Insights into the length and breadth of methodologies harnessed to study human telomeres.

Telomeres are protective structures at the end of eukaryotic chromosomes that are strongly implicated in ageing and ill health. They attrition upon every cellular reproductive cycle. Evidence suggests that short telomeres trigger DNA damage responses that lead to cellular senescence.

Canadian colorectal cancer screening programs: How do they measure up using the International Agency for Research on Cancer criteria for organized screening?

Background: Canada has one of the highest incidences of colorectal cancer (CRC) worldwide. CRC screening improves CRC outcomes and is cost-effective. This study compares Canadian CRC screening programs using essential elements of an organized screening program outlined by the International Agency for Research on Cancer (IARC).

SOX2 represses c-MYC transcription by altering the co-activator landscape of the c-MYC super-enhancer and promoter regions.

Our previous studies determined that elevating SOX2 in a wide range of tumor cells leads to a reversible state of tumor growth arrest. Efforts to understand how tumor cell growth is inhibited led to the discovery of a SOX2:MYC axis that is responsible for downregulating c-MYC (MYC) when SOX2 is elevated. Although we had determined that elevating SOX2 downregulates MYC transcription, the mechanism responsible was not determined.

Sustained transmission over two decades of a previously unrecognised MPT64 negative strain in Queensland, Australia: a whole genome sequencing study.

Background: MPT64 is a key protein used for (MTB) complex strain identification. We describe protracted transmission of an MPT64 negative MTB strain in Queensland, Australia, and explore genomic factors related to its successful spread.

Methods: All MPT64 negative strains identified between 2002 and 2022 by the Queensland Mycobacteria Reference Laboratory, and an additional 2 isolates from New South Wales (NSW), were whole genome sequenced.

Co-occurring conditions during pregnancy and hospitalizations in the first year postpartum among persons with opioid use disorder.

Introduction: Pregnant persons with opioid use disorder (OUD) face a multitude of comorbid conditions that may increase the risk of adverse drug and health outcomes. This study characterizes typologies of comorbidities among pregnant persons with OUD and assesses the associations of these typologies with hospitalizations in the first year postpartum.

Methods: A cohort of pregnant persons with OUD at delivery in 2018 were identified in a Pennsylvania statewide hospital dataset (n = 2055).

Impact of the introduction of the national antimicrobial stewardship standard across Queensland Health hospitals: ecological observational study exploring patterns of antimicrobial use.

Background: Antimicrobial stewardship programmes are a critical tool for addressing the rising threat of antimicrobial resistance.

Aim: To determine changes in patterns of antimicrobial use in Queensland public hospitals following introduction of the National Safety and Quality Health Service antimicrobial stewardship standard.

Methods: A retrospective pre/post intervention study was conducted across Queensland public hospitals at the ecological level using Queensland Health's MedTRx database.

Healthcare Providers' and Pregnant People's Preferences for a Preventive to Protect Infants from Serious Illness Due to Respiratory Syncytial Virus.

We assessed the impact of respiratory syncytial virus (RSV) preventive characteristics on the intentions of pregnant people and healthcare providers (HCPs) to protect infants with a maternal vaccine or monoclonal antibodies (mAbs). Pregnant people and HCPs who treated pregnant people and/or infants were recruited via convenience sample from a general research panel to complete a cross-sectional, web-based survey, including a discrete choice experiment (DCE) wherein respondents chose between hypothetical RSV preventive profiles varying on five attributes (effectiveness, preventive type [maternal vaccine vs. mAb], injection recipient/timing, type of medical visit required to receive the injection, and duration of protection during RSV season) and a no-preventive option.

From Qualitative Research to Quantitative Preference Elicitation: An Example in Invasive Meningococcal Disease.

Background: Qualitative research is fundamental for designing discrete choice experiments (DCEs) but is often underreported in the preference literature. We developed a DCE to elicit preferences for vaccination against invasive meningococcal disease (IMD) among adolescents and young people (AYP) and parents and legal guardians (PLG) in the United States. This article reports the targeted literature review and qualitative interviews that informed the DCE design and demonstrates how to apply the recent reporting guidelines for qualitative developmental work in preference studies.

Defining an Optimized Workflow for Enriching and Analyzing Residual Tumor Populations Using Intracellular Markers.

Tumor relapse is well recognized to arise from treatment-resistant residual populations. Strategies enriching such populations for in-depth downstream analyses focus on tumor-specific surface markers; however, enrichment using intracellular biomarkers remains challenging. Using B-cell lymphoma as an exemplar, we demonstrate feasibility to enrich B-cell lymphoma 2 (BCL2) populations, a surrogate marker for t(14;18)+ lymphomas, for use in downstream applications.

Loss-of-function mutations in do not confer delamanid, ethionamide, isoniazid, or pretomanid resistance in .

Results from clinical strains and knockouts of the H37Rv and CDC1551 laboratory strains demonstrated that () is not a resistance-conferring gene for isoniazid, ethionamide, delamanid, or pretomanid in . This difference in the susceptibility to NAD-adduct-forming drugs compared with other mycobacteria may be driven by differences in the absolute intrabacterial NADH concentration.

USP1 Expression Driven by EWS::FLI1 Transcription Factor Stabilizes Survivin and Mitigates Replication Stress in Ewing Sarcoma.

Unlabelled: In this study, we identify USP1 as a transcriptional target of EWS::FLI1 and demonstrate the requisite function of USP1 in Ewing sarcoma (EWS) cell survival in response to endogenous replication stress. EWS::FLI1 oncogenic transcription factor drives most EWS, a pediatric bone cancer. EWS cells display elevated levels of R-loops and replication stress.

Astrocyte-specific Ca activity: Mechanisms of action, experimental tools, and roles in ethanol-induced dysfunction.

Astrocytes are a subtype of non-neuronal glial cells that reside in the central nervous system. Astrocytes have extensive peripheral astrocytic processes that ensheathe synapses to form the tripartite synapse. Through a multitude of pathways, astrocytes can influence synaptic development and structural maturation, respond to neuronal signals, and modulate synaptic transmission.

Psychometric Properties of a Risk Tool Across Indigenous Māori and European Samples in Aotearoa New Zealand: Measurement Invariance, Discrimination, and Calibration for Predicting Criminal Recidivism.

Due to recent legal cases highlighting a lack of cross-ethnicity validity research using correctional risk assessment tools, we evaluated psychometric properties of Dynamic Risk Assessment for Offender Re-entry (DRAOR) scores across Māori ( = 1,812) and New Zealand (NZ) European samples ( = 1,211) in Aotearoa NZ. Using routine administrative data, our analyses suggested scoring properties were invariant across ethnicity for 15 of 19 items. Discrimination properties were also equivalent, but we observed a higher recidivism base rate among Māori participants, consistent with official statistics.

Patient experiences of methadone treatment changes during the first wave of COVID-19: a national community-driven survey.

Background: During COVID-19, the Substance Abuse and Mental Health Services Administration (SAMHSA) allowed Methadone Maintenance Treatment (MMT) programs to relax in-person MMT requirements to reduce COVID-19 exposure. This study examines patient-reported changes to in-person methadone clinic attendance requirements during COVID-19.

Methods: From June 7, 2020, to July 15, 2020, a convenience sample of methadone patients (N = 392) were recruited in collaboration with National Survivors Union (NSU) in 43 states and Washington D.

Enzyme-Triggered l-α/d-Peptide Hydrogels as a Long-Acting Injectable Platform for Systemic Delivery of HIV/AIDS Drugs.

Eradicating HIV/AIDS by 2030 is a central goal of the World Health Organization. Patient adherence to complicated dosage regimens remains a key barrier. There is a need for convenient long-acting formulations that deliver drugs over sustained periods.

An Investigation on the Efficacy of Orotic Acid as a Bio-Nucleating Agent for Poly-Lactic Acid under Quiescent Condition and Injection Molding.

Polylactic acid (PLA) is a bio-based biodegradable polymer and is considered to be an environmentally friendly alternative to petroleum-based polymers for various applications. Neat PLA requires an extended period at elevated temperatures to attain its maximum crystallinity, which can be mitigated by the addition of nucleating agents. Orotic acid is a natural heterocyclic nucleating agent in PLA.

Patient Preferences for Pharmaceutical and Device-Based Treatments for Uncontrolled Hypertension: Discrete Choice Experiment.

Background: Discrete choice experiment is a survey method used to understand how individuals make decisions and to quantify the relative importance of features. Using discrete choice experiment methods, we quantified patient benefit-risk preferences for hypertension treatments, including pharmaceutical and interventional treatments, like renal denervation.

Methods: Respondents from the United States with physician-confirmed uncontrolled hypertension selected between treatments involving a procedure or pills, using a structured survey.

A novel dual epigenetic approach targeting BET proteins and HDACs in Group 3 (MYC-driven) Medulloblastoma.

Background: Medulloblastoma (MB) patients with MYC oncogene amplification or overexpression exhibit extremely poor clinical outcomes and respond poorly to current therapies. Epigenetic deregulation is very common in MYC-driven MB. The bromodomain extra-terminal (BET) proteins and histone deacetylases (HDACs) are epigenetic regulators of MYC transcription and its associated tumorigenic programs.

A diagnostic classifier for pediatric chronic graft-versus-host disease: results of the ABLE/PBMTC 1202 study.

The National Institutes of Health Consensus criteria for chronic graft-versus-host disease (cGVHD) diagnosis can be challenging to apply in children, making pediatric cGVHD diagnosis difficult. We aimed to identify diagnostic pediatric cGVHD biomarkers that would complement the current clinical criteria and help differentiate cGVHD from non-cGVHD. The Applied Biomarkers of Late Effects of Childhood Cancer (ABLE) study, open at 27 transplant centers, prospectively evaluated 302 pediatric patients after hematopoietic cell transplant (234 evaluable).

Impact of harm reduction care in HIV clinical settings on stigma and health outcomes for people with HIV who use drugs: study protocol for a mixed-methods, multisite, observational study.

Introduction: Our previous pilot work suggests relational harm reduction strengthens relationships between people with HIV (PWH) who use drugs and their healthcare providers and improves HIV health outcomes. However, there is limited research examining ways that structural (eg, strategies like syringe service programmes) and/or relational (patient-provider relationship) harm reduction approaches in HIV clinical settings can mitigate experiences of stigma, affect patient-provider relationships and improve outcomes for PWH who use drugs. Our mixed methods, multisite, observational study aims to fill this knowledge gap and develop an intervention to operationalise harm reduction care for PWH who use drugs in HIV clinical settings.

Malignancy Assessment Using Gene Identification in Captured Cells Algorithm for the Prediction of Malignancy in Women With a Pelvic Mass.

Objective: To evaluate the detection of malignancy in women with a pelvic mass by using multiplexed gene expression analysis of cells captured from peripheral blood.

Methods: This was an IRB-approved, prospective clinical study. Eligible patients had a pelvic mass and were scheduled for surgery or biopsy.

A high-resolution single-molecule sequencing-based Arabidopsis transcriptome using novel methods of Iso-seq analysis.

Background: Accurate and comprehensive annotation of transcript sequences is essential for transcript quantification and differential gene and transcript expression analysis. Single-molecule long-read sequencing technologies provide improved integrity of transcript structures including alternative splicing, and transcription start and polyadenylation sites. However, accuracy is significantly affected by sequencing errors, mRNA degradation, or incomplete cDNA synthesis.

Direct Comparison of Chol-siRNA Polyplexes and Chol-DsiRNA Polyplexes Targeting STAT3 in a Syngeneic Murine Model of TNBC.

RNA interference (RNAi) molecules have tremendous potential for cancer therapy but are limited by insufficient potency after intravenous (IV) administration. We previously found that polymer complexes (polyplexes) formed between 3'-cholesterol-modified siRNA (Chol-siRNA) or DsiRNA (Chol-DsiRNA) and the cationic diblock copolymer PLL[30]-PEG[5K] greatly increase RNAi potency against stably expressed LUC mRNA in primary syngeneic murine breast tumors after daily IV dosing. Chol-DsiRNA polyplexes, however, maintain LUC mRNA suppression for ~48 h longer after the final dose than Chol-siRNA polyplexes, which suggests that they are the better candidate formulation.