Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Connections among family socioeconomic status, aerobic fitness, executive function, and the positive experiences of childhood physical activity.

A family's socioeconomic status (SES) can be linked to a child's physical and cognitive health, with children from low-SES families often experiencing poor developmental outcomes. Early positive childhood experiences that include structured and unstructured physical activities (SUPAs) offer a potential avenue to promote positive health and cognitive development during early childhood. However, prior to school entry, it is not well-understood whether SES is related to participation in SUPAs or how SUPAs relate to early health and cognitive indicators such as aerobic fitnessand executive function (EF).

Bioisosteric replacement of pyridoxal-5'-phosphate to pyridoxal-5'-tetrazole targeting Bacillus subtilis GabR.

Antimicrobial resistance is a significant cause of mortality globally due to infections, a trend that is expected to continue to rise. As existing treatments fail and new drug discovery slows, the urgency to develop novel antimicrobial therapeutics grows stronger. One promising strategy involves targeting bacterial systems exclusive to pathogens, such as the transcription regulator protein GabR.

Trans-Specific Polymorphisms Between Cryptic Daphnia Species Affect Fitness and Behavior.

Shared polymorphisms, loci with identical alleles across species, are of unique interest in evolutionary biology as they may represent cases of selection maintaining ancient genetic variation post-speciation, or contemporary selection promoting convergent evolution. In this study, we investigate the abundance of shared polymorphism between two members of the Daphnia pulex species complex. We test whether the presence of shared mutations is consistent with the action of balancing selection or alternative hypotheses such as hybridization, incomplete lineage sorting or convergent evolution.

COVID-19-related lockdowns and changes in overweight and obesity, movement behaviours, diet quality, and health-related quality of life among regional Australian primary school children: A repeat cross-sectional study.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, the Australian state of Victoria (in particular, its capital, Melbourne) experienced some of the longest lockdowns in the world.

Objective: This repeated cross-sectional study examined changes between March to June 2019 (pre-pandemic) and April to August 2022 (6 to 11 months following pandemic-related lockdowns) in overweight and obesity prevalence, physical activity, sedentary behaviour, sleep, diet quality, and health-related quality of life (HRQoL) among primary school children in north-east Victoria, Australia.

Methods: Height and weight were measured for Grade 2, 4, and 6 students in 2019 (3889 children) and 2022 (1816 children).

Overall survival, cause of death and time interval between diagnosis and death after type B acute aortic dissection (TBAAD).

Objectives: This study aimed to assess survival rates and the causes of both early and late mortality in patients with Stanford type B aortic dissection (TBAAD).

Methods: A retrospective analysis was conducted on all consecutive patients presenting with TBAAD from 2000 to 2018 at a single tertiary care center. The primary end-point was early (<3 months) and late (>3 months) survival following TBAAD, with causes of both early and late mortality evaluated.

Understanding European patterns of deprescribing antithrombotic medication during end-of-life care in patients with cancer.

Background: Even though antithrombotic therapy (ATT) probably has little or even negative effect on the well-being of patients with cancer near the end of life, it is often continued until death, possibly leading to excess bleeding complications, increased disease burden, reduced quality of life and higher healthcare costs.

Aim: To explore and describe European practice patterns and perspectives of healthcare professionals from different disciplines and specialties on ATT in the end-of-life care (EOLC) of patients with cancer.

Methods: We performed a two-week international cross-sectional survey study using flash-mob research methodology.

Geographically widespread and novel hemotropic mycoplasmas and bartonellae in Mexican free-tailed bats and sympatric North American bat species.

Unlabelled: Bacterial pathogens remain poorly characterized in bats, especially in North America. We describe novel (and in some cases panmictic) hemoplasmas (10.1% positivity) and bartonellae (25.

Necrotizing fasciitis that led to unexpected and fulminant deterioration in less than 24 hours: a case report.

Necrotizing fasciitis (NF) is a rapidly progressing condition with a high mortality rate. The poor prognosis is often due to delayed diagnosis, which is typically made clinically or radiologically. This case report highlights a rare instance of fulminant NF with an atypical presentation-no initial clinical signs and an unusual radiological appearance.

Role of Myofibroblasts in the Repair of Iatrogenic Preterm Membranes Subjected to Mechanical Stimulation.

Objective: We examined the role of myofibroblasts in regulating Cx43 and collagen structure in iatrogenic preterm amniotic membrane (AM) defects subjected to mechanical stimulation.

Method: Preterm AM specimens were collected from women undergoing planned preterm caesarean section after in utero intervention for correction of spina bifida by open fetal surgery (n = 4 patients; preterm delivery at 34 + 0 weeks to 35 + 0 weeks). Control specimens taken 5 cm away from the open fetal surgery defect site were compared with wound edge AM.

Immediate Treatment of Seizure Clusters: A Conceptual Roadmap to Expedited Seizure Management.

Some patients with epilepsy continue to have seizures despite daily treatment with antiseizure medications. This includes seizure clusters (also known as acute repetitive seizures), which are an increase in seizure frequency that is different from the usual seizure pattern for that patient. In the literature, the term "rescue" is used for pharmacologic treatment for seizure clusters, but clarity regarding timing or whether a caregiver or patient should wait until a moment of life-threatening urgency before administering the medication is lacking.

DNA methylation correlates with transcriptional noise in response to elevated pCO in the eastern oyster ().

Ocean acidification significantly affects marine calcifiers like oysters, warranting the study of molecular mechanisms like DNA methylation that contribute to adaptive plasticity in response to environmental change. However, a consensus has not been reached on the extent to which methylation modules gene expression, and in turn plasticity, in marine invertebrates. In this study, we investigated the impact of pCO on gene expression and DNA methylation in the eastern oyster, .

Three-year behavioural, health-related quality of life, and body mass index outcomes from the RESPOND randomized trial.

Objectives: Evaluate RESPOND, a community-based systems intervention to prevent childhood obesity and non-communicable diseases (NCD).

Study Design: Cluster randomized trial of building community capacity to use systems science for child obesity and NCD prevention in 10 local government areas in northeast Victoria, Australia. Four-year stepped wedge trial, adapted due to COVID-19 restrictions METHODS: Cluster randomized trial of building community capacity to use systems science for child obesity and NCD prevention in 10 local government areas in northeast Victoria, Australia.

Studying bats using a One Health lens: bridging the gap between bat virology and disease ecology.

Accumulating data suggest that some bat species host emerging viruses that are highly pathogenic in humans and agricultural animals. Laboratory-based studies have highlighted important adaptations in bat immune systems that allow them to better tolerate viral infections compared to humans. Simultaneously, ecological studies have discovered critical extrinsic factors, such as nutritional stress, that correlate with virus shedding in wild-caught bats.

Environmental Quality, Extreme Heat, and Healthcare Expenditures.

Although the effects of the environment on human health are well-established, the literature on the relationship between the quality of the environment and expenditures on healthcare is relatively sparse and disjointed. In this study, the Environmental Quality Index developed by the Environmental Protection Agency and heatwave days were compared against per capita Medicare spending at the county level. A general additive model with a Markov Random Field smoothing term was used for the analysis to ensure that spatial dependence did not undermine model results.

Improvement of serum folate status in the US women of reproductive age with fortified iodised salt with folic acid (FISFA study).

Objective: Mandatory folic acid fortification of enriched grains has reduced neural tube defect prevalence in several countries. We examined salt as an additional vehicle for folic acid fortification. The primary objective was to examine the change in serum folate concentration after 1 month of consumption of fortified iodised salt with folic acid (FISFA) among women of reproductive age.

Aligning Incentives for Surgical Innovation: Review of the Literature and Best Practices.

Innovation in the clinical surgical space is often generated by the insight and ideas of practicing surgeons whose ideas solve direct and relevant clinical problems with both novel products and reimagined processes. Despite some successes in both product and process development, innovation in the practicing surgical space does not occur with the frequency one might expect and does not consistently result in adoption of profitable or health-improving new products or processes. One barrier to successful innovation is the misalignment of incentives for early-stage innovation in the clinical surgical enterprise.

Noncovalent Inhibition and Covalent Inactivation of Proline Dehydrogenase by Analogs of -Propargylglycine.

The flavoenzyme proline dehydrogenase (PRODH) catalyzes the first step of proline catabolism, the oxidation of l-proline to Δ-pyrroline-5-carboxylate. The enzyme is a target for chemical probe discovery because of its role in the metabolism of certain cancer cells. -propargylglycine is the first and best characterized mechanism-based covalent inactivator of PRODH.

Distal Endovascular Extension After FET: Short and Mid-Term Outcome in a High-Volume Single-Center Experience.

Background: This study aims to investigate results and outcomes of distal endovascular extensions after frozen elephant trunk (FET) procedure.

Methods: Between September 2018 and December 2022, all consecutive patients who underwent thoracic endovascular aortic repair (TEVAR) or complex thoraco-abdominal repair (TAA-EVAR) after FET were included in the study. Patients were assigned to "Aneurysm" group or to "Dissection" group according to underlying patology before FET repair.

The Use of Short Dilator Tip in Endovascular Branched Arch Repair: A Case Series.

Objectives: The aim of the study was to investigate the safety and feasibility of branched endovascular arch repair (b-TEVAR) with a custom-made double or triple inner branched arch endograft using a short dilator tip (35 mm) in patients with aortic arch pathologies.

Methods: Retrospective analysis of all consecutive patients undergoing b-TEVAR with a short dilator tip for the treatment of aortic arch pathologies in a high-volume tertiary center between January 2019 and July 2023. The combined primary endpoint was technical success and perioperative complications caused by the endograft, including tip-induced cardiac injury and trackability issues.