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Nuclear spin hyperpolarization enables real-time observation of metabolism and intermolecular interactions in vivo. 1-13C-pyruvate is the leading hyperpolarized tracer currently under evaluation in several clinical trials as a promising molecular imaging agent. Still, the quest for a simple, fast, and efficient hyperpolarization technique is ongoing. Here, we describe that continuous, weak irradiation in the audio-frequency range of the 13C spin at the 121 μT magnetic field (approximately twice Earth’s field) enables spin order transfer from parahydrogen to 13C magnetization of 1-13C-pyruvate. These so-called LIGHT-SABRE pulses couple nuclear spin states of parahydrogen and pyruvate via the J-coupling network of reversibly exchanging Ir-complexes. Using ∼100% parahydrogen at ambient pressure, we polarized 51 mM 1-13C-pyruvate in the presence of 5.1 mM Ir-complex continuously and repeatedly to a polarization of 1.1% averaged over free and catalyst-bound pyruvate. The experiments were conducted at −8 °C, where almost exclusively bound pyruvate was observed, corresponding to an estimated 11% polarization on bound pyruvate. The obtained hyperpolarization levels closely match those obtained via SABRE-SHEATH under otherwise identical conditions. The creation of three different types of spin orders was observed: transverse 13C magnetization along the applied magnetic field, 13C z-magnetization along the main field B0, and 13C–1H zz-spin order. With a superconducting quantum interference device (SQUID) for detection, we found that the generated spin orders result from 1H–13C J-coupling interactions, which are not visible even with our narrow linewidth below 0.3 Hz and at −8 °C.

Objectives To evaluate the WHO-5 tool in pediatric and young adult subjects with type 1 diabetes, and to analyse associations with demographic/psychological characteristics. Methods We included 944 patients with type 1 diabetes 9–25 years of age, documented in the Diabetes Patient Follow-up Registry between 2018 and 2021. We used ROC curve analysis to determine optimal cut-off values for the WHO-5 scores to predict psychiatric comorbidity (ICD-10-diagnoses) and analysed associations with obesity, HbA1c, therapy regimen, and lifestyle via logistic regression. All models were adjusted for age, sex, and diabetes duration. Results In the total cohort (54.8% male), the median score was 17 [Q1-Q3: 13–20]. Adjusted for age, sex, and diabetes duration, the WHO-5 scores Conclusions The WHO-5 questionnaire is a useful tool to predict depression in adolescents with type 1 diabetes. ROC analysis suggests a slightly higher cut-off for conspicuous questionnaire results compared to previous reports. Due to the high rate of deviant results, adolescents and young adults with type-1 diabetes should be screened regularly for signs of psychiatric comorbidity.

Satire describes “a genre of art (literature, caricature, film) that uses exaggeration, irony and ridicule to criticize people and events, to expose them to ridicule, to denounce conditions, to castigate them with sharp wit” (Duden, last access: 15.05.2023). This study examines satire as a form of expression of persuasive communication and to what extent it helps to influence climate change perception within young adults. Current research suggests that satire can be used to increase climate change perception (Brewer & McKnight, 2015). In the current study the Climate Change Perception Scale by van Valkengoed et al., 2021 is applied. This scale has been created to make comparison and integration of climate change perception findings easier (van Valkengoed et al., 2021). It has been found that young adults aged 18-25 strongly respond to satire in the context of environmental communication (Skurka et al., 2022). The psychological mechanisms of action cited in the literature as to why satire has a particular effect on young adults are the increased attention of this age group (Eisend, 2009). Furthermore, according to Martin & Ford (2018), the hedonistic emotion mirth or pleasure is evoked, creating more openness towards the topic. Also, the authors Skurka et al., 2022 argue that young adults in particular form their world views and political attitudes in this very phase of life and precisely then respond especially to messages that are presented in a captivating and rousing manner (Boukes et al., 2015; Skurka et al., 2022). To date, no research has tested the impact of satirical Instagram posts on perception of climate change. However, research demonstrates that consumption of satirical television news programs was associated with greater attention to news about science and technology, news about the environment, and information about global warming (Feldman et al., 2011). By packaging information in an entertaining way (Baum, 2003), satirical news programs therefore offer an alternative route by which their viewers, including those who do not consume much traditional news, can acquire information about topics such as climate change (Brewer & McKnight, 2015). Also, previous research has found that satirical television programs cover public affairs in ways that have the potential to inform and shape public understandings and further shape audience’ understandings of climate change (Baym, 2005, 2007). The current study investigates if a similar effect on climate change perception can be found in satirical Instagram posts since social media significantly shapes and contributes to the everyday life of young people. Social media posts from the platform "Instagram" are used for manipulation in the present study. The posts in the experimental group correspond to real posts by the German satirist and influencer Sebastian Hotz, also known as "Elhotzo". The Instagram posts in the control group are fictitious and written by the researchers. To sum up, the present study wants to show that climate change perception (dependent variable) can be increased by a climate-related message that uses satire or information in Instagram posts (independent variable). A more positive effect in the experimental group (satire) as compared to the control group (information) on climate change perception is postulated.

This is a replication study based on results of Trope and Liberman (1998, sudy 4), testing the hypothesis that the impact of interest on choice is significantly greater in distant future, than in near future."

Tires are complex articles by virtue of chemistry, usage and disposal. They have served Humanity at powerful “enablers” for connecting the World by transportation and commerce. However, they also pose environmental issues primarily after their relatively short service lives. This chapter touches these various aspects from “cradle to grave”.

Hyperbolic polynomials are real multivariate polynomials with only real roots along a fixed pencil of lines. Testing whether a given polynomial is hyperbolic is a difficult task in general. We examine different ways of translating hyperbolicity into nonnegativity conditions, which can then be tested via sum-of-squares relaxations., 12 pages, 1 figure; minor changes in Section 2 and a few corrections

The development of hyperpolarization technologies enabled several yet exotic NMR applications at low and ultra‐low fields (ULF), where without hyperpolarization even the detection of a signal from analytes is a challenge. Herein, we present a method for the simultaneous excitation and observation of homo‐ and heteronuclear multiple quantum coherences (from zero up to the third‐order), which give an additional degree of freedom for ULF NMR experiments, where the chemical shift variation is negligible. The approach is based on heteronuclear correlated spectroscopy (COSY); its combination with a phase‐cycling scheme allows the selective observation of multiple quantum coherences of different orders. The nonequilibrium spin state and multiple spin orders are generated by signal amplification by reversible exchange (SABRE) and detected at ULF with a superconducting quantum interference device (SQUID)‐based NMR system., Ultra‐low field COrrelation SpectroscopY (ULF COSY): Hyperpolarized homo‐ and heteronuclear (1H‐19F) multiple quantum coherences (MQCs) from zero to the third order were observed at 91 μT by SQUID based NMR. MQCs were assigned by using density matrix simulations and measured here by a phase cycling modified ULF COSY sequence. The method allowed us to look deeper inside hyperpolarization processes at low magnetic fields.

Introduction The G protein-coupled oestrogen receptor 1 (GPER-1) is a potential prognostic marker in breast cancer. However, its role in male breast cancer (MBC) is still unknown. This study evaluates the expression of GPER-1 in MBC samples and correlates these data with clinical and pathological parameters including patients' survival. Material and methods For this retrospective analysis of a prospectively maintained cohort of patients with MBC, we examined 161 specimens for GPER-1 expression using immunohistochemistry. An immunoreactive score (IRS) was calculated based on staining intensity and the percentage of positive tumour cells. Then, we correlated GPER-1 IRS with clinical and pathological parameters, and overall and relapse-free survival. Results About 40% of MBC samples were positive for GPER-1 expression (IRS ≥ 4). There was no significant correlation with clinicopathological parameters, such as hormone receptor status or grading. However, a statistical trend was observed for tumour size (≥ 2 cm, p = 0.093). Kaplan-Meier survival analysis revealed no significant correlation with relapse-free survival. However, there was a significant correlation with overall survival, but when we adjusted the log-rank p-value to compensate for the cut-off point optimization method, it rose above 0.1. Additionally, GPER-1-positive patients were older at diagnosis. When adjusted for age by multivariable Cox regression analysis, the significance of GPER-1 status for survival was further reduced. Conclusions We found no significant prognostic value of GPER-1 in this MBC cohort as anticipated from studies on female BC. Future studies with higher sample size are needed to further verify a potential sex-specific role of GPER-1.

Parahydrogen (pH2 ) is a convenient and cost-efficient source of spin order to enhance the magnetic resonance signal. Previous work showed that transient interaction of pH2 with a metal organic complex in a signal amplification by reversible exchange (SABRE) experiment enabled more than 10 % polarization for some 15 N molecules. Here, we analyzed a variant of SABRE, consisting of a magnetic field alternating between a low field of ∼1 μT, where polarization transfer is expected to take place, and a higher field >50 μT (alt-SABRE). These magnetic fields affected the amplitude and frequency of polarization transfer. Deviation of a lower magnetic field from a "perfect" condition of level anti-crossing increases the frequency of polarization transfer that can be exploited for polarization of short-lived transient SABRE complexes. Moreover, the coherences responsible for polarization transfer at a lower field persisted during magnetic field variation and continued their spin evolution at higher field with a frequency of 2.5 kHz at 54 μT. The latter should be taken into consideration for an efficient alt-SABRE. Theoretical and experimental findings were exemplified with Iridium N-heterocyclic carbene SABRE complex and 15 N-acetonitrole, where a 30 % higher 15 N polarization with alt-SABRE compared to common SABRE was reached.

Aims To examine the association of frozen shoulder (FS) with demographic and diabetes-related outcomes in individuals with type 1 (T1D) or type 2 (T2D) diabetes aged ≥30 years. Materials and methods Multivariable logistic regression models, adjusted for demographics were used to calculate the proportion of FS in association with age, gender, diabetes duration, body mass index (BMI), haemoglobin A1C (HbA1c) and diabetes treatment. Results The unadjusted percentage of FS was higher in T1D compared to T2D (0.22% vs. 0.06%). In T1D, adjusted regression models revealed higher prevalence of FS in women than men (0.26 [0.20–0.34] % vs. 0.15 [0.11–0.21] %, p=0.010). No significant relationship of age and BMI with FS was found in both diabetes types. Longer diabetes duration was associated with a higher proportion of FS in T1D (p7% was related to a higher proportion of FS compared to HbA1c ≤7% (0.25 [0.19–0.32] vs. 0.12 [0.08–0.20] %, p=0.007), while an inverse relationship was found in T2D (HbA1c ≤7%: 0.08 [0.07–0.10] vs. HbA1c >7%: 0.05 [0.04–0.06] %, p=0.001). Conclusions Different associations of FS with gender and HbA1c were observed for T1D and T2D; however, longer diabetes duration increases the risk for FS independent of diabetes type. Musculoskeletal diseases are still underreported in individuals with diabetes and awareness should be raised for FS as a specific diabetes complication.

Our study aimed to analyse treatment strategies after failure of initial metformin mono-therapy in adult patients with type-2 diabetes (T2DM). The DIVE and DPV databases were combined and 16,681 adult patients with T2DM and metformin mono-therapy identified. Patients were analysed depending on whether metformin was continued (MET), or whether it was combined with other oral antidiabetics (OAD), with GLP-1 antagonists (GLP-1) or with basal insulin (BOT/BOT plus). Metabolic control, body weight and hypoglycaemia, micro- and macro-vascular events were compared within 1 year. A total of 11,911 (71%) participants continued MET until the end of the observation period, 3334 (20.0%) were intensified using OAD, 579 (3%) started on GLP-1, and 857 (5%) were initiated on BOT/BOTplus. Predictors of OAD and BOT/BOTplus therapy were elevated HbA1c, longer diabetes duration and the presence of micro- and macro-vascular diseases, while GLP-1 therapy was predicted by younger age, female sex, higher body weight and shorter diabetes duration. Micro- and macro-vascular diseases were negative predictors of GLP-1 therapy. Effects on HbA1c were highest in the BOT/BOTplus and OAD group, while GLP-1 treatment had the best effect on body weight. BOT/BOTplus and OAD show good HbA1c reduction even in patients with longer diabetes duration and in older patients. GLP-1 therapy is effective concerning weight loss in overweight patients and is more often used in females and patients with shorter diabetes duration. Interestingly, despite several studies showing positive effects on micro- and macro-vascular outcomes, prevalent macro-vascular diseases are no predictors of GLP-1 use.

(5S,6S)-Aminotenuazonic acid, a new 3-acyltetramic acid, related to the well-known mycotoxin tenuazonic acid has been isolated from fruiting bodies of Laccaria bicolor. Its structure was mostly established by analysis of its 2D NMR and HR-(+)-ESI-MS spectra. A total synthesis starting from N-Boc-l-isoleucine gave (5S,6S)-aminotenuazonic acid in 8 % yield over nine steps (67 % de). The key steps of the total synthesis are a light-initiated Hofmann-Löffler-Freytag radical chain reaction and a Dieckmann cyclisation. The relative and absolute configurations of the natural product were determined by comparison of its NMR and CD spectra with those of the corresponding enantiopure synthetic compounds. Metabolic profiling of crude extracts of different mushrooms showed that aminotenuazonic acid is present in all four of the investigated Laccaria species. Aminotenuazonic acid shows phytotoxic activities against the root and shoot growth of Lepidium sativum, Pinus sylvestris and Arabidopsis thaliana comparable to those of tenuazonic acid.

A number of Ir–N-heterocyclic carbene (Ir–NHC) complexes with asymmetric N-heterocyclic carbene (NHC) ligands have been prepared and examined for signal amplification by reversible exchange (SABRE). Pyridine was chosen as model compound for hyperpolarization experiments. This substrate was examined in a solvent mixture using several Ir–NHC complexes, which differ in their NHC ligands. The SABRE polarization was created at 6 mT and the 1H nuclear magnetic resonance signals were detected at 7 T. We show that asymmetric NHC ligands, because of their favorable chemistry, can adapt the SABRE active complexes to different chemical scenarios.

Deficits of disparity divergence found with objective eye movement recordings may not be apparent with standard clinical measures of negative fusional vergence (NFV) in children with symptomatic convergence insufficiency.This study aimed to determine whether NFV is normal in untreated children with symptomatic convergence insufficiency and whether NFV improves after vergence/accommodative therapy.This secondary analysis of NFV measures before and after office-based vergence/accommodative therapy reports changes in (1) objective eye movement recording responses to 4° disparity divergence step stimuli from 12 children with symptomatic convergence insufficiency compared with 10 children with normal binocular vision (NBV) and (2) clinical NFV measures in 580 children successfully treated in three Convergence Insufficiency Treatment Trial studies.At baseline, the Convergence Insufficiency Treatment Trial cohort's mean NFV break (14.6 ± 4.8Δ) and recovery (10.6 ± 4.2Δ) values were significantly greater (P.001) than normative values. The post-therapy mean improvements for blur, break, and recovery of 5.2, 7.2, and 1.3Δ, respectively, were statistically significant (P.0001). Mean pre-therapy responses to 4° disparity divergence step stimuli were worse in the convergence insufficiency group compared with the NBV group for peak velocity (P.001), time to peak velocity (P = .01), and response amplitude (P.001). After therapy, the convergence insufficiency group showed statistically significant improvements in mean peak velocity (11.63°/s; 95% confidence interval [CI], 6.6 to 16.62°/s), time to peak velocity (-0.12 seconds; 95% CI, -0.19 to -0.05 seconds), and response amplitude (1.47°; 95% CI, 0.83 to 2.11°), with measures no longer statistically different from the NBV cohort (P.05).Despite clinical NFV measurements that seem greater than normal, children with symptomatic convergence insufficiency may have deficient NFV when measured with objective eye movement recordings. Both objective and clinical measures of NFV can be improved with vergence/accommodative therapy.

BACKGROUND Physical inactivity is a major contributor to the development and persistence of chronic diseases. Mobile health apps that foster physical activity have the potential to assist in behavior change. However, the quality of the mobile health apps available in app stores is hard to assess for making informed decisions by end users and health care providers. OBJECTIVE This study aimed at systematically reviewing and analyzing the content and quality of physical activity apps available in the 2 major app stores (Google Play and App Store) by using the German version of the Mobile App Rating Scale (MARS-G). Moreover, the privacy and security measures were assessed. METHODS A web crawler was used to systematically search for apps promoting physical activity in the Google Play store and App Store. Two independent raters used the MARS-G to assess app quality. Further, app characteristics, content and functions, and privacy and security measures were assessed. The correlation between user star ratings and MARS was calculated. Exploratory regression analysis was conducted to determine relevant predictors for the overall quality of physical activity apps. RESULTS Of the 2231 identified apps, 312 met the inclusion criteria. The results indicated that the overall quality was moderate (mean 3.60 [SD 0.59], range 1-4.75). The scores of the subscales, that is, information (mean 3.24 [SD 0.56], range 1.17-4.4), engagement (mean 3.19 [SD 0.82], range 1.2-5), aesthetics (mean 3.65 [SD 0.79], range 1-5), and functionality (mean 4.35 [SD 0.58], range 1.88-5) were obtained. An efficacy study could not be identified for any of the included apps. The features of data security and privacy were mainly not applied. Average user ratings showed significant small correlations with the MARS ratings (r=0.22, 95% CI 0.08-0.35; P CONCLUSIONS Apps for physical activity showed a broad range of quality ratings, with moderate overall quality ratings. Given the present privacy, security, and evidence concerns inherent to most rated apps, their medical use is questionable. There is a need for open-source databases of expert quality ratings to foster informed health care decisions by users and health care providers.

Background Physical inactivity is a major contributor to the development and persistence of chronic diseases. Mobile health apps that foster physical activity have the potential to assist in behavior change. However, the quality of the mobile health apps available in app stores is hard to assess for making informed decisions by end users and health care providers. Objective This study aimed at systematically reviewing and analyzing the content and quality of physical activity apps available in the 2 major app stores (Google Play and App Store) by using the German version of the Mobile App Rating Scale (MARS-G). Moreover, the privacy and security measures were assessed. Methods A web crawler was used to systematically search for apps promoting physical activity in the Google Play store and App Store. Two independent raters used the MARS-G to assess app quality. Further, app characteristics, content and functions, and privacy and security measures were assessed. The correlation between user star ratings and MARS was calculated. Exploratory regression analysis was conducted to determine relevant predictors for the overall quality of physical activity apps. Results Of the 2231 identified apps, 312 met the inclusion criteria. The results indicated that the overall quality was moderate (mean 3.60 [SD 0.59], range 1-4.75). The scores of the subscales, that is, information (mean 3.24 [SD 0.56], range 1.17-4.4), engagement (mean 3.19 [SD 0.82], range 1.2-5), aesthetics (mean 3.65 [SD 0.79], range 1-5), and functionality (mean 4.35 [SD 0.58], range 1.88-5) were obtained. An efficacy study could not be identified for any of the included apps. The features of data security and privacy were mainly not applied. Average user ratings showed significant small correlations with the MARS ratings (r=0.22, 95% CI 0.08-0.35; P

Tumor-mediated immunosuppression via regulatory T-cells is a key player among the various immune-escape mechanisms in multiple myeloma. We analyzed the generation, distribution, function and immunophenotype of CD8+CD28- regulatory T-cells in patients with multiple myeloma. Functionality of CD8+CD28- T-cells was assessed by immunological assays using ex vivo generated antigen-specific T-cells from patients with plasma cell dyscrasias and healthy donors. Detailed analysis of distribution, immunophenotype and cytotoxic potential of CD8+CD28- T-cells was performed by flow cytometry and ELISA. We found that the amount of CD8+CD28- T-cells was directly correlated with the suppression of antigen-specific T-cell responses in patients with plasma cell dyscrasia. Analyzing the CD8+CD28- T-cells in detail, increased numbers of these cells were observed in the bone marrow (i.e., tumor microenvironment) of patients with plasma cell dyscrasia. Furthermore, we identified the expression of lymphocyte function-associated antigen 1 (LFA-1) as a marker of immunosuppression and defined the CD8+CD28-CD57+LFA-1high population as the relevant immunosuppressive compartment. These regulatory T-cells act as immunosuppressors via soluble factors and incubation with IL-10 augmented their immunosuppressive capacity. The immunosuppressive regulatory network of IL-10 and the CD8+CD28-CD57+LFA-1high regulatory T-cells show unique characteristics and contribute to the tumor immune escape mechanism in patients with multiple myeloma.

Die Magnetresonanz (MR) von Kernspins ist einer der nützlichsten physikalischen Effekte für die humane Bildgebung, ebenso wie für die Aufklärung von molekularen Strukturen und die chemische Analyse. Das volle Potential der MR kann jedoch kaum genutzt werden, da nur ein geringer Bruchteil aller Kernspins polarisiert, sprich in einem äußeren magnetischen Feld ausgerichtet werden. Hyperpolarisierungsmethoden versuchen, die Polarisierung und damit das MR-Signal auf anderem Wege zu erhöhen. Eine einzigartige Quelle reiner Spinordnung ist das langlebige, verschränkte Kernspin-Singulett-Isomer des Wasserstoffmoleküls, genannt Parawasserstoff (pH2). Mithilfe dieser “Spinordnung auf Abruf” kann das MR-Signal um mehrere Größenordnungen verstärkt werden, wenn pH2 in Kontakt mit einem anderen Molekül gebracht wird. In Bezug auf eine biomedizinische Anwendung von pH2-hyperpolarisierten Kontrastmitteln haben in den letzten zehn Jahren beeindruckende Fortschritte stattgefunden. Das Ziel dieses Aufsatzes ist es, diese Entwicklungen in den Bereichen der Spinphysik, Katalyse, Instrumentierung, Kontrastmittel und Anwendungen gebündelt und verständlich darzustellen.

Substrates containing 19 F can serve as background-free reporter molecules for NMR and MRI. However, in vivo applications are still limited due to the lower signal-to-noise ratio (SNR) when compared with 1 H NMR. Although hyperpolarization can increase the SNR, to date, only photo-chemically induced dynamic nuclear polarization (photo-CIDNP) allows for hyperpolarization without harmful metal catalysts. Photo-CIDNP was shown to significantly enhance 19 F NMR signals of 3-fluoro-DL-tyrosine in aqueous solution using flavins as photosensitizers. However, lasers were used for photoexcitation, which is expensive and requires appropriate protection procedures in a medical or lab environment. Herein, we report 19 F MR hyperpolarization at 4.7 T and 7 T with a biocompatible system using a low-cost and easy-to-handle LED-based set-up. First hyperpolarized 19 F MR images could be acquired, because photo-CIDNP enabled repetitive hyperpolarization without adding new substrates.