Functional validation of a novel STAT3 'variant of unknown significance' identifies a new case of STAT3 GOF Syndrome and reveals broad immune cell defects.

Introduction: STAT3 orchestrates crucial immune responses through its pleiotropic functions as a transcription factor. Patients with germline monoallelic dominant negative or hypermorphic STAT3 variants, who present with immunodeficiency and/or immune dysregulation, have revealed the importance of balanced STAT3 signaling in lymphocyte differentiation and function, and immune homeostasis. Here, we report a novel missense variant of unknown significance in the DNA binding domain of STAT3 in a patient who experienced hypogammaglobulinemia, lymphadenopathy, hepatosplenomegaly, immune thrombocytopenia, eczema and enteropathy over a 35-year period.

Allergen Specific IgE is a Stronger Predictor of Remission Following Peanut Oral Immunotherapy Than Age in Children Aged 1-10 Years.

Background: Remission is the desired outcome following OIT as it allows individuals to discontinue treatment and eat the allergen freely. Early initiation of OIT in infants and toddlers has been embraced as an approach to increase the likelihood of remission. However, there is no high-quality evidence supporting younger age as an independent factor driving remission; available studies are limited by small samples of younger subjects and lack of adjustment for confounding covariates, particularly peanut-specific IgE (sIgE) levels which is closely correlated with age.

Low latency carbon budget analysis reveals a large decline of the land carbon sink in 2023.

In 2023, the CO growth rate was 3.37 ± 0.11 ppm at Mauna Loa, which was 86% above that of the previous year and hit a record high since observations began in 1958, while global fossil fuel CO emissions only increased by 0.

Inborn errors of immunity reveal molecular requirements for generation and maintenance of human CD4 IL-9-expressing cells.

Background: CD4 T cells play essential roles in adaptive immunity. Distinct CD4 T-cell subsets-T1, T2, T17, T22, T follicular helper, and regulatory T cells-have been identified, and their contributions to host defense and immune regulation are increasingly well defined. IL-9-producing T9 cells were first described in 2008 and appear to play both protective and pathogenic roles in human immunity.

Motif mapping during chickpea germination reveals a complex sequential activation of different proteolytic activities.

Despite the importance of grains and legumes in the human diet, little is known regarding peptide release and the temporal changes of protease activities during seed germination. LC/MS-MS peptidomic analysis of two cultivars of germinating chickpea followed by computational analyses indicated cleavage dominated by proteases with a single position preference (mainly before (P1) or after cleavage (P1'): L at P2 (cysEP-like); R or K at P1 (vignain-like), N or Q at P1 (legumain-like); and previously unidentified K, R, A and S at P1'; A at P2'). While P1 N cleavages were relatively constant, P1' K/R preferences were high in soaked garbanzo (kabuli) seeds, declined by four days, and returned at six days, but were much rarer in the brown (desi) cultivar.

UK Foot and Ankle Thromboembolism (UK-FATE).

Aims: Venous thromboembolism (VTE) is a potential complication of foot and ankle surgery. There is a lack of agreement on contributing risk factors and chemical prophylaxis requirements. The primary outcome of this study was to analyze the 90-day incidence of symptomatic VTE and VTE-related mortality in patients undergoing foot and ankle surgery and Achilles tendon (TA) rupture.

Use of a Single-Fiber Optical Probe for the Detection of Tumor Fluorescence in High-Grade Glioma.

Background And Objectives: High-grade glioma (HGG) is the most common primary brain tumor in adults. The overall median survival is between 14 and 16 months. Fluorescence-guided surgery by detection of protoporphyrin IX (PpIX) fluorescence has been shown to improve the extent of resection, translating to improved progression-free survival.

Pathophysiology, blood biomarkers, and functional deficits after intimate partner violence-related brain injury: Insights from emergency department patients and a new rat model.

Intimate partner violence is a serious, but underappreciated, issue that predominantly affects women and often results in concussion (i.e., mild traumatic brain injury).

Successful management of idiopathic early-onset scoliosis: effect of curve correction and bracing after Mehta casting.

Study Design: Patients with idiopathic EOS treated by Mehta casting followed by bracing or observation from a single institution.

Objectives: To determine casting protocol parameters leading to successful management; to determine efficacy of bracing vs. observation after cast discontinuance.

Vitamin D, periodontitis and tooth loss in older Irish adults.

The aim of this study is to investigate whether 25-hydroxyvitamin D (25(OH)D) is associated with periodontitis and tooth loss in older adults. A total of 2346 adults underwent a detailed dental examination as part of the health assessment of a national population study - The Irish Longitudinal Study of Ageing. 25(OH)D analysis was performed on frozen non-fasting total plasma using LC-MS.

Localisation of function in the brain: a rethink.

A modular view of brain function dominates the teaching of medical students and clinical psychologists and is implicit in day-to-day clinical practice. This view glosses over a long-standing debate. The extent of one-to-one mappings between region and function remains a controversial topic.

Orthodontic bonding in special circumstances.

This clinical paper provides an in-depth exploration of advanced techniques for bonding orthodontic attachments under special circumstances. Challenges arise when bonding brackets to non-enamel surfaces, such as dental restorations, and in conditions such as amelogenesis imperfecta, which affect enamel integrity. Distinct approaches required for bonding to different restorative materials, including glassy ceramics, zirconia, resin composites and metals, are outlined.

Transorbital Microsurgery: An Anatomical Description of a Minimally Invasive Corridor to the Anterior Cranial Fossa and Paramedian Structures.

 Transorbital neuroendoscopic surgery (TONES) has ignited interest in the transorbital access corridor, increasing its use for single and multi-portal skull base interventions. However, the crowding of a small corridor and two-dimensional viewing restrict this access portal.  Cadaveric qualitative study to assess the feasibility of transorbital microsurgery (TMS).

Two-year post-treatment outcomes following peanut oral immunotherapy in the Probiotic and Peanut Oral Immunotherapy-003 Long-Term (PPOIT-003LT) study.

Background: Few studies have examined long-term outcomes following oral immunotherapy (OIT); none have examined long-term risks and benefits associated with distinct clinical outcomes (desensitization, remission).

Methods: Participants completing the probiotic and peanut oral immunotherapy (PPOIT) -003 randomized trial were enrolled in a follow-on study, PPOIT-003LT. Peanut ingestion, reactions, and health-related quality of life (HRQOL) were monitored prospectively.

An examination of the impact of unmelted, melted, and deconstructed cheese on lipid metabolism: a 6-week randomised trial.

: Evidence suggests cheese has a favourable or neutral effect on cardiometabolic health, compared to butter. To date, studies have only considered the cheese matrix in its unmelted form, while the effect of melted cheese remains unknown. : To test the effect of 6-week daily consumption of ∼40 g dairy fat, eaten in either as unmelted cheese, melted cheese, or in a fully deconstructed form, on markers of metabolic health in overweight adults aged ≥50 years of age.

Cardiovascular risk factors are associated with cognitive trajectory in the first year after stroke.

Introduction: Stroke often leads to cognitive impairment, but its progression and influencing factors over time remain poorly understood. This study evaluates immediate post-stroke cognitive impacts and investigates the influence of concurrent factors on cognitive evolution over the first year.

Patients And Methods: In the STRATEGIC study, 179 patients with first symptomatic ischemic stroke underwent neuropsychological assessments within three months post-stroke, and 141 were re-evaluated at 12 months.

Evaluating the harmonization potential of oral health-related questionnaires in national longitudinal birth and child cohort surveys.

Background/objectives: Effective use of longitudinal study data is challenging because of divergences in the construct definitions and measurement approaches over time, between studies and across disciplines. One approach to overcome these challenges is data harmonization. Data harmonization is a practice used to improve variable comparability and reduce heterogeneity across studies.

Immunogenicity, reactogenicity, and IgE-mediated immune responses of a mixed whole-cell and acellular pertussis vaccine schedule in Australian infants: A randomised, double-blind, noninferiority trial.

Background: In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule.

The protocol for an observational Australian cohort study of CADASIL: The AusCADASIL study.

Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression.

Methods: Participants will be recruited from six study centres across Australia for an observational study of CADASIL.

Ultrasound-guided deployment of ProGlide™ device in transfemoral transcatheter aortic valve implantation and risk reduction of vascular complications: A propensity-matched cohort study.

Background: ProGlide is a percutaneous suture-mediated closure device used in arterial and venous closure following percutaneous intervention. Risk of vascular complications from use, particularly related to failure in hemostasis, or acute vessel closure, remains significant and often related to improper suture deployment. We describe a technique of ultrasound-guided ProGlide deployment in transfemoral transcatheter aortic valve implantation (TF-TAVI).