Chimeric antigen receptor macrophages (CAR-M) sensitize HER2+ solid tumors to PD1 blockade in pre-clinical models.

We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we develop clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduce tumor burden, prolong survival, remodel the TME, increase intratumoral T cell and natural killer (NK) cell infiltration, and induce antigen spreading.

Guidance on selecting and evaluating AI auto-segmentation systems in clinical radiotherapy: insights from a six-vendor analysis.

Artificial Intelligence (AI) based auto-segmentation has demonstrated numerous benefits to clinical radiotherapy workflows. However, the rapidly changing regulatory, research, and market environment presents challenges around selecting and evaluating the most suitable solution. To support the clinical adoption of AI auto-segmentation systems, Selection Criteria recommendations were developed to enable a holistic evaluation of vendors, considering not only raw performance but associated risks uniquely related to the clinical deployment of AI.

Evaluating the prognostic value of radiomics and clinical features in metastatic prostate cancer using [Ga]Ga-PSMA-11 PET/CT.

Prostate cancer is a significant global health issue due to its high incidence and poor outcomes in metastatic disease. This study aims to develop models predicting overall survival for patients with metastatic biochemically recurrent prostate cancer, potentially helping to identify high-risk patients and enabling more tailored treatment options. A multi-centre cohort of 180 such patients underwent [Ga]Ga-PSMA-11 PET/CT scans, with lesions semi-automatically segmented and radiomic features extracted from lesions.

Measurable residual disease and posttransplantation gilteritinib maintenance for patients with FLT3-ITD-mutated AML.

BMT CTN 1506 ("MORPHO"; NCT02997202) was a randomized phase 3 study of gilteritinib compared to placebo as maintenance therapy after hematopoietic stem cell transplantation (HCT) for patients with FLT3-ITD-mutated acute myeloid leukemia (AML). A key secondary endpoint was to determine the impact on survival of pre- and/or post-HCT measurable residual disease (MRD), as determined using a highly sensitive assay for FLT3-ITD mutations. Generally, gilteritinib maintenance therapy was associated with improved relapse-free survival (RFS) for participants with detectable peri-HCT MRD, whereas no benefit was evident for those lacking detectable MRD.

Pica practices, anemia, and oral health outcomes: a systemic review.

Objectives: Pica is a non-nutritive eating behavior. The potential impact of pica on oral health and the association between pica and anemia are understudied. We examined the current evidence on the relationship between pica practices, anemia, and oral health outcomes.

Fractionated low-dose radiotherapy primes the tumor microenvironment for immunotherapy in a murine mesothelioma model.

Combination immune checkpoint inhibitors (nivolumab and ipilimumab) are currently a first-line treatment for mesothelioma; however, not all patients respond. The efficacy of treatment is influenced by the tumor microenvironment. Murine mesothelioma tumors were irritated with various radiotherapy doses.

Monte Carlo in the mechanistic modelling of the FLASH effect: a review.

FLASH radiotherapy employs ultra-high dose rates of >40 Gy/s, which may reduce normal tissue complication as compared to conventional dose rate treatments, while still ensuring the same level of tumour control. The potential benefit this can offer to patients has been the cause of great interest within the radiation oncology community, but this has not translated to a direct understanding of the FLASH effect. The oxygen depletion and inter-track interaction hypotheses are currently the leading explanations as to the mechanisms behind FLASH, but these are still not well understood, with many questions remaining about the exact underpinnings of FLASH and the treatment parameters required to optimally induce it.

Total hip arthroplasty preoperative planning for childhood hip disorders' sequelae: Focus on developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) poses significant challenges in both childhood and adulthood, affecting up to 10 per 1000 live births in the United Kingdom and United States. While newborn screening aims to detect DDH early, missed diagnoses can lead to severe complications such as hip dysplasia and early onset osteoarthritis in adults. Treatment options range from less invasive procedures like hip-preserving surgery to more extensive interventions such as total hip arthroplasty (THA), depending on the severity of the condition.

Chest Pain at Rest With Unremarkable ECG and Cardiac Enzymes: Case Study Emphasising the Importance of Clinical Suspicion in the Diagnosis of Coronary Artery Disease.

Background: Coronary artery disease (CAD), primarily caused by atherosclerosis, is a leading cause of death, presenting as angina or myocardial infarction. Advances in cardiac imaging, angiography, and procedures like percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery have improved early detection and management of this condition. This report presents the case of a man who experienced worsening exertional chest pain and discomfort while at rest.

Correlation of Preclinical Imaging Modalities and Immunohistochemistry for Tumor Hypoxia and Vasculature.

Background/aim: Tumors exhibit impaired blood flow and hypoxic areas, which can reduce the effectiveness of treatments. Characterizing these tumor features can inform treatment decisions, including the use of vasculature modulation therapies. Imaging provides insight into these characteristics, with techniques varying between clinical and preclinical settings.

Tumor Lysis Syndrome in Acute Myeloid Leukemia Patients Treated With a Venetoclax Based Regimen.

Venetoclax with hypomethylating agents (HMA) is the standard of care for acute myeloid leukemia (AML) in patients ineligible for intensive chemotherapy and is associated with tumor lysis syndrome (TLS). TLS prophylaxis and the use of Cairo Bishop versus Howard diagnostic criteria are not standardized. Here we report TLS prophylaxis and incidence in a retrospective cohort of 100 consecutive AML patients treated with venetoclax and HMA.

Psychosocial determinants of oral health outcomes in young children.

Objective: To examine the social determinants of early childhood caries (ECC), one of the greatest public health risks affecting children, and examine alternative pathways of influence.

Methods: A physically healthy, socio-demographically high-risk sample of initially caries-free children, aged 1-4 years, was prospectively studied for 2 years. At 6-month intervals, assessments were made of caries presence from a standard dental exam; oral microbiology was assayed from saliva samples; oral hygiene behaviors and psychological and psychosocial risk exposure were derived from interviews and questionnaires.

A conserved role for ALG10/ALG10B and the -glycosylation pathway in the sleep-epilepsy axis.

Congenital disorders of glycosylation (CDG) comprise a class of inborn errors of metabolism resulting from pathogenic variants in genes coding for enzymes involved in the asparagine-linked glycosylation of proteins. Unexpectedly to date, no CDG has been described for , encoding the alpha-1,2-glucosyltransferase catalyzing the final step of lipid-linked oligosaccharide biosynthesis. Genome-wide association studies (GWAS) of human traits in the UK Biobank revealed significant SNP associations with short sleep duration, reduced napping frequency, later sleep timing and evening diurnal preference as well as cardiac traits at a genomic locus containing a pair of paralogous enzymes and .

Artificial intelligence in risk prediction and diagnosis of vertebral fractures.

With the increasing prevalence of vertebral fractures, accurate diagnosis and prognostication are essential. This study assesses the effectiveness of AI in diagnosing and predicting vertebral fractures through a systematic review and meta-analysis. A comprehensive search across major databases selected studies utilizing AI for vertebral fracture diagnosis or prognosis.

'QuickDASH' to find unique genes and biological processes associated with shoulder osteoarthritis: a prospective case-control study.

Objective: Osteoarthritis (OA) is a disease impacting the synovial joint complex, yet transcriptional changes specific to shoulder OA remain underexplored. This study aims to profile transcriptomic changes in periarticular tissues from patients undergoing shoulder replacement for OA. By correlating these profiles with QuickDASH scores-a validated measure of worsening shoulder function-this research seeks to understand the gene expression changes associated with clinical decline.

New therapeutic approaches for fibrosis: harnessing translational regulation.

Idiopathic pulmonary fibrosis (IPF) is a progressive and debilitating lung disease characterized by excessive extracellular matrix deposition and tissue scarring. The median survival of patients with IPF is only 4.5 years following diagnosis, and effective treatment options are scarce.

Discovery of 6-Fluoro-5-{4-[(5-fluoro-2-methyl-3-oxo-3,4-dihydroquinoxalin-6-yl)methyl]piperazin-1-yl}--methylpyridine-2-carboxamide (AZD9574): A CNS-Penetrant, PARP1-Selective Inhibitor.

PARP inhibitors have attracted considerable interest in drug discovery due to the clinical success of first-generation agents such as olaparib, niraparib, rucaparib, and talazoparib. Their success lies in their ability to trap PARP to DNA; however, first-generation PARP inhibitors were not strictly optimized for trapping nor for selectivity among the PARP enzyme family. Previously we described the discovery of the second-generation PARP inhibitor AZD5305, a selective PARP1-DNA trapper.

Renal Function as a Predictor of Mortality and Functional Outcomes in Acute Stroke: A Prospective Study.

Background: Stroke is a leading cause of global morbidity and mortality, and understanding modifiable predictors of stroke outcomes is crucial. This study explores the relationship between renal function, assessed via estimated glomerular filtration rate (eGFR) and serum creatinine, and stroke mortality and functional outcomes in a cohort of acute stroke patients in India.

Methods: A prospective observational study was conducted from February 2021 to October 2022, including 104 acute stroke patients from MS Ramaiah Medical College and Hospital, Bengaluru, India.

Clonal Hematopoiesis of Indeterminate Potential and its Association with Treatment Outcomes and Adverse Events in Patients with Solid Tumors.

Liquid biopsy is increasingly being used in oncology for tumor molecular characterization. CHIP is a common incidental finding in cfDNA, and its prevalence increases with age. This study builds on growing evidence of common CHIP variants in patients with solid tumors.