Multiomics approach to evaluating personalized biomarkers of allergen immunotherapy.

Recent advancements in genomics and "omic" technologies have ushered in a transformative era referred to as personalized or precision medicine. This innovative approach considers the unique genetic profiles of individuals, along with a range of variability factors, to devise tailored disease treatments and prevention strategies that cater to the distinct needs of each patient. Although the terms personalized medicine and precision medicine are frequently utilized interchangeably, it is essential to delineate the subtle distinctions between them.

CLCN4-Related Neurodevelopmental Condition: Characterization of Speech and Language Abilities.

Speech and language difficulties are a core feature of the CLCN4-related neurodevelopmental condition, but these have not been well described. Here we systematically phenotype speech and language in 13 participants (10 female, aged 1 year 10 months-41 years 10 months) with pathogenic CLCN4 variants (12 missense de novo, 1 premature stop codon maternal inheritance). Speech, language, and augmentative and alternative communication (AAC) methods were examined.

Modulation of Cellular, Molecular, and Humoral Responses by PQ Grass 27,600 SU for the Treatment of Seasonal Allergic Rhinitis: A Randomised Double Blind Placebo Control Exploratory Field Study.

Background: A short-course pre-seasonal subcutaneous injection of PQ Grass is clinically effective for the treatment of allergic rhinitis, though its mechanism remains unclear. The aim of the study was to interrogate immunological mechanisms induced by PQ Grass conventional and extended regimens.

Methods: A RDBPC exploratory field study involving participants that either received injections of PQ Grass with a cumulative dose of 27,600 SU conventional (six once weekly injections) or extended regimen (three once weekly injections followed by three once monthly injections) or placebo containing microcrystalline tyrosine (MCT) (placebo + MCT) or saline (placebo) was performed.

The ClinGen Syndromic Disorders Gene Curation Expert Panel: Assessing the clinical validity of 111 gene-disease relationships.

Purpose: The Clinical Genome Resource (ClinGen) Gene Curation Expert Panels have historically focused on specific organ systems or phenotypes; thus, the ClinGen Syndromic Disorders Gene Curation Expert Panel (SD-GCEP) was formed to address an unmet need.

Methods: The SD-GCEP applied ClinGen's framework to evaluate the clinical validity of genes associated with rare syndromic disorders. A total of 111 gene-disease relationships (GDRs) associated with 100 genes spanning the clinical spectrum of syndromic disorders were curated.

Developing genetic literacy in high school students with intellectual disability: Teachers' experiences and perspectives.

Genetics is a rapidly evolving field with the potential to achieve improved health outcomes through precision medicine. People with intellectual disability have asked to know more about genetic conditions that they may have, but require education to build their genetic literacy, thereby empowering them to make informed healthcare decisions. Key to this is ensuring students with intellectual disability can access and participate in genetics education at school.

Mechanisms and Treatment of Type 2 High and Low Asthma Endotypes.

Asthma is a complex, heterogeneous disease characterised by clinical phenotypes demonstrating distinct and overlapping immunological mechanisms, classified into type-2 high and type-2 low asthma endotypes. Both allergic and eosinophilic non-allergic asthma are driven through an underlying type-2 high-endotype, which can be targeted using therapeutic approaches such as allergen-specific immunotherapy (AIT) for allergic asthma and biologics. AIT demonstrates efficacy for the treatment of allergic asthma.

Fulfilling the needs of caregivers in delivering health services to children with developmental and epileptic encephalopathies.

Introduction: Patients with developmental and epileptic encephalopathies (DEEs) have multiple comorbidities and high healthcare needs. Whether health services meet the needs of this patient population and their families is not well understood. We explored caregiver perspectives on their child's health service use, satisfaction with health services, and priorities for improvement.

"All doctors should be trained in that": The coproduction and mixed-methods evaluation of an educational toolkit to enable safe, high-quality genetic health care for people with intellectual disability.

Purpose: People with intellectual disability inequitably access high-quality genetic health care. However, they are keen to understand genetic health care and recommend that clinicians need education on delivering more inclusive care and that multimodal genetic health literacy resources should be coproduced.

Methods: Our inclusive research team applied best-practice coproduction principles to deliver a suite of resources, the GeneEQUAL Toolkit.

A field resource for the glioma cerebrospinal fluid proteome: Impacts of resection and location on biomarker discovery.

Background: While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples for monitoring biomarker discovery, including anatomical location and post-surgical changes, remains unknown.

Methods: Aptamer-based proteomics was performed on 147 CSF samples from 74 patients; 71 of whom had grade 2-4 astrocytomas or grade 2-3 oligodendrogliomas.

Integrated Care for People Living With Rare Disease: A Scoping Review on Primary Care Models in Organization for Economic Cooperation and Development Countries.

Introduction/objectives: Individually rare, rare diseases are collectively common resulting in frequent health system use. Navigating the health system persists as a challenge. Primary care provides longitudinal contact with the health system and is placed to provide integrated rare-disease-care.

Ara h 2-expressing cucumber mosaic virus-like particle (VLP Peanut) induces in vitro tolerogenic cellular responses in peanut-allergic individuals.

Background: Peanut allergy (PA) is one of the most prevalent food allergies with a lack of favorable safety/efficacy treatment. A cucumber mosaic virus-like particle expressing peanut allergen component Ara h 2 (VLP Peanut) has been developed as a novel therapeutic approach for PA.

Objective: We assessed the tolerogenic properties and reactivity of VLP Peanut.

Codesign and evaluation of advanced therapeutic information resources for and with families of children with neurological conditions: a mixed methods cross-sectional study.

Objective: Parents and caregivers of children with neurological conditions express interest in new and developing treatments and trials; however, they have limited knowledge of, and access to, reliable information. This study aims to empower and equip decision-making and support communication in the application of advanced neurotherapeutics and personalised medicine, covering gene therapy, stem cell therapy, neurostimulation and neuroimmunotherapies.

Design: A suite of online psychoeducational resources has been created and evaluated to establish implementation success.

Pushing the boundaries of rare disease diagnostics with the help of the first Undiagnosed Hackathon.

The first-ever Undiagnosed Hackathon was a groundbreaking event held by the Wilhelm Foundation, the Karolinska Undiagnosed Disease Program, and PhenoTips in collaboration with UDNI to solve medical mysteries and advance diagnostics for undiagnosed rare diseases. Nearly 100 healthcare professionals and researchers from 28 countries participated, working intensively for 48 hours to diagnose 10 families with undiagnosed rare diseases. This innovative approach to precision diagnostics highlighted the power of international, multidisciplinary collaboration and patient partnership, yielding promising results for patients seeking answers and benefiting the entire rare diseases community.

Equity in action: The Diagnostic Working Group of The Undiagnosed Diseases Network International.

Rare diseases are recognized as a global public health priority. A timely and accurate diagnosis is a critical enabler for precise and personalized health care. However, barriers to rare disease diagnoses are especially steep for those from historically underserved communities, including low- and middle-income countries.

Complete genome sequence of strain JM503A, a genetically tractable dental abscess clinical isolate.

is a pathobiont of humans that is often found in abundance at sites of mucosal inflammation as well as within malignant tumors. Here, we report the complete genome sequence of strain JM503A, which is a genetically tractable clinical isolate derived from a human odontogenic abscess specimen.

Psychosocial experiences of clinicians providing care for children with severe neurological impairment.

Aim: To investigate clinicians' psychosocial experiences navigating interdisciplinary care for children with severe neurological impairment (SNI), for example children with a developmental epileptic encephalopathy; secondarily, to identify preferences for future interventions to support clinicians caring for children with SNI.

Method: We conducted a qualitative descriptive study with interdisciplinary clinicians by using a purposeful sampling recruitment strategy. Twenty-four participants with expertise caring for children with SNI completed in-depth, semi-structured interviews.

The dynamic impact of location and resection on the glioma CSF proteome.

Unlabelled: While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples, including anatomical location and post-surgical changes, remains unknown. To that end, pre- versus post-resection intracranial CSF samples were obtained at early (1-16 days; n=20) or delayed (86-153 days; n=11) timepoints for patients with glioma.

'High hopes for treatment': Australian stakeholder perspectives of the clinical translation of advanced neurotherapeutics for rare neurological diseases.

Introduction: Advanced therapies offer unprecedented opportunities for treating rare neurological disorders (RNDs) in children. However, health literacy, perceptions and understanding of novel therapies need elucidation across the RND community. This study explored healthcare professionals' and carers' perspectives of advanced therapies in childhood-onset RNDs.

variants in the non-coding spliceosomal snRNA gene are a frequent cause of syndromic neurodevelopmental disorders.

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes. Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA as a novel syndromic NDD gene.

Psychological wellbeing among parents of a child living with a serious chronic illness: A cross-sectional survey study.

Parents of a child with a chronic illness can experience greater distress than the average population, yet little is understood about differences between illness groups. This cross-sectional survey study aimed to compare parents' psychological distress and perceived wellbeing across five chronic illnesses. Parents from one Australian pediatric hospital completed the Kessler Psychological Distress Scale and seven purpose-designed items about their wellbeing.

FLP: Factor lattice pattern-based automated detection of Parkinson's disease and specific language impairment using recorded speech.

Background: Timely detection of neurodevelopmental and neurological conditions is crucial for early intervention. Specific Language Impairment (SLI) in children and Parkinson's disease (PD) manifests in speech disturbances that may be exploited for diagnostic screening using recorded speech signals. We were motivated to develop an accurate yet computationally lightweight model for speech-based detection of SLI and PD, employing novel feature engineering techniques to mimic the adaptable dynamic weight assignment network capability of deep learning architectures.

Nasal allergen-neutralizing antibodies correlate closely with tolerated intranasal allergen challenge dose following grass pollen subcutaneous immunotherapy in patients with local allergic rhinitis.

Background: Local allergic rhinitis (LAR) is defined by chronic nasal symptoms, absence of atopy, positive nasal allergen challenge (NAC) and a good response to subcutaneous allergen immunotherapy (SCIT). We sought to investigate SCIT capacity to induce local and systemic blocking antibodies in LAR patients.

Methods: A RDBPC study of grass SCIT was performed, with participants receiving either SCIT (Group A; n = 10) or placebo (Group B; n = 14) in the first 6 months.