Postoperative Morbidity and Interstage Hemodynamics Following Stage I Palliation in Patients with Turner Syndrome and Hypoplastic Left Heart Syndrome.

BACKGROUND: Turner syndrome (TS) is associated with left-sided cardiac lesions, including hypoplastic left heart syndrome (HLHS). Mortality as high as 80-90% has been reported following stage I single-ventricle palliation (S1P) in patients with TS and HLHS (TS + HLHS). The specific factors that relate to poor outcomes are not well understood. METHODS: This is a single-center, retrospective cohort study that includes 197 patients with HLHS who underwent S1P between 2008 and 2022. The clinical outcomes and interstage hemodynamics of TS + HLHS patients (N = 11) were compared with HLHS without TS (TS-HLHS), (N = 186). RESULTS: Of the 11 TS + HLHS patients, 10 underwent S1P; 4 underwent Glenn and 1 had hemodynamics considered prohibitive for Glenn; only 1 survived to Fontan palliation. Post-S1P mortality was higher in TS + HLHS (60 v 25%, p = 0.017). Following S1P, TS + HLHS had higher rates of postoperative ECMO (70 v 28%, p = 0.006), surgical necrotizing enterocolitis (20 v 3%, p = 0.007), peritoneal drain placement (70 v 31%, p = 0.012), urinary tract infection (30 v 9%, p = 0.035), and ICU readmissions (median 5 v 1, p = 0.035). Interstage hemodynamics demonstrated higher right ventricular end diastolic, (11 v 8mmHg, p = 0.033), mean pulmonary artery (20 v 13mmHg) (p = 0.002), and left atrial pressures (9 v 6mmHg, p = 0.047) in TS + HLHS. CONCLUSION: High mortality rates are described in TS + HLHS patients following S1P. In our cohort, despite most surviving more than 30 days post-S1P, long-term survival remained poor. Interstage catheterization data suggest poor physiologic candidacy for subsequent stages of single-ventricle palliation. Understanding the clinical and hemodynamic factors related to poor outcomes in TS + HLHS will help inform management for this population.

Organisms as sensors in biohybrid entities as a novel tool for in-field aquatic monitoring.

Rapidly intensifying global warming and water pollution calls for more efficient and continuous environmental monitoring methods. Biohybrid systems connect mechatronic components to living organisms and this approach can be used to extract data from the organisms. Compared to conventional monitoring methods, they allow for a broader data collection over long periods, minimizing the need for sampling processes and human labour. We aim to develop a methodology for creating various bioinspired entities, here referred to as 'biohybrids', designed for long-term aquatic monitoring. Here, we test several aspects of the development of the biohybrid entity: autonomous power source, lifeform integration and partial biodegradability. An autonomous power source was supplied by microbial fuel cells which exploit electron flows from microbial metabolic processes in the sediments. Here, we show that by stacking multiple cells, sufficient power can be supplied. We integrated lifeforms into the developed bioinspired entity which includes organisms such as the zebra musselDreissena polymorphaand water fleaDaphniaspp. The setups developed allowed for observing their stress behaviours. Through this, we can monitor changes in the environment in a continuous manner. The further development of this approach will allow for extensive, long-term aquatic data collection and create an early-warning monitoring system.

Prenatally diagnosed coronary artery abnormalities in hypoplastic left heart syndrome are associated with a higher probability of heart transplantation.

OBJECTIVE: Coronary artery abnormalities (CA) occur in patients with hypoplastic left heart syndrome (HLHS) and may be associated with higher mortality and heart transplantation (HT). We aimed to determine whether fetuses with HLHS and prenatal CA have a higher risk of death or HT. METHODS: We performed a retrospective review of fetal echocardiograms with HLHS from 2011 to 2018. We excluded fetuses with ventricular septal defects, elective termination, death in utero, planned postnatal non-intervention, or absent follow-up data. Presence or absence of CA was determined by review of serial fetal echocardiograms. Survival analysis was used to evaluate the relationship between prenatal CA and death or HT. RESULTS: Of 86 patients with fetal HLHS, 11 had prenatal diagnosis of CA. Of these, six required HT and five died (one after undergoing HT); only one remains alive without HT. Of those without prenatal CA (n = 75), 25 died and 7 underwent HT. Patients with prenatal diagnosis of HLHS and CA had a significantly increased likelihood of death or HT (p-value <0.05). CONCLUSION: Prenatal diagnosis of CA in our cohort of patients with HLHS was associated with increased risk of death or HT. These data have significance for prenatal counseling and postnatal management.

Incidence and effect of early postoperative ventricular arrhythmias after congenital heart surgery.

BACKGROUND: Postoperative arrhythmias after pediatric congenital heart disease (CHD) surgery are a known cause of morbidity and are associated with mortality. A comprehensive evaluation of early postoperative ventricular arrhythmias (VAs) after CHD surgery has not been reported. OBJECTIVES: We sought to determine the incidence of in-hospital VAs after CHD surgery and assess the clinical relevance of this arrhythmia during the postoperative hospital course. METHODS: Patients undergoing CHD surgery at our center from September 2007 through December 2016 were prospectively enrolled. Univariate and multivariate analysis was used to assess the association between postoperative VAs and in-hospital mortality, adjusting for postoperative extracorporeal membrane oxygenation and stage 1 single ventricle palliation operations. RESULTS: A total of 2503 postoperative courses in 1835 patients were included. In all, 464 (18.5%) had VAs, of whom 135 (29.1%) received treatment. Monomorphic ventricular tachycardia was the most frequently treated ventricular arrhythmia (TVA; n=91 [62.3%]). TVAs were associated with increased postoperative extracorporeal membrane oxygenation (13.3% vs 5.5%; P < .001) and in-hospital mortality (14.9% vs 4.0%; P < .001). In multivariate analysis, TVA was an independent risk factor for in-hospital mortality (adjusted odds ratio 2.44; 95% confidence interval 1.21-4.92). CONCLUSION: Early postoperative VAs after CHD surgery are more common than previously reported. Postoperative VAs are associated with increased in-hospital mortality, and the subgroup of TVAs is an independent risk factor for in-hospital mortality.

Robots mediating interactions between animals for interspecies collective behaviors.

Self-organized collective behavior has been analyzed in diverse types of gregarious animals. Such collective intelligence emerges from the synergy between individuals, which behave at their own time and spatial scales and without global rules. Recently, robots have been developed to collaborate with animal groups in the pursuit of better understanding their decision-making processes. These biohybrid systems make cooperative relationships between artificial systems and animals possible, which can yield new capabilities in the resulting mixed group. However, robots are currently tailor-made to successfully engage with one animal species at a time. This limits the possibilities of introducing distinct species-dependent perceptual capabilities and types of behaviors in the same system. Here, we show that robots socially integrated into animal groups of honeybees and zebrafish, each one located in a different city, allowing these two species to interact. This interspecific information transfer is demonstrated by collective decisions that emerge between the two autonomous robotic systems and the two animal groups. The robots enable this biohybrid system to function at any distance and operates in water and air with multiple sensorimotor properties across species barriers and ecosystems. These results demonstrate the feasibility of generating and controlling behavioral patterns in biohybrid groups of multiple species. Such interspecies connections between diverse robotic systems and animal species may open the door for new forms of artificial collective intelligence, where the unrivaled perceptual capabilities of the animals and their brains can be used to enhance autonomous decision-making, which could find applications in selective "rewiring" of ecosystems.

Integrative analysis of single-cell expression data reveals distinct regulatory states in bidirectional promoters.

BACKGROUND: Bidirectional promoters (BPs) are prevalent in eukaryotic genomes. However, it is poorly understood how the cell integrates different epigenomic information, such as transcription factor (TF) binding and chromatin marks, to drive gene expression at BPs. Single-cell sequencing technologies are revolutionizing the field of genome biology. Therefore, this study focuses on the integration of single-cell RNA-seq data with bulk ChIP-seq and other epigenetics data, for which single-cell technologies are not yet established, in the context of BPs. RESULTS: We performed integrative analyses of novel human single-cell RNA-seq (scRNA-seq) data with bulk ChIP-seq and other epigenetics data. scRNA-seq data revealed distinct transcription states of BPs that were previously not recognized. We find associations between these transcription states to distinct patterns in structural gene features, DNA accessibility, histone modification, DNA methylation and TF binding profiles. CONCLUSIONS: Our results suggest that a complex interplay of all of these elements is required to achieve BP-specific transcriptional output in this specialized promoter configuration. Further, our study implies that novel statistical methods can be developed to deconvolute masked subpopulations of cells measured with different bulk epigenomic assays using scRNA-seq data.

Corrigendum: High-throughput discovery of novel developmental phenotypes.

This corrects the article DOI: 10.1038/nature19356.

Visual diagnosis: 4-month-old girl with diffuse, varied dermatitis and bullae.

Pediatric autoimmune blistering disorders are exceedingly rare. Of these, childhood bullous pemphigoid (CBP) is the most common IgG-mediated subepidermal bullous disease in the pediatric population. Tense acral blisters, especially on the soles and palms, are characteristic of the infantile presentation. Patients with CBP present with varied dermatoses, making clinical diagnosis alone difficult. Definitive diagnosis is made with direct immunofluorescence revealing linear deposition of IgG and/or C3 at the basement membrane zone (BMZ) or indirect immunofluorescence revealing IgG antibodies reacting with the BMZ. First-line treatment is oral prednisolone dosed at 1 to 2 mg/kg and then tapered slowly to avoid rebound disease. The length of treatment depends on the rate of remission.

Heterogeneity and chronology of PTEN deletion and ERG fusion in prostate cancer.

TMPRSS2:ERG fusions, in combination with deletion of the phosphatase and tensin homolog (PTEN) tumor suppressor, have been suggested to cooperatively drive tumor progression in prostate cancer. We utilized a novel heterogeneity tissue microarray containing samples from 10 different tumor blocks of 189 prostatectomy specimens to study heterogeneity of genomic PTEN alterations in individual foci. PTEN alterations were found in 48/123 (39%) analyzable individual tumor foci, including 40 foci with deletions, 7 with deletion and rearrangement, and 1 focus with rearrangement only. PTEN was homogeneously aberrant in only 4 (8%) and heterogeneously in 44 (92%) of the foci. We found a specific sequence of molecular events from PTEN breakage followed by deletion of DNA sequences flanking the breakpoint, resulting in homozygous deletion. The observation that 16 of 19 foci with homogeneous ERG positivity had focal PTEN alterations but none of 10 foci with PTEN alterations had focal ERG positivity (P<0.0001) suggests that PTEN alterations typically develop subsequent to ERG fusions. We demonstrate a high level of intratumoral heterogeneity of PTEN alterations with deletions and rearrangements that challenges potential PTEN routine diagnosis testing in biopsies. The observation that PTEN alterations develop subsequent to ERG fusion strongly suggests that ERG expression may directly drive development of PTEN aberrations.

CHD1 is a 5q21 tumor suppressor required for ERG rearrangement in prostate cancer.

Deletions involving the chromosomal band 5q21 are among the most frequent alterations in prostate cancer. Using single-nucleotide polymorphism (SNP) arrays, we mapped a 1.3 megabase minimally deleted region including only the repulsive guidance molecule B (RGMB) and chromodomain helicase DNA-binding protein 1 (CHD1) genes. Functional analyses showed that CHD1 is an essential tumor suppressor. FISH analysis of 2,093 prostate cancers revealed a strong association between CHD1 deletion, prostate-specific antigen (PSA) biochemical failure (P = 0.0038), and absence of ERG fusion (P < 0.0001). We found that inactivation of CHD1 in vitro prevents formation of ERG rearrangements due to impairment of androgen receptor (AR)-dependent transcription, a prerequisite for ERG translocation. CHD1 is required for efficient recruitment of AR to responsive promoters and regulates expression of known AR-responsive tumor suppressor genes, including NKX3-1, FOXO1, and PPARγ. Our study establishes CHD1 as the 5q21 tumor suppressor gene in prostate cancer and shows a key role of this chromatin remodeling factor in prostate cancer biology.