Prognostic and morphological factors in pediatric cerebellar contusions.

Background: Although uncommon, cerebellar contusions are associated with significant morbidity and mortality. Literature is lacking in the prognostic and morphological factors relating to their clinical picture and outcomes, especially within children. The objective of this study is to evaluate prognostic and anatomic factors in the clinical picture of cerebellar contusions, including effacement of the 4th ventricle and cisterna magna. Methods: This is a retrospective chart review over 11 years across two medical centers. Patients included were under 18 years who presented with a cerebellar contusion. Patients were stratified within the study group based on discharge Glasgow outcome scale (GOS) and reviewed for prognostic factors contributing to outcome. Mid sagittal area of the 4th ventricle and cisterna magna were measured using magnetic resonance imaging and compared within the groups. Results: A total of 21 patients met the study criteria, of which 16 (76.2%) were male, with an average patient age of 8.65 years. Poor outcome at discharge (GOS <4) was associated with decreased admission Glasgow coma scale (P = 0.003), admission motor response (P = 0.006), pupil reactivity (P = 0.014), presence of concomitant subarachnoid hemorrhage (P = 0.010), contusion volume (P < 0.001), and decreased area of the cisterna magna (P = 0.012). Patients with poor outcomes were also more likely to require surgical intervention (P = 0.042). Conclusion: There are multiple prognostic factors associated with the overall outcome following cerebellar contusions. The rate of good outcomes in this study was superior to that in previous studies in adults.

Assessment of trace and macroelement accumulation in cyprinid juveniles as bioindicators of aquatic pollution: effects of diets and habitat preferences.

Juveniles of three cyprinids with various diets and habitat preferences were collected from the Szamos River (Hungary) during a period of pollution in November 2013: the herbivorous, benthic nase (Chondrostoma nasus), the benthivorous, benthic barbel (Barbus barbus), and the omnivorous, pelagic chub (Squalius cephalus). Our study aimed to assess the accumulation of these elements across species with varying diets and habitat preferences, as well as their potential role in biomonitoring efforts. The Ca, K, Mg, Na, Cd, Cr, Cu, Fe, Mn, Pb, Sr, and Zn concentration was analyzed in muscle, gills, and liver using MP-AES. The muscle and gill concentrations of Cr, Cu, Fe, and Zn increased with trophic level. At the same time, several differences were found among the trace element patterns related to habitat preferences. The trace elements, including Cd, Pb, and Zn, which exceeded threshold concentrations in the water, exhibited higher accumulations mainly in the muscle and gills of the pelagic chub. Furthermore, the elevated concentrations of trace elements in sediments (Cr, Cu, Mn) demonstrated higher accumulation in the benthic nase and barbel. Our findings show habitat preference as a key factor in juvenile bioindicator capability, advocating for the simultaneous use of pelagic and benthic juveniles to assess water and sediment pollution status.

The retinoid X receptor has a critical role in synthetic rexinoid-induced increase in cellular all-trans-retinoic acid.

Rexinoids are agonists of nuclear rexinoid X receptors (RXR) that heterodimerize with other nuclear receptors to regulate gene transcription. A number of selective RXR agonists have been developed for clinical use but their application has been hampered by the unwanted side effects associated with the use of rexinoids and a limited understanding of their mechanisms of action across different cell types. Our previous studies showed that treatment of organotypic human epidermis with the low toxicity UAB30 and UAB110 rexinoids resulted in increased steady-state levels of all-trans-retinoic acid (ATRA), the obligatory ligand of the RXR-RAR heterodimers. Here, we investigated the molecular mechanism underlying the increase in ATRA levels using a dominant negative RXRα that lacks the activation function 2 (AF-2) domain. The results demonstrated that overexpression of dnRXRα in human organotypic epidermis markedly reduced signaling by resident ATRA, suggesting the existence of endogenous RXR ligand, diminished the biological effects of UAB30 and UAB110 on epidermis morphology and gene expression, and nearly abolished the rexinoid-induced increase in ATRA levels. Global transcriptome analysis of dnRXRα-rafts in comparison to empty vector-transduced rafts showed that over 95% of the differentially expressed genes in rexinoid-treated rafts constitute direct or indirect ATRA-regulated genes. Thus, the biological effects of UAB30 and UAB110 are mediated through the AF-2 domain of RXRα with minimal side effects in human epidermis. As ATRA levels are known to be reduced in certain epithelial pathologies, treatment with UAB30 and UAB110 may represent a promising therapy for normalizing the endogenous ATRA concentration and signaling in epithelial tissues.

The metabolic domestication syndrome of budding yeast.

Cellular metabolism evolves through changes in the structure and quantitative states of metabolic networks. Here, we explore the evolutionary dynamics of metabolic states by focusing on the collection of metabolite levels, the metabolome, which captures key aspects of cellular physiology. Using a phylogenetic framework, we profiled metabolites in 27 populations of nine budding yeast species, providing a graduated view of metabolic variation across multiple evolutionary time scales. Metabolite levels evolve more rapidly and independently of changes in the metabolic network's structure, providing complementary information to enzyme repertoire. Although metabolome variation accumulates mainly gradually over time, it is profoundly affected by domestication. We found pervasive signatures of convergent evolution in the metabolomes of independently domesticated clades of Saccharomyces cerevisiae. Such recurring metabolite differences between wild and domesticated populations affect a substantial part of the metabolome, including rewiring of the TCA cycle and several amino acids that influence aroma production, likely reflecting adaptation to human niches. Overall, our work reveals previously unrecognized diversity in central metabolism and the pervasive influence of human-driven selection on metabolite levels in yeasts.

A serine metabolic enzyme is flexing its muscle to help repair skeletal muscle.

Metabolic reprogramming of stem cells is a targetable pathway to control regeneration. Activation of stem cells results in down-regulation of oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) and turns on glycolysis to provide fuel for proliferation and specific signaling events. How cell type-specific events are regulated is unknown. In this issue of Genes & Development Ciuffoli and colleagues (pp. 151-167) use metabolomic, gene inactivation, and functional approaches to show that phosphoserine aminotransferase (Psat1), an enzyme in serine biosynthesis, is activated in muscle stem cells and contributes to cell expansion and skeletal muscle regeneration via the production of α-ketoglutarate and glutamine.

Legionella pneumophila usurps host cell lipids for vacuole expansion and bacterial growth.

Vacuolar pathogens reside in membrane-bound compartments within host cells. Maintaining the integrity of this compartment is paramount to bacterial survival and replication as it protects against certain host surveillance mechanisms that function to eradicate invading pathogens. Preserving this compartment during bacterial replication requires expansion of the vacuole membrane to accommodate the increasing number of bacteria, and yet, how this is accomplished remains largely unknown. Here, we show that the vacuolar pathogen Legionella pneumophila exploits multiple sources of host cell fatty acids, including inducing host cell fatty acid scavenging pathways, in order to promote expansion of the replication vacuole and bacteria growth. Conversely, when exogenous lipids are limited, the decrease in host lipid availability restricts expansion of the replication vacuole membrane, resulting in a higher density of bacteria within the vacuole. Modifying the architecture of the vacuole prioritizes bacterial growth by allowing the greatest number of bacteria to remain protected by the vacuole membrane despite limited resources for its expansion. However, this trade-off is not without risk, as it can lead to vacuole destabilization, which is detrimental to the pathogen. However, when host lipid resources become extremely scarce, for example by inhibiting host lipid scavenging, de novo biosynthetic pathways, and/or diverting host fatty acids to storage compartments, bacterial replication becomes severely impaired, indicating that host cell fatty acid availability also directly regulates L. pneumophila growth. Collectively, these data demonstrate dual roles for host cell fatty acids in replication vacuole expansion and bacterial proliferation, revealing the central functions for these molecules and their metabolic pathways in L. pneumophila pathogenesis.

Affective super-traits and/or individual patterns: a variable-centered and a person-centered approach of primary emotional aspects of personality.

Theoretical approaches of personality structure are diverse. We examine the primary emotional aspects of personality as the correspondence of two mainstream constructs: the lexically-based Big Five (BIG5) and the biologically-based Affective Neuroscience Theory (ANT) within two approaches. In the variable-centered approach (VCA), our aim is to identify affective super-traits; while in the person-centered approach (PCA) to uncover latent profile patterns. 240 participants (177 women, 63 men) completed the 112-item affective neuroscience personality scales (ANPS), and the 44-item Big Five Inventory (BFI). We identified four super-traits: Negative emotions (FEAR, SADNESS, Emotional instability), Positive emotions and stimulation (SEEK, Extraversion), Affiliation and social bonds (reversed ANGER, CARE, Agreeableness), Self-regulation (PLAY, Conscientiousness. Based on the VCA, we conclude that the four super-traits represent two main affective tendencies (Positive emotions and approaching, Negative emotions and avoidance), interpersonal (Affiliation) and intrapersonal (Self-regulation) dynamics of personality. As a result of Latent Profile Analysis in the PCA, we explored three latent groups with different patterns of primary emotional traits based on their responsiveness (Highly emotional, Balanced, Low emotional). Our findings provide a holistic approach to emotional aspects of personality, and might have further implications for clinical psychology, neuroscience, and cross-cultural studies on emotions.

Snowball: a novel gene family required for developmental patterning of fruiting bodies of mushroom-forming fungi (Agaricomycetes).

The morphogenesis of sexual fruiting bodies of fungi is a complex process determined by a genetically encoded program. Fruiting bodies reached the highest complexity levels in the Agaricomycetes; yet, the underlying genetics is currently poorly known. In this work, we functionally characterized a highly conserved gene termed snb1, whose expression level increases rapidly during fruiting body initiation. According to phylogenetic analyses, orthologs of snb1 are present in almost all agaricomycetes and may represent a novel conserved gene family that plays a substantial role in fruiting body development. We disrupted snb1 using CRISPR/Cas9 in the agaricomycete model organism Coprinopsis cinerea. snb1 deletion mutants formed unique, snowball-shaped, rudimentary fruiting bodies that could not differentiate caps, stipes, and lamellae. We took advantage of this phenotype to study fruiting body differentiation using RNA-Seq analyses. This revealed differentially regulated genes and gene families that, based on wild-type RNA-Seq data, were upregulated early during development and showed tissue-specific expression, suggesting a potential role in differentiation. Taken together, the novel gene family of snb1 and the differentially expressed genes in the snb1 mutants provide valuable insights into the complex mechanisms underlying developmental patterning in the Agaricomycetes. IMPORTANCE: Fruiting bodies of mushroom-forming fungi (Agaricomycetes) are complex multicellular structures, with a spatially and temporally integrated developmental program that is, however, currently poorly known. In this study, we present a novel, conserved gene family, Snowball (snb), termed after the unique, differentiation-less fruiting body morphology of snb1 knockout strains in the model mushroom Coprinopsis cinerea. snb is a gene of unknown function that is highly conserved among agaricomycetes and encodes a protein of unknown function. A comparative transcriptomic analysis of the early developmental stages of differentiated wild-type and non-differentiated mutant fruiting bodies revealed conserved differentially expressed genes which may be related to tissue differentiation and developmental patterning fruiting body development.

Lineage-determining transcription factor-driven promoters regulate cell type-specific macrophage gene expression.

Mammalian promoters consist of multifarious elements, which make them unique and support the selection of the proper transcript variants required under diverse conditions in distinct cell types. However, their direct DNA-transcription factor (TF) interactions are mostly unidentified. Murine bone marrow-derived macrophages (BMDMs) are a widely used model for studying gene expression regulation. Thus, this model serves as a rich source of various next-generation sequencing data sets, including a large number of TF cistromes. By processing and integrating the available cistromic, epigenomic and transcriptomic data from BMDMs, we characterized the macrophage-specific direct DNA-TF interactions, with a particular emphasis on those specific for promoters. Whilst active promoters are enriched for certain types of typically methylatable elements, more than half of them contain non-methylatable and prototypically promoter-distal elements. In addition, circa 14% of promoters-including that of Csf1r-are composed exclusively of 'distal' elements that provide cell type-specific gene regulation by specialized TFs. Similar to CG-rich promoters, these also contain methylatable CG sites that are demethylated in a significant portion and show high polymerase activity. We conclude that this unusual class of promoters regulates cell type-specific gene expression in macrophages, and such a mechanism might exist in other cell types too.

Probing the biological consequences of a previously undescribed de novo mutation of ZMYND11 in a schizophrenia patient by CRISPR genome editing and induced pluripotent stem cell based in vitro disease-modeling.

BACKGROUND: Schizophrenia (SCZ) is a severe neuropsychiatric disorder of complex, poorly understood etiology, associated with both genetic and environmental factors. De novo mutations (DNMs) represent a new source of genetic variation in SCZ, however, in most cases their biological significance remains unclear. We sought to investigate molecular disease pathways connected to DNMs in SCZ by combining human induced pluripotent stem cell (hiPSC) based disease modeling and CRISPR-based genome editing. METHODS: We selected a SCZ case-parent trio with the case individual carrying a potentially disease causing 1495C > T nonsense DNM in the zinc finger MYND domain-containing protein 11 (ZMYND11), a gene implicated in biological processes relevant for SCZ. In the patient-derived hiPSC line the mutation was corrected using CRISPR, while monoallelic or biallelic frameshift mutations were introduced into a control hiPSC line. Isogenic cell lines were differentiated into hippocampal neuronal progenitor cells (NPCs) and functionally active dentate gyrus granule cells (DGGCs). Immunofluorescence microscopy and RNA sequencing were used to test for morphological and transcriptomic differences at NPC and DGCC stages. Functionality of neurons was investigated using calcium-imaging and multi-electrode array measurements. RESULTS: Morphology in the mutant hippocampal NPCs and neurons was preserved, however, we detected significant transcriptomic and functional alterations. RNA sequencing showed massive upregulation of neuronal differentiation genes, and downregulation of cell adhesion genes. Decreased reactivity to glutamate was demonstrated by calcium-imaging. CONCLUSIONS: Our findings lend support to the involvement of glutamatergic dysregulation in the pathogenesis of SCZ. This approach represents a powerful model system for precision psychiatry and pharmacological research.

ContScout: sensitive detection and removal of contamination from annotated genomes.

Contamination of genomes is an increasingly recognized problem affecting several downstream applications, from comparative evolutionary genomics to metagenomics. Here we introduce ContScout, a precise tool for eliminating foreign sequences from annotated genomes. It achieves high specificity and sensitivity on synthetic benchmark data even when the contaminant is a closely related species, outperforms competing tools, and can distinguish horizontal gene transfer from contamination. A screen of 844 eukaryotic genomes for contamination identified bacteria as the most common source, followed by fungi and plants. Furthermore, we show that contaminants in ancestral genome reconstructions lead to erroneous early origins of genes and inflate gene loss rates, leading to a false notion of complex ancestral genomes. Taken together, we offer here a tool for sensitive removal of foreign proteins, identify and remove contaminants from diverse eukaryotic genomes and evaluate their impact on phylogenomic analyses.

Add-on Sacubitril/Valsartan Therapy Induces Left Ventricular Remodeling in Non-responders to Cardiac Resynchronization Therapy to a Similar Extent as in Heart Failure Patients Without Resynchronization.

INTRODUCTION: Non-responders to cardiac resynchronization therapy (CRT-NR) have poor prognosis. Sacubitril/valsartan (SV) treatment improved the outcome of patients with heart failure with reduced left ventricular (LV) ejection fraction (HFrEF) in randomized trials with no data on the specific cohort of CRT-NRs. The aim of this study was to compare the echocardiographic and biomarker changes in CRT-NR patients treated with versus without SV, and in patients with HFrEF on SV therapy. METHODS: CRT-NR patients initiated on SV (group I), CRT-NR patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) (group II), and patients with HFrEF (without CRT) initiated on SV (group III) were identified in our heart failure (HF) registry. CRT-NR was defined as < 10% improvement in left ventricular ejection fraction (LV EF) 6 months after the implantation. Echocardiographic parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at baseline and at the end of follow-up were compared. RESULTS: A total of 275 patients (group I, 70; group II, 70; and group III, 135) were included. After a follow-up of 7.54 ± 1.8 months (mean ± standard deviation [SD]), LV EF (%) increased in group I (25.2 ± 5.7 versus 29.4% ± 6.7; p < 0.001) and in group III (26.6 ± 6.4 versus 29.9 ± 6.7; p < 0.001). LV end-systolic diameters (mm) decreased in group I (56.6 ± 9.0 versus 54.3 ± 8.7; p = 0.004) and in group III (55.9 ± 9.9 versus 54.3 ± 11.2; p = 0.021). The levels of NT-proBNP (pg/mL) decreased in group I (2058.86 [1041.07-4502.51] versus 1121.55 [545-2541]; p < 0.001) and in group III (2223.35 [1233.03-4795.96] versus 1123.09 [500.38-2651.27]; p < 0.001). The extent of improvement was similar in groups I and III (p > 0.05). No significant changes were detected in group II. CONCLUSION: SV therapy induced similar improvements in echocardiographic parameters and in NT-proBNP levels in CRT-NR patients and in patients with HFrEF without resynchronization.

AutophagyNet: high-resolution data source for the analysis of autophagy and its regulation.

Macroautophagy/autophagy is a highly-conserved catabolic procss eliminating dysfunctional cellular components and invading pathogens. Autophagy malfunction contributes to disorders such as cancer, neurodegenerative and inflammatory diseases. Understanding autophagy regulation in health and disease has been the focus of the last decades. We previously provided an integrated database for autophagy research, the Autophagy Regulatory Network (ARN). For the last eight years, this resource has been used by thousands of users. Here, we present a new and upgraded resource, AutophagyNet. It builds on the previous database but contains major improvements to address user feedback and novel needs due to the advancement in omics data availability. AutophagyNet contains updated interaction curation and integration of over 280,000 experimentally verified interactions between core autophagy proteins and their protein, transcriptional and post-transcriptional regulators as well as their potential upstream pathway connections. AutophagyNet provides annotations for each core protein about their role: 1) in different types of autophagy (mitophagy, xenophagy, etc.); 2) in distinct stages of autophagy (initiation, expansion, termination, etc.); 3) with subcellular and tissue-specific localization. These annotations can be used to filter the dataset, providing customizable download options tailored to the user's needs. The resource is available in various file formats (e.g. CSV, BioPAX and PSI-MI), and data can be analyzed and visualized directly in Cytoscape. The multi-layered regulation of autophagy can be analyzed by combining AutophagyNet with tissue- or cell type-specific (multi-)omics datasets (e.g. transcriptomic or proteomic data). The resource is publicly accessible at http://autophagynet.org.Abbreviations: ARN: Autophagy Regulatory Network; ATG: autophagy related; BCR: B cell receptor pathway; BECN1: beclin 1; GABARAP: GABA type A receptor-associated protein; IIP: innate immune pathway; LIR: LC3-interacting region; lncRNA: long non-coding RNA; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; miRNA: microRNA; NHR: nuclear hormone receptor; PTM: post-translational modification; RTK: receptor tyrosine kinase; TCR: T cell receptor; TLR: toll like receptor.

Importance of aligning the implementation of new payment models for innovative pharmaceuticals in European countries.

INTRODUCTION: The uptake of complex technologies and platforms has resulted in several challenges in the pricing and reimbursement of innovative pharmaceuticals. To address these challenges, plenty of concepts have already been described in the scientific literature about innovative value judgment or payment models, which are either (1) remaining theoretical; or (2) applied only in pilots with limited impact on patient access; or (3) applied so heterogeneously in many different countries that it prevents the health care industry from meeting expectations of HTA bodies and health care payers in the evidence requirements or offerings in different jurisdictions. AREAS COVERED: This paper provides perspectives on how to reduce the heterogeneity of pharmaceutical payment models across European countries in five areas, including 1) extended evaluation frameworks, 2) performance-based risk-sharing agreements, 3) pooled procurement for low volume or urgent technologies, 4) alternative access schemes, and 5) delayed payment models for technologies with high upfront costs. EXPERT OPINION: Whilst pricing and reimbursement decisions will remain a competence of EU member states, there is a need for alignment of European pharmaceutical payment model components in critical areas with the ultimate objective of improving the equitable access of European patients to increasingly complex pharmaceutical technologies.

A Morphometric Study Analyzing the Anterior Epidural Space Volume Throughout Childhood.

BACKGROUND: Following disc herniations, fragments migrate into the anterior epidural space within the lumbar spine. Although the volume of this area has been previously described in the adult population, the volume is relatively unknown within children. OBJECTIVES: Investigate the relative volume in the lumbar anterior epidural space within the growing spine by using imaging studies. STUDY DESIGN: Retrospective chart review. SETTING: University Medical Center in Lubbock Texas. A teaching hospital affiliated with Texas Tech University Health Sciences Center. METHODS: We conducted a retrospective review of the charts of pediatric patients seen at our institution from 2018 through 2020. Charts chosen for our investigation contained computed tomography imaging of the lumber spine, showing no deformities. Thirty patients were stratified equally among 3 age groups, 2-5 years old, 10-12 years old, and 16-18 years old. The anterior epidural space was measured in each patient 3 times using the previously reported method used by Teske et al (1). Results were compared with a combination of analysis of variance (ANOVA) and single tail paired t test. RESULTS: There was a statistically significant difference in the anterior epidural space size among age groups at all levels of the lumbar spine. When comparing only 2 groups together, the younger age group had anterior epidural space sizes significantly smaller than the other age group for all levels of the lumbar spine. The 10-12 age group had a significantly smaller space in the anterior epidural space than the 16-18-year olds only at the level of L2, L4, and L5 (P = 0.048,0.039, and 0.031, respectively). Within the 16-18-year age group, the anterior epidural space was significantly different between L4 and L3 and L2 and L3 (P < 0.001 and P = 0.019, respectively). LIMITATIONS: Our study is limited by its retrospective nature and the sample size of the patient groups. Furthermore, the use of computed tomography imaging and not making physical measurements limits our accuracy. CONCLUSION: The volume of the anterior epidural space is smaller in the pediatric population than the adult population. The inability of herniated discs to fit within the epidural space in children and adolescents could potentially be the cause of the increased failure of conservative treatment for pediatric lumbar disc herniations.

Analysis of the timing and the usage of drains following cranioplasty on outcomes and the incidence of bone resorption.

Background: Pediatric cranioplasty is associated with a high rate of complications, including bone resorption (BR) in 20-50% of cases. We aimed to evaluate factors contributing to BR, including the effect of the timing of cranioplasty and the use of post-surgical drains. Methods: This is a dual institution retrospective review of all patients under 18 years old who underwent a cranioplasty following a decompressive craniectomy (DC) for the treatment of traumatic brain injury between 2011 and 2021. Early cranioplasty was defined as within 30 days after DC and late cranioplasty as >30 days. Patients were grouped by BR and separately by timing to cranioplasty. Groups were compared based on the Glasgow Outcome Scale (GOS) and postoperative drain usage. Results: A total of 30 patients were included in the study. The mean age was 7.39 (standard deviation = 6.52) and 60% were male. The median time to cranioplasty was 13 days (interquartile range = 10-17). BR was present in 16.7% of cases. A subgaleal drain was utilized in 93.3% and an external ventricular drain (EVD) in 63.3% of patients following cranioplasty. Drain usage was not associated with BR and timing to cranioplasty was not associated with discharge or 6-month GOS. Conclusion: This study demonstrates that early cranioplasty following DC may have similar outcomes to late cranioplasty. Post-surgical EVDs and subgaleal drains did not increase the incidence of BR, suggesting their importance in the postoperative management of these patients.

Right superior pulmonary vein parameter determined by three-dimensional transesophageal echocardiography is an independent predictor of the outcome after cryoballoon isolation of the pulmonary veins.

BACKGROUND: A direct comparison of three-dimensional transesophageal echocardiography (3DTEE) and cardiac computed tomography imaging has demonstrated good inter-technique agreement for the following pulmonary vein (PV) parameters: the ostium area of the right superior PV (RSPV) and its major (a) and minor axis (b) diameters, the left lateral ridge and the minor axis (b) diameter of the left superior PV. Herein, under investigation, was the predictive value of these parameters for arrhythmia recurrence (AR) after PV isolation with the 28 mm second generation cryoballoon (CBG2). METHODS: One hundred eleven patients (67 men, mean age 58.06 ± 10.58 years) undergoing 3DTEE before PV isolation with the CBG2 for paroxysmal atrial fibrillation were followed. "Point by point" redo intervention was offered in case of AR and reconnected PVs were defined. RESULTS: During a mean follow-up of 617 ± 258.86 days, 65 (58.9%) patients remained free of AR. Longer RSPV b was found to be the only significant predictor for AR (hazard ratio [HR] 1.059; 95% confidence interval [CI] 1.000-1.121; p = 0.048). RSPV b ≥ 28 mm resulted in a threefold (HR 3.010; 95% CI 1.270-7.134, p = 0.012) increase in the risk of AR. The association of RSPV b with AR was independent of the biophysical parameters of cryoapplications. In 25 "redo" patients, reconnections were found 1.75 times more likely in the RSPV than in the other 3 PVs altogether. CONCLUSIONS: Right superior PV b measured with 3DTEE might be a significant predictor of AR after PV isolation with the CBG2. In case of RSPV b exceeding 28 mm, alternative PV isolation techniques or use of a larger balloon might be considered.

Vertical and horizontal gene transfer shaped plant colonization and biomass degradation in the fungal genus Armillaria.

The fungal genus Armillaria contains necrotrophic pathogens and some of the largest terrestrial organisms that cause tremendous losses in diverse ecosystems, yet how they evolved pathogenicity in a clade of dominantly non-pathogenic wood degraders remains elusive. Here we show that Armillaria species, in addition to gene duplications and de novo gene origins, acquired at least 1,025 genes via 124 horizontal gene transfer events, primarily from Ascomycota. Horizontal gene transfer might have affected plant biomass degrading and virulence abilities of Armillaria, and provides an explanation for their unusual, soft rot-like wood decay strategy. Combined multi-species expression data revealed extensive regulation of horizontally acquired and wood-decay related genes, putative virulence factors and two novel conserved pathogenicity-induced small secreted proteins, which induced necrosis in planta. Overall, this study details how evolution knitted together horizontally and vertically inherited genes in complex adaptive traits of plant biomass degradation and pathogenicity in important fungal pathogens.

Outcomes of Pediatric Traumatic Brain Injury Patients Presenting with or Developing Cerebral Herniation.

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in children. Previous studies evaluated outcomes of adult patients; however, few assessed outcomes of pediatric TBI patients presenting with herniation. This study investigated outcome data in pediatric patients presenting with TBI and cerebral herniation and the interventional strategies used for each patient in a rural community. METHODS: A dual-institution retrospective review of 50 pediatric patients presenting with TBI and cerebral herniation from January 2011 to December 2020 was conducted. Mechanism of injury; herniation based on radiology findings; admission, presurgery, and postsurgery Glasgow Coma Scale scores; intracranial pressure values; discharge Glasgow Outcome Scale scores; length of stay; intensive care unit length of stay; procedures performed; and 30-day mortality/morbidity were collected for each patient. RESULTS: Although a nonsurgical approach led to better outcomes (29.4% vs. 48.4% mortality rate), early intervention with decompressive craniectomy improved morbidity in patients with severe TBI and cerebral herniation. Male patients presenting with TBI complicated by herniation were more likely to have a fatal outcome compared with female patients (51.6% vs. 26.3%). Behavior and age at injury may play a role in these differences. CONCLUSIONS: TBI remains a serious concern in the pediatric population with no clear guidelines on the optimal treatment. This study highlights the advantage of integrating more aggressive surgical intervention, such as decompressive craniectomy, in rural communities earlier in the hospital course. Future studies should explore additional factors that could contribute to outcomes in this patient population.

Corrigendum: Editorial: Cross-talk between heterogeneous cell types in skeletal muscle: implications for glucose metabolism.

[This corrects the article DOI: 10.3389/fendo.2023.1185725.].