Anatomical, subset, and HIV-dependent expression of viral sensors and restriction factors.

We developed viral sensor and restriction factor-cytometry by time of flight (VISOR-CyTOF), which profiles 19 viral sensors and restriction factors (VISORs) simultaneously in single cells, and applied it to 41 postmortem tissues from people with HIV. Mucosal myeloid cells are well equipped with SAMHD1 and sensors of viral capsid and DNA while CD4 T cells are not. In lymph node CD4 Tfh, VISOR expression patterns reflect those favoring integration but blocking HIV gene expression, thus favoring viral latency.

Aurora B inhibition induces hyper-polyploidy and loss of long-term proliferative potential in RB and p53 defective cells.

Polyploidy is a common outcome of chemotherapies, but there is conflicting evidence as to whether polyploidy is an adverse, benign or even favourable outcome. We show Aurora B kinase inhibitors efficiently promote polyploidy in many cell types, resulting in the cell cycle exit in RB and p53 functional cells, but hyper-polyploidy in cells with loss of RB and p53 function. These hyper-polyploid cells (>8n DNA content) are viable but have lost long-term proliferative potential in vitro and fail to form tumours in vivo.

Barriers to and facilitators of breast, cervical and colorectal cancer screening and cancer screening histories of Métis people in Alberta, Canada.

Comprehensive evaluation of cancer screening activities based on individual experiences is urgently needed to address the burden of cancer among Métis people. In this co-designed and co-led study, a cancer screening questionnaire developed for Métis people to evaluate their cancer screening histories and to explore barriers and facilitators to cancer screening was used. Adult Métis Albertans were invited to participate in the anonymous survey through a multi-modal strategy used for community consultations.

Aurora B inhibitors promote RB hypophosphorylation and senescence independent of p53-dependent CDK2/4 inhibition.

Aurora B kinase (AURKB) inhibitors have been trialled in a range of different tumour types but are not approved for any indication. Expression of the human papilloma virus (HPV) oncogenes and loss of retinoblastoma (RB) protein function has been reported to increase sensitivity to AURKB inhibitors but the mechanism of their contribution to sensitivity is poorly understood. Two commonly reported outcomes of AURKB inhibition are polyploidy and senescence, although their relationship is unclear.

Selection of DNA aptamers against Chikungunya virus Envelope 2 Protein and their application in sandwich ELASA.

Chikungunya fever, caused by Chikungunya virus (CHIKV) exhibits clinical features that mimic that of other arbovirus infections such as dengue. CHIKV Envelope 2 (E2) protein, an antigenic epitope of CHIKV, has been identified as an ideal marker for diagnostics. The current CHIKV antigen detection tests are largely based on antibodies but are beleaguered by issues such as sensitivity to high temperature, expensive and prone to batch-to-batch variations.

New Zealand's world-first smokefree legislation 'goes up in smoke': A setback in ending the tobacco epidemic.

For several decades, Aotearoa New Zealand has maintained a relatively strict regulatory approach towards tobacco. In response to the significant impact of tobacco-related illnesses, many countries worldwide have worked to enhance tobacco control measures. These efforts include introducing plain tobacco packaging with graphic health warnings, improving access to smoking cessation services and offering supportive treatments for tobacco dependence.

Exploring the role of physician associates in Aotearoa New Zealand primary health care.

Introduction New Zealand's health care system faces significant shortages in health care workers. To address workforce challenges and meet the population's health needs, health care systems around the world have introduced new clinical roles, such as physician associates/assistants (PAs) into existing health care teams. Aim This article aims to examine the benefits, challenges, and broader implications of regulating PAs in the context of New Zealand's primary care sector, with a specific emphasis on how it may impact general practice.

Understanding the "Infodemic" Threat: A Case Study of the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic is notable among infectious diseases for its distinctive impact, which has halted millions of livelihoods owing to strict social distancing rules and lockdowns. Consequently, millions of individuals have turned to online sources, particularly social media, to remain informed about the virus. The transition to digital sources has resulted in an abundance of information, including both accurate and misleading or false content being shared and consumed on online platforms, contributing to what is commonly referred to as an "infodemic.

Impact of individual level uncertainty of lung cancer polygenic risk score (PRS) on risk stratification.

Background: Although polygenic risk score (PRS) has emerged as a promising tool for predicting cancer risk from genome-wide association studies (GWAS), the individual-level accuracy of lung cancer PRS and the extent to which its impact on subsequent clinical applications remains largely unexplored.

Methods: Lung cancer PRSs and confidence/credible interval (CI) were constructed using two statistical approaches for each individual: (1) the weighted sum of 16 GWAS-derived significant SNP loci and the CI through the bootstrapping method (PRS-16-CV) and (2) LDpred2 and the CI through posteriors sampling (PRS-Bayes), among 17,166 lung cancer cases and 12,894 controls with European ancestry from the International Lung Cancer Consortium. Individuals were classified into different genetic risk subgroups based on the relationship between their own PRS mean/PRS CI and the population level threshold.

ACC and treatment injuries: is it time to rethink injury causation?

In Aotearoa New Zealand, personal injuries resulting from medical treatment are covered under the Accident Compensation Act 2001. However, before victims of medical injury can receive cover and compensation, they must first satisfy several legal tests. Much criticism and legal action have surrounded the interpretation and application of these legal tests, primarily because of its focus lying on injury causation instead of supporting the incapacitated.

Potential applications and implications of large language models in primary care.

The recent release of highly advanced generative artificial intelligence (AI) chatbots, including ChatGPT and Bard, which are powered by large language models (LLMs), has attracted growing mainstream interest over its diverse applications in clinical practice, including in health and healthcare. The potential applications of LLM-based programmes in the medical field range from assisting medical practitioners in improving their clinical decision-making and streamlining administrative paperwork to empowering patients to take charge of their own health. However, despite the broad range of benefits, the use of such AI tools also comes with several limitations and ethical concerns that warrant further consideration, encompassing issues related to privacy, data bias, and the accuracy and reliability of information generated by AI.

Matched analysis of detailed peripheral blood and tumor immune microenvironment profiles in bladder cancer.

Bladder cancer and therapy responses hinge on immune profiles in the tumor microenvironment (TME) and blood, yet studies linking tumor-infiltrating immune cells to peripheral immune profiles are limited. DNA methylation cytometry quantified TME and matched peripheral blood immune cell proportions. With tumor immune profile data as the input, subjects were grouped by immune infiltration status and consensus clustering.

Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2.

Long COVID (LC) occurs after at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, yet its etiology remains poorly understood. We used 'omic" assays and serology to deeply characterize the global and SARS-CoV-2-specific immunity in the blood of individuals with clear LC and non-LC clinical trajectories, 8 months postinfection. We found that LC individuals exhibited systemic inflammation and immune dysregulation.

Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies.

Background: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer.

Methods: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants.

CYP2A6 Activity and Cigarette Consumption Interact in Smoking-Related Lung Cancer Susceptibility.

Unlabelled: Cigarette smoke, containing both nicotine and carcinogens, causes lung cancer. However, not all smokers develop lung cancer, highlighting the importance of the interaction between host susceptibility and environmental exposure in tumorigenesis. Here, we aimed to delineate the interaction between metabolizing ability of tobacco carcinogens and smoking intensity in mediating genetic susceptibility to smoking-related lung tumorigenesis.

Identification of genetically predicted DNA methylation markers associated with non-small cell lung cancer risk among 34,964 cases and 448,579 controls.

Background: Although the associations between genetic variations and lung cancer risk have been explored, the epigenetic consequences of DNA methylation in lung cancer development are largely unknown. Here, the genetically predicted DNA methylation markers associated with non-small cell lung cancer (NSCLC) risk by a two-stage case-control design were investigated.

Methods: The genetic prediction models for methylation levels based on genetic and methylation data of 1595 subjects from the Framingham Heart Study were established.

Evaluation of the Catheter Clamp over Hydrophilic Guide Wire Central Venous Catheter Exchange Technique for Air Embolism Prophylaxis in an In Vitro Model.

Purpose: To develop a reproducible in vitro model simulating central venous catheter (CVC) exchange with high potential for air embolization and test the hypothesis that a closed catheter clamp over hydrophilic guide wire exchange technique will significantly reduce the volume of air introduced during CVC exchange.

Materials And Methods: The model consisted of a 16-F valved sheath, 240-mL container, and pressure transducer submerged in water in a 1,200-mL suction canister system. Continuous wall suction was applied to the canister to maintain negative pressure at -7 mm Hg or -11 mm Hg.