Publications by authors named "Alexander I"

Background: Despite that globally the percent of women and men who tested positive for COVID-19 appears equal and that men with COVID-19 were 60% more likely than women to be severely ill and to die from complications (Rozenberg et al., 2020), studies of sex differences show that women compared with men are more likely to manifest persistent post-COVID-19 syndrome (PPCS).

Purpose: In this paper, we address some of the extant evidence for impact of the PPCS on women's health and well-being to underpin our suggestions for research and policy considerations.

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When people must flee their homes due to persecution or conflict, they embark on a journey from loss toward safety that is a global concern and the resettlement country's responsibility. Refugees experience stressors as they secure basic needs such as adequate nutrition, healthcare, transportation, housing, education, and income-generating activities. For refugee women, these stressors are further exacerbated by gender-related roles and experiences.

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Article Synopsis
  • - Gene therapies using recombinant adeno-associated virus (AAV) vectors have shown significant success in treating genetic disorders, and newer improved vectors could enhance these therapies even further by optimizing their characteristics.
  • - Directed evolution helps identify beneficial variants in AAV capsid libraries, but traditional characterizations have relied on low-throughput Sanger sequencing, which can be slow and limiting.
  • - The use of advanced long-read sequencing technologies, specifically Oxford Nanopore Technologies, combined with a new bioinformatic tool called AAVolve, enables more efficient and comprehensive analysis of AAV capsid libraries, ultimately leading to better gene therapy outcomes.
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Background: Conventional adeno-associated viral (AAV) vectors, while highly effective in quiescent cells such as hepatocytes in the adult liver, confer less durable transgene expression in proliferating cells owing to episome loss. Sustained therapeutic success is therefore less likely in liver disorders requiring early intervention. We have previously developed a hybrid, dual virion approach, recombinant AAV (rAAV)/piggyBac transposon system capable of achieving stable gene transfer in proliferating hepatocytes at levels many fold above conventional AAV vectors.

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To date, 3,900 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical activity from trial databases, official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors. This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide.

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Recombinant adeno-associated virus (rAAV) vector gene delivery systems have demonstrated great promise in clinical trials but continue to face durability and dose-related challenges. Unlike rAAV gene therapy, integrating gene addition approaches can provide curative expression in mitotically active cells and pediatric populations. We explored a novel in vivo delivery approach based on an engineered transposase, Sleeping Beauty (SB100X), delivered as an mRNA within a lipid nanoparticle (LNP), in combination with an rAAV-delivered transposable transgene.

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The National Institute of Health (NIH) policy, Consideration of Sex as a Biological Variable (SABV) in NIH-funded Research (2015), focuses on the expectation that researchers account for the influence of SABV in vertebrate animal and human studies and provide a strong justification for single-sex investigations. When SABV is considered in the research design, data analyses, and reporting, the rigor and reproducibility of the research are elevated and inform best practices and precision health for all people. Additional recommendations include the appropriate use of terminology, integration into curricula, intersection with social determinants of health, and application of sex and gender equity guidelines when disseminating research.

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Monoclonal antibodies (mAbs) are useful tools to dissect the neutralizing antibody response against the adeno-associated virus (AAV) capsids used as gene therapy delivery vectors. This study structurally characterizes the interactions of 21 human-derived antibodies from patients treated with the AAV9 vector, Zolgensma , utilizing high-resolution cryo-electron microscopy. The majority of the bound antibodies do not conform to the icosahedral symmetry of the capsid, thus requiring localized reconstructions.

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Black, Indigenous, and People of Color (BIPOC), and other minoritized populations are insufficiently represented in research on therapeutic psychedelics. This research was a phenomenological qualitative exploration of a culturally diverse (Hispanic, African American, Asian, Native American, biracial, or LGBTQIA+) and low-income sample of 15 individuals receiving ketamine-assisted psychotherapy (KAP) at a sliding-scale fee community clinic. Participants were interviewed after a ketamine session, after a ketamine integration session, and one month later.

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This retrospective descriptive study sought to explore the lived experiences of Black mothers with HIV navigating HIV medical care while parenting dependent children. Six themes were generated from the semi-structured interviews conducted with mothers ( N = 9) related to motherhood, interactions with health care systems and providers, coping, social support, HIV self-management, and HIV prevention. Findings suggested that supportive interpersonal relationships with HIV health care providers, HIV nondisclosure to family and friends, and social network support, inclusive of health care providers, were protective factors in achieving optimal treatment adherence and viral suppression.

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Gene therapies and associated technologies are transforming biomedical research and enabling novel therapeutic options for patients living with debilitating and incurable genetic disorders. The vector system based on recombinant adeno-associated viral vectors (AAVs) has shown great promise in recent clinical trials for genetic diseases of multiple organs, such as the liver and the nervous system. Despite recent successes toward the development of novel bioengineered AAV variants for improved transduction of primary human tissues and cells, vectors that can efficiently transduce human Schwann cells (hSCs) have yet to be identified.

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Despite the availability of life-saving corticosteroids for 70 years, treatment for adrenal insufficiency is not able to recapitulate physiological diurnal cortisol secretion and results in numerous complications. Gene therapy is an attractive possibility for monogenic adrenocortical disorders such as congenital adrenal hyperplasia; however, requires further development of gene transfer/editing technologies and knowledge of the target progenitor cell populations. Vectors based on adeno-associated virus are the leading system for direct gene delivery but have limitations in targeting replicating cell populations such as in the adrenal cortex.

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Article Synopsis
  • * Researchers used a gene therapy approach with a specific virus to increase levels of trimeric APN in the liver of 5xFAD mice, which led to higher APN levels in the brain and reduced harmful amyloid-beta proteins.
  • * Treatment with APN gene therapy improved memory and reduced inflammation by lowering certain inflammatory markers in the mice, suggesting a promising potential therapy for Alzheimer's disease.
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  • Developing predictive models for gene transfer and editing is crucial in personalized medicine, especially for liver therapies due to the liver's complexity.
  • This study used human liver explants in a perfusion system to test 14 adeno-associated viral (AAV) vectors, showing AAV-SYD12 and AAV-LK03 had high performance without neutralizing antibodies.
  • In the presence of human antibodies, AAV2/AAV3b variants were heavily neutralized, while AAV8 variants remained effective, highlighting the potential of liver perfusion models for testing new gene therapies.
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Background: A clinical preceptor (CP) provides the vital link to apply didactic learning in clinical practice for nurse practitioner (NP) students. A nationwide shortage of CPs continues. The goal of this pilot project was to evaluate a model for developing preceptors from the school of nursing alumni that addressed modifiable academic barriers to precepting.

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Directed evolution of natural AAV9 using peptide display libraries have been widely used in the search for an optimal recombinant AAV (rAAV) for transgene delivery across the blood-brain barrier (BBB) to the CNS following intravenous ( IV) injection. In this study, we used a different approach by creating a shuffled rAAV capsid library based on parental AAV serotypes 1 through 12. Following selection in mice, 3 novel variants closely related to AAV1, AAV-BBB6, AAV-BBB28, and AAV-BBB31, emerged as top candidates.

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Purpose: Glucocorticoid (GC)-induced hyperglycemia is a frequent issue, however there are no specific guidelines for this diabetes subtype. Although treat-to-target insulin is recommended in general to correct hyperglycemia, it remains unclear which treatment strategy has a positive effect on outcomes. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess whether treating GC-induced hyperglycemia improves clinical outcomes.

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Introduction: Evaluating employee performance is important for organisational success however, limited research exists across the allied health workforce.

Objective: This study investigated allied health clinician and manager experiences and perceptions of the appropriateness of the performance and development (PAD) framework.

Design: A mixed methods design with purposive sampling was conducted in a medium size hospital and health service in regional Queensland to investigate the appropriateness of the PAD framework.

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Recombinant adeno-associated viruses (rAAVs) have emerged as one of the most promising gene therapy vectors that have been successfully used in pre-clinical models of heart disease. However, this has not translated well to humans due to species differences in rAAV transduction efficiency. As a result, the search for human cardiotropic capsids is a major contemporary challenge.

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Introduction: Being choked/strangled during partnered sex is an emerging sexual behavior, particularly prevalent among young adult women. Using a multiparameter morphometric imaging approach, we aimed to characterize neuroanatomical differences between young adult women (18-30 years old) who were exposed to frequent sexual choking and their choking naïve controls.

Methods: This cross-sectional study consisted of two groups (choking [≥4 times in the past 30 days] vs.

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Globally, adeno-associated virus (AAV) vectors have been increasingly used for clinical gene therapy trials. In Australia, AAV-based gene therapy is available for hereditary diseases such as retinal dystrophy or spinal muscular atrophy 1 (SMA1). Many preclinical studies have used AAV vectors for gene therapy in models of cardiac disease with outcomes of varying translational potential.

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Article Synopsis
  • Researchers are exploring the therapeutic potential of epigenetic editing for treating ornithine transcarbamylase (OTC) deficiency, particularly in female patients with this X-linked condition.
  • The study utilized diseased liver cells from affected infants to create chimeric mouse-human livers, allowing for the examination of disease mechanisms and potential epigenetic treatments.
  • Findings showed that the models accurately reflected the patients' disease characteristics and demonstrated a treatable metabolic phenotype, suggesting a promising avenue for therapeutic development.
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Cannabis use has become popular among athletes, many of whom are exposed to repetitive subconcussive head impacts. We aimed to test whether chronic cannabis use would be neuroprotective or exacerbating against acute subconcussive head impacts. This trial included 43 adult soccer players (Cannabis group using cannabis at least once a week for the past 6 months, n = 24; non-cannabis control group, n = 19).

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Article Synopsis
  • * Over the past 30 years, various innovative genetic technologies have been tested to effectively address UCDs and enhance the quality of life for affected individuals.
  • * This review discusses the evolution of gene therapy for UCDs, highlighting key advancements and current challenges that will shape future research and development in this field.
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Success in the treatment of infants with spinal muscular atrophy (SMA) underscores the potential of vectors based on adeno-associated virus (AAV). However, a major obstacle to the full realization of this potential is pre-existing natural and therapy-induced anti-capsid humoral immunity. Structure-guided capsid engineering is one possible approach to surmounting this challenge but necessitates an understanding of capsid-antibody interactions at high molecular resolution.

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