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Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been repli-cated in the Diabetes Prevention Program (DPP). To as-sess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (P

The insect central complex appears to encode and process spatial information through vector manipulation. Here, we draw on recent insights into circuit structure to fuse previous models of sensory-guided navigation, path integration and vector memory. Specifically, we propose that the allocentric encoding of location provided by path integration creates a spatially stable anchor for converging sen

Objective: The class II transactivator (CIITA), encoded by the CIITA gene, controls expression of immune response regulators, which affect bone homeostasis. Previously, we investigated a functional CIITA polymorphism in elderly women. Women carrying the allele associated with lower CIITA levels displayed higher bone mineral density (BMD), but also higher bone loss. The present exploratory study in

Using scanning tunneling microscopy and spectroscopy, for a monolayer of transition metal dichalcogenide H-NbS2 grown by molecular beam epitaxy on graphene, we provide unambiguous evidence for a charge density wave (CDW) with a 3 × 3 superstructure, which is not present in bulk NbS2. Local spectroscopy displays a pronounced gap on the order of 20 meV at the Fermi level. Within the gap, low-energy

We propose a single-shot, high-repetition rate measurement scheme of the carrier-envelope phase offset of ultrashort laser pulses. The spectral fringes resulting from f-2f nonlinear interferometry, encoding the carrier-envelope-phase, are evaluated completely optically via an optical Fourier transform. For demonstration, the carrier-envelope-phase of a 200 kHz, few-cycle optical parametric chirped

Advancing ultrafast high-repetition-rate lasers to shortest pulse durations comprising only a few optical cycles while pushing their energy into the multi-millijoule regime opens a route toward terawatt-class peak powers at unprecedented average power. We explore this route via efficient post-compression of high-energy 1.2 ps pulses from an ytterbium InnoSlab laser to 9.6 fs duration using gas-fil

Objective: Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is a chronic relapsing condition with unknown etiology. To gain insight into the molecular processes underlying the disease, we examined biomarkers in blood samples collected prior to symptom onset. Methods: The National Patient Register and Cause of Death register were searched for AAV-related International Classifi

Background: Lead exposure is associated with cardiovascular disease. Atherosclerosis has been hypothesized to be one of the underlying mechanisms behind this association. Aim: To investigate whether lead exposure is associated with an increased risk of atherosclerosis in the carotid arteries in a large Swedish population-based cohort. Methods: We performed a cross-sectional study using data from t

Cardiometabolic disease is a major threat to global health. Precision medicine has great potential to help to reduce the burden of this common and complex disease cluster, and to enhance contemporary evidence-based medicine. Its key pillars are diagnostics; prediction (of the primary disease); prevention (of the primary disease); prognosis (prediction of complications of the primary disease); trea

Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report

Despite its simplicity and relevance for the description of electronic correlations in solids, the Hubbard model is seldom inarguably realized in real materials. Here, we show that monolayer Nb3Cl8 is an ideal candidate to be described within a single-orbital Hubbard model, constructed within a “molecular” rather than atomic basis set using ab initio constrained random phase approximation calculat

Metalloporphyrins with open d-shell ions can drive biochemical energy cycles. However, their utilization in photoconversion is hampered by rapid deactivation. Mapping the relaxation pathways is essential for elaborating strategies that can favorably alter the charge dynamics through chemical design and photoexcitation conditions. Here, we combine transient optical absorption spectroscopy and trans

The interplay of electronic and nuclear degrees of freedom presents an outstanding problem in condensed matter physics and chemistry. Computational challenges arise especially for large systems, long time scales, in nonequilibrium, or in systems with strong correlations. In this work, we show how downfolding approaches facilitate complexity reduction on the electronic side and thereby boost the si

Temperature is a crucial parameter of gas flow fields. Here, we present a novel thermometry technique for gas flow based on femtosecond laser-induced cyano (CN) luminescence. Specifically, a femtosecond laser with a central wavelength of 267 nm is used to induce CN violet emissions in a nitrogen flow seeded with a trace amount of methane. The spectral peak of CN B2Σ+- X2Σ+ (0,0) transitions shift

Prediabetes is a metabolic condition associated with gut mi-crobiome composition, although mechanisms remain elu-sive. We searched for fecal metabolites, a readout of gut microbiome function, associated with impaired fasting glucose (IFG) in 142 individuals with IFG and 1,105 healthy individuals from the UK Adult Twin Registry (TwinsUK). We used the Cooperative Health Research in the Region of Aug

In recent years, there have been notable advancements in the ability to programme human cell identity, enabling us to design and manipulate cell function in a Petri dish. However, current protocols for generating target cell types often lack efficiency and precision, resulting in engineered cells that do not fully replicate the desired identity or functional output. This applies to different metho

Cardiometabolic diseases are the leading preventable causes of death in most geographies. The causes, clinical presentations, and pathogenesis of cardiometabolic diseases vary greatly worldwide, as do the resources and strategies needed to prevent and treat them. Therefore, there is no single solution and health care should be optimised, if not to the individual (ie, personalised health care), the

Diabetes is a highly heterogeneous condition; yet, it is diagnosed by measuring a single blood-borne metabolite, glucose, irrespective of aetiology. Although pragmatically helpful, disease classification can become complex and limit advances in research and medical care. Here, we describe diabetes heterogeneity, highlighting recent approaches that could facilitate management by integrating three d

Human genetic variation in PPARGC1B has been associated with adiposity, but the genetic variants that affect PPARGC1B expression have not been experimentally determined. Here, guided by previous observational data, we used CRISPR/Cas9 to scarlessly edit the alleles of the candidate causal genetic variant rs10071329 in a human brown adipocyte cell line (hBAs). Switching the rs10071329 genotype from