The Blind Spot of PSMA-PET Staging? Intraductal Carcinoma of the Prostate Is Overrepresented in Patients With No Uptake Pattern on Prostate-Specific Membrane Antigen Positron Emission Tomography and High-Grade Prostate Cancer.

Purpose: Prostate-specific membrane antigen positron emission tomography (PSMA PET) is increasingly used to diagnose and stage prostate cancer. A PRIMARY score uses anatomical localization and uptake patterns to improve diagnostic accuracy. We evaluated the histopathology of patients with no uptake pattern (PRIMARY score 1) and the prevalence of intraductal carcinoma of the prostate (IDC-P) in this subset compared with those with an uptake pattern (PRIMARY score ≥ 2).

Macrophage Metabolic Reprogramming in Inflammatory Bowel Diseases: From Pathogenesis to Therapy.

Inflammatory bowel disease (IBD), encompassing two subtypes, ulcerative colitis, and Crohn's disease, is a chronic, non-specific gastrointestinal disorder with a complex etiology stemming from various factors. The incidence of IBD has been steadily rising in the past few years, causing great physical and mental strain on patients. Traditional IBD therapeutic drugs include anti-inflammatory drugs, immunosuppressants, and biologics; however, they may have serious adverse effects.

Chronic Pain in Parkinson's Disease: Prevalence, Sex Differences, Regional Anatomy and Comorbidities.

Objective: Chronic pain is prevalent among people living with Parkinson's disease (PD). We analyzed data from 10,631 Australian individuals with PD to assess the prevalence, age and sex differences, severity, anatomical distribution, clinical history, and associated factors.

Methods: We analysed data from 10,631 participants with PD enrolled in the Australian Parkinson's Genetics Study (APGS), an ongoing nationwide cohort.

Nanopore- and AI-empowered microbial viability inference.

Background: The ability to differentiate between viable and dead microorganisms in metagenomic data is crucial for various microbial inferences, ranging from assessing ecosystem functions of environmental microbiomes to inferring the virulence of potential pathogens from metagenomic analysis. Established viability-resolved genomic approaches are labor-intensive as well as biased and lacking in sensitivity.

Results: We here introduce a new fully computational framework that leverages nanopore sequencing technology to assess microbial viability directly from freely available nanopore signal data.

Utilization of Biospecimens as a Biobank Output for Biomedical Research-A Report from the ISBER Annual Meeting 2024 Annual Meeting Roundtable Discussions.

Despite widespread recognition of the need to increase sample utilization, the utilization rate of collected biospecimens for research is still low. In recent years, funders have shifted priorities towards supporting biobanks/collections with high utilization. Given the imperative to upscale sample utilization, a roundtable was held to discuss the considerations for maximizing and measuring the utilization of biospecimens and the output models that biobanks can employ to ensure greater impact and directly attributable advancements in medical science.

Capillary constrictions prime cancer cell tumorigenicity through PIEZO1.

Metastasis is responsible for most cancer-related deaths. However, only a fraction of circulating cancer cells succeed in forming secondary tumours, indicating that adaptive mechanisms during circulation play a part in dissemination. Here, we report that constriction during microcapillary transit triggers reprogramming of melanoma cells to a tumorigenic cancer stem cell-like state.

Effect of Sound Amplification on Central Auditory Plasticity: Endbulb of Held as a Substrate.

Background: Hearing loss is known to cause structural and functional abnormalities in the central auditory pathways. Interventions with hearing aids that amplify acoustic signals have been developed to combat hearing loss. However, little is known about how such devices may affect the brain and mitigate the progression of hearing loss.

Advancing Type 1 Diabetes Management: Integrating Novel Therapies, Technologies, and Adjunctive Approaches.

In type 1 diabetes, a condition that necessitates lifelong exogenous insulin replacement, there is heavy reliance on technology-assisted insulin delivery and glucose monitoring. Yet, people living with type 1 diabetes still face dysglycemia, weight gain, vascular complications, ketoacidosis and severe hypoglycemia, and psychological distress. Cardiovascular and kidney disease remain the leading causes of morbidity and mortality, yet traditional risk factors (smoking, hypertension, hyperlipidemia, obesity, hyperglycemia) incompletely explain this excess burden.

Signal Transducer and Activator of Transcription 3 (STAT3) Variant p.K709N Causes Hyper-IgE Syndrome Likely by Impaired STAT3-Dimer Formation.

STAT3-hyper-IgE syndrome (STAT3-HIES) is an inborn error of immunity caused by heterozygous dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT3). In this study, we evaluate the functional relevance of a previously undescribed heterozygous STAT3 variant in a patient with clinical findings of STAT3-HIES. Flow cytometry, quantitative real-time PCR, pull-down assays, native PAGE, DNA-binding ELISA, and 3D-structural data analysis were performed.

Malat1 regulates female Th2 cell cytokine expression through controlling early differentiation and response to IL-2.

Identifying cell intrinsic regulators of immune sexual dimorphism is critical for treatment of several immunopathologies. We show that Malat1 is required for appropriate cytokine expression in female but not male T helper 2 (Th2) cells. Malat1 deficiency impairs in vitro Th2 differentiation of naïve CD4+ T cells from female mice, characterized by transcriptome-wide effects and suppression of cytokine expression, particularly interleukin (IL)-10.

Dominant negative ATP5F1A variants disrupt oxidative phosphorylation causing neurological disorders.

ATP5F1A encodes the α-subunit of complex V of the respiratory chain, which is responsible for mitochondrial ATP synthesis. We describe 6 probands with heterozygous de novo missense ATP5F1A variants that presented with developmental delay, intellectual disability, and movement disorders. All variants were located at the contact points between the α- and β-subunits.

Increasing pathogenic germline variant diagnosis rates in precision medicine: current best practices and future opportunities.

The accurate diagnosis of pathogenic variants is essential for effective clinical decision making within precision medicine programs. Despite significant advances in both the quality and quantity of molecular patient data, diagnostic rates remain suboptimal for many inherited diseases. As such, prioritisation and identification of pathogenic disease-causing variants remains a complex and rapidly evolving field.

Family history of fracture and fracture risk: a meta-analysis to update the FRAX® risk assessment tool.

Unlabelled: In the largest meta-analysis of international cohorts to date, a family history of fracture is confirmed as a significant BMD-independent predictor of future fracture risk. Parental and sibling histories of fracture carry the same significance for future fracture, including the impact of family hip fracture on future hip fracture risk.

Purpose: We have undertaken a meta-analysis of international prospective cohorts to quantify the relationship between a family history of fracture and future fracture incidence.

Standardization, Education, and Resourcing: The Way Forward for Implementing Polygenic Risk Scores in Hereditary Breast and Ovarian Cancer.

The clinical utility and implementation of polygenic risk scores (PRS) in the setting of personalized risk assessment for hereditary breast and ovarian cancer (HBOC) continues to be investigated. We aimed to explore and analyze genetic healthcare providers' perspectives toward national implementation in Australia, acknowledging the vitality of provider knowledge, priorities, and support. A two-phase exploratory, cross-sectional, mixed-method study was conducted, consisting of semistructured interviews and a national online survey.

DNA methylation biomarkers for the diagnosis and treatment management of breast cancer: where are we now?

Breast cancer is one of the most commonly diagnosed cancers worldwide and is a significant contributor to the global cancer burden. It is a clinically heterogeneous disease and reliable tools are needed to support treatment decisions, including patient risk, prediction of therapeutic response and monitoring patients throughout their cancer journey. DNA methylation alterations are an early occurring, highly pervasive and stable modification during tumorigenesis, making DNA methylation an attractive target for the development of biomarkers.

Prognostic Role of Myocarditis-Like Episodes and Their Treatment in Patients With Pathogenic Desmoplakin Variants.

Background: Inflammatory, myocarditis-like episodes precede and are associated with higher risk of sustained ventricular arrhythmias and heart failure in patients with pathogenic or likely pathogenic desmoplakin (DSP) variants. Whether the recurrence and treatment of myocarditis-like episodes influence the outcomes in this population is unknown. This study aimed to assess the prognostic impact of the recurrence and treatment of myocarditis-like episodes in patients with pathogenic or likely pathogenic DSP variants.

Cardiac arrest while using the toilet: not uncommon and associated with adverse resuscitation profile.

Background: Out-of-hospital cardiac arrest (OHCA) on the toilet has been reported to be common and possibly driven by straining or vagal stimulus. Toilet-associated OHCA may also create a challenging resuscitation environment.

Methods: The national Danish sudden death registry and state-wide Australian End Unexplained Cardiac Death (EndUCD) registry were examined Persons with a fatal OHCA aged 5-50 years with autopsy-confirmed cardiac or unascertained aetiology were included.

JNK pathway suppression mediates insensitivity to combination endocrine therapy and CDK4/6 inhibition in ER+ breast cancer.

CDK4/6 inhibitors in combination with endocrine therapy are now used as front-line treatment for patients with estrogen-receptor positive (ER+) breast cancer. While this combination improves overall survival, the mechanisms of disease progression remain poorly understood. Here, we performed unbiased genome-wide CRISPR/Cas9 knockout screens using endocrine sensitive ER+ breast cancer cells to identify novel drivers of resistance to combination endocrine therapy (tamoxifen) and CDK4/6 inhibitor (palbociclib) treatment.

A near telomere-to-telomere phased genome assembly and annotation for the Australian central bearded dragon Pogona vitticeps.

Background: The central bearded dragon (Pogona vitticeps) is widely distributed in central eastern Australia and adapts readily to captivity. Among other attributes, it is distinctive because it undergoes sex reversal from ZZ genotypic males to phenotypic females at high incubation temperatures. Here, we report an annotated near telomere-to-telomere phased assembly of the genome of a female ZW central bearded dragon.

The Impact of Sedentary Behavior and Physical Activity on Bone Health: A Narrative Review from the Rehabilitation Working Group of the International Osteoporosis Foundation.

Physical activity (PA) and sedentary behavior (SB) are two key lifestyle factors with profound implications for bone health across the lifespan. While PA is recognized for its positive effects on bone mineral density (BMD) and fracture prevention, emerging evidence highlights the detrimental consequences of prolonged sedentary time, independent of PA levels. This review synthesizes current knowledge on the impact of PA and SB on bone health outcomes, focusing on BMD and fracture risk in children, adolescents, adults, and older populations.

2025 ADS/ANZCA/GESA/NACOS clinical practice recommendations on the peri-procedural use of GLP-1/GIP receptor agonists.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for the treatment of type 2 diabetes and/or obesity. The physiological actions of endogenous GLP-1, and synthetic GLP-1RAs include inhibition of gastric emptying. This has peri-procedural implications due to the potential increased risk of retained gastric contents which may result in pulmonary aspiration.

Consensus on acromegaly therapeutic outcomes: an update.

The 15th Acromegaly Consensus Conference in September 2023 updated recommendations on therapeutic outcomes for acromegaly. Since the publication of medical management guidelines in 2018, new pharmacological agents and new treatment approaches have been developed. Fifty-two experts in the management of acromegaly reviewed the current literature and assessed changes in drug approvals, clinical practice standards and management.

Titin-related familial dilated cardiomyopathy: factors associated with disease onset.

Background And Aims: Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv.

Methods: An international multicentre retrospective observational study was performed in families with TTNtv-related DCM.

Body mass index and subsequent fracture risk: A meta-analysis to update FRAX®.

The aim of this international meta-analysis was to quantify the predictive value of body mass index (BMI) for incident fracture and relationship of this risk with age, sex, follow-up time and bone mineral density (BMD). 1 667 922 men and women from 32 countries (63 cohorts), followed for a total of 16.0 million person-years were studied.

variants cause lysosomal and autophagic defects resulting in a hypomyelinating leukodystrophy with epileptic encephalopathy.

encodes a subunit shared by the BLOC-1 and BORC hetero-octameric complexes that regulate various endolysosomal processes. Here, we report the identification of seven distinct variants in in eleven individuals from seven independent families presenting with early psychomotor delay, hypotonia, spasticity, epileptic encephalopathy, optic atrophy, and leuko-axonopathy with hypomyelination. A subset of the affected individuals also have features of hypopigmentation and ocular albinism that are similar, although milder, than those of individuals with BLOC-1-related Hermansky-Pudlak syndrome.