Variants in SART3 cause a spliceosomopathy characterised by failure of testis development and neuronal defects.

Squamous cell carcinoma antigen recognized by T cells 3 (SART3) is an RNA-binding protein with numerous biological functions including recycling small nuclear RNAs to the spliceosome. Here, we identify recessive variants in SART3 in nine individuals presenting with intellectual disability, global developmental delay and a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Knockdown of the Drosophila orthologue of SART3 reveals a conserved role in testicular and neuronal development.

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma.

Background: Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease.

Methods: In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care.

Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial.

Background: Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women.

Methods: In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13-26 weeks' gestation in primary care and outpatient settings across two regions in southern Malawi.

Current state of radiomic research in pancreatic cancer: focusing on study design and reproducibility of findings.

Objectives: To critically appraise methodology and reproducibility of published studies on CT radiomics of pancreatic ductal adenocarcinoma (PDAC).

Methods: PRISMA literature search of MEDLINE, PubMed, and Scopus databases was conducted from June to August 2022 relating to CT radiomics human research articles pertaining to PDAC diagnosis, treatment, and/ or prognosis, utilising Image Biomarker Standardisation Initiative-compliant (IBSI) radiomic software. Keyword search included [pancreas OR pancreatic] AND [radiomic OR [quantitative AND imaging] OR [texture AND analysis]].

Functional and Phenotypic Characterisations of Common Syngeneic Tumour Cell Lines as Estrogen Receptor-Positive Breast Cancer Models.

Estrogen receptor-positive breast cancers (ER BCas) are the most common form of BCa and are increasing in incidence, largely due to changes in reproductive practices in recent decades. Tamoxifen is prescribed as a component of standard-of-care endocrine therapy for the treatment and prevention of ER BCa. However, it is poorly tolerated, leading to low uptake of the drug in the preventative setting.

Impact of concurrent tumour events on the prostate cancer outcomes of germline BRCA2 mutation carriers.

Background: Several studies have reported the association of germline BRCA2 (gBRCA2) mutations with poor clinical outcomes in prostate cancer (PCa), but the impact of concurrent somatic events on gBRCA2 carriers survival and disease progression is unknown.

Patients And Methods: To ascertain the role of frequent somatic genomic alterations and histology subtypes in the outcomes of gBRCA2 mutation carriers and non-carriers, we correlated the tumour characteristics and clinical outcomes of 73 gBRCA2 and 127 non-carriers. Fluorescent in-situ hybridisation and next-generation sequencing were used to detect copy number variations in BRCA2, RB1, MYC and PTEN.

Supplementation With Iron Syrup or Iron-Containing Multiple Micronutrient Powders Alters Resting Brain Activity in Bangladeshi Children.

Background: Anemia and iron deficiency have been associated with poor child cognitive development. A key rationale for the prevention of anemia using supplementation with iron has been the benefits to neurodevelopment. However, little causal evidence exists for these gains.

Exercise across the Lung Cancer Care Continuum: An Overview of Systematic Reviews.

Background: Growing evidence supports exercise for people with lung cancer. This overview aimed to summarise exercise intervention efficacy and safety across the care continuum.

Methods: Eight databases (including Cochrane and Medline) were searched (inception-February 2022) for systematic reviews of RCTs/quasi-RCTs.

Ocular Brachytherapy (Interventional Radiotherapy): Preserving the Vision.

Uveal melanoma represents the most common intraocular neoplasia among adults. Brachytherapy (interventional radiotherapy; IRT) has a great advantage, when compared with enucleation, both in terms of organ and function sparing. The Collaborative Ocular Melanoma Study introduced into clinical practice a standardised procedure that allowed the equivalence of IRT with enucleation in terms of overall survival to be demonstrated.

Effects of iron supplementation on neural indices of habituation in Bangladeshi children.

Background: Iron deficiency and anemia have been associated with poor cognition in children, yet the effects of iron supplementation on neurocognition remain unclear.

Objective: We aimed to examine the effects of supplementation with iron on neural indices of habituation using auditory event-related brain potentials (ERPs).

Methods: This substudy was nested within a 3-arm, double-blind, double-dummy, individual randomized trial in Bangladesh, in which 3300 8-mo-old children were randomly selected to receive 3 mo of daily iron syrup (12.

Asystole following spinal anaesthesia: the hazards of intrinsic cardiac reflexes.

Unwanted initiation of intrinsic cardiac reflexes can precipitate bradycardia and cardiac arrest after spinal anaesthesia. We report the case of a 40-year-old man who suffered sudden asystolic cardiac arrest following spinal anaesthesia prior to planned abdominal surgery, likely due to the initiation of one or more intrinsic cardiac reflexes including the Bezold-Jarisch reflex, the reverse Bainbridge reflex and the pacemaker stretch reflex. The characteristics of this patient placed him at increased risk of this underappreciated cause of bradycardia and hypotension.

Functional genomics for curation of variants in telomere biology disorder associated genes: A systematic review.

Purpose: Patients with an underlying telomere biology disorder (TBD) have variable clinical presentations, and they can be challenging to diagnose clinically. A genomic diagnosis for patients presenting with TBD is vital for optimal treatment. Unfortunately, many variants identified during diagnostic testing are variants of uncertain significance.

Cost-effectiveness of universal iron supplementation and iron-containing micronutrient powders for anemia among young children in rural Bangladesh: analysis of a randomized, placebo-controlled trial.

Background: Universal provision of iron supplements or iron-containing multiple micronutrient powders (MNPs) is widely used to prevent anemia in young children in low- and middle-income countries. The BRISC (Benefits and Risks of Iron Interventions in Children) trial compared iron supplements and MNPs with placebo in children <2 y old in rural Bangladesh.

Objectives: We aimed to assess the cost-effectiveness of iron supplements or iron-containing MNPs among young children in rural Bangladesh.

Effective Preparation of [F]Flumazenil Using Copper-Mediated Late-Stage Radiofluorination of a Stannyl Precursor.

(1) Background: [18F]Flumazenil 1 ([18F]FMZ) is an established positron emission tomography (PET) radiotracer for the imaging of the gamma-aminobutyric acid (GABA) receptor subtype, GABAA in the brain. The production of [18F]FMZ 1 for its clinical use has proven to be challenging, requiring harsh radiochemical conditions, while affording low radiochemical yields. Fully characterized, new methods for the improved production of [18F]FMZ 1 are needed.

A Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP): Statistical analysis plan.

Anaemia affects more than half of Africa's pregnancies. Standard care, with oral iron tablets, often fails to achieve results, with compliance and gastrointestinal side-effects being a significant issue. In recent years, intravenous iron formulations have become safe, effective, and quick to administer, allowing the complete iron requirements of pregnancy to be provided in one 15-minute infusion.

Inhibition of mutant IDH1 promotes cycling of acute myeloid leukemia stem cells.

Approximately 20% of acute myeloid leukemia (AML) patients carry mutations in IDH1 or IDH2 that result in over-production of the oncometabolite D-2-hydroxyglutarate (2-HG). Small molecule inhibitors that block 2-HG synthesis can induce complete morphological remission; however, almost all patients eventually acquire drug resistance and relapse. Using a multi-allelic mouse model of IDH1-mutant AML, we demonstrate that the clinical IDH1 inhibitor AG-120 (ivosidenib) exerts cell-type-dependent effects on leukemic cells, promoting delayed disease regression.

Large-scale manipulation of promoter DNA methylation reveals context-specific transcriptional responses and stability.

Background: Cytosine DNA methylation is widely described as a transcriptional repressive mark with the capacity to silence promoters. Epigenome engineering techniques enable direct testing of the effect of induced DNA methylation on endogenous promoters; however, the downstream effects have not yet been comprehensively assessed.

Results: Here, we simultaneously induce methylation at thousands of promoters in human cells using an engineered zinc finger-DNMT3A fusion protein, enabling us to test the effect of forced DNA methylation upon transcription, chromatin accessibility, histone modifications, and DNA methylation persistence after the removal of the fusion protein.

Patient and clinician perspectives of pelvic floor dysfunction after gynaecological cancer.

Purpose: To explore and compare patient and clinician experiences, knowledge and preferences in relation to screening and management of pelvic floor (PF) dysfunction in the gynaecology-oncology setting.

Methods: Semi-structured interviews were conducted with women reporting PF symptoms after gynaecological cancer treatment, and gynaecology-oncology clinicians. Interviews were transcribed and thematically analysed and were conducted until data saturation was reached.

Real-world staging computed tomography scanning technique and important reporting discrepancies in pancreatic ductal adenocarcinoma.

Background: Computed tomography (CT) is the first-line staging imaging modality for pancreatic ductal adenocarcinoma (PDAC) which determines resectability and treatment pathways.

Methods: Between January 2016 and December 2019, prospectively collated data from two Australian cancer centres was extracted from the PURPLE Pancreatic Cancer registry. Real-world staging CTs and corresponding reports were blindly reviewed by a sub-specialist radiologist and compared to initial reports.

Inhibition of pyrimidine biosynthesis targets protein translation in acute myeloid leukemia.

The mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) catalyzes one of the rate-limiting steps in de novo pyrimidine biosynthesis, a pathway that provides essential metabolic precursors for nucleic acids, glycoproteins, and phospholipids. DHODH inhibitors (DHODHi) are clinically used for autoimmune diseases and are emerging as a novel class of anticancer agents, especially in acute myeloid leukemia (AML) where pyrimidine starvation was recently shown to reverse the characteristic differentiation block in AML cells. Herein, we show that DHODH blockade rapidly shuts down protein translation in leukemic stem cells (LSCs) and has potent and selective activity against multiple AML subtypes.

SUVfdg: A standard-uptake-value (SUV) body habitus normalizer specific to fluorodeoxyglucose (FDG) in humans.

Purpose: To devise a new body-habitus normalizer to be used in the calculation of an SUV that is specific to the PET tracer 18F-FDG.

Methods: A cohort of 481-patients was selected for analysis of 18F-FDG uptake into tissues unaffected by their disease. Among these, 65-patients had only brain concentrations measured and the remaining 416 were randomly divided into an 86-patient test set and a 330-patient training set.