One hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them.

Leukopoiesis is lethally arrested in mice lacking the master transcriptional regulator PU.1. Depending on the animal model, subtotal PU.

Diffusive topology preserving manifold distances for single-cell data analysis.

Manifold learning techniques have emerged as crucial tools for uncovering latent patterns in high-dimensional single-cell data. However, most existing dimensionality reduction methods primarily rely on 2D visualization, which can distort true data relationships and fail to extract reliable biological information. Here, we present DTNE (diffusive topology neighbor embedding), a dimensionality reduction framework that faithfully approximates manifold distance to enhance cellular relationships and dynamics.

Incidence of 12-month postoperative cognitive decline following regional vs. general anaesthesia in older patients undergoing hip fracture surgery: follow-up of the RAGA trial.

Introduction: Data regarding the incidence of 12-month postoperative cognitive decline following regional or general anaesthesia in older patients undergoing hip fracture surgery remain observational. Compared with general anaesthesia, we hypothesised that regional anaesthesia would decrease the incidence of 12-month postoperative cognitive decline.

Methods: This is substudy of a multicentre randomised trial of regional anaesthesia with no sedation vs.

Iodinated Contrast Adsorption in Cartridges With Styrene-Divinylbenzene Sorbent.

Background: Contrast-associated acute kidney injury (CA-AKI) is frequent in patients with chronic kidney disease who are submitted to cardiac endovascular procedures using iodinated contrast. In hemoadsorption, cartridges containing styrene-divinylbenzene sorbent resin are applied to remove substances from the blood through an extracorporeal circuit. Importantly, iodinated contrast is also removed via adsorption.

Two London Memorials to "James Parkinson [1755-1824], Esq. Surgeon, Late of Hoxton-Square".

Of all London memorials commemorating historical medical personalities, none perhaps have been so frequented by neurologists as those honoring James Parkinson (1755-1824) of Hoxton square. Situated in the historical London borough of Hackney, there are two well-known memorials to James Parkinson that can still be easily visited: The first, a large, inscribed marble memorial tablet at St Leonard's Church that Parkinson was closely affiliated with throughout life; the second, a historical blue plaque marking the site of Parkinson's birthplace and former home practice at 1 Hoxton Square. Although many contemporary neurologists would freely recall the historical significance of these locations, very few now living can detail the circumstances leading up to these memorials being erected.

Prenatal diagnosis following preimplantation genetic testing for monogenic conditions: a single centre record linkage study.

Purpose: Professional bodies currently advise all pregnant individuals undertake confirmatory prenatal diagnostic testing following preimplantation genetic testing for monogenic conditions (PGT-M). We aimed to ascertain the uptake of prenatal diagnostic testing following PGT-M in a large single-centre population.

Methods: This observational linkage study was undertaken using routinely collected outcome data from PGT-M cycles performed at one of Australia's largest PGT-M providers and a statewide dataset of all prenatal samples undergoing cytogenetic analysis in Victoria, Australia, between 2015 and 2022.

Remote Food Security Research Project: Applying an Indigenist Research Lens.

This paper aimed to reflect on how Rigney's model of Indigenist research informed the research design of a project which explored community-led solutions to improve food security in remote Aboriginal and Torres Strait Islander communities. The project was conducted in partnership with two Aboriginal Community Controlled Health Organisations (ACCHOs); Apunipima Cape York Health Council (Apunipima) and Central Australian Aboriginal Congress (Congress), communities in Central Australia and Cape York, Queensland and researchers from the University of Queensland, Monash University, Dalhousie University and Menzies School of Health Research. On reflection the principles of Indigenist research were evident providing a means of resistance to oppression through Indigenous stakeholders being in control of research to address social determinants, in this case food security.

Targeting Kv7 Potassium Channels for Epilepsy.

Voltage-gated Kv7 potassium channels, particularly Kv7.2 and Kv.7.

Paracetamol, its metabolites, and their transfer between maternal circulation and fetal brain in mono- and combination therapies.

Background: Due to its availability and perceived safety, paracetamol is recommended even during pregnancy and for neonates. It is used frequently alone or in combination with other drugs required for the treatment of various chronic conditions. The aim of this study was to investigate potential effects of drug interactions on paracetamol metabolism and its placental transfer and entry into the developing brain.

The Potential Role of Toxoplasma gondii Infection in Multiple Sclerosis Development: A Seroepidemiological Study in North Khorasan Province, Iran.

Pourpose: This study aimed to investigate the seroepidemiological status of Toxoplasma gondii (T. gondii) infection in Multiple Sclerosis (MS) patients compared to controls.

Methods: The present study included 98 MS patients and 100 controls.

Different PD-L1 Assays Reveal Distinct Immunobiology and Clinical Outcomes in Urothelial Cancer.

Testing for PD-L1 expression by immunohistochemistry (IHC) is used to predict immune checkpoint blockade (ICB) benefit but has performed inconsistently in urothelial cancer (UC) clinical trials. Different approaches are used for PD-L1 IHC. We analyzed paired PD-L1 IHC data on UC samples using the SP142 and 22C3 assays from the phase 3 IMvigor130 trial and found discordant findings summarized by four phenotypes: PD-L1 positive by both assays (PD-L1 double positive; PD-L1DP), PD-L1 positive by the SP142 assay only (SP142 single positive; SP142SP), PD-L1 positive by the 22C3 assay only (22C3 single positive; 22C3SP), and PD-L1 negative by both assays double negative (PD-L1 double negative; PD-L1DN).

ACQUIRED MUTATIONS IN PATIENTS WITH RELAPSED/REFRACTORY CLL WHO PROGRESSED IN THE ALPINE STUDY.

Some CLL patients who develop progressive disease (PD) during treatment with covalent Bruton tyrosine kinase inhibitors (cBTKi) acquire pathway resistance mutations in BTK or PLCG2. Here, we report gene mutation data from paired baseline and PD peripheral blood samples from 52 patients (zanubrutinib, n=24; ibrutinib, n=28) who, at an early median follow-up time of 25.7 months, progressed on zanubrutinib or ibrutinib treatment in the ALPINE trial (NCT03734016).

Nivolumab and rituximab in treatment naive follicular lymphoma: the phase II '1st FLOR' study.

Follicular lymphoma (FL) outcomes are heavily influenced by host immune activity with immune anti-tumor activity mitigated by PD-1/PD-L1 pathway engagement. Combination CD20-directed therapy plus PD-1 inhibition (PD-1i) increases T-cell tumor killing and NK-cell antibody-dependent cell cytotoxicity (ADCC). Mounting evidence supports immune-priming using PD-1i before cancer-directed agents.

and infection in led to species-specific regulatory responses in the host and pathogen.

In recent decades, has surpassed as the leading cause of shigellosis, possibly due to species-specific differences in their transcriptomic responses. This study used dual RNA sequencing to analyse the transcriptomic responses of and the two species at early (10 minutes) and late (24 hours) stages of infection. While the nematode defence response was downregulated during both infections, only infection by led to downregulation of sphingolipid metabolism, cadmium ion response and xenobiotic response in .

The Deadly Details: How Clear and Complete Are Publicly Available Sources of Human Rabies Information?

Human rabies is preventable but almost always fatal once symptoms appear, causing 59,000 global deaths each year. Limited awareness and inconsistent access to post-exposure prophylaxis hinder prevention efforts. To identify gaps and opportunities for improvement in online rabies information, we assessed the readability, understandability, actionability, and completeness of online public rabies resources from government and health agencies in Australia and similar countries, with the aim of identifying gaps and opportunities for improvement.

: Co-Design of a Novel Approach for Engaging People with Dementia in Physical Activity.

Background: Promoting physical activity among people living with dementia is critical to maximise physical, cognitive and social benefits; yet the lack of knowledge, skills and confidence among health professionals, informal care partners and people with dementia deters participation. As the initial phase of a larger feasibility study, co-design was employed to develop a new model of community care, to facilitate the physical activity participation of older people living with mild dementia.

Methods: Co-design methodology was utilised with nine stakeholders (with experience in referring to or providing physical activity programs and/or contributing to policy and program planning) over three workshops plus individual interviews with four care partners of people with dementia.

Reporting Standards for Bayesian Network Modelling.

Reproducibility is a key measure of the veracity of a modelling result or finding. In other research areas, notably in medicine, reproducibility is supported by mandating the inclusion of an agreed set of details into every research publication, facilitating systematic reviews, transparency and reproducibility. Governments and international organisations are increasingly turning to modelling approaches in the development and decision-making for policy and have begun asking questions about accountability in model-based decision making.

Model Selection from Multiple Model Families in Species Distribution Modeling Using Minimum Message Length.

Species distribution modeling is fundamental to biodiversity, evolution, conservation science, and the study of invasive species. Given environmental data and species distribution data, model selection techniques are frequently used to help identify relevant features. Existing studies aim to find the relevant features by selecting the best models using different criteria, and they deem the predictors in the best models as the relevant features.

Evaluation of an Interdisciplinary Educational Program to Foster Learning Health Systems: Education Evaluation.

Background: Learning health systems (LHS) have the potential to use health data in real time through rapid and continuous cycles of data interrogation, implementing insights to practice, feedback, and practice change. However, there is a lack of an appropriately skilled interprofessional informatics workforce that can leverage knowledge to design innovative solutions. Therefore, there is a need to develop tailored professional development training in digital health, to foster skilled interprofessional learning communities in the health care workforce in Australia.

Targeting LMO2-induced autocrine FLT3 signaling to overcome chemoresistance in early T-cell precursor acute lymphoblastic leukemia.

Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL) is an immature subtype of T-cell acute lymphoblastic leukemia (T-ALL) commonly show deregulation of the LMO2-LYL1 stem cell transcription factors, activating mutations of cytokine receptor signaling, and poor early response to intensive chemotherapy. Previously, studies of the Lmo2 transgenic mouse model of ETP-ALL identified a population of stem-like T-cell progenitors with long-term self-renewal capacity and intrinsic chemotherapy resistance linked to cellular quiescence. Here, analyses of Lmo2 transgenic mice, patient-derived xenografts, and single-cell RNA-sequencing data from primary ETP-ALL identified a rare subpopulation of leukemic stem cells expressing high levels of the cytokine receptor FLT3.

Concentration of Povidone-Iodine Pocket Irrigation in Implant-Based Breast Surgery: A Scoping Review.

Background: In implant-based breast surgery, microbial contamination of implant surfaces predisposes complications such as overt periprosthetic infection and has been linked to capsular contracture (CC). Anti-microbial practices, including povidone-iodine (PVP-I) breast pocket irrigation, are routinely employed to minimise these risks. No standardised protocol for using this antiseptic exists, particularly concerning the ideal concentration.