A specific gene expression program underlies antigen archiving by lymphatic endothelial cells in mammalian lymph nodes.

Lymph node (LN) lymphatic endothelial cells (LEC) actively acquire and archive foreign antigens. Here, we address questions of how LECs achieve durable antigen archiving and whether LECs with high levels of antigen express unique transcriptional programs. We used single cell sequencing in dissociated LN tissue and spatial transcriptomics to quantify antigen levels in LEC subsets and dendritic cell populations at multiple time points after immunization and determined that ceiling and floor LECs archive antigen for the longest duration.

Neurophobia amongst medical students: Hype or reality.

Introduction: 'Neurophobia' is a well reported phenomenon in the literature where in medical students and junior doctors have an inherent nervousness or 'fear' of neurology and neurosurgery

Research Question: Why do less medical students choose neurology and neurosurgery as a career and identify if neurophobia is an ingrained belief or learned behaviour?

Materials And Methods: We developed a questionnaire to assess medical student views and beliefs in connection with a career in neurosurgery. Specifically we examined the following domains: considering a career in neurology and neurosurgery, confidence with neuro anatomy and pathology, traits associated with neurosurgeons and neurologists and finally, their perceived barriers to a neuro career.

Results: 264 medical students completed the survey.

Bone marrow microenvironment signatures associate with patient survival after guadecitabine and atezolizumab therapy in HMA-resistant MDS.

Almost 50% of patients with myelodysplastic syndrome (MDS) are refractory to first-line hypomethylating agents (HMAs), which presents a significant clinical challenge considering the lack of options for salvage. Past work revealed that immune checkpoint molecules on peripheral myeloblasts and immune cells are up-regulated after HMA treatment. Therefore, we conducted a Phase I/II clinical trial combining guadecitabine (an HMA) and atezolizumab (an immune checkpoint inhibitor) to treat HMA-relapsed or refractory (HMA-R/R) MDS patients.

Pain Management during Bromelain-Based Enzymatic Debridement (NexoBrid) in a USA Adult Burn Center.

Outside the United States, bromelain-based enzymatic debridement (BBED) has become an effective tool for the removal of burn eschar. A primary concern with BBED is that it is a painful procedure requiring appropriate analgesia. The purpose of this study was to describe our experience using NexoBrid (NXB), with a particular focus on pain management.

Changes in facial soft tissue support with and without a maxillary labial flange.

Purpose: To quantify facial esthetic outcomes of prosthetic upper lip support in both full animation and repose for patients with an existing implant-supported fixed complete dental prosthesis (ISFCDP).

Materials And Methods: Twenty patients had a removable prosthetic labial flange fabricated for their existing maxillary prosthesis. The 3dMDface system was used to capture video sets of each patient going from repose to high smile with and without the labial flange.

Redundant pathways for removal of defective RNA polymerase II complexes at a promoter-proximal pause checkpoint.

The biological purpose of Integrator and RNA polymerase II (RNAPII) promoter-proximal pausing remains uncertain. Here, we show that loss of INTS6 in human cells results in increased interaction of RNAPII with proteins that can mediate its dissociation from the DNA template, including the CRL3 E3 ligase, which ubiquitylates CTD serine-phosphorylated RPB1 for degradation. ARMC5-dependent RNAPII ubiquitylation is activated by defects in factors acting at the promoter-proximal pause, including Integrator, DSIF, and capping enzyme.

Pediatric Burn Care for Burn Injury: Outcomes by Timing of Referral Using a U.S. Single-Center Retrospective Cohort, 2005-2019.

Objectives: Burn centers offer specialized care to pediatric patients with burn injuries. However, data about outcome in relation to timing of transfer are limited. We examined these timings and outcomes among burn-injured pediatric patients.

The experiences and perspectives of abortion seekers who travel for care: a qualitative evidence synthesis.

This is a protocol for a Cochrane Review (qualitative). The objectives are as follows: This QES aims to address the following question: What are the lived experiences and perceptions of abortion seekers (i.e.

BOTTS: broadband optimized time-temperature superposition for vastly accelerated viscoelastic data acquisition.

Modern materials design strategies take advantage of the increasing amount of materials property data available and increasingly complex algorithms to take advantage of those data. However, viscoelastic materials resist this trend towards increased data rates due to their inherent time-dependent properties. Therefore, viscoelasticity measurements present a roadblock for data collection in an important aspect of material design.

The Unkempt RNA binding protein reveals a local translation program in centriole overduplication.

Excess centrosomes cause defects in mitosis, cell-signaling, and cell migration, and therefore their assembly is tightly regulated. Plk4 controls centriole duplication at the heart of centrosome assembly, and elevation of Plk4 promotes centrosome amplification (CA), a founding event of tumorigenesis. Here, we investigate the transcriptional consequences of elevated Plk4 and find Unkempt, a gene encoding an RNA binding protein with roles in translational regulation, to be one of only two upregulated mRNAs.

Development and Evaluation of Conformal Prediction Methods for Quantitative Structure-Activity Relationship.

The quantitative structure-activity relationship (QSAR) regression model is a commonly used technique for predicting the biological activities of compounds using their molecular descriptors. Besides accurate activity estimation, obtaining a prediction uncertainty metric like a prediction interval is highly desirable. Quantifying prediction uncertainty is an active research area in statistical and machine learning (ML), but the implementation for QSAR remains challenging.

Fractional CO2 Laser for Burn Scars: A Comparison of Patient-Reported Outcomes Between Those With and Without Laser Treatment.

Burn reconstruction outcomes are an area of growing investigation. Although there is evidence of measured physical improvements in scar characteristics after laser treatment, there is little information on patient-reported outcomes. The purpose of this study is to compare patient-reported outcomes between burn survivors with and without laser treatment.

deficiency modulates the stromal environment in the pretumorigenic rat mammary gland.

Background: Neurofibromin, coded by the tumor suppressor gene, is the main negative regulator of the RAS pathway and is frequently mutated in various cancers. Women with Neurofibromatosis Type I (NF1)-a tumor predisposition syndrome caused by a germline mutation-have an increased risk of developing aggressive breast cancer with poorer prognosis. The mechanism by which mutations lead to breast cancer tumorigenesis is not well understood.

Critical Care of the Pediatric Burn Patient.

Life-saving pediatric burn care is often initiated in hospitals that are not designated as a pediatric burn center. Therefore, familiarity with critical care of pediatric burn patients is crucial for physicians working in all healthcare settings equipped to care for children. Management of airway, mechanical ventilation, preservation of ideal circulatory status, and establishment of vascular access in pediatric burn patients requires many unique considerations.

Accuracy and resolution of conventional and additively manufactured silicone elastomers as applied in maxillofacial therapies.

Statement Of Problem: Silicone elastomers are becoming more readily available for additive manufacturing, which may be advantageous for fabricating maxillofacial prostheses. However, the properties of three-dimensionally (3D) printed silicone as compared with conventionally processed silicone have not been well studied.

Purpose: The purpose of this in vitro study was to compare the dimensional accuracy and surface resolution of additively manufactured with conventional room-temperature vulcanized (RTV) silicones.

Association Between MR Elastography Liver Stiffness and Histologic Liver Fibrosis in Children and Young Adults With Autoimmune Liver Disease.

Liver fibrosis is an important clinical endpoint of the progression of autoimmune liver disease (AILD); its monitoring would benefit from noninvasive imaging tools. The purpose of this study was to assess the relationship between MR elastography (MRE) liver stiffness measurements and histologic liver fibrosis, as well as to evaluate the performance of MRE and biochemical-based clinical markers for stratifying histologic liver fibrosis severity, in children and young adults with AILD. This retrospective study used an existing institutional registry of children and young adults diagnosed with AILD (primary sclerosing cholangitis [PSC], autoimmune sclerosing cholangitis [ASC], or autoimmune hepatitis [AIH]).

A specific and portable gene expression program underlies antigen archiving by lymphatic endothelial cells.

Antigens from protein subunit vaccination traffic from the tissue to the draining lymph node, either passively via the lymph or carried by dendritic cells at the local injection site. Lymph node (LN) lymphatic endothelial cells (LEC) actively acquire and archive foreign antigens, and archived antigen can be released during subsequent inflammatory stimulus to improve immune responses. Here, we answer questions about how LECs achieve durable antigen archiving and whether there are transcriptional signatures associated with LECs containing high levels of antigen.

p53 modulates kinase inhibitor resistance and lineage plasticity in NF1-related MPNSTs.

Malignant peripheral nerve sheath tumors (MPNSTs) are chemotherapy resistant sarcomas that are a leading cause of death in neurofibromatosis type 1 (NF1). Although NF1-related MPNSTs derive from neural crest cell origin, they also exhibit intratumoral heterogeneity. TP53 mutations are associated with significantly decreased survival in MPNSTs, however the mechanisms underlying TP53-mediated therapy responses are unclear in the context of NF1-deficiency.

Multiple Myeloma Derived Extracellular Vesicle Uptake by Monocyte Cells Stimulates IL-6 and MMP-9 Secretion and Promotes Cancer Cell Migration and Proliferation.

Multiple Myeloma (MM) is an incurable haematological malignancy caused by uncontrolled growth of plasma cells. MM pathogenesis is attributed to crosstalk between plasma cells and the bone marrow microenvironment, where extracellular vesicles (EVs) play a role. In this study, EVs secreted from a panel of MM cell lines were isolated from conditioned media by ultracentrifugation and fluorescently stained EVs were co-cultured with THP-1 monocyte cells.

The predictive role of symptoms in COVID-19 diagnostic models: A longitudinal insight.

To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain.

Chikungunya virus infection disrupts lymph node lymphatic endothelial cell composition and function via MARCO.

Infection with chikungunya virus (CHIKV) causes disruption of draining lymph node (dLN) organization, including paracortical relocalization of B cells, loss of the B cell-T cell border, and lymphocyte depletion that is associated with infiltration of the LN with inflammatory myeloid cells. Here, we found that, during the first 24 hours of infection, CHIKV RNA accumulated in MARCO-expressing lymphatic endothelial cells (LECs) in both the floor and medullary LN sinuses. The accumulation of viral RNA in the LN was associated with a switch to an antiviral and inflammatory gene expression program across LN stromal cells, and this inflammatory response - including recruitment of myeloid cells to the LN - was accelerated by CHIKV-MARCO interactions.