A developmental biliary lineage program cooperates with Wnt activation to promote cell proliferation in hepatoblastoma.

Cancers evolve not only through the acquisition and clonal transmission of somatic mutations but also by epigenetic mechanisms that modify cell phenotype. Here, we use histology-guided and spatial transcriptomics to characterize hepatoblastoma, a childhood liver cancer that exhibits significant histologic and proliferative heterogeneity despite clonal activating mutations in the Wnt/β-catenin pathway. Highly proliferative regions with embryonal histology show high expression of Wnt target genes, the embryonic biliary transcription factor SOX4, and striking focal expression of the growth factor FGF19.

Synthesis and antifungal activity of novel piperidinyl thiazole derivatives.

Background: As an investigative program around the development of novel oomycetes fungicides, a systematic exploration of piperidinyl thiazole fungicides employing a bioisosteric replacement strategy was planned.

Results: A series of novel piperidinyl thiazole analogues were designed, synthesised, and evaluated as fungicides in vitro and in vivo against three oomycete fungal pathogens: Phytophthora infestans (P. infestans), Plasmopara viticola (P.

Single-cell transcriptomic atlas reveals increased regeneration in diseased human inner ear balance organs.

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown.

Prevalence of hearing impairment in neonatal encephalopathy due to hypoxia-ischemia: a systematic review and meta-analysis.

Background: This systematic review was undertaken to estimate the overall prevalence of hearing impairment in survivors of neonatal HIE.

Methods: PubMed, EMBASE, CINAHL, EMCARE and Cochrane databases, mednar (gray literature) were searched till January 2023. Randomized controlled trials and observational studies were included.

Topical glyceryl trinitrate to increase radial artery diameter in neonates: study protocol for a randomized controlled trial.

Background: Newborn infants admitted to the neonatal intensive care unit require arterial cannulation for hemodynamic monitoring and blood sampling. Arterial access is achieved through catheterization of umbilical or peripheral arteries. Peripheral artery cannulation is performed in critically ill newborns, but artery localization and cannulation is often challenging and unsuccessful.

Combined near infrared photoacoustic imaging and ultrasound detects vulnerable atherosclerotic plaque.

Atherosclerosis is an inflammatory process resulting in the deposition of cholesterol and cellular debris, narrowing of the vessel lumen and clot formation. Characterization of the morphology and vulnerability of the lesion is essential for effective clinical management. Here, near-infrared auto-photoacoustic (NIRAPA) imaging is shown to detect plaque components and, when combined with ultrasound imaging, to differentiate stable and vulnerable plaque.

Combined near infrared photoacoustic imaging and ultrasound detects vulnerable atherosclerotic plaque.

Atherosclerosis is an inflammatory process resulting in the deposition of cholesterol and cellular debris, narrowing of the vessel lumen and clot formation. Characterization of the morphology and vulnerability of the lesion is essential for effective clinical management. Photoacoustic imaging has sufficient penetration and sensitivity to map and characterize human atherosclerotic plaque.

Solvent Free Upgrading of 5-Hydroxymethylfurfural (HMF) with Levulinic Acid to HMF Levulinate Using Tin Exchanged Tungstophosphoric Acid Supported on K-10 Catalyst.

The manufacture of high-value products from biomass derived platform chemicals is becoming an integral part of the biorefinery industry. In this study, we demonstrate a green catalytic process using solvent free conditions for the synthesis of hydroxymethylfurfural (HMF) levulinate from HMF and levulinic acid (LA) over tin exchanged tungstophosphoric acid (DTP) supported on K-10 (montmorillonite K-10 clay) as the catalyst. The structural properties of solid acid catalysts were characterized by using XRD, FT-IR, UV-vis, titration, and SEM techniques.

Multiplexed evaluation of mouse wound tissue using oligonucleotide barcoding with single-cell RNA sequencing.

Despite its rapidly increased availability for the study of complex tissue, single-cell RNA sequencing remains prohibitively expensive for large studies. Here, we present a protocol using oligonucleotide barcoding for the tagging and pooling of multiple samples from healing wounds, which are among the most challenging tissue types for this application. We describe steps to generate skin wounds in mice, followed by tissue harvest and oligonucleotide barcoding.

A case of soft-tissue tumor over the sternum: A rare case report.

The objective is to report a rare case of extragonadal seminoma over the manubrium sterni on the chest wall. A 42-year-old male patient, a chronic alcoholic for 10 years presented with a firm mass of approximate size 10 cm × 12 cm overlying the manubrium part of the sternum. A clinical diagnosis of soft-tissue tumor was made.

Multiomic analysis reveals conservation of cancer-associated fibroblast phenotypes across species and tissue of origin.

Cancer-associated fibroblasts (CAFs) are integral to the solid tumor microenvironment. CAFs were once thought to be a relatively uniform population of matrix-producing cells, but single-cell RNA sequencing has revealed diverse CAF phenotypes. Here, we further probed CAF heterogeneity with a comprehensive multiomics approach.

Post-infusion CAR T cells identify patients resistant to CD19-CAR therapy.

Approximately 60% of patients with large B cell lymphoma treated with chimeric antigen receptor (CAR) T cell therapies targeting CD19 experience disease progression, and neurotoxicity remains a challenge. Biomarkers associated with resistance and toxicity are limited. In this study, single-cell proteomic profiling of circulating CAR T cells in 32 patients treated with CD19-CAR identified that CD4Helios CAR T cells on day 7 after infusion are associated with progressive disease and less severe neurotoxicity.

Utility of the Ages and Stages Questionnaire to Identify Developmental Delay in Children Aged 12 to 60 Months: A Systematic Review and Meta-analysis.

Importance: The Ages and Stages Questionnaire (ASQ) is a commonly used developmental screening tool, but its utility is debated.

Objectives: To conduct a a systematic review and meta-analysis to evaluate ASQ's utility as a screening or diagnostic tool to identify developmental delay in children aged 12-60 months.

Data Sources: Medline, EMBASE, CINAHL, PsycINFO, and Mednar were searched from inception until December 2021.

Local nitroglycerin to facilitate peripheral arterial cannulation in children: systematic review and meta-analysis.

Background: Neonates and children admitted to intensive care units require peripheral arterial cannulation to monitor their blood pressures and for blood sampling, but many times it is unsuccessful.

Objective: To conduct a systematic review and meta-analysis to evaluate the efficacy and safety of local nitroglycerin (NTG) to facilitate peripheral artery cannulation in neonates and children.

Review Methods: PubMed, EMBASE, CINAHL, Emcare and Cochrane library were searched till August 2021.

Effect of Treatment of Clinical Seizures vs Electrographic Seizures in Full-Term and Near-Term Neonates: A Randomized Clinical Trial.

Importance: Seizures in the neonatal period are associated with increased mortality and morbidity. Bedside amplitude-integrated electroencephalography (aEEG) has facilitated the detection of electrographic seizures; however, whether these seizures should be treated remains uncertain.

Objective: To determine if the active management of electrographic and clinical seizures in encephalopathic term or near-term neonates improves survival free of severe disability at 2 years of age compared with only treating clinically detected seizures.

Integrated spatial multiomics reveals fibroblast fate during tissue repair.

In the skin, tissue injury results in fibrosis in the form of scars composed of dense extracellular matrix deposited by fibroblasts. The therapeutic goal of regenerative wound healing has remained elusive, in part because principles of fibroblast programming and adaptive response to injury remain incompletely understood. Here, we present a multimodal -omics platform for the comprehensive study of cell populations in complex tissue, which has allowed us to characterize the cells involved in wound healing across both time and space.

Prospective, Randomized, Open-Label, Blinded End Point, Two-Arm, Comparative Clinical Study to Evaluate the Efficacy and Safety of a Fixed Ayurvedic Regimen (FAR) as Add-on to Conventional Treatment in the Management of Mild and Moderate COVID-19 Patients.

Background: The traditional healthcare systems are being avidly looked into in the quest for effective remedies to tackle the menace of COVID-19 pandemic.

Objective: This was a prospective randomized, controlled open-label, blinded end point (PROBE) study to evaluate the efficacy and safety of a fixed ayurvedic regimen (FAR) as an add-on to conventional treatment/standard of care (SOC) in the management of mild-to-moderate COVID-19 infection.

Methodology: A total of 68 patients were recruited who consumed either FAR + SOC ( = 35) or SOC only ( = 33) for 28 days.

Characterization of Diabetic and Non-Diabetic Foot Ulcers Using Single-Cell RNA-Sequencing.

Recent advances in high-throughput single-cell sequencing technologies have led to their increasingly widespread adoption for clinical applications. However, challenges associated with tissue viability, cell yield, and delayed time-to-capture have created unique obstacles for data processing. Chronic wounds, in particular, represent some of the most difficult target specimens, due to the significant amount of fibrinous debris, extracellular matrix components, and non-viable cells inherent in tissue routinely obtained from debridement.

Early neurodevelopmental outcomes of congenital gastrointestinal surgical conditions: a single-centre retrospective study.

Background: Evidence is emerging that surgery in the neonatal period is associated with increased risk of suboptimal neurodevelopmental outcomes (SNDO). The aim of this study was to describe neurodevelopmental outcomes (at 1 year) of neonatal surgery for congenital gastrointestinal surgical conditions (CGSC) and to explore risk factors.

Methods: Retrospective study (2005-2014) of infants born ≥34 weeks gestation with CGSC and admitted to the surgical neonatal intensive care unit of Perth Children's Hospital, Western Australia.

Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.

Coronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-α (IFN-α) production by plasmacytoid dendritic cells.

Upregulation of CD47 Is a Host Checkpoint Response to Pathogen Recognition.

It is well understood that the adaptive immune response to infectious agents includes a modulating suppressive component as well as an activating component. We now show that the very early innate response also has an immunosuppressive component. Infected cells upregulate the CD47 "don't eat me" signal, which slows the phagocytic uptake of dying and viable cells as well as downstream antigen-presenting cell (APC) functions.

Inter-rater reliability of amplitude-integrated EEG for the detection of neonatal seizures.

Background: Amplitude-integrated electroencephalogram (aEEG) is being used increasingly for seizure detection in neonates. However, data regarding inter-rater reliability among neonatologists for the use of aEEG for the detection of neonatal seizures is lacking.

Methods: Term and late-preterm infants at risk of seizures were monitored simultaneously with 24-h video-electroencephalography (vEEG) and aEEG.

Beyond Maternal Mortality: A Systematic Review of Evidences on Mistreatment and Disrespect During Childbirth in Health Facilities in India.

The aim of this systematic review is to examine current evidence on the nature and extent of disrespect and abuse (D&A), mistreatment and practices of respectful maternity care of women during childbirth in India. Electronic databases were searched for published studies relevant to the topic. The search was conducted from May to September 2018.

Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis.

In response to various stimuli, vascular smooth muscle cells (SMCs) can de-differentiate, proliferate and migrate in a process known as phenotypic modulation. However, the phenotype of modulated SMCs in vivo during atherosclerosis and the influence of this process on coronary artery disease (CAD) risk have not been clearly established. Using single-cell RNA sequencing, we comprehensively characterized the transcriptomic phenotype of modulated SMCs in vivo in atherosclerotic lesions of both mouse and human arteries and found that these cells transform into unique fibroblast-like cells, termed 'fibromyocytes', rather than into a classical macrophage phenotype.