Effect of Hypoxia on Siglec-7 and Siglec-9 Receptors and Sialoglycan Ligands and Impact of Their Targeting on NK Cell Cytotoxicity.

Background/objectives: Tumor microenvironmental hypoxia is an established hallmark of solid tumors. It significantly contributes to tumor aggressiveness and therapy resistance and has been reported to affect the balance of activating/inhibitory surface receptors' expression and activity on NK cells. In the current study, we investigated the impact of hypoxia on the surface expression of Siglec-7 and Siglec-9 (Sig-7/9) and their ligands in NK cells and tumor target cells.

The visual experience dataset: Over 200 recorded hours of integrated eye movement, odometry, and egocentric video.

We introduce the Visual Experience Dataset (VEDB), a compilation of more than 240 hours of egocentric video combined with gaze- and head-tracking data that offer an unprecedented view of the visual world as experienced by human observers. The dataset consists of 717 sessions, recorded by 56 observers ranging from 7 to 46 years of age. This article outlines the data collection, processing, and labeling protocols undertaken to ensure a representative sample and discusses the potential sources of error or bias within the dataset.

Development of CD33-Targeted Dual Drug-Loaded Nanoparticles for the Treatment of Pediatric Acute Myeloid Leukemia.

Paediatric acute myeloid leukemia (AML) is a heterogeneous hematological malignancy still heavily reliant on traditional chemotherapeutic approaches. Combination treatments have shown to be a superior approach, but their success is often hindered by side effects and different drugs' pharmacokinetics. Here, we investigated ABT-737 and Purvalanol A as a potential drug pairing for pediatric AML and described the development of CD33-targeted polymeric nanoparticles (NPs) to enable their simultaneous targeted codelivery.

Acute presentation of abusive head trauma.

Child abuse is a major cause of morbidity and mortality in the United States. The leading cause of child physical abuse related deaths is abusive head trauma, formerly known as shaken baby syndrome, making the rapid identification and assessment of these children critical. The clinical presentation of cases of abusive head trauma ranges from neurological complaints, such as seizures, to vague or subtle symptoms, such as vomiting.

Comprehensive Ocular and Systemic Safety Evaluation of Polysialic Acid-Decorated Immune Modulating Therapeutic Nanoparticles (PolySia-NPs) to Support Entry into First-in-Human Clinical Trials.

An inflammation-resolving polysialic acid-decorated PLGA nanoparticle (PolySia-NP) has been developed to treat geographic atrophy/age-related macular degeneration and other conditions caused by macrophage and complement over-activation. While PolySia-NPs have demonstrated pre-clinical efficacy, this study evaluated its systemic and intraocular safety. PolySia-NPs were evaluated in vitro for mutagenic activity using strains and , with and without metabolic activation; cytotoxicity was evaluated based on its interference with normal mitosis.

Nanoencapsulation of MDM2 Inhibitor RG7388 and Class-I HDAC Inhibitor Entinostat Enhances their Therapeutic Potential Through Synergistic Antitumor Effects and Reduction of Systemic Toxicity.

Inhibitors of the p53-MDM2 interaction such as RG7388 have been developed to exploit latent tumor suppressive properties in p53 in 50% of tumors in which p53 is wild-type. However, these agents for the most part activate cell cycle arrest rather than death, and high doses in patients elicit on-target dose-limiting neutropenia. Recent work from our group indicates that combination of p53-MDM2 inhibitors with the class-I HDAC inhibitor Entinostat (which itself has dose-limiting toxicity issues) has the potential to significantly augment cell death in p53 wild-type colorectal cancer cells.

Analysis of SARS-CoV-2 antibody seroprevalence in Northern Ireland during 2020-2021.

Background: With the spread of SARS-CoV-2 impacting upon public health directly and socioeconomically, further information was required to inform policy decisions designed to limit virus spread during the pandemic. This study sought to contribute to serosurveillance work within Northern Ireland to track SARS-CoV-2 progression and guide health strategy.

Methods: Sera/plasma samples from clinical biochemistry laboratories were analysed for anti-SARS-CoV-2 antibodies.

Dual-Hit Strategy for Therapeutic Targeting of Pancreatic Cancer in Patient-Derived Xenograft Tumors.

Purpose: Paracrine activation of pro-fibrotic hedgehog (HH) signaling in pancreatic ductal adenocarcinoma (PDAC) results in stromal amplification that compromises tumor drug delivery, efficacy, and patient survival. Interdiction of HH-mediated tumor-stroma crosstalk with smoothened (SMO) inhibitors (SHHi) "primes" PDAC patient-derived xenograft (PDX) tumors for increased drug delivery by transiently increasing vascular patency/permeability, and thereby macromolecule delivery. However, patient tumor isolates vary in their responsiveness, and responders show co-induction of epithelial-mesenchymal transition (EMT).

The role of texture summary statistics in material recognition from drawings and photographs.

Material depictions in artwork are useful tools for revealing image features that support material categorization. For example, artistic recipes for drawing specific materials make explicit the critical information leading to recognizable material properties (Di Cicco, Wjintjes, & Pont, 2020) and investigating the recognizability of material renderings as a function of their visual features supports conclusions about the vocabulary of material perception. Here, we examined how the recognition of materials from photographs and drawings was affected by the application of the Portilla-Simoncelli texture synthesis model.

PolySialic acid-nanoparticles inhibit macrophage mediated inflammation through Siglec agonism: a potential treatment for age related macular degeneration.

Age-related macular degeneration (AMD) is a chronic, progressive retinal disease characterized by an inflammatory response mediated by activated macrophages and microglia infiltrating the inner layer of the retina. In this study, we demonstrate that inhibition of macrophages through Siglec binding in the AMD eye can generate therapeutically useful effects. We show that Siglecs-7, -9 and -11 are upregulated in AMD associated M0 and M1 macrophages, and that these can be selectively targeted using polysialic acid (PolySia)-nanoparticles (NPs) to control dampen AMD-associated inflammation.

Spatial Scene Memories Are Biased Towards a Fixed Amount of Semantic Information.

Scene memory has known spatial biases. Boundary extension is a well-known bias whereby observers remember visual information beyond an image's boundaries. While recent studies demonstrate that boundary contraction also reliably occurs based on intrinsic image properties, the specific properties that drive the effect are unknown.

Impact of the COVID-19 pandemic on early intervention utilization and need for referral after NICU discharge in VLBW infants.

Objective: To examine the impact of COVID-19 pandemic on early intervention (EI) services in VLBW infants.

Study Design: 208 VLBW infants seen in NICU follow-up (FU) pre-COVID-19 were compared to 132 infants seen during COVID-19 at 4, 8 and 20 months corrected age (CA) in terms of enrollment in Child and Family Connections (CFC; intake agency for EI), EI therapies, need for CFC referral and Bayley scores.

Results: Infants seen during COVID-19 at 4, 8 and 20 months CA were 3.

Recognizing Nonaccidental Trauma in a Pediatric Tertiary Hospital: A Quality Improvement Imperative.

Unlabelled: Abusive injuries can go unrecognized or improperly managed by medical providers. This study sought to standardize the nonaccidental trauma (NAT) workup and improve NAT evaluation completion for children <7 months with concerning injuries in the pediatric emergency department (PED) and inpatient settings at an urban, tertiary care children's hospital.

Methods: The quality improvement (QI) team created hospital guidelines for suspected NAT, including age-based recommendations (care bundle).

Modular Chemical Construction of IgG-like Mono- and Bispecific Synthetic Antibodies (SynAbs).

In recent years there has been rising interest in the field of protein-protein conjugation, especially related to bispecific antibodies (bsAbs) and their therapeutic applications. These constructs contain two paratopes capable of binding two distinct epitopes on target molecules and are thus able to perform complex biological functions (mechanisms of action) not available to monospecific mAbs. Traditionally these bsAbs have been constructed through protein engineering, but recently chemical methods for their construction have started to (re)emerge.

Preemie study protocol: a randomised controlled factorial trial testing web-based parent training and coaching with parents of children born very preterm.

Introduction: Children born very preterm (VPT; gestational age <32 weeks) are twice as likely to demonstrate behaviour problems such as aggression, non-compliance, temper tantrums and irritability compared with their term-born peers. While behavioural parent training (BPT), also referred to as behaviour therapy is a gold standard for prevention and treatment of childhood problem behaviours, there are limited accessible and effective BPT interventions for families with children born VPT. The purpose of this paper is to describe a multicentre, randomised controlled protocol for a factorial design trial evaluating the independent and combined effects of the Parent BPT intervention plus brief, weekly coaching calls on parent and child outcomes for families with toddlers born VPT.

Association of Economic Recession and Social Distancing With Pediatric Non-accidental Trauma During COVID-19.

Introduction: There has been concern that the incidence of non-accidental trauma (NAT) cases in children would rise during the COVID-19 pandemic due to the combination of social isolation and economic depression. Our goal was to evaluate NAT incidence and severity during the pandemic across multiple US cities.

Methods: Multi-institutional, retrospective cohort study comparing NAT rates in children <18 y old during the COVID-19 pandemic (March-August 2020) with a recent historical data (January 2015-February 2020) and during a previous economic recession (January 2007-December 2011) at level 1 Pediatric Trauma Centers.

The relationship between emergency medical services use and social service needs in a pediatric emergency department population.

Background: Emergency Medical Services (EMS) use for children is correlated with areas of resource deprivation as well as child maltreatment. Households using EMS may have more social needs and be willing to accept services.

Objective: To compare social service needs and willingness to accept services in families arriving to a pediatric emergency department (ED) via EMS vs non-EMS, before and during COVID-19.

Nanomedicine in Pancreatic Cancer: Current Status and Future Opportunities for Overcoming Therapy Resistance.

The development of drug resistance remains one of the greatest clinical oncology challenges that can radically dampen the prospect of achieving complete and durable tumour control. Efforts to mitigate drug resistance are therefore of utmost importance, and nanotechnology is rapidly emerging for its potential to overcome such issues. Studies have showcased the ability of nanomedicines to bypass drug efflux pumps, counteract immune suppression, serve as radioenhancers, correct metabolic disturbances and elicit numerous other effects that collectively alleviate various mechanisms of tumour resistance.

Dynamic Electrode-to-Image (DETI) mapping reveals the human brain's spatiotemporal code of visual information.

A number of neuroimaging techniques have been employed to understand how visual information is transformed along the visual pathway. Although each technique has spatial and temporal limitations, they can each provide important insights into the visual code. While the BOLD signal of fMRI can be quite informative, the visual code is not static and this can be obscured by fMRI's poor temporal resolution.

Enhanced target-specific delivery of docetaxel-loaded nanoparticles using engineered T cell receptors.

For effective targeted therapy of cancer with chemotherapy-loaded nanoparticles (NPs), antigens that are selective for cancer cells should be targeted to minimise off-tumour toxicity. Human leukocyte antigens (HLAs) are attractive cancer targets as they can present peptides from tumour-selective proteins on the cell surface, which can be recognised by T cells T cell receptors (TCRs). In this study, docetaxel-loaded polymeric NPs were conjugated to recombinant affinity-enhanced TCRs to target breast cancer cells presenting a tumour-selective peptide-HLA complex.

Neurodevelopmental Outcome in Very Low Birth Weight Infants Exposed to Donor Milk.

Objective: This study was aimed to evaluate the impact of donor milk (DM) received in the first 28 days of life (DOL) on neurodevelopmental (ND) outcome at 20-months corrected age (CA) in very low birth weight (VLBW) infants.

Study Design: A total of 84 infants born in 2011 to 2012 who received only mother's own milk (MOM) and/or preterm formula (PF) was compared with 69 infants born in 2013 to 2014 who received MOM and/or DM. Daily enteral intake of MOM, DM, and PF was collected through 28 DOL.