Using a learning health system framework to examine COVID-19 pandemic planning and response at a Canadian Health Centre.

Background: The COVID-19 pandemic has presented a unique opportunity to explore how health systems adapt under rapid and constant change and develop a better understanding of health system transformation. Learning health systems (LHS) have been proposed as an ideal structure to inform a data-driven response to a public health emergency like COVID-19. The aim of this study was to use a LHS framework to identify assets and gaps in health system pandemic planning and response during the initial stages of the COVID-19 pandemic at a single Canadian Health Centre.

Morning chronotype and digestive tract cancers: Mendelian randomization study.

Morning chronotype has been associated with a reduced risk of prostate and breast cancer. However, few studies have examined whether chronotype is associated with digestive tract cancer risk. We conducted a Mendelian randomization (MR) study to assess the associations of chronotype with major digestive tract cancers.

Coffee consumption and cancer risk: a Mendelian randomisation study.

Background: Coffee contains many bioactive chemicals and associations with cancer have been reported in observational studies. In this Mendelian randomisation (MR) study we investigated the causal associations of coffee consumption with a broad range of cancers.

Materials And Methods: Twelve independent genetic variants proxied coffee consumption.

Dispersal, kin aggregation, and the fitness consequences of not spreading sibling larvae.

Dispersal has far-reaching implications for individuals, populations, and communities, especially in sessile organisms. Escaping competition with conspecifics and with kin are theorized to be key factors leading to dispersal as an adaptation. However, manipulative approaches in systems in which adults are sessile but offspring have behaviors is required for a more complete understanding of how competition affects dispersal.

Christine Guthrie (1945-2022).

RNA trailblazer who illuminated splicing mechanics.

L-carnitine, a friend or foe for cardiovascular disease? A Mendelian randomization study.

Background: L-carnitine is emerging as an item of interest for cardiovascular disease (CVD) prevention and treatment, but controversy exists. To examine the effectiveness and safety of L-carnitine, we assessed how genetically different levels of L-carnitine are associated with CVD risk and its risk factors. Given higher CVD incidence and L-carnitine in men, we also examined sex-specific associations.

Cross-fitted instrument: A blueprint for one-sample Mendelian randomization.

Bias from weak instruments may undermine the ability to estimate causal effects in instrumental variable regression (IVR). We present here a new approach to handling weak instrument bias through the application of a new type of instrumental variable coined 'Cross-Fitted Instrument' (CFI). CFI splits the data at random and estimates the impact of the instrument on the exposure in each partition.

Prevalence and distribution of extended-spectrum β-lactamase and AmpC-producing in two New Zealand dairy farm environments.

Antimicrobial resistance (AMR) is a global threat to human and animal health, with the misuse and overuse of antimicrobials being suggested as the main driver of resistance. In a global context, New Zealand (NZ) is a relatively low user of antimicrobials in animal production. However, the role antimicrobial usage on pasture-based dairy farms, such as those in NZ, plays in driving the spread of AMR within the dairy farm environment remains equivocal.

Circulating vitamin C and digestive system cancers: Mendelian randomization study.

Background & Aims: Vitamin C is an antioxidant with a potential role in the prevention of digestive system cancers, but there is yet no consensus whether vitamin C has a causal role in these cancers. The aim of this study was to utilize Mendelian randomization to decipher the potential causal associations of vitamin C with risk of digestive system cancers.

Methods: Ten genetic variants previously found to be significantly associated with circulating vitamin C were used as instrumental variables.

Genetically predicted cortisol levels and risk of venous thromboembolism.

Introduction: In observational studies, venous thromboembolism (VTE) has been associated with Cushing's syndrome and with persistent mental stress, two conditions associated with higher cortisol levels. However, it remains unknown whether high cortisol levels within the usual range are causally associated with VTE risk. We aimed to assess the association between plasma cortisol levels and VTE risk using Mendelian randomization.

Soybean photosynthesis and crop yield are improved by accelerating recovery from photoprotection.

Crop leaves in full sunlight dissipate damaging excess absorbed light energy as heat. This protective dissipation continues after the leaf transitions to shade, reducing crop photosynthesis. A bioengineered acceleration of this adjustment increased photosynthetic efficiency and biomass in tobacco in the field.

Cophylogeny and specificity between cryptic coral species (Pocillopora spp.) at Mo'orea and their symbionts (Symbiodiniaceae).

The congruence between phylogenies of tightly associated groups of organisms (cophylogeny) reflects evolutionary links between ecologically important interactions. However, despite being a classic example of an obligate symbiosis, tests of cophylogeny between scleractinian corals and their photosynthetic algal symbionts have been hampered in the past because both corals and algae contain genetically unresolved and morphologically cryptic species. Here, we studied co-occurring, cryptic Pocillopora species from Mo'orea, French Polynesia, that differ in their relative abundance across depth.

Associations of genetically predicted IL-6 signaling with cardiovascular disease risk across population subgroups.

Background: Interleukin 6 (IL-6) signaling is being investigated as a therapeutic target for atherosclerotic cardiovascular disease (CVD). While changes in circulating high-sensitivity C-reactive protein (hsCRP) are used as a marker of IL-6 signaling, it is not known whether there is effect heterogeneity in relation to baseline hsCRP levels or other cardiovascular risk factors. The aim of this study was to explore the association of genetically predicted IL-6 signaling with CVD risk across populations stratified by baseline hsCRP levels and cardiovascular risk factors.

Arterial Stiffness and Diabetes Risk in Framingham Heart Study and UK Biobank.

Background: Microvascular damage from large artery stiffness (LAS) in pancreatic, hepatic, and skeletal muscles may affect glucose homeostasis. Our goal was to evaluate the association between LAS and the risk of type 2 diabetes using prospectively collected, carefully phenotyped measurements of LAS as well as Mendelian randomization analyses.

Methods: Carotid-femoral pulse wave velocity (CF-PWV) and brachial and central pulse pressure were measured in 5676 participants of the FHS (Framingham Heart Study) without diabetes.

Alcohol consumption and telomere length: Mendelian randomization clarifies alcohol's effects.

Alcohol's impact on telomere length, a proposed marker of biological aging, is unclear. We performed the largest observational study to date (in n = 245,354 UK Biobank participants) and compared findings with Mendelian randomization (MR) estimates. Two-sample MR used data from 472,174 participants in a recent genome-wide association study (GWAS) of telomere length.

Reassessing the causal role of obesity in breast cancer susceptibility: a comprehensive multivariable Mendelian randomization investigating the distribution and timing of exposure.

Background: Previous Mendelian randomization (MR) studies on obesity and risk of breast cancer adopted a small number of instrumental variables and focused mainly on the crude total effect. We aim to investigate the independent causal effect of obesity on breast cancer susceptibility, considering the distribution of fat, covering both early and late life.

Methods: Using an enlarged set of female-specific genetic variants associated with adult general [body mass index (BMI)] and abdominal obesity [waist-to-hip ratio (WHR) with and without adjustment for BMI, WHR and WHRadjBMI] as well as using sex-combined genetic variants of childhood obesity (childhood BMI), we performed a two-sample univariable MR to re-evaluate the total effect of each obesity-related exposure on overall breast cancer (Ncase = 133 384, Ncontrol = 113 789).

Conventional and genetic risk factors for chronic Hepatitis B virus infection in a community-based study of 0.5 million Chinese adults.

Despite universal vaccination of newborns, the prevalence of chronic hepatitis virus B (HBV) infection and the associated disease burden remain high among adults in China. We investigated risk factors for chronic HBV infection in a community-based study of 512,726 individuals aged 30-79 years recruited from ten diverse areas during 2004-2008. Multivariable logistic regression was used to estimate odds ratios (ORs) of hepatitis B surface antigen (HBsAg) positivity recorded at baseline by sociodemographic and lifestyle factors, and medical history.

Genome-wide analyses of 200,453 individuals yield new insights into the causes and consequences of clonal hematopoiesis.

Clonal hematopoiesis (CH), the clonal expansion of a blood stem cell and its progeny driven by somatic driver mutations, affects over a third of people, yet remains poorly understood. Here we analyze genetic data from 200,453 UK Biobank participants to map the landscape of inherited predisposition to CH, increasing the number of germline associations with CH in European-ancestry populations from 4 to 14. Genes at new loci implicate DNA damage repair (PARP1, ATM, CHEK2), hematopoietic stem cell migration/homing (CD164) and myeloid oncogenesis (SETBP1).

When the anchor's away, meiotic telomeres go astray.

During meiosis, microtubules emanate from the centrosome to cluster telomeres in the bouquet configuration and facilitate chromosome pairing. In a recent issue of Science, Mytlis et al. establish that a cilium in zebrafish anchors the centrosome and is important for telomere clustering and germ cell development.