Versatile tissue-injectable hydrogels capable of the extended hydrolytic release of bioactive protein therapeutics.

Hydrogels are extensively employed in healthcare due to their adaptable structures, high water content, and biocompatibility, with FDA-approved applications ranging from spinal cord regeneration to local therapeutic delivery. However, clinical hydrogels encounter challenges related to inconsistent therapeutic exposure, unmodifiable release windows, and difficulties in subsurface polymer insertion. Addressing these issues, we engineered injectable, biocompatible hydrogels as a local therapeutic depot, utilizing poly(ethylene glycol) (PEG)-based hydrogels functionalized with bioorthogonal SPAAC handles for network polymerization and functionalization.

Effect of incubation conditions of cellulase hydrolysis on mechanical pulp fibre morphology.

The mechanical pulp industry is diversifying through the manufacture of high-value paper products, such as microfibrillated cellulose. However, the development of fibre quality is still energy-intensive. Enzymatic hydrolysis is hypothesized to promote fibre cutting, greater fibrillation, and reduce refining energy costs.

Impact of chlorpyrifos exposure on lung function in Egyptian adolescent agriculture workers.

Chlorpyrifos (CPF) is a widely used organophosphate insecticide that has been linked to detrimental health effects that range from neurological impacts to respiratory disease. The objective of this study was to assess respiratory symptoms associated with CPF exposure throughout the application season. Urine samples were collected from Egyptian adolescent applicators ( = 206) and non-applicators ( = 72) to assess 3,5,6-trichloro-2-pyridinol (TCPy), a biomarker for CPF exposure, along with spirometry measures to determine lung ventilatory function.

A gH/gL-encoding replicon vaccine elicits neutralizing antibodies that protect humanized mice against EBV challenge.

Epstein-Barr virus (EBV) is associated with several malignancies, neurodegenerative disorders and is the causative agent of infectious mononucleosis. A vaccine that prevents EBV-driven morbidity and mortality remains an unmet need. EBV is orally transmitted, infecting both B cells and epithelial cells.

activity is required to prevent mitotic arrest, spindle assembly checkpoint activation and lethality in glioblastoma and other cancers.

Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. To identify genes differentially required for the viability of GBM stem-like cells (GSCs), we performed functional genomic lethality screens comparing GSCs and control human neural stem cells. Among top-scoring hits in a subset of GBM cells was the F-box-containing gene , which was also predicted to be essential in ∼15% of cell lines derived from a broad range of cancers.

Sensitive bispecific chimeric T cell receptors for cancer therapy.

The expression of a synthetic chimeric antigen receptor (CAR) to redirect antigen specificity of T cells is transforming the treatment of hematological malignancies and autoimmune diseases [1-7]. In cancer, durable efficacy is frequently limited by the escape of tumors that express low levels or lack the target antigen [8-12]. These clinical results emphasize the need for immune receptors that combine high sensitivity and multispecificity to improve outcomes.

Polycyclic aromatic hydrocarbons in silicone wristbands of Uruguayan children: measurement and exposure source exploration.

Polycyclic aromatic hydrocarbons (PAHs) pose health risks to children, potentially resulting in stunted growth, obesity, and cognitive deficits, but lack of reliable and noninvasive means to measure PAHs results in poor understanding of exposure patterns and sources in this vulnerable population. In this study, 24 children aged ∼7 years (9 boys and 15 girls) from Montevideo, Uruguay wore silicone wristbands for 8 days to monitor the exposure of 27 PAHs. Wristbands were extracted using a modified ethyl acetate tandem solid phase extraction clean up and then analyzed gas chromatography with tandem mass spectrometry.

CYpHER: Catalytic extracellular targeted protein degradation with high potency and durable effect.

Many disease-causing proteins have multiple pathogenic mechanisms, and conventional inhibitors struggle to reliably disrupt more than one. Targeted protein degradation (TPD) can eliminate the protein, and thus all its functions, by directing a cell's protein turnover machinery towards it. Two established strategies either engage catalytic E3 ligases or drive uptake towards the endolysosomal pathway.

N-cadherin dynamically regulates pediatric glioma cell migration in complex environments.

Pediatric high-grade gliomas are highly invasive and essentially incurable. Glioma cells migrate between neurons and glia, along axon tracts, and through extracellular matrix surrounding blood vessels and underlying the pia. Mechanisms that allow adaptation to such complex environments are poorly understood.

Temperature stability of urinary F-isoprostane and 8-hydroxy-2-deoxyguanosine.

Background: Clinical and epidemiological studies employ long-term temperature storage but the effect of temperature on the stability of oxidative stress (OS) markers is unknown. We investigated the effects of storage at -20 °C and -80 °C over 4-9 months on F-isoprostanes (F-IsoP) and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in urine of children, a population group among whom the measurement of these markers is still limited.

Methods: Paired spot urine samples from 87 children aged 8.

Signaling via a CD27-TRAF2-SHP-1 axis during naive T cell activation promotes memory-associated gene regulatory networks.

The interaction of the tumor necrosis factor receptor (TNFR) family member CD27 on naive CD8 T (Tn) cells with homotrimeric CD70 on antigen-presenting cells (APCs) is necessary for T cell memory fate determination. Here, we examined CD27 signaling during Tn cell activation and differentiation. In conjunction with T cell receptor (TCR) stimulation, ligation of CD27 by a synthetic trimeric CD70 ligand triggered CD27 internalization and degradation, suggesting active regulation of this signaling axis.

Systemically administered low-affinity HER2 CAR T cells mediate antitumor efficacy without toxicity.

Background: The paucity of tumor-specific targets for chimeric antigen receptor (CAR) T-cell therapy of solid tumors necessitates careful preclinical evaluation of the therapeutic window for candidate antigens. Human epidermal growth factor receptor 2 (HER2) is an attractive candidate for CAR T-cell therapy in humans but has the potential for eliciting on-target off-tumor toxicity. We developed an immunocompetent tumor model of CAR T-cell therapy targeting murine HER2 (mHER2) and examined the effect of CAR affinity, T-cell dose, and lymphodepletion on safety and efficacy.

N-cadherin dynamically regulates pediatric glioma cell migration in complex environments.

Pediatric high-grade gliomas are highly invasive and essentially incurable. Glioma cells migrate between neurons and glia, along axon tracts, and through extracellular matrix surrounding blood vessels and underlying the pia. Mechanisms that allow adaptation to such complex environments are poorly understood.

Dietary Predictors of Urinary Biomarkers of Pyrethroids in the General Population - A Scoping Review.

Background: Pyrethroid pesticides are ubiquitous environmental contaminants, contributing to chronic and potentially harmful exposure among the general population. Although studies have measured pesticide residues on agricultural products, the link between food intake and concentrations of pyrethroid biomarkers in urine remains unclear.

Objective: This scoping review aims to analyze peer-reviewed publications investigating dietary predictors of pyrethroid exposure through urinary biomarkers.

Preclinical pediatric brain tumor models for immunotherapy: Hurdles and a way forward.

Brain tumors are the most common solid tumor in children and the leading cause of cancer-related deaths. Over the last few years, improvements have been made in the diagnosis and treatment of children with Central Nervous System tumors. Unfortunately, for many patients with high-grade tumors, the overall prognosis remains poor.

Versatile Tissue-Injectable Hydrogels with Extended Hydrolytic Release of Bioactive Protein Therapeutics.

Hydrogels generally have broad utilization in healthcare due to their tunable structures, high water content, and inherent biocompatibility. FDA-approved applications of hydrogels include spinal cord regeneration, skin fillers, and local therapeutic delivery. Drawbacks exist in the clinical hydrogel space, largely pertaining to inconsistent therapeutic exposure, short-lived release windows, and difficulties inserting the polymer into tissue.

Designing an Alternative, Community Integrated Model of Residential Aged Care for People Living with Dementia: Nominal Group Technique and Thematic Analysis.

Background: Small-scale models of dementia care are a potential solution to deinstitutionalize residential aged care and have been associated with improved resident outcomes, including quality of life and reduced hospitalizations for people living with dementia.

Objective: This study aimed to generate strategies and ideas on how homes for people living with dementia in a village setting within a suburban community, could be designed and function without external boundaries. In particular, how could residents of the village and members of the surrounding community access and engage safely and equitably so that interpersonal connections might be fostered?

Methods: Twenty-one participants provided an idea for discussion at three Nominal Group Technique workshops, including people living with dementia, carers or former carers, academics, researchers, and clinicians.

Using Drugs or Non-Drugs Alternatives to Alter Mental States in the Online, Virtual Era.

: In the 1970s a body of literature was generated advocating the alternatives approach for drug misuse prevention and rehabilitation which encouraged healthy nonchemical behaviors leading to reinforcing moods. Although this behaviorally oriented approach was overshadowed with the popularity of cognitive therapy in the 1980s, many of the recommended alternative behaviors remain embedded in cognitive approaches for drug misuse prevention and rehabilitation. One objective of the present study was to replicate, in part, two studies conducted in the 1970s which examined usage patterns of non-drug alternatives.

Pyrethroid and Chlorpyrifos Pesticide Exposure, General Intellectual Abilities, and Executive Functions of School Children from Montevideo, Uruguay.

Children's developing brains are susceptible to pesticides. Less is known about the effect of exposure to chlorpyrifos and pyrethroids on executive functions (EF). We measured urinary 3,5,6-trichloro-2-pyridinol (TCPy), a metabolite of chlorpyrifos, and urinary 3-phenoxybenzoic acid (3-PBA), a general, nonspecific metabolite of pyrethroids in first-grade children from Montevideo, Uruguay ( = 241, age 80.

Reducing the complexity of high-dimensional environmental data: An analytical framework using LASSO with considerations of confounding for statistical inference.

Purpose: Frameworks for selecting exposures in high-dimensional environmental datasets, while considering confounding, are lacking. We present a two-step approach for exposure selection with subsequent confounder adjustment for statistical inference.

Methods: We measured cognitive ability in 338 children using the Woodcock-Muñoz General Intellectual Ability (GIA) score, and potential associated features across several environmental domains.

Functional genomic analysis of adult and pediatric brain tumor isolates.

Background: Adult and pediatric tumors display stark differences in their mutation spectra and chromosome alterations. Here, we attempted to identify common and unique gene dependencies and their associated biomarkers among adult and pediatric tumor isolates using functional genetic lethal screens and computational modeling.

Methods: We performed CRISRP-Cas9 lethality screens in two adult glioblastoma (GBM) tumor isolates and five pediatric brain tumor isolates representing atypical teratoid rhabdoid tumors (ATRT), diffuse intrinsic pontine glioma, GBM, and medulloblastoma.