A type VI secretion system in species and triggers distinct macrophage death pathways independent of the pyrin inflammasome.

The complex contains opportunistic pathogens that cause chronic infections and inflammation in the lungs of people with cystic fibrosis. Two closely related species within this complex are and the recently classified and encode a type VI secretion system and the effector TecA, which is detected by the pyrin/caspase-1 inflammasome, and triggers macrophage inflammatory death. We previously showed that the pyrin inflammasome was dispensable for lung inflammation in mice infected with AU1054 indicating this species activates an alternative pathway of macrophage inflammatory death.

Supporting emotion regulation in children on the autism spectrum: co-developing a digital mental health application for school-based settings with community partners.

Objective: KeepCalm is a digital mental health application, co-designed with community partners, that incorporates wearable biosensing with support for teams to address challenging behaviors and emotion dysregulation in children on the autism spectrum.

Methods: We followed a user-centered design framework. Before app development, we conducted design workshops, needs assessment interviews, a systematic review, and created an Expert Advisory Board.

The World Society for Pediatric and Congenital Heart Surgery: 2024 Update of the World Database for Pediatric and Congenital Heart Surgery.

Background: The World Database for Pediatric and Congenital Heart Surgery (WDPCHS), sponsored by the World Society for Pediatric and Congenital Heart Surgery (WSPCHS), provides complex congenital heart surgery outcomes analyses for member programs. This report represents the seven-year descriptive analysis of outcomes from active members of the WDPCHS.

Methods: Individual institutions submit data based on the specific procedure via a password protected platform.

Physiological and communicative emotional disconcordance in children on the autism spectrum.

Background: Individuals on the autism spectrum commonly have differences from non-autistic people in expressing their emotions using communicative behaviors, such as facial expressions. However, it is not yet clear if this reduced expressivity stems from reduced physiological reactivity in emotional contexts or if individuals react internally, but do not show these reactions externally to others. We hypothesized that autism is characterized by a discordance between in-the-moment internal psychophysiological arousal and external communicative expressions of emotion.

Spike sorting with Kilosort4.

Spike sorting is the computational process of extracting the firing times of single neurons from recordings of local electrical fields. This is an important but hard problem in neuroscience, made complicated by the nonstationarity of the recordings and the dense overlap in electrical fields between nearby neurons. To address the spike-sorting problem, we have been openly developing the Kilosort framework.

A Case of Neonatal Monkeypox Treated With Oral Tecovirimat.

Since the Monkeypox virus outbreak erupted in May 2022, infection has been reported across all ages. Few cases exist in the medical literature about Monkeypox infection in neonates, and little is known about its clinical manifestations, disease course, or side effects of available antiviral agents in this age group. In this report, we describe the case of a 10-day-old neonate from the southern United States who presented with fevers and generalized papulopustular rash.

Activation of the aryl hydrocarbon receptor inhibits neuropilin-1 upregulation on IL-2-responding CD4 T cells.

Neuropilin-1 (Nrp1), a transmembrane protein expressed on CD4 T cells, is mostly studied in the context of regulatory T cell (Treg) function. More recently, there is increasing evidence that Nrp1 is also highly expressed on activated effector T cells and that increases in these Nrp1-expressing CD4 T cells correspond with immunopathology across several T cell-dependent disease models. Thus, Nrp1 may be implicated in the identification and function of immunopathologic T cells.

An investigation of temperature and fever burdens in patients with sepsis admitted from the emergency department to the hospital.

Aim: We sought to collect granular data on temperature burden to further explore existing conflicting information on the relationship between temperature alterations and outcomes in patients with sepsis requiring hospital admission.

Methods: This was a prospective cohort study that enrolled a convenience sample of patients with sepsis or septic shock admitted to the hospital from the emergency department (ED). A "unit of temperature burden (UTB)" was defined as >1°C (1.

Primary or Delayed Repair for Complete Atrioventricular Septal Defect, Tetralogy of Fallot, and Ventricular Septal Defect: Relationship to Country Economic Status.

Objective: Primary repair in the first six months of life is routine for tetralogy of Fallot, complete atrioventricular septal defect, and ventricular septal defect in high-income countries. The objective of this analysis was to understand the utilization and outcomes of palliative and reparative procedures in high versus middle-income countries.

Methods: The World Database of Pediatric and Congenital Heart Surgery identified patients who underwent surgery for: tetralogy of Fallot, complete atrioventricular septal defect, and ventricular septal defect.

Exosc9 Initiates SUMO-Dependent lncRNA TERRA Degradation to Impact Telomeric Integrity in Endocrine Therapy Insensitive Hormone Receptor-Positive Breast Cancer.

Long, noncoding RNAs (lncRNAs) are indispensable for normal cell physiology and, consequently, are tightly regulated in human cells. Yet, unlike mRNA, substantially less is known about the mechanisms for lncRNA degradation. It is important to delineate the regulatory control of lncRNA degradation, particularly for lncRNA telomeric repeat-containing RNA (TERRA), as the TERRA-telomere R-loops dictate cell cycle progression and genomic stability.

Activation of the aryl hydrocarbon receptor inhibits neuropilin-1 upregulation on IL-2 responding CD4 T cells.

Neuropilin-1 (Nrp1), a transmembrane protein expressed on CD4 T cells, is mostly studied in the context of regulatory T cell (Treg) function. More recently, there is increasing evidence that Nrp1 is also highly expressed on activated effector T cells and that increases in these Nrp1-expressing CD4 T cells correspond with immunopathology across several T cell-dependent disease models. Thus, Nrp1 may be implicated in the identification and function of immunopathologic T cells.

The Impact of Preventive Treatment for Multidrug- and Rifampin-Resistant Tuberculosis Exceeds Trial-Based Estimates.

Background: Several clinical trials of tuberculosis preventive treatment (TPT) for household contacts of patients with multidrug- or rifampin-resistant tuberculosis (MDR/RR-TB) are nearing completion. The potential benefits of delivering TPT to MDR/RR-TB contacts extend beyond the outcomes that clinical trials can measure.

Methods: We developed an agent-based, household-structured TB and MDR/RR-TB transmission model, calibrated to an illustrative setting in India.

Hospital Mortality and Adverse Events Following Repair of Congenital Heart Defects in Developing Countries.

Background: Mortality associated with the correction of congenital heart disease has decreased to approximately 2% in developed countries and major adverse events are uncommon. Outcomes in developing countries are less well defined. The World Database for Pediatric and Congenital Heart Surgery was utilized to compare mortality and adverse events in developed and developing countries.

A Digital Mental Health App Incorporating Wearable Biosensing for Teachers of Children on the Autism Spectrum to Support Emotion Regulation: Protocol for a Pilot Randomized Controlled Trial.

Background: As much as 80% of children on the autism spectrum exhibit challenging behaviors (ie, behaviors dangerous to the self or others, behaviors that interfere with learning and development, and behaviors that interfere with socialization) that can have a devastating impact on personal and family well-being, contribute to teacher burnout, and even require hospitalization. Evidence-based practices to reduce these behaviors emphasize identifying triggers (events or antecedents that lead to challenging behaviors); however, parents and teachers often report that challenging behaviors surface with little warning. Exciting recent advances in biometric sensing and mobile computing technology allow the measurement of momentary emotion dysregulation using physiological indexes.

A convolutional neural network provides a generalizable model of natural sound coding by neural populations in auditory cortex.

Convolutional neural networks (CNNs) can provide powerful and flexible models of neural sensory processing. However, the utility of CNNs in studying the auditory system has been limited by their requirement for large datasets and the complex response properties of single auditory neurons. To address these limitations, we developed a population encoding model: a CNN that simultaneously predicts activity of several hundred neurons recorded during presentation of a large set of natural sounds.

Coastal upwelling drives ecosystem temporal variability from the surface to the abyssal seafloor.

Long-term biological time series that monitor ecosystems across the ocean's full water column are extremely rare. As a result, classic paradigms are yet to be tested. One such paradigm is that variations in coastal upwelling drive changes in marine ecosystems throughout the water column.

Deprescribing Strategies for Opioids and Benzodiazepines with Emphasis on Concurrent Use: A Scoping Review.

While the Food and Drug Administration's black-box warnings caution against concurrent opioid and benzodiazepine (OPI-BZD) use, there is little guidance on how to deprescribe these medications. This scoping review analyzes the available opioid and/or benzodiazepine deprescribing strategies from the PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases (01/1995-08/2020) and the gray literature. We identified 39 original research studies (opioids: n = 5, benzodiazepines: n = 31, concurrent use: n = 3) and 26 guidelines (opioids: n = 16, benzodiazepines: n = 11, concurrent use: n = 0).

Efficacy of intrathecal morphine administration in pediatric patients undergoing selective dorsal rhizotomy.

Purpose: The purpose of this study was to evaluate the effectiveness of intrathecal morphine following selective dorsal rhizotomy in pediatric patients previously diagnosed with cerebral palsy.

Methods: This was a retrospective, cohort analysis over the course of four years. The analysis consisted of a treatment group which received intrathecal morphine (5 mcg/kg) injection and a control group that did not receive the injection prior to dural closure.

Trials underestimate the impact of preventive treatment for household contacts exposed to multidrug-resistant tuberculosis: a simulation study.

Background: Several clinical trials of tuberculosis preventive treatment (TPT) for household contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are nearing completion. The potential benefits of TPT for MDR-TB contacts extend beyond the outcomes that clinical trials can measure.

Methods: We developed an agent-based, household-structured TB and MDR-TB transmission model, calibrated to an illustrative setting in India, the country accounting for 26% of global MDR-TB burden.

Imaging the Plant Cytoskeleton by High-Pressure Freezing and Electron Tomography.

Electron tomography (ET) imaging of high-pressure frozen/freeze-substituted samples provides a unique opportunity to study structural details of organelles and cytoskeletal arrays in plant cells. In this chapter, we discuss approaches for sample preparation by cryofixation at high pressure, freeze substitution, and resin embedding. We also include pipelines for data collection for electron tomography at ambient temperature, tomogram calculation, and segmentation.