Total testosterone, sex hormone-binding globulin, and free testosterone concentrations and risk of primary liver cancer: A prospective analysis of 200,000 men and 180,000 postmenopausal women.

In most countries, males have ~2-3 times higher incidence of primary liver cancer than females. Sex hormones have been hypothesized to contribute to these differences, but the evidence remains unclear. Using data from the UK Biobank, which included ~200,000 males and ~180,000 postmenopausal females who provided blood samples at recruitment, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for a doubling in hormone concentration from multivariable adjusted Cox regression for circulating total testosterone, sex-hormone binding globulin (SHBG), and free testosterone concentrations and risk of primary liver cancer.

Tracking and Transition Probability of Blood Pressure From Childhood to Midadulthood.

Importance: Despite its relevance for pediatric blood pressure (BP) screening, the long-term predictive utility and natural progression of pediatric BP classification remain understudied.

Objective: To evaluate BP tracking from childhood to midadulthood using the American Academy of Pediatrics (AAP) thresholds and estimate transition probabilities among BP classifications over time considering multiple time points.

Design, Setting, And Participants: The analyses were performed in 2023 using data gathered from September 1980 to August 2018 within the longitudinal Cardiovascular Risk in Young Finns Study.

Evaluating campaign concepts aimed at replacing sugar-sweetened beverages with water.

Issue Addressed: The study addresses the global health concern of sugar overconsumption, particularly focusing on the prevalence of sugar-sweetened beverage consumption among young people.

Methods: The study tested three different health promotion campaign concepts, designed to reduce sugar-sweetened beverage intake and promote water consumption as a healthier alternative. A total of 402 young adults (18-29) were recruited from a university campus and an online panel.

A systematic scoping review and content analysis of organizational health literacy responsiveness assessment tools.

The characteristics of health literate organizations have been variously described in recognition that it is important for organizations to respond to the diversity of people's health literacy strengths and challenges. A systematic scoping review was conducted to identify, assess and classify international self-assessment tools aimed at measuring the capability of organizations to embody health literate characteristics. Following the JBI Scoping Manual, a search was conducted in six databases and identified 2693 articles.

Tracking of serum lipid levels from childhood to adulthood: Systematic review and meta-analysis.

Background And Aims: The utility of lipid screening in pediatric settings for preventing adult atherosclerotic cardiovascular diseases partly depends on the lifelong tracking of lipid levels. This systematic review aimed to quantify the tracking of lipid levels from childhood and adolescence to adulthood.

Methods: We systematically searched MEDLINE, Embase, Web of Science, and Google Scholar in March 2022.

Absolute neutrophil count clinical trial eligibility criteria for pediatric oncology phase I and phase I/II trials by sponsorship.

Normal absolute neutrophil count (ANC) variations, as seen with Duffy-null associated neutrophil count (DANC), are not accounted for in trial eligibility, which may contribute to racial enrollment disparities. We describe ANC eligibility for pediatric oncology phase I/II clinical trials according to primary sponsorship from 2010 to 2023 using ClinicalTrials.gov.

Brazilin is a natural product inhibitor of the NLRP3 inflammasome.

Excessive or aberrant NLRP3 inflammasome activation has been implicated in the progression and initiation of many inflammatory conditions; however, currently no NLRP3 inflammasome inhibitors have been approved for therapeutic use in the clinic. Here we have identified that the natural product brazilin effectively inhibits both priming and activation of the NLRP3 inflammasome in cultured murine macrophages, a human iPSC microglial cell line and in a mouse model of acute peritoneal inflammation. Through computational modeling, we predict that brazilin can adopt a favorable binding pose within a site of the NLRP3 protein which is essential for its conformational activation.

An extensive disulfide bond network prevents tail contraction in Agrobacterium tumefaciens phage Milano.

A contractile sheath and rigid tube assembly is a widespread apparatus used by bacteriophages, tailocins, and the bacterial type VI secretion system to penetrate cell membranes. In this mechanism, contraction of an external sheath powers the motion of an inner tube through the membrane. The structure, energetics, and mechanism of the machinery imply rigidity and straightness.

Associations between types and sources of dietary carbohydrates and liver fat: a UK Biobank study.

Background And Aims: Excess energy intake can lead to metabolic dysfunction-associated steatotic liver disease (MASLD), but the relationship between dietary carbohydrate intake and liver fat content remains unclear. This study aimed to examine the associations between types and sources of dietary carbohydrates and liver fat content.

Methods: UK Biobank participants with no pre-existing diabetes, liver disease or cardiovascular disease reported dietary intake of types and sources of carbohydrates (total carbohydrates, free sugars, non-free sugars, starch from whole grains, starch from refined grains, and fibre) on at least two 24-h dietary assessments.

Neck and capsid architecture of the robust Agrobacterium phage Milano.

Large gaps exist in our understanding of how bacteriophages, the most abundant biological entities on Earth, assemble and function. The structure of the "neck" region, where the DNA-filled capsid is connected to the host-recognizing tail remains poorly understood. We describe cryo-EM structures of the neck, the neck-capsid and neck-tail junctions, and capsid of the Agrobacterium phage Milano.

Increased dietary fiber is associated with weight loss among Full Plate Living program participants.

Introduction: Prior studies have demonstrated that an intake of foods rich in dietary fiber is associated with a favorable impact on health status and body weight. However, the association between fiber intake and weight loss has not been well-studied in employer settings. This research aimed to assess the relationship between dietary fiber and weight loss among individuals participating in the Full Plate Living (FPL) program.

Associations between types and sources of dietary carbohydrates and cardiovascular disease risk: a prospective cohort study of UK Biobank participants.

Background: Recent studies have reported that the associations between dietary carbohydrates and cardiovascular disease (CVD) may depend on the quality, rather than the quantity, of carbohydrates consumed. This study aimed to assess the associations between types and sources of dietary carbohydrates and CVD incidence. A secondary aim was to examine the associations of carbohydrate intakes with triglycerides within lipoprotein subclasses.

A Study of the Reliability, Validity, and Physiological Changes of Sit-to-Stand Tests in People With Heart Failure.

Purpose: The objective of this study was to describe the psychometric properties and physiological response of the five times sit-to-stand (STST-5) and 60-sec sit-to-stand test (STST-60) in adults with heart failure (HF).

Methods: People with HF enrolled in a 12-wk exercise rehabilitation program completed two STST-5 and two STST-60 as part of their usual baseline and follow-up assessments. Test-retest reliability, validity, and responsiveness of the two STSTs were described.

Evaluation of the New Individual Fatty Acid Dataset for UK Biobank: Analysis of Intakes and Sources in 207,997 Participants.

The Oxford WebQ is an online 24 h dietary assessment tool used by several large prospective studies. This study describes the creation of the new individual fatty acid (FA) dataset for the Oxford WebQ and reports intakes and sources of dietary individual FAs in the UK Biobank. Participants who completed ≥1 (maximum of five) 24 h dietary assessments were included ( = 207,997).

Health Benefits of a 16-Week Whole Food, High Fiber, Plant Predominant Diet among U.S. Employees.

Purpose: To assess improvements in eating behaviors and health measures among adults participating in a whole food plant predominant diet, Full Plate Living (FPL) program.

Design: Retrospective, post hoc analysis of self-reported 16-week pre-post participant data obtained over a 3 year program period (2017-19).

Setting: Wellness offering for employees in Southwest U.

Intra-S phase checkpoint kinase Chk1 dissociates replication proteins Treslin and TopBP1 through multiple mechanisms during replication stress.

Replication stress impedes DNA polymerase progression causing activation of the ataxia telangiectasia and Rad3-related signaling pathway, which promotes the intra-S phase checkpoint activity through phosphorylation of checkpoint kinase 1 (Chk1). Chk1 suppresses replication origin firing, in part, by disrupting the interaction between the preinitiation complex components Treslin and TopBP1, an interaction that is mediated by TopBP1 BRCT domain-binding to two cyclin-dependent kinase (CDK) phosphorylation sites, T968 and S1000, in Treslin. Two nonexclusive models for how Chk1 regulates the Treslin-TopBP1 interaction have been proposed in the literature: in one model, these proteins dissociate due to a Chk1-induced decrease in CDK activity that reduces phosphorylation of the Treslin sites that bind TopBP1 and in the second model, Chk1 directly phosphorylates Treslin, resulting in dissociation of TopBP1.

Risk of cancer in regular and low meat-eaters, fish-eaters, and vegetarians: a prospective analysis of UK Biobank participants.

Background: Following a vegetarian diet has become increasingly popular and some evidence suggests that being vegetarian may be associated with a lower risk of cancer overall. However, for specific cancer sites, the evidence is limited. Our aim was to assess the associations of vegetarian and non-vegetarian diets with risks of all cancer, colorectal cancer, postmenopausal breast cancer, and prostate cancer and to explore the role of potential mediators between these associations.

A randomised multiple baseline case series of a novel imagery rescripting protocol for intrusive trauma memories in people with psychosis.

Background And Objectives: There has been limited investigation of therapies targeting trauma-related psychological mechanisms hypothesised to play a role in post-traumatic and psychosis symptoms. Imagery rescripting (ImRs) is a therapeutic technique which involves transforming images, such as episodic memories, to modify associated distressing beliefs. This study is the first ImRs study for psychosis to incorporate experimental controls.

Repurposing Ceritinib Induces DNA Damage and Enhances PARP Inhibitor Responses in High-Grade Serous Ovarian Carcinoma.

PARP inhibitors (PARPi) have activity in homologous recombination (HR) repair-deficient, high-grade serous ovarian cancers (HGSOC). However, even responsive tumors develop PARPi resistance, highlighting the need to delay or prevent the appearance of PARPi resistance. Here, we showed that the ALK kinase inhibitor ceritinib synergizes with PARPis by inhibiting complex I of the mitochondrial electron transport chain, which increases production of reactive oxygen species (ROS) and subsequent induction of oxidative DNA damage that is repaired in a PARP-dependent manner.

Characterization of a -silenced high-grade serous ovarian cancer model during development of PARP inhibitor resistance.

Acquired PARP inhibitor (PARPi) resistance in - or -mutant ovarian cancer often results from secondary mutations that restore expression of functional protein. is a less commonly studied ovarian cancer susceptibility gene whose promoter is sometimes methylated, leading to homologous recombination (HR) deficiency and PARPi sensitivity. For this study, the PARPi-sensitive patient-derived ovarian cancer xenograft PH039, which lacks HR gene mutations but harbors promoter methylation, was selected for PARPi resistance by cyclical niraparib treatment .