A phase I clinical trial of intrahepatic artery delivery of TG6002 in combination with oral 5-fluorocytosine in patients with liver-dominant metastatic colorectal cancer.

Background: Effective treatment for patients with metastatic cancer is limited, particularly for colorectal cancer patients with metastatic liver lesions (mCRC), where accessibility to numerous tumours is essential for favourable clinical outcomes. Oncolytic viruses (OVs) selectively replicate in cancer cells; however, direct targeting of inaccessible lesions is limited when using conventional intravenous or intratumoural administration routes.

Methods: We conducted a multi-centre, dose-escalation, phase I study of vaccinia virus, TG6002, via intrahepatic artery (IHA) delivery in combination with the oral pro-drug 5-fluorocytosine to fifteen mCRC patients.

Lifestyle factors and other predictors of common mental disorders in diagnostic machine learning studies: A systematic review.

Background: Machine Learning (ML) models have been used to predict common mental disorders (CMDs) and may provide insights into the key modifiable factors that can identify and predict CMD risk and be targeted through interventions. This systematic review aimed to synthesise evidence from ML studies predicting CMDs, evaluate their performance, and establish the potential benefit of incorporating lifestyle data in ML models alongside biological and/or demographic-environmental factors.

Methods: This systematic review adheres to the PRISMA statement (Prospero CRD42023401194).

Towards predicting PTSD symptom severity using portable EEG-derived biomarkers.

Posttraumatic Stress Disorder (PTSD) is a heterogeneous mental health disorder that occurs following traumatic experience. Understanding its neurobiological basis is crucial to advance early diagnosis and treatment. Electroencephalography (EEG) can be used to explore the neurobiological basis of PTSD.

Models and approaches for building knowledge translation capacity and capability in health services: a scoping review.

Background: Building healthcare service and health professionals' capacity and capability to rapidly translate research evidence into health practice is critical to the effectiveness and sustainability of healthcare systems. This review scoped the literature describing programmes to build knowledge translation capacity and capability in health professionals and healthcare services, and the evidence supporting these.

Methods: This scoping review was undertaken using the Joanna Briggs Institute scoping review methodology.

Quality of life in south-eastern Australia: normative values for the WHOQOL-BREF in a population-based sample of adults.

Objectives: The abbreviated World Health Organisation Quality of Life tool (WHOQOL-BREF) is a short-form quality of life (QoL) assessment commonly used worldwide in both healthy and ill populations. Normative data for the Australian general population are limited. The objective of this study was to present normative data for the WHOQOL-BREF based on a general population sample.

Research translation mentoring for emerging clinician researchers in rural and regional health settings: a qualitative study.

Background: Building clinician and organisation-level research translation capacity and capability is fundamental for increasing the implementation of research into health practice and policy and improving health outcomes. Research translation capacity and capability building is particularly crucial in rural and regional settings to address complex problems impacting these socially and economically disadvantaged communities. Programs to build clinicians' research translation capability typically involve training and mentoring.

Obesity and sarcopenic obesity characterized by low-grade inflammation are associated with increased risk for major depression in women.

Background: We aimed to determine women's risk of major depressive disorder (MDD) in relation to obesity phenotypes characterized by levels of circulating high-sensitivity C-reactive protein (hsCRP).

Methods: This population-based retrospective cohort study comprised 808 women (ages 20-84 y) recruited 1994-1997 and followed for a median 16.1 y (IQR 11.

Intratemporal facial nerve neurofibroma causing facial paralysis in an infant: Case report and review of the literature.

This article describes the first recorded case of intratemporal neurofibroma in an infant. A literature review of all other existing cases of intratemporal neurofibroma is performed, finding that the majority of cases involve multiple segments and can be found in the mastoid segment most often. Most common symptoms described included facial paralysis, otalgia, and conductive hearing loss, respectively.

Light-Seq: light-directed in situ barcoding of biomolecules in fixed cells and tissues for spatially indexed sequencing.

We present Light-Seq, an approach for multiplexed spatial indexing of intact biological samples using light-directed DNA barcoding in fixed cells and tissues followed by ex situ sequencing. Light-Seq combines spatially targeted, rapid photocrosslinking of DNA barcodes onto complementary DNAs in situ with a one-step DNA stitching reaction to create pooled, spatially indexed sequencing libraries. This light-directed barcoding enables in situ selection of multiple cell populations in intact fixed tissue samples for full-transcriptome sequencing based on location, morphology or protein stains, without cellular dissociation.

Phase I trial of sargramostim/pelareorep therapy in pediatric patients with recurrent or refractory high-grade brain tumors.

Background: Brain tumors are the leading cause of cancer death for pediatric patients. Pelareorep, an immunomodulatory oncolytic reovirus, has intravenous efficacy in preclinical glioma models when preconditioned with GM-CSF (sargramostim). We report a phase I trial with the primary goal of evaluating the safety of sargramostim/pelareorep in pediatric patients with recurrent or refractory high-grade brain tumors and a secondary goal of characterizing immunologic responses.

How Well Do Low Population-Specific Values for Muscle Parameters Associate with Indices of Poor Physical Health? Cross-Sectional Data from the Geelong Osteoporosis Study.

We aimed to examine associations between skeletal muscle deficits and indices of poor health. Cut-points for skeletal muscle deficits were derived using data from the Geelong Osteoporosis Study and definitions from the revised European Consensus on Definition and Diagnosis and the Foundation for the National Institutes of Health. Participants ( = 665; 323 women) aged 60-96 year had handgrip strength measured by dynamometry and appendicular lean mass by whole-body dual-energy X-ray absorptiometry.

The Relationship Between Adverse Childhood Experiences and Alzheimer's Disease: A Systematic Review.

Background: Alzheimer's disease is a global health concern, and with no present cure, prevention is critical. Exposure to adverse childhood experiences may increase the risk of developing Alzheimer's disease. This systematic review was conducted to synthesize the evidence on the associations between adverse childhood experiences (<18 years) and the risk of Alzheimer's disease in adulthood.

Research education and training for nurses and allied health professionals: a systematic scoping review.

Background: Research capacity building (RCB) initiatives have gained steady momentum in health settings across the globe to reduce the gap between research evidence and health practice and policy. RCB strategies are typically multidimensional, comprising several initiatives targeted at different levels within health organisations. Research education and training is a mainstay strategy targeted at the individual level and yet, the evidence for research education in health settings is unclear.

Intravenous Oncolytic Vaccinia Virus Therapy Results in a Differential Immune Response between Cancer Patients.

is an engineered Wyeth-strain vaccinia oncolytic virus (OV), which has been tested extensively in clinical trials, demonstrating enhanced cytotoxic T cell infiltration into tumours following treatment. Favourable immune consequences to include the induction of an interferon (IFN) response, followed by inflammatory cytokine/chemokine secretion. This promotes tumour immune infiltration, innate and adaptive immune cell activation and T cell priming, culminating in targeted tumour cell killing, i.

Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anticancer Immunity in Patients.

Improving the chances of curing patients with cancer who have had surgery to remove metastatic sites of disease is a priority area for cancer research. Pexa-Vec (Pexastimogene Devacirepvec; JX-594, TG6006) is a principally immunotherapeutic oncolytic virus that has reached late-phase clinical trials. We report the results of a single-center, nonrandomized biological end point study (trial registration: EudraCT number 2012-000704-15), which builds on the success of the presurgical intravenous delivery of oncolytic viruses to tumors.

Antioxidant and lipid supplementation improve the development of photoreceptor outer segments in pluripotent stem cell-derived retinal organoids.

The generation of retinal organoids from human pluripotent stem cells (hPSC) is now a well-established process that in part recapitulates retinal development. However, hPSC-derived photoreceptors that exhibit well-organized outer segment structures have yet to be observed. To facilitate improved inherited retinal disease modeling, we determined conditions that would support outer segment development in maturing hPSC-derived photoreceptors.

Fatty Liver Index and Skeletal Muscle Density.

Accumulation of fat in the liver and skeletal muscle is associated with obesity and poor health outcomes. Liver steatosis is a characteristic of non-alcoholic fatty liver disease (NAFLD) and myosteatosis, of poor muscle quality in sarcopenia. In this study of 403 men (33-96 years), we investigated associations between the fatty liver index (FLI) and muscle density, as markers of fat accumulation in these organs.

Spatiotemporal patterns of neuronal subtype genesis suggest hierarchical development of retinal diversity.

How do neuronal subtypes emerge during development? Recent molecular studies have profiled existing neuronal diversity, but neuronal subtype genesis remains elusive. The 15 types of mouse retinal bipolar interneurons are characterized by distinct functions, morphologies, and transcriptional profiles. Here, we develop a comprehensive spatiotemporal map of bipolar subtype genesis in the murine retina.

Is sarcopenia associated with anxiety symptoms and disorders? A systematic review and meta-analysis protocol.

Introduction: Sarcopenia is a skeletal muscle disorder characterised by a progressive decline in muscle mass and function (strength and performance). Sarcopenia is associated with numerous adverse health outcomes and has recently been linked to neurological and psychiatric disorders, including dementia and depression. Whether sarcopenia is related to other common psychiatric illnesses, such as anxiety, is unclear.

Development and diversification of bipolar interneurons in the mammalian retina.

The bipolar interneurons of the mammalian retina have evolved as a diverse set of cells with distinct subtype characteristics, which reflect specialized contributions to visual circuitry. Fifteen subtypes of bipolar interneurons have been identified in the mouse retina, each with characteristic gene expression, morphology, and light responses. This review provides an overview of the developmental events that underlie the generation of the diverse bipolar cell class, summarizing the current knowledge of genetic programs that establish and maintain bipolar subtype fates, as well as the events that shape the final distribution of bipolar subtypes.

Nanotube-like processes facilitate material transfer between photoreceptors.

Neuronal communication is typically mediated via synapses and gap junctions. New forms of intercellular communication, including nanotubes (NTs) and extracellular vesicles (EVs), have been described for non-neuronal cells, but their role in neuronal communication is not known. Recently, transfer of cytoplasmic material between donor and host neurons ("material transfer") was shown to occur after photoreceptor transplantation.

Relationship between adverse childhood experiences and Alzheimer's disease: a systematic review and meta-analysis protocol.

Introduction: Alzheimer's disease has a high prevalence and a substantial impact on society, as well as the individual. Findings from clinical studies to date, suggest that multiple factors are likely to contribute to the variability seen in the progression of Alzheimer's disease. However, despite this accumulating evidence, current identified factors do not explain the full extent of disease onset.