12-lead electrocardiograms using deep learning: a comparison of four models on a contemporary, freely available dataset.

The 12-lead electrocardiogram (ECG) is routine in clinical use and deep learning approaches have been shown to have the identify features not immediately apparent to human interpreters including age and sex. Several models have been published but no direct comparisons exist.We implemented three previously published models and one unpublished model to predict age and sex from a 12-lead ECG and then compared their performance on an open-access data set.

Circulating GDF-15: a biomarker for metabolic dysregulation and aging in people living with HIV.

Despite effective control of HIV replication by antiretroviral therapy (ART), a significant number of people living with HIV (PLWH) fail to achieve complete immune reconstitution and thus are deemed immune non-responders (INRs). Compared with immune responders (IRs) who have restored their CD4 T cell numbers and functions, CD4 T cells from these INRs exhibit prominent mitochondrial dysfunction and premature aging, which play a major role in increasing the incidence of non-AIDS, non-communicable diseases (NCDs). To date, there are no reliable biomarkers that can be used to typify and manage PLWH, especially INRs with non-AIDS NCDs.

Response to von Schmalensee et al.

Von Schmalensee et al. present two concerns about our study. While the first stems from a general disagreement about our simulation methodology, the second is a useful observation of a modelling choice we made that affected simulation outcomes, but in ways that do not invalidate our original conclusions.

Prospective validation of clinical deterioration predictive models prior to intensive care unit transfer among patients admitted to acute care cardiology wards.

. Very few predictive models have been externally validated in a prospective cohort following the implementation of an artificial intelligence analytic system. This type of real-world validation is critically important due to the risk of data drift, or changes in data definitions or clinical practices over time, that could impact model performance in contemporaneous real-world cohorts.

PKIB, a Novel Target for Cancer Therapy.

The serine-threonine kinase protein kinase A (PKA) is a cyclic AMP (cAMP)-dependent intracellular protein with multiple roles in cellular biology including metabolic and transcription regulation functions. The cAMP-dependent protein kinase inhibitor β (PKIB) is one of three known endogenous protein kinase inhibitors of PKA. The role of PKIB is not yet fully understood.

Apnea, Intermittent Hypoxemia, and Bradycardia Events Predict Late-Onset Sepsis in Infants Born Extremely Preterm.

Objective: The objective of this study was to examine the association of cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, with late-onset sepsis for extremely preterm infants (<29 weeks of gestational age) on vs off invasive mechanical ventilation.

Study Design: This is a retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.gov identifier NCT03174301), an observational study in 5 level IV neonatal intensive care units.

Cardiorespiratory Dynamics During Prone Positioning for Severe Ards: A Retrospective Cohort Study.

Objectives: To elucidate the changes in cardiorespiratory dynamics during neuromuscular blockade and prone positioning and determine the associations between changes in cardiorespiratory dynamics following prone positioning and mortality.

Design: Single center retrospective cohort study of patients admitted to the medical ICU between June 1, 2020 and September 1, 2022 who received prone positioning while mechanically ventilated.

Results: Our final cohort consisted of 136 patients.

Age Prediction From 12-lead Electrocardiograms Using Deep Learning: A Comparison of Four Models on a Contemporary, Freely Available Dataset.

Objective: The 12-lead electrocardiogram (ECG) is routine in clinical use and deep learning approaches have been shown to have the identify features not immediately apparent to human interpreters including age and sex. Several models have been published but no direct comparisons exist.

Approach: We implemented three previously published models and one unpublished model to predict age and sex from a 12-lead ECG and then compared their performance on an open-access data set.

Apnea, Intermittent Hypoxemia, and Bradycardia Events Predict Late-Onset Sepsis in Extremely Preterm Infants.

Objectives: Detection of changes in cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, may facilitate earlier detection of sepsis. Our objective was to examine the association of cardiorespiratory events with late-onset sepsis for extremely preterm infants (<29 weeks' gestational age (GA)) on versus off invasive mechanical ventilation.

Study Design: Retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.

Pathophysiological Responses to Bloodstream Infection in Critically Ill Transplant Recipients Compared With Non-Transplant Recipients.

Background: Identification of bloodstream infection (BSI) in transplant recipients may be difficult due to immunosuppression. Accordingly, we aimed to compare responses to BSI in critically ill transplant and non-transplant recipients and to modify systemic inflammatory response syndrome (SIRS) criteria for transplant recipients.

Methods: We analyzed univariate risks and developed multivariable models of BSI with 27 clinical variables from adult intensive care unit (ICU) patients at the University of Virginia (UVA) and at the University of Pittsburgh (Pitt).

The master antioxidant defense is activated during EBV latent infection.

To our knowledge, this is the first report delineating the activation of the master antioxidant defense during EBV latency. We show that EBV-triggered reactive oxygen species production activates the Keap1-NRF2 pathway in EBV-transformed cells, and LMP1 plays a major role in this event, and the stress-related kinase TBK1 is required for NRF2 activation. Moreover, we show that the Keap1-NRF2 pathway is important for cell proliferation and EBV latency maintenance.

Maturation of cardioventilatory physiological trajectories in extremely preterm infants.

Background: In extremely preterm infants, persistence of cardioventilatory events is associated with long-term morbidity. Therefore, the objective was to characterize physiologic growth curves of apnea, periodic breathing, intermittent hypoxemia, and bradycardia in extremely preterm infants during the first few months of life.

Methods: The Prematurity-Related Ventilatory Control study included 717 preterm infants <29 weeks gestation.

The experience of childhood sexual abuse: An exploratory description of psychological and adaptive functioning in Canadian men.

Background: Childhood sexual abuse (CSA) affects a number of men yet knowledge gaps remain around comprehensively describing psychological and adaptive outcomes for this population.

Objective: Examine how a Canadian sample of men with and without CSA histories compares on broader areas of psychological and adaptive functioning.

Participants And Setting: This exploratory study included 109 adult men aged 25-60 years who were grouped according to whether they experienced CSA (n = 69) or not (n = 40).

Synthetic gRNA/Cas9 ribonucleoprotein targeting HBV DNA inhibits viral replication.

The presence of hepatitis B virus (HBV) covalently closed circular (ccc) DNA (cccDNA), which serves as a template for viral replication and integration of HBV DNA into the host cell genome, sustains liver pathogenesis and constitutes an intractable barrier to the eradication of chronic HBV infection. The current antiviral therapy for HBV infection, using nucleos(t)ide analogues (NAs), can suppress HBV replication but cannot eliminate integrated HBV DNA and episomal cccDNA. Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 is a powerful genetic tool that can edit integrated HBV DNA and minichromosomal cccDNA for gene therapy, but its expression and delivery require a viral vector, which poses safety concerns for therapeutic applications in humans.

ROS-Induced Mitochondrial Dysfunction in CD4 T Cells from ART-Controlled People Living with HIV.

We have previously demonstrated mitochondrial dysfunction in aging CD4 T cells from antiretroviral therapy (ART)-controlled people living with HIV (PLWH). However, the underlying mechanisms by which CD4 T cells develop mitochondrial dysfunction in PLWH remain unclear. In this study, we sought to elucidate the mechanism(s) of CD4 T cell mitochondrial compromise in ART-controlled PLWH.

Inflammatory and mental health sequelae of COVID-19.

The COVID-19 pandemic has caused significant negative consequences to mental health. Increased inflammatory factors and neuropsychiatric symptoms, such as cognitive impairment ("brain fog"), depression, and anxiety are associated with long COVID [post-acute sequelae of SARS-CoV-2 infection (PASC), termed neuro-PASC]. The present study sought to examine the role of inflammatory factors as predictors of neuropsychiatric symptom severity in the context of COVID-19.

Cardiorespiratory Monitoring Data to Predict Respiratory Outcomes in Extremely Preterm Infants.

Immature control of breathing is associated with apnea, periodic breathing, intermittent hypoxemia, and bradycardia in extremely preterm infants. However, it is not clear if such events independently predict worse respiratory outcome. To determine if analysis of cardiorespiratory monitoring data can predict unfavorable respiratory outcomes at 40 weeks postmenstrual age (PMA) and other outcomes, such as bronchopulmonary dysplasia at 36 weeks PMA.

Neighborhood Deprivation and Association With Neonatal Intensive Care Unit Mortality and Morbidity for Extremely Premature Infants.

Importance: Socioeconomic status affects pregnancy and neurodevelopment, but its association with hospital outcomes among premature infants is unknown. The Area Deprivation Index (ADI) is a validated measure of neighborhood disadvantage that uses US Census Bureau data on income, educational level, employment, and housing quality.

Objective: To determine whether ADI is associated with neonatal intensive care unit (NICU) mortality and morbidity in extremely premature infants.

Race, Class, and Place Modify Mortality Rates for the Leading Causes of Death in the United States, 1999-2021.

Background: Race and ethnicity, socioeconomic class, and geographic location are well-known social determinants of health in the US. Studies of population mortality often consider two, but not all three of these risk factors.

Objectives: To disarticulate the associations of race (whiteness), class (socioeconomic status), and place (county) with risk of cause-specific death in the US.

A Comparison of Variable Versus Fixed Insulin Infusion Rate on Resolution of Diabetic Ketoacidosis.

Background: Diabetic ketoacidosis (DKA) is a well-known, potentially fatal complication of diabetes. The American Diabetes Association hyperglycemic crises guidelines suggest the use of intravenous insulin in patients presenting with DKA, along with a recommended rate of glucose reduction of 50-75 mg/dL/h. However, no specific guidance is provided regarding how to best achieve this rate of glucose decline.

Evolutionary constraints mediate extinction risk under climate change.

Mounting evidence suggests that rapid evolutionary adaptation may rescue some organisms from the impacts of climate change. However, evolutionary constraints might hinder this process, especially when different aspects of environmental change generate antagonistic selection on genetically correlated traits. Here, we use individual-based simulations to explore how genetic correlations underlying the thermal physiology of ectotherms might influence their responses to the two major components of climate change-increases in mean temperature and thermal variability.

Overt and Occult Hypoxemia in Patients Hospitalized With COVID-19.

Unlabelled: Progressive hypoxemia is the predominant mode of deterioration in COVID-19. Among hypoxemia measures, the ratio of the Pao to the Fio (P/F ratio) has optimal construct validity but poor availability because it requires arterial blood sampling. Pulse oximetry reports oxygenation continuously (ratio of the Spo to the Fio [S/F ratio]), but it is affected by skin color and occult hypoxemia can occur in Black patients.