Mesoscale landscaping of the TRIM protein family reveals a novel human condensatopathy.

The mesoscale organization of cells is central to cellular physiology and pathology. Cellular condensates often form via biomolecular phase separation, mediated by intrinsically disordered regions (IDRs) and represent a key mechanism for mesoscale organization. The TRI-partite Motif (TRIM) family of ubiquitin ligases is implicated in diverse cellular functions and disease, yet the role of biomolecular condensation in TRIM family organization remains understudied.

Testicular mapping-guided sperm retrieval upfront microTESE in non-obstructive azoospermia: a comparison of sperm retrieval, pregnancy and live-birth rates.

Background: Sperm extraction by Microscopic Testicular Sperm Extraction (microTESE) has become the standard of care for sperm retrieval (SR) in men with non-obstructive azoospermia (NOA) but is costly and has a 40-50% chance of failure. Fine needle aspiration mapping (FNAM) can be performed prior to microTESE as a predictor of success to reduce the likelihood of failure to retrieve sperm but there is limited evidence that directly compares these methods. The objective of this study was to compare success rate of SR, pregnancy, and live birth rates in men who underwent upfront microTESE versus FNAM.

Transcription factors form a ternary complex with NIPBL/MAU2 to localize cohesin at enhancers.

While the cohesin complex is a key player in genome architecture, how it localizes to specific chromatin sites is not understood. Recently, we and others have proposed that direct interactions with transcription factors lead to the localization of the cohesin-loader complex (NIPBL/MAU2) within enhancers. Here, we identify two clusters of LxxLL motifs within the NIPBL sequence that regulate NIPBL dynamics, interactome, and NIPBL-dependent transcriptional programs.

Sociodemographic and clinical factors associated with low muscle mass and composition in people treated with (chemo)radiotherapy for lung cancer.

Background: This study examined (1) associations between sociodemographic and clinical variables with low muscle mass and radiodensity and their loss relative to treatment commencement in patients with lung cancer; and (2) the magnitude of change in muscle mass and association with treatment outcomes and survival.

Methods: Prospective study in patients planned for curative (chemo)radiotherapy for lung cancer. Low skeletal muscle mass and radiodensity and muscle loss were determined from pre- and post-treatment computed tomography images.

A cost-effectiveness analysis of stereotactic ablative radiotherapy versus conventionally fractionated radiotherapy in the management of stage 1 non-small-cell lung cancer: Results from the TROG 09.02 CHISEL study.

Introduction: Stereotactic ablative radiotherapy (SABR) is a standard of care treatment for medically inoperable early-stage non-small-cell lung cancer (NSCLC). The CHISEL trial was a phase 3 randomised controlled trial that compared SABR to conventional radiation therapy (CRT). Using patient-level data, we compared the cost-effectiveness of SABR and CRT for early-stage NSCLC.

Preimplantation genetic testing for aneuploidy is associated with reduced live birth rates in fresh but not frozen donor oocyte in vitro fertilization cycles: an analysis of 18,562 donor cycles reported to Society for Assisted Reproductive Technology Clinic Outcome Reporting System.

Objective: To evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on first transfer live birth rate (LBR) and cumulative LBR (CLBR) in donor oocyte in vitro fertilization (IVF) cycles.

Design: Retrospective cohort study of the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database.

Setting: Fertility centers reporting to Society for Assisted Reproductive Technology.

Living with low muscle mass and its impact throughout curative treatment for lung cancer: A qualitative study.

Objectives: To 1) explore the experience of patients with lung cancer with low muscle mass or muscle loss during treatment and the ability to cope with treatment, complete self-care, and 2) their receptiveness and preferences for nutrition and exercise interventions to halt or treat low muscle mass/muscle loss.

Methods: This was a qualitative study using individual semi-structured interviews conducted using purposive sampling in adults with a diagnosis of non-small cell lung cancer (NSCLC) or small-cell lung cancer (SCLC), treated with curative intent chemo-radiotherapy or radiotherapy. Patients who presented with computed tomography-assessed low muscle mass at treatment commencement or experienced loss of muscle mass throughout treatment were included.

Crossing boundaries of light microscopy resolution discerns novel assemblies in the nucleolus.

The nucleolus is the largest membraneless organelle and nuclear body in mammalian cells. It is primarily involved in the biogenesis of ribosomes, essential macromolecular machines responsible for synthesizing all proteins required by the cell. The assembly of ribosomes is evolutionarily conserved and accounts for the most energy-consuming cellular process needed for cell growth, proliferation, and homeostasis.

Functional Lung Avoidance Planning Using Multicriteria Optimization.

Purpose: Functional lung avoidance (FLA) radiation therapy is an evolving field. The aim of FLA planning is to reduce dose to areas of functioning lung, with comparable target coverage and dose to organs at risk. Multicriteria optimization (MCO) is a planning tool that may assist with FLA planning.

Recessive variants in the intergenic locus cause monogenic kidney disease responsive to anti-proteinuric treatment.

In genetic disease, an accurate expression landscape of disease genes and faithful animal models will enable precise genetic diagnoses and therapeutic discoveries, respectively. We previously discovered that variants in , encoding nitric oxide synthase 1 (NOS1) adaptor protein, cause monogenic nephrotic syndrome (NS). Here, we determined that an intergenic splice product of N / and neighboring , which precludes NOS1 binding, is the predominant isoform in mammalian kidney transcriptional and proteomic data.

The impact of pre-treatment smoking status on survival after chemoradiotherapy for locally advanced non-small-cell lung cancer.

Introduction: Smoking is a risk factor for the development of lung cancer and reduces life expectancy within the general population. Retrospective studies suggest that non-smokers have better outcomes after treatment for lung cancer. We used a prospective database to investigate relationships between pre-treatment smoking status and survival for a cohort of patients with stage III non-small-cell lung cancer (NSCLC) treated with curative-intent concurrent chemoradiotherapy (CRT).

Assessing the impact of discordant antibiotic treatment on adverse outcomes in community-onset UTI: a retrospective cohort study.

Objectives: To investigate the risk of adverse outcomes following discordant antibiotic treatment (urinary organism resistant) for culture-confirmed community-onset lower urinary tract infection (UTI).

Methods: Cohort study using routinely collected linked primary care, secondary care and microbiology data from patients with culture-confirmed community-onset lower UTI (COLUTI). Antibiotic treatment within ±3 days was considered concordant if the urinary organism was sensitive and discordant if resistant.

Impact on Pulmonary Function in a Randomized Trial of Single-Fraction and Multifraction Stereotactic Body Radiation Therapy for Pulmonary Oligometastatic Disease: An Analysis of TROG 13.01 (SAFRON II).

Purpose: The TROG 13.01 (SAFRON II) trial was a phase 2 multicenter trial comparing single-fraction (SF) and multifraction (MF) stereotactic body radiation therapy. Patients with 1 to 3 peripheral pulmonary oligometastases were randomized 1:1 between 28 Gy in 1 fraction and 48 Gy in 4 fractions.

Early circulating tumor DNA dynamics at the commencement of curative-intent radiotherapy or chemoradiotherapy for NSCLC.

Background: The kinetics of circulating tumor DNA (ctDNA) release following commencement of radiotherapy or chemoradiotherapy may reflect early tumour cell killing. We hypothesised that an increase in ctDNA may be observed after the first fraction of radiotherapy and that this could have clinical significance.

Materials And Methods: ctDNA analysis was performed as part of a prospective, observational clinical biomarker study of non-small cell lung cancer (NSCLC) patients, treated with curative-intent radiotherapy or chemoradiotherapy.

Risk-Directed Ambulatory Thromboprophylaxis in Lung and Gastrointestinal Cancers: The TARGET-TP Randomized Clinical Trial.

Importance: Thromboprophylaxis for individuals receiving systemic anticancer therapies has proven to be effective. Potential to maximize benefits relies on improved risk-directed strategies, but existing risk models underperform in cohorts with lung and gastrointestinal cancers.

Objective: To assess clinical benefits and safety of biomarker-driven thromboprophylaxis and to externally validate a biomarker thrombosis risk assessment model for individuals with lung and gastrointestinal cancers.

Fine-tuning the dose of recombinant human follicle-stimulating hormone alfa to individualize treatment in ovulation induction and ovarian stimulation cycles: a real-world database analysis.

Introduction: Fine-tuning of injectable gonadotropin doses during ovulation induction (OI) or ovarian stimulation (OS) treatment cycles with the aim of using doses low enough to minimize the risk of excessive ovarian response while maintaining optimal efficacy may be facilitated by using an adjustable-dose pen injector. We examined the incidence and magnitude of individualized gonadotropin dose adjustments made during cycles of OI or OS, followed by either timed intercourse or intrauterine insemination, with or without oral medications, and assessed the relationship between patient characteristics and dosing changes using real-world evidence.

Methods: This was an observational, retrospective cohort study using electronic medical records from a large US database of fertility centers.

Bayesian analysis dissects kinetic modulation during non-stationary gene expression.

Labelling of nascent stem loops with fluorescent proteins has fostered the visualization of transcription in living cells. Quantitative analysis of recorded fluorescence traces can shed light on kinetic transcription parameters and regulatory mechanisms. However, existing methods typically focus on steady state dynamics.

Hospital admission after primary care consultation for community-onset lower urinary tract infection: a cohort study of risks and predictors using linked data.

Background: Urinary tract infections (UTIs) are a common indication for antibiotic prescriptions, reductions in which would reduce antimicrobial resistance (AMR). Risk stratification of patients allows reductions to be made safely.

Aim: To identify risk factors for hospital admission following UTI, to inform targeted antibiotic stewardship.

Architectural basis for cylindrical self-assembly governing Plk4-mediated centriole duplication in human cells.

Proper organization of intracellular assemblies is fundamental for efficient promotion of biochemical processes and optimal assembly functionality. Although advances in imaging technologies have shed light on how the centrosome is organized, how its constituent proteins are coherently architected to elicit downstream events remains poorly understood. Using multidisciplinary approaches, we showed that two long coiled-coil proteins, Cep63 and Cep152, form a heterotetrameric building block that undergoes a stepwise formation into higher molecular weight complexes, ultimately generating a cylindrical architecture around a centriole.

Virtual Risk Management-Exploring Effects of Childhood Risk Experiences through Innovative Methods (ViRMa) for Primary School Children in Norway: Study Protocol for the ViRMa Project.

Background: Research indicates that risky play benefits children's risk assessment and risk management skills and offers several positive health effects such as resilience, social skills, physical activity, well-being, and involvement. There are also indications that the lack of risky play and autonomy increases the likelihood of anxiety. Despite its well-documented importance, and the willingness of children to engage in risky play, this type of play is increasingly restricted.

The HI-FIVE Trial: A Prospective Trial Using 4-Dimensional Ga Ventilation-Perfusion Positron Emission Tomography-Computed Tomography for Functional Lung Avoidance in Locally Advanced Non-small Cell Lung Cancer.

Purpose: Functional lung avoidance (FLA) radiation therapy aims to spare regions of functional lung to reduce toxicity. We report the results of the first prospective trial of FLA using 4-dimensional gallium 68 ventilation-perfusion positron emission tomography-computed tomography (Ga-4D-V/Q PET/CT).

Methods And Materials: Inclusion criteria required a diagnosis of stage III non-small cell lung cancer and the ability to undergo radical-intent chemoradiation therapy.

Distinct Interaction Modes for the Eukaryotic RNA Polymerase Alpha-like Subunits.

Eukaryotic DNA-dependent RNA polymerases (Pols I-III) encode two distinct alpha-like heterodimers where one is shared between Pols I and III, and the other is unique to Pol II. Human alpha-like subunit mutations are associated with several diseases including Treacher Collins Syndrome (TCS), 4H leukodystrophy, and primary ovarian sufficiency. Yeast is commonly used to model human disease mutations, yet it remains unclear whether the alpha-like subunit interactions are functionally similar between yeast and human homologs.

Long-Term Outcomes of TROG 13.01 SAFRON II Randomized Trial of Single- Versus Multifraction Stereotactic Ablative Body Radiotherapy for Pulmonary Oligometastases.

JCO In a randomized phase II clinical trial, the Trans Tasman Radiation Oncology Group compared single- versus multifraction stereotactic ablative body radiotherapy (SABR) in 90 patients with 133 oligometastases to the lung. The study found no differences in safety, efficacy, systemic immunogenicity, or survival between arms, with single-fraction SABR picked as the winner on the basis of cost-effectiveness. In this article, we report the final updated survival outcome analysis.

Comparison of Changes in Pulmonary Function After Stereotactic Body Radiation Therapy Versus Conventional 3-Dimensional Conformal Radiation Therapy for Stage I and IIA Non-Small Cell Lung Cancer: An Analysis of the TROG 09.02 (CHISEL) Phase 3 Trial.

Purpose: The TROG 09.02 CHISEL trial compared conventional radiation therapy (CRT) with stereotactic body radiation therapy (SBRT) in patients with inoperable early-stage non-small cell lung cancer. Patients randomized to SBRT had less local failure and improved overall survival.