When Health Care Needs a Centre, When It Doesn't, and Why It Matters.

This paper examines the concept of centredness in health care, with a particular focus on person-centred care. While the principle of centring care is widely accepted, the concept of a 'centre' remains ambiguous, complicating its implementation. The paper defines centredness, questions the necessity of a central focus and explores alternative models.

HCV- and HBV-mediated liver cancer converge on similar transcriptomic landscapes and immune profiles.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide, and a large proportion is attributable to viral causes, including hepatitis B (HBV) and C viruses (HCV). The pathogenesis of viral-mediated HCC can differ between HBV and HCV, but it is unclear how much these differences influence the tumors' final molecular and immune profiles. Additionally, there are known sex differences in the molecular etiology of HCC, but sex differences have not been explored in the context of viral-mediated HCC.

Autoinflammation in patients with leukocytic CBL loss of heterozygosity is caused by constitutive ERK-mediated monocyte activation.

Patients heterozygous for germline CBL loss-of-function (LOF) variants can develop myeloid malignancy, autoinflammation, or both, if some or all of their leukocytes become homozygous for these variants through somatic loss of heterozygosity (LOH) via uniparental isodisomy. We observed an upregulation of the inflammatory gene expression signature in whole blood from these patients, mimicking monogenic inborn errors underlying autoinflammation. Remarkably, these patients had constitutively activated monocytes that secreted 10 to 100 times more inflammatory cytokines than those of healthy individuals and CBL LOF heterozygotes without LOH.

Who uses yoga and why? Who teaches yoga? Insights from a national survey in New Zealand.

Introduction Globally, yoga has gained popularity as a health-promoting and disease-prevention discipline. The common health conditions prompting yoga use include musculoskeletal disorders, mental health conditions, asthma, fibromyalgia, arthritis, diabetes, and cancers. Although the therapeutic benefits of using yoga are well documented, little is known about the characteristics of yoga instructors (YIs) and yoga users (YUs) in New Zealand (NZ).

Cost-effective solutions for high-throughput enzymatic DNA methylation sequencing.

Characterizing DNA methylation patterns is important for addressing key questions in evolutionary biology, geroscience, and medical genomics. While costs are decreasing, whole-genome DNA methylation profiling remains prohibitively expensive for most population-scale studies, creating a need for cost-effective, reduced representation approaches (i.e.

Design and implementation of an asynchronous online course-based undergraduate research experience (CURE) in computational genomics.

As genomics technologies advance, there is a growing demand for computational biologists trained for genomics analysis but instructors face significant hurdles in providing formal training in computer programming, statistics, and genomics to biology students. Fully online learners represent a significant and growing community that can contribute to meet this need, but they are frequently excluded from valuable research opportunities which mostly do not offer the flexibility they need. To address these opportunity gaps, we developed an asynchronous course-based undergraduate research experience (CURE) for computational genomics specifically for fully online biology students.

Immune-Mediated Liver Effects Associated With Administration of a Human Anti-IL-21 Receptor Antibody (ATR-107) in Rats.

The toxicity of ATR-107, a human anti-interleukin-21 receptor (IL-21R) monoclonal antibody (mAb), was evaluated in CD-1 mice and cynomolgus monkeys after single-dose intravenous (IV) administration, and in Sprague-Dawley (SD) rats and cynomolgus monkeys after weekly IV and subcutaneous (SC) administration in 13-week toxicity studies that included recovery. Adverse liver necrosis, diffuse bridging fibrosis, and higher liver enzymes occurred in rats in the low-dose IV group (10 mg/kg), but not at 50 or 250 mg/kg IV, and not following SC administration despite overlapping systemic ATR-107 exposures. Similar findings were not seen in mice or cynomolgus monkeys.

HCV- and HBV-mediated liver cancer converge on similar transcriptomic landscapes and immune profiles.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide, and a large proportion of HCC is attributable to viral causes including hepatitis B (HBV) and C virus (HCV). The pathogenesis of viral-mediated HCC can differ between HBV and HCV, but it is unclear how much these differences influence the tumors' final molecular and immune profiles. Additionally, there are known sex differences in the molecular etiology of HCC, but sex differences have not been explored in the context of viral-mediated HCC.

Distinct sets of molecular characteristics define tumor-rejecting neoantigens.

Challenges in identifying tumor-rejecting neoantigens limit the efficacy of neoantigen vaccines to treat cancers, including cutaneous squamous cell carcinoma (cSCC). A minority of human cSCC tumors shared neoantigens, supporting the need for personalized vaccines. Using a UV-induced mouse cSCC model which recapitulated the mutational signature and driver mutations found in human disease, we found that CD8 T cells constrain cSCC.

Pharmacokinetics, pharmacodynamics, and toxicity of a PD-1-targeted IL-15 in cynomolgus monkeys.

PF-07209960 is a novel bispecific fusion protein composed of an anti-PD-1 antibody and engineered IL-15 cytokine mutein with reduced binding affinity to its receptors. The pharmacokinetics (PK), pharmacodynamics (PD), and toxicity of PF-07209960 were evaluated following once every other week subcutaneous (SC) or intravenous (IV) administration to cynomolgus monkeys in a repeat-dose PKPD (0.01-0.

Standardizing default electronic health record tools to improve safety for hospitalized patients with Parkinson's disease.

Electronic Health Record (EHR) systems are often configured to address challenges and improve patient safety for persons with Parkinson's disease (PWP). For example, EHR systems can help identify Parkinson's disease (PD) patients across the hospital by flagging a patient's diagnosis in their chart, preventing errors in medication and dosing through the use of clinical decision support, and supplementing staff education through care plans that provide step-by-step road maps for disease-based care of a specific patient population. However, most EHR-based solutions are locally developed and, thus, difficult to scale widely or apply uniformly across hospital systems.

Poor Oral Health Is Associated With Inflammation, Aortic Valve Calcification, and Brain Volume Among Forager-Farmers.

Poor oral health is associated with cardiovascular disease and dementia. Potential pathways include sepsis from oral bacteria, systemic inflammation, and nutritional deficiencies. However, in post-industrialized populations, links between oral health and chronic disease may be confounded because the lower socioeconomic exposome (poor diet, pollution, and low physical activity) often entails insufficient dental care.

Testosterone is positively associated with coronary artery calcium in a low cardiovascular disease risk population.

Background: In industrialized populations, low male testosterone is associated with higher rates of cardiovascular mortality. However, coronary risk factors like obesity impact both testosterone and cardiovascular outcomes. Here, we assess the role of endogenous testosterone on coronary artery calcium in an active subsistence population with relatively low testosterone levels, low cardiovascular risk and low coronary artery calcium scores.

PTEN deficiency exposes a requirement for an ARF GTPase module for integrin-dependent invasion in ovarian cancer.

Dysregulation of the PI3K/AKT pathway is a common occurrence in high-grade serous ovarian carcinoma (HGSOC), with the loss of the tumour suppressor PTEN in HGSOC being associated with poor prognosis. The cellular mechanisms of how PTEN loss contributes to HGSOC are largely unknown. We here utilise time-lapse imaging of HGSOC spheroids coupled to a machine learning approach to classify the phenotype of PTEN loss.

ε is associated with higher fecundity in a natural fertility population.

In many populations, the aε (ε) allele increases the risk for several chronic diseases of aging, including dementia and cardiovascular disease; despite these harmful effects at later ages, the ε allele remains prevalent. We assess the impact of ε on fertility and its proximate determinants (age at first reproduction, interbirth interval) among the Tsimane, a natural fertility population of forager-horticulturalists. Among 795 women aged 13 to 90 (20% ε carriers), those with at least one ε allele had 0.

Ocular Safety and Toxicokinetics of Bevacizumab-bvzr (Zirabev), a Bevacizumab Biosimilar, Administered to Cynomolgus Monkeys by Intravitreal Injection.

Bevacizumab-bvzr (Zirabev), a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor and a biosimilar to bevacizumab, is approved for intravenous administration for various indications worldwide. The objectives of this study were to evaluate the ocular toxicity, systemic tolerability, and toxicokinetics (TKs) of bevacizumab-bvzr following repeat intravitreal (IVT) injection to cynomolgus monkeys. Male monkeys were administered saline, vehicle, or bevacizumab-bvzr at 1.

Natural selection of immune and metabolic genes associated with health in two lowland Bolivian populations.

A growing body of work has addressed human adaptations to diverse environments using genomic data, but few studies have connected putatively selected alleles to phenotypes, much less among underrepresented populations such as Amerindians. Studies of natural selection and genotype-phenotype relationships in underrepresented populations hold potential to uncover previously undescribed loci underlying evolutionarily and biomedically relevant traits. Here, we worked with the Tsimane and the Moseten, two Amerindian populations inhabiting the Bolivian lowlands.

The role of Neanderthal introgression in liver cancer.

Background: Neanderthal introgressed DNA has been linked to different normal and disease traits including immunity and metabolism-two important functions that are altered in liver cancer. However, there is limited understanding of the relationship between Neanderthal introgression and liver cancer risk. The aim of this study was to investigate the relationship between Neanderthal introgression and liver cancer risk.

Characterization of Morreton virus as an oncolytic virotherapy platform for liver cancers.

Background: Morreton virus (MORV) is an oncolytic Vesiculovirus , genetically distinct from vesicular stomatitis virus (VSV).

Aim: To report that MORV induced potent cytopathic effects (CPEs) in cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) in vitro models.

Approach And Results: In preliminary safety analyses, high intranasal doses (up to 10 10 50% tissue culture infectious dose [TCID 50 ]) of MORV were not associated with significant adverse effects in immune competent, non-tumor-bearing mice.

Regulatory Experience Assessing the Carcinogenic Potential of a Monoclonal Antibody Inhibiting PCSK9, Bococizumab, Including a 2-Year Carcinogenicity Study in Rats.

Bococizumab is an anti-PCSK9 monoclonal antibody that was intended for the treatment of hypercholesterolemia. After reviewing the 6-month rat toxicity study data, in which there was a low spontaneous tumor incidence, unrelated to bococizumab administration, the U.S.