Impact of care coordination on service utilisation for children with medically complex cerebral palsy.

Aim: Complex care programmes for children with medically complex cerebral palsy (CP) exist; however, evidence for their impact is limited. This study (i) explored the impact of The Royal Children's Hospital Complex Care Hub (CCH) on hospital service utilisation rates over a 3-year period for children with medically complex CP compared with those eligible but received routine care, and (ii) compared health, disability and socio-demographic characteristics of children and their families in both groups.

Methods: Electronic medical record data from 78 children (mean age 9.

Decoding the inflammatory signature of the major depressive episode: insights from peripheral immunophenotyping in active and remitted condition, a case-control study.

Depression is a prevalent and incapacitating condition with a significant impact on global morbidity and mortality. Although the immune system's role in its pathogenesis is increasingly recognized, there is a lack of comprehensive understanding regarding the involvement of innate and adaptive immune cells. To address this gap, we conducted a multicenter case-control study involving 121 participants matched for sex and age.

Clinical relevance and therapeutic predictive ability of hypoxia biomarkers in head and neck cancer tumour models.

Tumour hypoxia promotes poor patient outcomes, with particularly strong evidence for head and neck squamous cell carcinoma (HNSCC). To effectively target hypoxia, therapies require selection biomarkers and preclinical models that can accurately model tumour hypoxia. We established 20 patient-derived xenograft (PDX) and cell line-derived xenograft (CDX) models of HNSCC that we characterised for their fidelity to represent clinical HNSCC in gene expression, hypoxia status and proliferation and that were evaluated for their sensitivity to hypoxia-activated prodrugs (HAPs).

The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods.

ChEMBL (https://www.ebi.ac.

School of cheminformatics in Latin America.

We report the major highlights of the School of Cheminformatics in Latin America, Mexico City, November 24-25, 2022. Six lectures, one workshop, and one roundtable with four editors were presented during an online public event with speakers from academia, big pharma, and public research institutions. One thousand one hundred eighty-one students and academics from seventy-nine countries registered for the meeting.

Clonal dynamics limits detection of selection in tumour xenograft CRISPR/Cas9 screens.

Transplantable in vivo CRISPR/Cas9 knockout screens, in which cells are edited in vitro and inoculated into mice to form tumours, allow evaluation of gene function in a cancer model that incorporates the multicellular interactions of the tumour microenvironment. To improve our understanding of the key parameters for success with this method, we investigated the choice of cell line, mouse host, tumour harvesting timepoint and guide RNA (gRNA) library size. We found that high gRNA (80-95%) representation was maintained in a HCT116 subline transduced with the GeCKOv2 whole-genome gRNA library and transplanted into NSG mice when tumours were harvested at early (14 d) but not late time points (38-43 d).

Maternal body condition and season influence RNA deposition in the oocytes of alfalfa leafcutting bees ().

Maternal effects are an important source of phenotypic variance, whereby females influence offspring developmental trajectory beyond direct genetic contributions, often in response to changing environmental conditions. However, relatively little is known about the mechanisms by which maternal experience is translated into molecular signals that shape offspring development. One such signal may be maternal RNA transcripts (mRNAs and miRNAs) deposited into maturing oocytes.

Examination of differential ratings of perceived exertion (dRPE) during bio-banded small-sided games.

The aims of the current study were to investigate the use of dRPE with academy soccer players to: 1) examine the effect of bio-banded and non-bio-banded maturity groups within SSG on players dRPE; 2) describe the multivariate relationships between dRPE measures investigating the sources of intra and inter-individual variation, and the effects of maturation and bio-banding. Using 32 highly trained under (U) 12 to U14 soccer players (mean (SD) age 12.9 (0.

Zika Virus Replication in a Mast Cell Model is Augmented by Dengue Virus Antibody-Dependent Enhancement and Features a Selective Immune Mediator Secretory Profile.

Zika virus and dengue virus are evolutionarily related and structurally similar mosquito-borne . These congruencies can lead to cross-reactive antibody binding, whereby antibodies generated from previous dengue virus immunity can augment Zika virus replication . This phenomenon, termed antibody-dependent enhancement, may participate in the clinical manifestations detected in areas with cocirculations where Zika virus is endemic; however, a causal relationship has yet to be determined.

The effect of bio-banding on technical and tactical indicators of talent identification in academy soccer players.

Aim: The aim of this study was to examine the effect of bio-banding on technical and tactical markers of talent identification in 11- to 14-year-old academy soccer players.

Methods: Using a repeated measures design, 92 players were bio-banded using percentage of estimated adult stature attainment (week 1), maturity-offset (week 2) and a mixed-maturity method (week 3). All players contested five maturity (mis)matched small-sided games with technical and tactical variables measured.

The effect of bio-banding on physical and psychological indicators of talent identification in academy soccer players.

The aim of this study was to examine the effect of bio-banding on indicators of talent identification in academy soccer players. Seventy-two 11 to 14-year-old soccer players were bio-banded using percentage of estimated adult stature attainment (week 1), maturity-offset (week 2) or a mixed-maturity method (week 3). Players contested five maturity (mis)matched small-sided games with physical and psychological determinants measured.

Circadian rhythms in immunity and host-parasite interactions.

The mammalian immune system adheres to a 24 h circadian schedule, exhibiting daily rhythmic patterns in homeostatic immune processes, such as immune cell trafficking, as well as the inflammatory response to infection. These diurnal rhythms are driven by endogenous molecular clocks within immune cells which are hierarchically coordinated by a light-entrained central clock in the suprachiasmatic nucleus of the hypothalamus and responsive to local rhythmic cues including temperature, hormones and feeding time. Circadian control of immunity may enable animals to anticipate daily pathogenic threat from parasites and gate the magnitude of the immune response, potentially enhancing fitness.

The effect of bio-banding on academy soccer player passing networks: Implications of relative pitch size.

The primary aims of this study were to examine the effects of bio-banding players on passing networks created during 4v4 small-sided games (SSGs), while also examining the interaction of pitch size using passing network analysis compared to a coach-based scoring system of player performance. Using a repeated measures design, 32 players from two English Championship soccer clubs contested mixed maturity and bio-banded SSGs. Each week, a different pitch size was used: Week 1) small (36.

ETS-Related Gene Activation Preserves Adherens Junctions and Permeability in Microvascular Endothelial Cells.

ERG (ETS-related gene) is a member of the ETS (Erythroblast-transformation specific) family of transcription factors abundantly present in vascular endothelial cells. Recent studies demonstrate that ERG has important roles in blood vessel stability and angiogenesis. However, it is unclear how ERG is potentially involved in microvascular barrier functions and permeability.

Protective effects of FK 506 against haemorrhagic shock-induced microvascular hyperpermeability.

Microvascular hyperpermeability, the excessive leakage of fluid and proteins from the intravascular space to the interstitium, is a devastating clinical concern in haemorrhagic shock (HS), sepsis, burn and so forth. Previous studies have shown that HS-induced microvascular hyperpermeability is associated with activation of the mitochondria-mediated 'intrinsic' apoptotic signalling cascade and caspase-3 mediated disruption of the endothelial cell barrier. In this study, our objective was to test if FK506, an immunomodulator that is also known to protect mitochondria, would protect barrier functions and decrease vascular hyperpermeability following HS by acting on this pathway.

Microglial transcriptome analysis in the rNLS8 mouse model of TDP-43 proteinopathy reveals discrete expression profiles associated with neurodegenerative progression and recovery.

The microglial reaction is a hallmark of neurodegenerative conditions, and elements thereof may exert differential effects on disease progression, either worsening or ameliorating severity. In amyotrophic lateral sclerosis (ALS), a syndrome characterized by cytoplasmic aggregation of TDP-43 protein and atrophy of motor neurons in the cortex and spinal cord, the transcriptomic signatures of microglia during disease progression are incompletely understood. Here, we performed longitudinal RNAseq analysis of cortical and spinal cord microglia from rNLS8 mice, in which doxycycline-regulatable expression of human TDP-43 (hTDP-43) in the cytoplasm of neurons recapitulates many features of ALS.

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs.

The safety of marketed drugs is an ongoing concern, with some of the more frequently prescribed medicines resulting in serious or life-threatening adverse effects in some patients. Safety-related information for approved drugs has been curated to include the assignment of toxicity class(es) based on their withdrawn status and/or black box warning information described on medicinal product labels. The ChEMBL resource contains a wide range of bioactivity data types, from early "Discovery" stage preclinical data for individual compounds through to postclinical data on marketed drugs; the inclusion of the curated drug safety data set within this framework can support a wide range of safety-related drug discovery questions.

The prevalence, odds and predictors of lifespan comorbid eating disorder among people with a primary diagnosis of bipolar disorders, and vice-versa: Systematic review and meta-analysis.

Background: There are scarce and discrepant data about the prevalence and correlates of co-occurring eating disorders (EDs) among people with a primary diagnosis of bipolar disorder (BD), and vice-versa, compelling a systematic review and meta-analysis on the matter.

Methods: MEDLINE/PsycINFO databases were systematically searched for original studies documenting BD⇌ED comorbidity across the lifespan, from inception up until April 20, 2020. Random-effects meta-analysis and meta-regression analyses were conducted, accounting for multiple moderators.

Network integration and modelling of dynamic drug responses at multi-omics levels.

Uncovering cellular responses from heterogeneous genomic data is crucial for molecular medicine in particular for drug safety. This can be realized by integrating the molecular activities in networks of interacting proteins. As proof-of-concept we challenge network modeling with time-resolved proteome, transcriptome and methylome measurements in iPSC-derived human 3D cardiac microtissues to elucidate adverse mechanisms of anthracycline cardiotoxicity measured with four different drugs (doxorubicin, epirubicin, idarubicin and daunorubicin).

Genetic variability of Arthurdendyus triangulatus (Dendy, 1894), a non-native invasive land planarian.

Arthurdendyus triangulatus (Dendy, 1894) is a land planarian native to New Zealand which has become established in the United Kingdom and the Faroe Islands during the last 60 years. The species has become prevalent and widely established in Scotland mediated by human activity mostly through the exchange of plants and associated soil. As a predator of earthworms, concerns regarding both the direct impact on earthworm abundance and diversity and the indirect impact on those birds and mammals that have earthworms as a primary dietary component led to A.

Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer.

The HER2-targeted antibody-drug conjugate trastuzumab emtansine (T-DM1) is approved for the treatment of metastatic, HER2-positive breast cancer after prior trastuzumab and taxane therapy, and has also demonstrated efficacy in the adjuvant setting in incomplete responders to neoadjuvant therapy. Despite its objective activity, intrinsic and acquired resistance to T-DM1 remains a major clinical challenge. T-DM1 mediates its activity in a number of ways, encompassing HER2 signalling blockade, Fc-mediated immune response and payload-mediated microtubule poisoning.

Discovery of an Aedes (Stegomyia) albopictus population and first records of Aedes (Stegomyia) aegypti in Canada.

A population of Aedes (Stegomyia) albopictus (Skuse) (Diptera: Culicidae), a vector of chikungunya, dengue, yellow fever, and Zika and West Nile viruses, has been detected in Windsor, Ontario, Canada from 2016 onwards. Here, we describe its seasonal distribution, as well as the various aquatic habitats from which this species was collected and its larval co-habitation. We collected immatures from tires, treeholes, extruded polystyrene foam containers, discarded plastic cups, old recycling bins and oviposition traps.