Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.

Using joint genomic-transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS-STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.

Tracking non-genetic evolution from primary to metastatic ccRCC: TRACERx Renal.

While the key aspects of genetic evolution and their clinical implications in clear cell renal-cell carcinoma (ccRCC) are well-documented, how genetic features co-evolve with the phenotype and tumor microenvironment (TME) remains elusive. Here, through joint genomic-transcriptomic analysis of 243 samples from 79 patients recruited to the TRACERx Renal study, we identify pervasive non-genetic intratumor heterogeneity, with over 40% not attributable to genetic alterations. By integrating tumor transcriptomes and phylogenetic structures, we observe convergent evolution to specific phenotypic traits, including cell proliferation, metabolic reprogramming and overexpression of putative cGAS-STING repressors amid high aneuploidy.

Elemental stoichiometry and insect chill tolerance: evolved and plastic changes in organismal Na+ and K+ content in Drosophila.

Acclimation and evolutionary adaptation can produce phenotypic changes that allow organisms to cope with challenges. Determining the relative contributions and the underlying mechanisms driving phenotypic shifts from acclimation and adaptation is of central importance to understanding animal responses to change. Rates of evolution have traditionally been considered slow relative to ecological processes that shape biodiversity.

Intraspecific diversity is critical to population-level risk assessments.

Environmental risk assessment (ERA) is critical for protecting life by predicting population responses to contaminants. However, routine toxicity testing often examines only one genotype from surrogate species, potentially leading to inaccurate risk assessments, as natural populations typically consist of genetically diverse individuals. To evaluate the importance of intraspecific variation in translating toxicity testing to natural populations, we quantified the magnitude of phenotypic variation between 20 Daphnia magna clones exposed to two levels of microcystins, a cosmopolitan cyanobacterial toxin.

A test for microbiome-mediated rescue via host phenotypic plasticity in .

Phenotypic plasticity is a primary mechanism by which organismal phenotypes shift in response to the environment. Host-associated microbiomes often exhibit considerable shifts in response to environmental variation and these shifts could facilitate host phenotypic plasticity, adaptation, or rescue populations from extinction. However, it is unclear how much shifts in microbiome composition contribute to host phenotypic plasticity, limiting our knowledge of the underlying mechanisms of plasticity and, ultimately, the fate of populations inhabiting changing environments.

Transgenerational epigenetic inheritance increases trait variation but is not adaptive.

Understanding processes that can produce adaptive phenotypic shifts in response to rapid environmental change is critical to reducing biodiversity loss. The ubiquity of environmentally induced epigenetic marks has led to speculation that epigenetic inheritance could potentially enhance population persistence in response to environmental change. Yet, the magnitude and fitness consequences of epigenetic marks carried beyond maternal inheritance are largely unknown.

A cohort profile of the Graham Roberts study cohort.

Purpose: The Graham Roberts Study was initiated in 2018 and is the first Trials Within Cohorts (TwiCs) study for bladder cancer. Its purpose is to provide an infrastructure for answering a breadth of research questions, including clinical, mechanistic, and supportive care centred questions for bladder cancer patients.

Participants: All consented patients are those aged 18 or older, able to provide signed informedconsent and have a diagnosis of new or recurrent bladder cancer.

Monkeypox (Mpox) Vaccine Hesitancy Among Mpox Cases: A Qualitative Study.

Human mpox has been an increasing concern in the United States and California since late 2022. While the Jynneos vaccine offers a degree of cross-protection against the disease, vaccine hesitancy is common among those recommended for vaccination. The purpose of this study was to assess vaccine knowledge, facilitators, and barriers to vaccine uptake among individuals previously diagnosed with mpox, or mpox cases, in Santa Clara County, California.

Intraspecific genetic variation is critical to robust toxicological predictions of aquatic contaminants.

Environmental risk assessment is a critical tool for protecting aquatic life and its effectiveness is predicated on predicting how natural populations respond to contaminants. Yet, routine toxicity testing typically examines only one genotype, which may render risk assessments inaccurate as populations are most often composed of genetically distinct individuals. To determine the importance of intraspecific variation in the translation of toxicity testing to populations, we quantified the magnitude of genetic variation within 20 clones derived from one lake using whole genome sequencing and phenotypic assays.

Integrating social services with disease investigation: A randomized trial of COVID-19 high-touch contact tracing.

COVID-19 exposed and exacerbated health disparities, and a core challenge has been how to adapt pandemic response and public health in light of these disproportionate health burdens. Responding to this challenge, the County of Santa Clara Public Health Department designed a model of "high-touch" contact tracing that integrated social services with disease investigation, providing continued support and resource linkage for clients from structurally vulnerable communities. We report results from a cluster randomized trial of 5,430 cases from February to May 2021 to assess the ability of high-touch contact tracing to aid with isolation and quarantine.

ExPeCT: a randomised trial examining the impact of exercise on quality of life in men with metastatic prostate cancer.

Purpose: All patients living with cancer, including those with metastatic cancer, are encouraged to be physically active. This paper examines the secondary endpoints of an aerobic exercise intervention for men with metastatic prostate cancer.

Methods: ExPeCT (Exercise, Prostate Cancer and Circulating Tumour Cells), was a multi-centre randomised control trial with a 6-month aerobic exercise intervention arm or a standard care control arm.

Cyanotoxins accumulate in Lake St. Clair fish yet their fillets are safe to eat.

Consuming fish exposed to cyanobacterial harmful algal blooms (HABs) may be a major route of microcystin toxin exposure to humans. However, it remains unknown whether fish can accumulate and retain microcystins temporally in waterbodies with recurring seasonal HABs, particularly before and after a HAB event when fishing is active. We conducted a field study on Largemouth Bass, Northern Pike, Smallmouth Bass, Rock Bass, Walleye, White Bass, and Yellow Perch to assess the human health risks to microcystin toxicity via fish consumption.

Lake Erie fish safe to eat yet afflicted by algal hepatotoxins.

Toxic harmful algal blooms (HABs) pose serious threats to human health and instances of wildlife death have been documented across taxa. However, the extent of toxicological impacts on wildlife species is largely unresolved, raising uncertainty about the repercussions of increasingly severe HABs on the biodiversity and functioning of aquatic ecosystems. Here, we conducted a field study to assess human health risks from consuming fish caught across all stages of a HAB and to determine the pervasiveness of potentially harmful levels of the cosmopolitan toxin microcystin on fish populations.

Automated vs. manual case investigation and contact tracing for pandemic surveillance: Evidence from a stepped wedge cluster randomized trial.

Background: Case investigation and contact tracing (CICT) is an important tool for communicable disease control, both to proactively interrupt chains of transmission and to collect information for situational awareness. We run the first randomized trial of COVID-19 CICT to investigate the utility of manual (, call-based) vs. automated (, survey-based) CICT for pandemic surveillance.

Evaluation of Allocation Schemes of COVID-19 Testing Resources in a Community-Based Door-to-Door Testing Program.

Importance: Overcoming social barriers to COVID-19 testing is an important issue, especially given the demographic disparities in case incidence rates and testing. Delivering culturally appropriate testing resources using data-driven approaches in partnership with community-based health workers is promising, but little data are available on the design and effect of such interventions.

Objectives: To assess and evaluate a door-to-door COVID-19 testing initiative that allocates visits by community health workers by selecting households in areas with a high number of index cases, by using uncertainty sampling for areas where the positivity rate may be highest, and by relying on local knowledge of the health workers.

Safe provision of systemic anti-cancer treatment for urological cancer patients during COVID-19: a tertiary centre experience in the first wave of COVID-19.

Background: Safe provision of systemic anti-cancer treatment (SACT) during the COVID-19 pandemic remains an ongoing concern amongst clinicians.

Methods: Retrospective analysis on uro-oncology patients who continued or started SACT between 1st March and 31st May 2020 during the pandemic (with 2019 as a comparator).

Results: 441 patients received SACT in 2020 (292 prostate, 101 renal, 38 urothelial, 10 testicular) compared to 518 patients in 2019 (340 prostate, 121 renal, 42 urothelial, 15 testicular).

Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476).

Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multiarm, multistage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3 years after the first results. Standard-of-care (SOC) was androgen deprivation therapy.

Invadopodia play a role in prostate cancer progression.

Background: Invadopodia, actin-rich structures that release metallo-proteases at the interface with extra-cellular matrix, in a punctate manner are thought to be important drivers of tumour invasion. Invadopodia formation has been observed in-vitro and in-vivo in numerous metastatic cell lines derived from multiple tumour types. However, prostate cancer cell lines have not been routinely reported to generate invadopodia and the few instances have always required external stimulation.

Imaging Modality and Frequency in Surveillance of Stage I Seminoma Testicular Cancer: Results From a Randomized, Phase III, Noninferiority Trial (TRISST).

Purpose: Survival in stage I seminoma is almost 100%. Computed tomography (CT) surveillance is an international standard of care, avoiding adjuvant therapy. In this young population, minimizing irradiation is vital.

Direct observation of adaptive tracking on ecological time scales in .

Direct observation of evolution in response to natural environmental change can resolve fundamental questions about adaptation, including its pace, temporal dynamics, and underlying phenotypic and genomic architecture. We tracked the evolution of fitness-associated phenotypes and allele frequencies genome-wide in 10 replicate field populations of over 10 generations from summer to late fall. Adaptation was evident over each sampling interval (one to four generations), with exceptionally rapid phenotypic adaptation and large allele frequency shifts at many independent loci.

The presenting dental status of solid tumours with bone metastases requiring bone-targeting agents - part 1: an overview.

Introduction Dental pre-assessment before bone-targeting agents (BTA) in oncology patients is a well-recognised practice; yet, guidance on this has typically been unable to differentiate between the intricacies of varying oncology groups. This study assesses the presenting dental status of oncology patients with bone metastases (BM) due to commence BTA, to determine whether differences exist with varying tumour groups.Materials and methods Data were retrospectively collected from a dedicated pre-BTA dental assessment clinic.

Qualitative Analysis of Interviews and Focus Groups Exploring Factors Contributing to Adherence to GnRH Agonists in Men with Prostate Cancer.

Objectives: Side effects from the prolonged use of gonadotropin-releasing hormone (GnRH) agonists may lead to nonadherence to the treatment in men with advanced prostate cancer (PCa). We investigated the reasons contributing to nonadherence to GnRH agonists through interviews with men with PCa and focus groups with their health care professionals.

Data Sources: The three stages of the study were validation of themes, interviews with men on GnRH agonists, and focus groups with oncology specialists and clinical nurse specialists.