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Nuclear spin hyperpolarization of 13 C-labelled metabolites by dissolution dynamic nuclear polarization can enhance the NMR signals of metabolites by several orders of magnitude, which has enabled in vivo metabolic imaging by MRI. However, because of the short lifetime of the hyperpolarized magnetization (typically <1 min), the polarization process must be carried out close to the point of use. Here we introduce a concept that markedly extends hyperpolarization lifetimes and enables the transportation of hyperpolarized metabolites. The hyperpolarized sample can thus be removed from the polarizer and stored or transported for use at remote MRI or NMR sites. We show that hyperpolarization in alanine and glycine survives 16 h storage and transport, maintaining overall polarization enhancements of up to three orders of magnitude. MRI imaging can be significantly enhanced by injecting highly magnetized chemical agents, but the short magnetization lifetime requires processing at the point of use. Here, the authors demonstrate a method that could extend the lifetime from seconds to hours, enabling remote preparation.

Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) has enabled promising applications in spectroscopy and imaging, but remains poorly widespread due to experimental complexity. Broad democratization of dDNP could be realized by remote preparation and distribution of hyperpolarized samples from dedicated facilities. Here we show the synthesis of hyperpolarizing polymers (HYPOPs) that can generate radical- and contaminant-free hyperpolarized samples within minutes with lifetimes exceeding hours in the solid state. HYPOPs feature tunable macroporous porosity, with porous volumes up to 80% and concentration of nitroxide radicals grafted in the bulk matrix up to 285 μmol g −1 . Analytes can be efficiently impregnated as aqueous/alcoholic solutions and hyperpolarized up to P ( 13 C) = 25% within 8 min, through the combination of 1 H spin diffusion and 1 H →  13 C cross polarization. Solutions of 13 C-analytes of biological interest hyperpolarized in HYPOPs display a very long solid-state 13 C relaxation times of 5.7 h at 3.8 K, thus prefiguring transportation over long distances. Hyperpolarization by dissolution dynamic nuclear polarization has brought highly sensitive magnetic resonance to reality but there still remains severe limitations. Here the authors show an approach relying on the generation of hyperpolarizing polymers that bear a dual function.

Hyperpolarization of substrates for magnetic resonance spectroscopy (MRS) and imaging (MRI) by dissolution dynamic nuclear polarization (D-DNP) usually involves saturating the ESR transitions of polarizing agents (PAs; e.g., persistent radicals embedded in frozen glassy matrices). This approach has shown enormous potential to achieve greatly enhanced nuclear spin polarization, but the presence of PAs and/or glassing agents in the sample after dissolution can raise concerns for in vivo MRI applications, such as perturbing molecular interactions, and may induce the erosion of hyperpolarization in spectroscopy and MRI. We show that D-DNP can be performed efficiently with hybrid polarizing solids (HYPSOs) with 2,2,6,6-tetramethyl-piperidine-1-oxyl radicals incorporated in a mesostructured silica material and homogeneously distributed along its pore channels. The powder is wetted with a solution containing molecules of interest (for example, metabolites for MRS or MRI) to fill the pore channels (incipient wetness impregnation), and DNP is performed at low temperatures in a very efficient manner. This approach allows high polarization without the need for glass-forming agents and is applicable to a broad range of substrates, including peptides and metabolites. During dissolution, HYPSO is physically retained by simple filtration in the cryostat of the DNP polarizer, and a pure hyperpolarized solution is collected within a few seconds. The resulting solution contains the pure substrate, is free from any paramagnetic or other pollutants, and is ready for in vivo infusion. Significance Hyperpolarization by dissolution dynamic nuclear polarization can dramatically enhance signal intensities in MRI and NMR, notably for metabolic tracers for imaging and diagnosis. It is applicable to a variety of substrates for in vivo imaging and chemistry but requires the use of contaminants (glassing agents and free radicals) that may interact with cells and proteins and can have potential side effects. These contaminants can sometimes be eliminated by precipitation followed by filtration or solvent extraction, but these methods are substrate-specific, are usually time-consuming, and typically result in signal loss. Here, production of pure hyperpolarized liquids free of contaminants is shown by a simple wetting–polarization–filtration sequence for a solid silica matrix containing homogeneously distributed persistent radicals.

Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) has enabled promising applications in spectroscopy and imaging, but remains poorly widespread due to experimental complexity. Broad democratization of dDNP could be realized by remote preparation and distribution of hyperpolarized samples from dedicated facilities. Here we show the synthesis of hyperpolarizing polymers (HYPOPs) that can generate radical- and contaminant-free hyperpolarized samples within minutes with lifetimes exceeding hours in the solid state. HYPOPs feature tunable macroporous porosity, with porous volumes up to 80% and concentration of nitroxide radicals grafted in the bulk matrix up to 285 μmol g ⁻¹ . Analytes can be efficiently impregnated as aqueous/alcoholic solutions and hyperpolarized up to P( ¹³ C) = 25% within 8 min, through the combination of¹ H spin diffusion and¹ H →¹³ C cross polarization. Solutions of¹³ C-analytes of biological interest hyperpolarized in HYPOPs display a very long solid-state¹³ C relaxation times of 5.7 h at 3.8 K, thus prefiguring transportation over long distances.

Low sensitivity is the primary limitation to extending nuclear magnetic resonance (NMR) techniques to more advanced chemical and structural studies. Photochemically induced dynamic nuclear polarization (photo-CIDNP) is an NMR hyperpolarization technique where light is used to excite a suitable donor–acceptor system, creating a spin-correlated radical pair whose evolution drives nuclear hy-perpolarization. Systems that exhibit photo-CIDNP in solids are not common and this effect has, up to now, only been observed for 13C and 15N nuclei. However, the low gyromagnetic ratio and natural abundance of these nuclei trap the local hyperpolarization in the vicinity of the chromophore and limit the utility for bulk hyperpolarization. Here we report the first example of optically enhanced solid-state 1H NMR spectroscopy in the high-field regime. This is achieved via photo-CIDNP of a donor–chromophore–acceptor molecule in a frozen solution at 0.3 T and 85 K, where spontaneous spin diffusion among the abundant strongly coupled 1H nuclei relays polarization through the whole sample, yielding a 16-fold bulk 1H signal enhancement under continuous laser irradiation at 450 nm. These findings enable a new strategy for hyperpolarized NMR beyond the current limits of conventional microwave-driven DNP.

Spermine oxidase (SMOX) catalyzes the oxidation of spermine to spermidine. Observational studies have reported SMOX as a source of reactive oxygen species associated with cancer, implying that inhibition of SMOX could be a target for chemoprevention. Here we test causality of SMOX levels with cancer risk using a Mendelian randomization analysis. We performed a GWAS of spermidine/spermine ratio to identify genetic variants associated with regulation of SMOX activity. Replication analysis was performed in two datasets of SMOX gene expression. We then did a Mendelian randomization analysis by testing the association between the SMOX genetic instrument and neuroblastoma, gastric, lung, breast, prostate, and colorectal cancers using GWAS summary statistics. GWAS of spermidine/spermine ratio identified SMOX locus (P = 1.34 × 10 –49 ) explaining 32% of the variance. The lead SNP rs1741315 was also associated with SMOX gene expression in newborns (P = 8.48 × 10 –28 ) and adults (P = 2.748 × 10 –8 ) explaining 37% and 6% of the variance, respectively. Genetically determined SMOX activity was not associated with neuroblastoma, gastric, lung, breast, prostate nor colorectal cancer (P > 0.05). A PheWAS of rs1741315 did not reveal any relevant associations. Common genetic variation in the SMOX gene was strongly associated with SMOX activity in newborns, and less strongly in adults. Genetic down-regulation of SMOX was not significantly associated with lower odds of neuroblastoma, gastric, lung, breast, prostate and colorectal cancer. These results may inform studies of SMOX inhibition as a target for chemoprevention.

Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant ( P <5 × 10 −8 ) loci, some including known iron-related genes ( HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6 ) and others novel ( ABO, ARNTL , FADS2, NAT2 , TEX14 ). SNPs at ARNTL, TF , and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease. Iron deficiency is the leading cause of anaemia and is known to compromise immune function. Here, the authors identify several new genes associated with iron status in European populations and provide insight into how iron levels may be linked to the risk of metabolic disease.

Understanding factors associated with COVID-19 vaccination can highlight issues in public health systems. Using machine learning, we considered the effects of 2,890 health, socio-economic and demographic factors in the entire Finnish population aged 30–80 and genome-wide information from 273,765 individuals. The strongest predictors of vaccination status were labour income and medication purchase history. Mental health conditions and having unvaccinated first-degree relatives were associated with reduced vaccination. A prediction model combining all predictors achieved good discrimination (area under the receiver operating characteristic curve, 0.801; 95% confidence interval, 0.799–0.803). The 1% of individuals with the highest predicted risk of not vaccinating had an observed vaccination rate of 18.8%, compared with 90.3% in the study population. We identified eight genetic loci associated with vaccination uptake and derived a polygenic score, which was a weak predictor in an independent subset. Our results suggest that individuals at higher risk of suffering the worst consequences of COVID-19 are also less likely to vaccinate. The authors use data on the entire Finnish population to develop a machine learning model for predicting COVID-19 vaccination uptake. Important predictors are proxies of socio-economic status, and those at high risk for COVID-19 consequences are less likely to get vaccinated.

Background Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology. Materials & Methods We investigated associations of age at menarche and age at menopause, pregnancy‐related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Results During 15 years of follow‐up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use. Conclusion Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology. Reproductive and hormonal factors are known to be associated with the risk of several cancers in women, but their role in kidney cancer is unclear. Despite the higher incidence of kidney cancer in men, its aetiology in women deserves further exploration. Using data from a large, prospective cohort study, we have found evidence of associations between pregnancy‐related exposures as well as hysterectomy and bilateral ovariectomy with risk of kidney cancer.

PurposeAutistic youth face higher risks for experiencing mental health crises. To develop and test a county-level social network measure of care coordination between police departments and other systems that support autistic youth experiencing suicidal crisis.Design/methodology/approachTo measure the structure of care coordination for autistic youth experiencing suicidal crisis, the authors created a roster of all police departments and youth servicing organizations in two East Coast counties in the United States. They met or exceeded the whole network recruitment threshold of 70% completion in both counties. From the data, the authors created a directed matrix for each county of all reported connections, which they used to create sociograms and calculate standard network measures, including indegree, outdegree and total degree for each organization in the network. Data management and processing were done using R-programming and ORA.FindingsSocial network findings indicated that about half of all police departments surveyed coordinate care for autistic youth in suicidal crisis. Coordination varied by county, with nonpolice organizations acting as connectors between police and other nonpolice organizations. Two structural configurations were found, including a nonpolice organizational hub structure and a lead police structure. More research is needed to determine how different police integration structures shape care coordination for autistic youth.Research limitations/implicationsLimitations include the small number of counties included in the study. A larger sample of counties is required for generalizable results.Practical implicationsThis article introduces new tools and approaches to assist police in building their capacity to measure and improve their coordination of care with other community systems during crisis situations for youth on the autism spectrum. Network science (e.g. matrix and graph theoretic algebra methods) can be used to measure the configuration of relationships police departments have with complex multi-level healthcare systems.Social implicationsImplications for findings include the consideration of police integration across systems in ways that produce new collaboration possibilities to support autistic youth experiencing suicidal crisis.Originality/valueWhile police departments play a critical role in coordinating care for youth in suicidal crisis, little is known if or how police departments collaborate with other systems to provide assistance for autistic youth during a suicidal crisis. Improving care continuity within and between systems could potentially address clinical and structural challenges and reduce risk for autistic youth experiencing a suicidal crisis.