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Choroid plexus tumors (CPT) are rare neoplasms accounting for 1–4% of all pediatric brain tumors. They are divided into choroid plexus papilloma (CPP), atypical choroid plexus papilloma (APP) and choroid plexus carcinoma (CPC). CPTs are known to primarily affect children less than 2 years of age. Gross total resection is the most important predictor of survival especially in CPC. Although small case series have been published, limited clinical data are available to describe treatment and outcome of CPTs. More clinical data would be necessary to complete the picture, particularly in populations that are not age limited. Here we share data from the two major hospitals in Cleveland to describe treatment and outcome of adult and pediatric patients. We performed a retrospective analysis of patients with CPT seen in Cleveland Clinic from 1990 to 2015 and at University Hospitals from 1994 to 2015. Results were compared to previously published historical controls. We identified 30 cases with CPT, including 22 pediatric and eight adult cases; 11 females and 19 males. The mean age at presentation was 12.4 years with a median age of 4.5 years (range 2 months–51 years). Gross total surgical resection was achieved in 22, subtotal resection in four, partial resection in two and unknown in two. The histology was CPP in 23 patients, two of whom developed recurrence requiring repeat resection and adjuvant therapy. Median event free survival (EFS) for CPP patients was 7.6 years. The histology was CPC in seven patients. All CPC patients were treated with adjuvant therapy. Median EFS of CPC patients was 4.4 years. Overall survival of all CPT patients was 100% with a median follow up of 7 years. A systematic literature review identified 1012 CPT patients treated from 1989 to 2013. The mean and median age of CPT patients was 13 and 3 years respectively. The median survival of 541 CPP patients was undefined vs. 2.7 years for the 452 CPC patients. The difference between the two populations was highly significant (p < 0.001). Kaplan–Meier survival curves comparing CPTs at Cleveland Clinic and University Hospitals versus a systematic literature review showed a statistically significant advancement in overall survival among the patients treated at Cleveland Clinic and University Hospitals. Our data are consistent with the literature review regarding epidemiology, clinical presentation, and treatment modalities but differed in regards to survival. Differences in survival may be related to different methods of data collection or details in patient care.

Does encountering information-processing conflict recruit general mechanisms of cognitive control or change only the representations of specific cues and responses? In the present experiments, a flanker task elicited responses to symbolic information (arrow meaning), whereas Stroop-like tasks elicited responses to nonsymbolic information (color of a letter or location of a target box). Despite these differences, when participants performed the flanker and Stroop tasks intermittently in randomized orders, the extent of information-processing conflict encountered on a particular trial modulated performance on the following trial. On across-task trial pairs, increases in response time to incongruent relative to congruent stimulus arrays were smaller immediately following incongruent trials than immediately following congruent trials. The degree of cognitive control exerted on a particular task thus appears to reflect not only the quality, but also the quantity, of recent experiences of information-processing conflict.

Does encountering information-processing conflict recruit general mechanisms of cognitive control or change only the representations of specific cues and responses? In the present experiments, a flanker task elicited responses to symbolic information (arrow meaning), whereas Stroop-like tasks elicited responses to nonsymbolic information (color of a letter or location of a target box). Despite these differences, when participants performed the flanker and Stroop tasks intermittently in randomized orders, the extent of information-processing conflict encountered on a particular trial modulated performance on the following trial. On across-task trial pairs, increases in response time to incongruent relative to congruent stimulus arrays were smaller immediately following incongruent trials than immediately following congruent trials. The degree of cognitive control exerted on a particular task thus appears to reflect not only the quality, but also the quantity, of recent experiences of information-processing conflict. [PUBLICATION ABSTRACT]

The importance of breastmilk in postnatal life lies in the strong association between breastfeeding and the reduction in the risk of infection and infection-related infant mortality. However, data regarding the induction and dynamics of breastmilk antibodies following administration of the Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine is scarce, as pregnant and lactating women were not included in the initial vaccine clinical trials. Here, we investigate the dynamics of the vaccine-specific antibody response in breastmilk and serum in a prospective cohort of ten lactating women who received two doses of the mRNA vaccine. We show that the antibody response is rapid and highly synchronized between breastmilk and serum, reaching stabilization 14 days after the second dose. The response in breastmilk includes both IgG and IgA with neutralization capacity. Maternal antibodies can reduce risk of infection of infants. Here, the authors show induction of IgG and IgA antibodies in breastmilk and serum of ten lactating women after immunization with the Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine.

Microglia are cells that defend the central nervous system. However, because they migrate into the brain during development, the changes that they undergo, including those that affect gene expression, have been difficult to document. Matcovitch-Natan et al. transcriptionally profiled gene expression and analyzed epigenetic signatures of microglia at the single-cell level in the early postnatal life of mice. They identified three stages of microglia development, which are characterized by gene expression and linked with chromatin changes, occurring in sync with the developing brain. Furthermore, they showed that the proper development of microglia is affected by the microbiome. Science , this issue p. 789 The microbiota help regulate the development of active immune defense in the central nervous system of mice. Microglia, the resident myeloid cells of the central nervous system, play important roles in life-long brain maintenance and in pathology. Despite their importance, their regulatory dynamics during brain development have not been fully elucidated. Using genome-wide chromatin and expression profiling coupled with single-cell transcriptomic analysis throughout development, we found that microglia undergo three temporal stages of development in synchrony with the brain—early, pre-, and adult microglia—which are under distinct regulatory circuits. Knockout of the gene encoding the adult microglia transcription factor MAFB and environmental perturbations, such as those affecting the microbiome or prenatal immune activation, led to disruption of developmental genes and immune response pathways. Together, our work identifies a stepwise microglia developmental program integrating immune response pathways that may be associated with several neurodevelopmental disorders.

The intestinal epithelium is a structured organ composed of crypts harboring Lgr5+ stem cells, and villi harboring differentiated cells. Spatial transcriptomics have demonstrated profound zonation of epithelial gene expression along the villus axis, but the mechanisms shaping this spatial variability are unknown. Here, we combine laser capture micro-dissection and single cell RNA sequencing to uncover spatially zonated populations of mesenchymal cells along the crypt-villus axis. These include villus tip telocytes (VTTs) that express Lgr5 , a gene previously considered a specific crypt epithelial stem cell marker. VTTs are elongated cells that line the villus tip epithelium and signal through Bmp morphogens and the non-canonical Wnt5a ligand. Their ablation is associated with perturbed zonation of enterocyte genes induced at the villus tip. Our study provides a spatially-resolved cell atlas of the small intestinal stroma and exposes Lgr5 + villus tip telocytes as regulators of the epithelial spatial expression programs along the villus axis. Epithelial gene expression has been shown to be zonated along the crypt-villus axis, but mechanisms shaping this spatial variability were unknown. Here, Bahar Halpern et al. uncover zonation of mesenchymal cells, including Lgr5+ telocytes, which regulate epithelial gene expression at the villus tip.

Screening and molecular characterization of human intestinal pathologies such as colorectal cancer (CRC) currently depends on colonoscopy, an invasive procedure associated with risks and poor adherence. A non-invasive method that captures host molecular changes could improve early detection and monitoring of intestinal diseases. Transcriptomic profiling of shed intestinal cells in stool has shown potential in neonates but is limited in adults by the dominance of bacterial RNA. To address this, we combined microbial ribosomal RNA (rRNA) depletion with unique molecular identifier (UMI)-based RNA sequencing to enrich and quantify human transcripts in stool. Applying this method to samples from 54 CRC patients and 24 healthy controls, we profiled thousands of human genes per sample. Stool-derived gene expression distinguished CRC from control samples with high accuracy (AUC = 0.86) and strongly correlated with matched tumor tissue signatures. Notably, stool transcriptomes reverted to control-like patterns after tumor resection. Our approach offers a powerful, non-invasive alternative to current CRC diagnostics and enables molecular insights into tumor biology. This method could complement or replace existing screening tools and may be applicable to other gastrointestinal diseases.

Background Increasing prevalence of Alzheimer’s Disease (AD) and limited pharmacological intervention benefits to decelerate early neurodegeneration have prompted exploration of non‐pharmacological options. Recent studies indicate that combining cognitive‐motor training enhances outcomes. Methods In a single‐blind, parallel‐group, randomized controlled trial of middle‐aged adults with a parental history of AD, the experimental group (N = 22) underwent training with newly developed “real‐world” intensive, progressive, virtual reality (VR) tasks, while walking on a treadmill. Tasks included challenges to sustained attention, selective attention, working memory, covert rule deduction, and planning, all in daily living contexts. An active control group without treadmill (N = 17) and another group walking on a treadmill while watching scientific documentaries (N = 16) were included. A passive control group received no training (N = 11). Training sessions were 45 minutes, twice a week, for twelve weeks. The primary neurobiological outcome, cerebral blood flow (CBF), in the superior (SFG), middle (MFG) and inferior (IFG) frontal gyri and middle temporal gyrus (MTG), was assessed using MRI arterial spin labeling at 12 weeks (i.e., post training) and at 6 months (3 months follow up). Linear mixed regression models, adjusting for age, sex, education and baseline cognition, assessed group differences. Results Participants averaged 56.2 (SD = 5.78), were primarily female (70%) and had undergraduate education (mean = 16.4; SD = 3.12). The groups did not differ in any baseline characteristics. The interaction of group X time on CBF of the MFG was significant (p = 0.04), such that the experimental group had an increase in CBF at 3 months which then plateaued, there were no changes in CBF in the active control groups, and the passive control group had a decline in CBF (see Figure). Similar trends were found for the SFG and IFG (p for interaction 0.07 and 0.08, respectively). No differences were found between the groups in the MTG. Conclusion The sustained increase in CBF, a major contributor to cognitive functioning, observed in the frontal cortex of the experimental group over three months, implies that our innovative VR intervention may beneficially affect cerebrovascular function, even in midlife. This trend underscores the potential effectiveness of our intervention in preserving healthy cognition among asymptomatic individuals at high AD risk.

There are considerable differences in tumour biology between adult and paediatric cancers. The existence of cancer initiating cells/cancer stem cells (CIC/CSC) in paediatric solid tumours is currently unclear. Here, we show the successful propagation of primary human Wilms' tumour (WT), a common paediatric renal malignancy, in immunodeficient mice, demonstrating the presence of a population of highly proliferative CIC/CSCs capable of serial xenograft initiation. Cell sorting and limiting dilution transplantation analysis of xenograft cells identified WT CSCs that harbour a primitive undifferentiated – NCAM1 expressing – “blastema” phenotype, including a capacity to expand and differentiate into the mature renal‐like cell types observed in the primary tumour. WT CSCs, which can be further enriched by aldehyde dehydrogenase activity, overexpressed renal stemness and genes linked to poor patient prognosis, showed preferential protein expression of phosphorylated PKB/Akt and strong reduction of the miR‐200 family. Complete eradication of WT in multiple xenograft models was achieved with a human NCAM antibody drug conjugate. The existence of CIC/CSCs in WT provides new therapeutic targets. →See accompanying article http://dx.doi.org/10.1002/emmm.201202173 Graphical Abstract Here, the authors report the isolation and characterisation of Wilms' tumour stem cells and show that targeting a cancer cell population enriched for cancer‐initiating cell activity leads to tumour eradication in a mouse model.

Patients receiving intraoperative ventilation during general anesthesia often have low end–tidal CO2 (etCO2). We examined the association of intraoperative etCO2 levels with the occurrence of postoperative pulmonary complications (PPCs) in a conveniently–sized international, prospective study named ‘Local ASsessment of Ventilatory management during General Anesthesia for Surgery’ (LAS VEGAS). Patients at high risk of PPCs were categorized as ‘low etCO2’ or ‘normal to high etCO2’ patients, using a cut–off of 35 mmHg. The primary endpoint was a composite of previously defined PPCs; the individual PPCs served as secondary endpoints. The need for unplanned oxygen was defined as mild PPCs and severe PPCs included pneumonia, respiratory failure, acute respiratory distress syndrome, barotrauma, and new invasive ventilation. We performed propensity score matching and LOESS regression to evaluate the relationship between the lowest etCO2 and PPCs. The analysis included 1843 (74 %) ‘low etCO2’ patients and 648 (26 %) ‘normal to high etCO2’ patients. There was no difference in the occurrence of PPCs between ‘low etCO2’ and ‘normal to high etCO2’ patients (20 % vs. 19 %; RR 1.00 [95 %–confidence interval 0.94 to 1.06]; P = 0.84). The proportion of severe PPCs among total occurring PPCs, were higher in ‘low etCO2’ patients compared to ‘normal to high etCO2’ patients (35 % vs. 18 %; RR 1.16 [1.08 to 1.25]; P < 0.001). Propensity score matching did not change these findings. LOESS plot showed an inverse relationship of intraoperative etCO2 levels with the occurrence of PPCs. In this cohort of patients at high risk of PPCs, the overall occurrence of PPCs was not different between ‘low etCO2’ patients and ‘normal to high etCO2’ patients, but severe PPCs occurred more often in ‘low etCO2’, with an inverse dose–dependent relationship between intraoperative etCO2 levels and PPCs. This analysis was performed without additional funding. LAS VEGAS was partially funded and endorsed by the European Society of Anesthesiology and Intensive Care (ESAIC) and the Amsterdam University Medical Centers, location ‘AMC’. LAS VEGAS was registered at Clinicaltrials.gov (NCT01601223), first posted on May 17, 2012. [Display omitted] •This secondary analysis of the LAS VEGAS study, aimed to examine the association between etCO₂ levels and the occurrence of PPCs.•No significant difference was found in overall PPCs between ‘low etCO₂ (below 35 mmHg)’ and ‘normal to high etCO₂ (≥35 mmHg)’ patients (20 % vs. 19 %).•Severe PPCs were more common in the ‘low etCO₂’ group (35 % vs. 18 %). Propensity score matching did not alter the results, showing a robust association.•Potential mechanisms include hyperventilation causing ventilator-induced lung injury, ventilation-perfusion mismatching, or an underlying pulmonary pathology.•Future prospective studies should explore the causality between low etCO₂ and severe PPCs.