Human GM-CSF/IL-3 enhance tumor immune infiltration in humanized HCC patient-derived xenografts.

Background & Aims: Response to immunotherapy in hepatocellular carcinoma (HCC) is suboptimal with no biomarkers to guide patient selection. "Humanized" mice represent promising models to address this deficiency but are limited by variable chimerism and underdeveloped myeloid compartments. We hypothesized that expression of human GM-CSF and IL-3 increases tumor immune cell infiltration, especially myeloid-derived cells, in humanized HCC patient-derived xenografts.

Control of striatal circuit development by the chromatin regulator .

The pathophysiology of neurodevelopmental disorders involves vulnerable neural populations, including striatal circuitry, and convergent molecular nodes, including chromatin regulation and synapse function. Despite this, how epigenetic regulation regulates striatal development is understudied. Recurrent de novo mutations in are associated with intellectual disability and autism.

Distinct metabolic phenotype renders β-catenin mutant hepatocellular carcinoma susceptible to treatment-induced ischemia.

Background & Aims: Transarterial chemoembolization (TACE) is the most common treatment for hepatocellular carcinoma (HCC) worldwide; however, response rates and durability vary widely. With the growing armamentarium of therapies for HCC patients, identifying predictors of response to TACE has become increasingly important for a patient population with limited hepatic reserve. We hypothesized that a distinct metabolic phenotype associated with β-catenin pathway mutations render HCC tumors more susceptible to TACE-induced ischemia.

Human GM-CSF/IL-3 enhance tumor immune infiltration in humanized HCC patient-derived xenografts.

Background & Aims: Responses to immunotherapies in hepatocellular carcinoma (HCC) are suboptimal with no biomarkers to guide patient selection. "Humanized" mice represent promising models to address this deficiency but are limited by variable chimerism and underdeveloped myeloid compartments. We hypothesized that expression of human GM-CSF and IL-3 increases tumor immune cell infiltration, especially myeloid-derived cells, in humanized HCC patient-derived xenografts (PDXs).

Transarterial Embolization Modulates the Immune Response within Target and Nontarget Hepatocellular Carcinomas in a Rat Model.

Background Transarterial embolization (TAE) is the most common treatment for hepatocellular carcinoma (HCC); however, there remain limited data describing the influence of TAE on the tumor immune microenvironment. Purpose To characterize TAE-induced modulation of the tumor immune microenvironment in a rat model of HCC and identify factors that modulate this response. Materials and Methods TAE was performed on autochthonous HCCs induced in rats with use of diethylnitrosamine.

Mentorship in Interventional Radiology: Addressing Obstacles to Pursuing Research and Innovation Among IR Trainees.

Rationale And Objectives: To ascertain the perceived obstacles that medical students and Interventional Radiology (IR) residents face performing IR research during training and incorporating research into their future careers.

Materials And Methods: The study was reviewed and exempt from Institutional Review Board review. Participants' attitudes and perceived barriers toward performing IR research, and experience with mentorship in IR were assessed using a 27-item survey sent to all members of the Society of Interventional Radiology Resident, Fellow and Student (SIR-RFS, n = 445), and Medical Student Council (SIR-MSC, n = 267) sections between July and September 2020.

Position and orientation of vaginal pessaries in situ on magnetic resonance imaging.

Introduction And Hypothesis: We hypothesize that there are differences in the position and orientation of ring and Gellhorn pessaries in situ on magnetic resonance imaging (MRI).

Methods: This was a retrospective cohort study comparing MRI findings in 25 women with pessaries in situ at the time of imaging. Scanner coordinates for anatomic and pessary landmarks were obtained and transformed to 3D Pelvic Inclination Correction System coordinates using MATLAB software.

Generation of cerebral cortical GABAergic interneurons from pluripotent stem cells.

The cerebral cortex functions by the complex interactions of intrinsic and extrinsic neuronal activities, glial actions, and the effects of humoral factors. The intrinsic neuronal influences are mediated by two major subclasses: excitatory glutamatergic neurons that generally have axonal projections extending beyond the neuron's locality and inhibitory GABAergic neurons that generally project locally. These interneurons can be grouped based on morphological, neurochemical, electrophysiological, axonal targeting, and circuit influence characteristics.

Hyperpolarized Metabolic Imaging Detects Latent Hepatocellular Carcinoma Domains Surviving Locoregional Therapy.

Background And Aims: Advances in cancer treatment have improved survival; however, local recurrence and metastatic disease-the principal causes of cancer mortality-have limited the ability to achieve durable remissions. Local recurrences arise from latent tumor cells that survive therapy and are often not detectable by conventional clinical imaging techniques. Local recurrence after transarterial embolization (TAE) of hepatocellular carcinoma (HCC) provides a compelling clinical correlate of this phenomenon.

Single-Step Method for Pull-Type Gastrostomy Tube Placement.

Single-step pull-type gastrostomy tube (PGT) placement is a method involving gastric puncture with a curved 18-gauge trocar needle allowing retrograde cannulation of the gastroesophageal junction without use of a sheath or snare. This retrospective review of 102 patients who underwent single-step PGT placement demonstrated 91% success in advancing the wire up the esophagus using only the curved trocar. Successful placement of a gastrostomy tube was 100%.

Establishment of hepatocellular carcinoma patient-derived xenografts from image-guided percutaneous biopsies.

While patient-derived xenograft (PDX) models of hepatocellular carcinoma (HCC) have been successfully generated from resected tissues, no reliable methods have been reported for the generation of PDXs from patients who are not candidates for resection and represent the vast majority of patients with HCC. Here we compare two methods for the creation of PDXs from HCC biopsies and find that implantation of whole biopsy samples without the addition of basement membrane matrix favors the formation of PDX tumors that resemble Epstein-Barr virus (EBV)-driven B-cell lymphomas rather than HCC tumors. In contrast, implantation with Matrigel supports growth of HCC cells and leads to a high rate of HCC tumor formation from these biopsies.

Retrospective comparison of outcomes and associated complications between large bore radiologically inserted gastrostomy tube types.

Purpose: Multiple approaches to radiologically inserted gastrostomy (RIG) exist. The goal of this study was to compare 30-day outcomes and associated complications between large bore balloon-retained (BR), loop-retained (LR), and pull-type (PT) RIG devices.

Methods: Data on 1477 patients who underwent RIG between January 1, 2005 and December 31, 2016 were collected retrospectively using a dedicated interventional radiology database and electronic medical record.

Differentiation of Mouse Embryonic Stem Cells into Cortical Interneuron Precursors.

GABAergic cortical interneurons are a heterogeneous population of cells that play critical roles in regulating the output of excitatory pyramidal neurons as well as synchronizing the outputs of pyramidal neuron ensembles. Deficits in interneuron function have been implicated in a variety of neuropsychiatric disorders, including schizophrenia, autism, and epilepsy. The derivation of cortical interneurons from embryonic stem cells not only allows for the study of their development and function, but provides insight into the molecular mechanisms underlying the pathogenesis of cortical interneuron-related disorders.

The NANCI-Nkx2.1 gene duplex buffers Nkx2.1 expression to maintain lung development and homeostasis.

A subset of long noncoding RNAs (lncRNAs) is spatially correlated with transcription factors (TFs) across the genome, but how these lncRNA-TF gene duplexes regulate tissue development and homeostasis is unclear. We identified a feedback loop within the NANCI (Nkx2.1-associated noncoding intergenic RNA)-Nkx2.

Loss of the neurodevelopmental gene Zswim6 alters striatal morphology and motor regulation.

The zinc-finger SWIM domain-containing protein 6 (ZSWIM6) is a protein of unknown function that has been associated with schizophrenia and limited educational attainment by three independent genome-wide association studies. Additionally, a putatively causal point mutation in ZSWIM6 has been identified in several cases of acromelic frontonasal dysostosis with severe intellectual disability. Despite the growing number of studies implicating ZSWIM6 as an important regulator of brain development, its role in this process has never been examined.

Atypical PKC and Notch Inhibition Differentially Modulate Cortical Interneuron Subclass Fate from Embryonic Stem Cells.

Recent studies indicate that the location of neurogenesis within the medial ganglionic eminence (MGE) critically influences the fate determination of cortical interneuron subgroups, with parvalbumin (Pv) interneurons originating from subventricular zone divisions and somatostatin (Sst) interneurons primarily arising from apical divisions. The aPKC-CBP and Notch signaling pathways regulate the transition from apical to basal progenitor and their differentiation into post-mitotic neurons. We find that aPKC inhibition enhances intermediate neurogenesis from stem cell-derived MGE progenitors, resulting in a markedly increased ratio of Pv- to Sst-expressing interneurons.

CC2D1A regulates human intellectual and social function as well as NF-κB signaling homeostasis.

Autism spectrum disorder (ASD) and intellectual disability (ID) are often comorbid, but the extent to which they share common genetic causes remains controversial. Here, we present two autosomal-recessive "founder" mutations in the CC2D1A gene causing fully penetrant cognitive phenotypes, including mild-to-severe ID, ASD, as well as seizures, suggesting shared developmental mechanisms. CC2D1A regulates multiple intracellular signaling pathways, and we found its strongest effect to be on the transcription factor nuclear factor κB (NF-κB).

RORβ induces barrel-like neuronal clusters in the developing neocortex.

Neurons in layer IV of the rodent whisker somatosensory cortex are tangentially organized in periodic clusters called barrels, each of which is innervated by thalamocortical axons transmitting sensory information from a single principal whisker, together forming a somatotopic map of the whisker pad. Proper thalamocortical innervation is critical for barrel formation during development, but the molecular mechanisms controlling layer IV neuron clustering are unknown. Here, we investigate the role in this mapping of the nuclear orphan receptor RORβ, which is expressed in neurons in layer IV during corticogenesis.

SOBP is mutated in syndromic and nonsyndromic intellectual disability and is highly expressed in the brain limbic system.

Intellectual disability (ID) affects 1%-3% of the general population. We recently reported on a family with autosomal-recessive mental retardation with anterior maxillary protrusion and strabismus (MRAMS) syndrome. One of the reported patients with ID did not have dysmorphic features but did have temporal lobe epilepsy and psychosis.

Mutations in WDR62, encoding a centrosome-associated protein, cause microcephaly with simplified gyri and abnormal cortical architecture.

Genes associated with human microcephaly, a condition characterized by a small brain, include critical regulators of proliferation, cell fate and DNA repair. We describe a syndrome of congenital microcephaly and diverse defects in cerebral cortical architecture. Genome-wide linkage analysis in two families identified a 7.