RNA Sequencing and Weighted Gene Co-Expression Network Analysis Highlight DNA Replication and Key Genes in Nucleolin-Depleted Hepatoblastoma Cells.

Background/objectives: Nucleolin is a major component of the nucleolus and is involved in various aspects of ribosome biogenesis. However, it is also implicated in non-nucleolar functions such as cell cycle regulation and proliferation, linking it to various pathologic processes. The aim of this study was to use differential gene expression analysis and Weighted Gene Co-expression Network analysis (WGCNA) to identify nucleolin-related regulatory pathways and possible key genes as novel therapeutic targets for cancer, viral infections and other diseases.

Optimizing parenting and child outcomes following parent-child interaction therapy - toddler: a randomized controlled trial.

Background: Parent-Child Interaction Therapy-Toddler (PCIT-T) is an attachment-informed intervention model designed to meet the specific developmental needs of toddlers aged 12-24 months presenting with challenging behaviors.

Methods: This study used a randomized controlled design to evaluate outcomes of PCIT-T for children aged 14-24 months with disruptive behaviors. Ninety toddlers with parent-reported disruptive behavior were randomly allocated to PCIT-T (intervention), an active control condition (Circle of Security- Parenting™; COS-P), or a non-treatment control condition (wait-list; WL).

MeCP2 is a naturally supercharged protein with cell membrane transduction capabilities.

The intrinsically disordered protein MeCP2 is a global transcriptional regulator encoded by the MECP2 gene. Although the structured domains of MeCP2 have been the subject of multiple studies, its unstructured regions have not been that extensively characterized. In this work, we show that MeCP2 possesses properties akin to those of supercharged proteins.

Artificial Intelligence (AI) Reveals Ethnic Disparities in Cataract Detection and Treatment.

Introduction: The aim of this work is to identify patients at risk of limited access to healthcare through artificial intelligence using a name-ethnicity classifier (NEC) analyzing the clinical stage of cataract at diagnosis and preoperative visual acuity.

Methods: This retrospective, cross-sectional study includes patients seen in the cataract clinic of a tertiary care hospital between September 2017 and February 2020 with subsequent cataract surgery in at least one eye. We analyzed 4971 patients and 8542 eyes undergoing surgery.

Three-year clinical outcome of XEN45 Gel Stent implantation versus trabeculectomy in patients with open angle glaucoma.

Objective: To reliably compare the three-year clinical outcome and safety of XEN45 Gel Stent implantation (XEN) vs. trabeculectomy (TRAB) in patients with glaucoma.

Subject/methods: We conducted a retrospective cohort study with patients with primary open angle or pseudoexfoliation glaucoma with uncontrolled intraocular pressure (IOP) undergoing XEN or TRAB at the Innsbruck University Clinic of Ophthalmology and Optometry, Austria and analysed changes in IOP, numbers of IOP-lowering medications, and complete surgical success (i.

IL-23 stabilizes an effector T cell program in the tumor microenvironment.

Interleukin-23 (IL-23) is a proinflammatory cytokine mainly produced by myeloid cells that promotes tumor growth in various preclinical cancer models and correlates with adverse outcomes. However, as to how IL-23 fuels tumor growth is unclear. Here, we found tumor-associated macrophages to be the main source of IL-23 in mouse and human tumor microenvironments.

Expression, Purification, Characterization and Cellular Uptake of MeCP2 Variants.

The transcriptional regulator Methyl-CpG-binding protein 2 (MeCP2) is an intrinsically disordered protein, mutations in which, are implicated in the onset of Rett Syndrome, a severe and debilitating neurodevelopmental disorder. Delivery of this protein fused to the cell-penetrating peptide TAT could allow for the intracellular replenishment of functional MeCP2 and hence potentially serve as a prospective Rett Syndrome therapy. This work outlines the expression, purification and characterization of various TAT-MeCP2 constructs as well as their full-length and shortened eGFP fusion variants.

TAT-MeCP2 protein variants rescue disease phenotypes in human and mouse models of Rett syndrome.

Rett syndrome (RTT) is a neurodevelopmental disorder caused by pathogenic variants leading to functional impairment of the MeCP2 protein. Here, we used purified recombinant MeCP2e1 and MeCP2e2 protein variants fused to a TAT protein transduction domain (PTD) to evaluate their transduction ability into RTT patient-derived fibroblasts and the ability to carry out their cellular function. We then assessed their transduction ability and therapeutic effects in a RTT mouse model.

Effects of Intravitreal Aflibercept on the Systemic Insulin-like Growth Factor-I and Vascular Endothelial Growth Factor-A in Patients with Diabetic Retinopathy and Age-Related Macular Degeneration.

Purpose: To analyze the effect of intravitreal aflibercept injections on systemic levels of insulin-like growth factor-1 and vascular endothelial growth factor-A in patients with diabetic retinopathy and age-related macular degeneration.

Methods: Vascular endothelial growth factor-A and insulin-like growth factor-1 levels were determined before and one week and four weeks after intravitreal injection of aflibercept (2.0 mg/50 l) for 19 patients with age-related macular degeneration (mean age, 76 ± 11 years) and 18 patients with diabetic retinopathy (mean age, 64 ± 14 years).

Efficiency benchmarks in the surgical management of primary rhegmatogenous retinal detachment: a monocentric register cohort study of operating room time metrics and influential factors.

Objectives: To investigate the effect of clinical, methodological and logistic factors on operating room (OR) efficiency in the surgical management of primary rhegmatogenous retinal detachment (RRD).

Design: Monocentric retrospective register cohort study.

Setting: Single tertiary centre in the western region of Austria.

Addressing the Evidence Gap: Protocol for an Effectiveness Study of Circle of Security Parenting, an Attachment-Based Intervention.

Parenting interventions informed by attachment theory are an increasingly popular choice for clinical services that work with parents of babies and young children. Circle of Security Parenting (COS-P) is one such intervention, which has had extraordinary uptake internationally. Evidence for COS-P is very limited, however; there are few published studies, most with very small samples, and findings are mixed.

CHANGES IN SYSTEMIC LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR AFTER INTRAVITREAL INJECTION OF AFLIBERCEPT OR BROLUCIZUMAB FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

Purpose: To analyze and compare the effects of intravitreal brolucizumab versus aflibercept on systemic vascular endothelial growth factor (VEGF)-A levels in patients with neovascular age-related macular degeneration.

Methods: In this prospective interventional case series study, brolucizumab (6.0 mg/50 µL) or aflibercept (2.

Distinct roles for dopamine clearance mechanisms in regulating behavioral flexibility.

Dopamine plays a crucial role in adaptive behavior, and dysfunctional dopamine is implicated in multiple psychiatric conditions characterized by inflexible or inconsistent choices. However, the precise relationship between dopamine and flexible decision making remains unclear. One reason is that, while many studies have focused on the activity of dopamine neurons, efficient dopamine signaling also relies on clearance mechanisms, notably the dopamine transporter (DAT), which predominates in striatum, and catechol-O-methyltransferase (COMT), which predominates in cortex.

The impact of compliance among patients with diabetic macular oedema treated with intravitreal aflibercept: a 48-month follow-up study.

Purpose: This study aimed to compare anatomical and functional outcomes between patients with non-proliferative diabetic retinopathy (NPDR) with diabetic macular oedema (DME) who adhered to intravitreal aflibercept therapy and patients lost to follow-up (LTFU).

Methods: We enrolled 200 patients and recorded the interval between each procedure and the subsequent follow-up visit. Moreover, visual acuity (VA) and anatomical outcomes were measured at each follow-up examination.

Parent and practitioner perspectives on Circle of Security Parenting (COS-P): A qualitative study.

Circle of Security Parenting (COS-P) is an attachment-theory-informed program for parents of infants and young children. Designed for scalability, COS-P has been widely adopted internationally. Evidence for the program's effectiveness is limited, however, restricting capacity to make informed decisions about program allocation, and threatening ongoing program funding.

Porous assembly of an antifungal protein mediated by zinc and sulfonato-calix[8]arene.

Controlled protein assembly holds great potential in the fabrication of biohybrid materials. However, the structural diversity and complexity of proteins present an obstacle to controlled assembly. Supramolecular chemistry is a possible solution as it offers tools to mediate self-assembly with molecular precision.

A randomized controlled trial comparing parent child interaction therapy - toddler, circle of security- parenting™ and waitlist controls in the treatment of disruptive behaviors for children aged 14-24 months: study protocol.

Background: It is common for toddlers to display disruptive behaviors (e.g., tantrums, aggression, irritability) but when these become severe and persistent they can be the start of a trajectory towards poor outcomes in childhood and adolescence.

Postintervention and follow-up changes in caregiving behavior and representations after individually or group delivered hybrid Circle of Security-intensive intervention with New Zealand caregiver-child dyads.

The Circle of Security Intensive intervention (COS-I) aims to improve child attachment security and reduce disorganisation by improving caregiver capacities, including caregiving behavior and representations. Research on COS-I effectiveness with these goals is limited and none examines if positive changes are sustained. A recently revised hybrid COS-I protocol (COS-I-RH) incorporates Circle of Security-Parenting (COS-P) material and individual or group delivery options.

An Electrochemiluminescence-Based Assay for MeCP2 Protein Variants.

The ECLIA is a versatile method which is able to quantify endogenous and recombinant protein amounts in a 96-well format. To demonstrate ECLIA efficiency, this assay was used to analyze intrinsic levels of MeCP2 in mouse brain tissue and the uptake of TAT-MeCP2 in human dermal fibroblasts. The MeCP2-ECLIA produces highly accurate and reproducible measurements with low intra- and inter-assay error.

Development of an Improved Peroxidase-Based High-Throughput Screening for the Optimization of D-Glycerate Dehydratase Activity.

Successful directed evolution examples span a broad range of improved enzyme properties. Nevertheless, the most challenging step for each single directed evolution approach is an efficient identification of improved variants from a large genetic library. Thus, the development and choice of a proper high-throughput screening is a central key for the optimization of enzymes.

Nutrient Excess Triggers the Expression of the Antifungal Protein PAFB.

Nutrient limitation and nonfavorable growth conditions have been suggested to be major triggers for the expression of small, cysteine-rich antimicrobial proteins (AMPs) of fungal origin, e.g., the antifungal protein (PAF), the antifungal protein (AFP), the antifungal protein (AnAFP).