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Permanent electric dipole moments (EDM) of fundamental systems are promising systems to find new CP violation beyond the Standard Model. Our EDM experiment is based on hyper-polarized liquid xenon droplets of sub-millimeter size on a micro-fabricated structure, placed in a low-field NMR setup. Implementation of rotating electric fields enables a conceptually new EDM measurement technique, allowing thorough investigation of systematic effects. Still, a Ramsey-type spin precession experiment with static electric field can be realized at similar sensitivity within the same setup. Employing superconducting pick-up coils and highly sensitive LTc-SQUIDs, a large array of independent measurements can be performed simultaneously. With our approach we aim to finally increase the sensitivity on the EDM of 129Xe by more than three orders of magnitude.

Digital and technological sovereignty are essential building blocks of the European Union's (EU) European ambition for a position in the new world order. However, the current dependencies and vulnerabilities along the entire value chain are a massive challenge in the realization of geopolitical claims to power. EUrope must manage the balancing act between a policy guided by values and one guided by interests in order not to lose its own credibility. Will the EU be able to cope with these challenges and project its regulatory power to create another Brussels effect? [ABSTRACT FROM AUTHOR]

The neutron's permanent electric dipole moment dn is constrained to below 3 × 10−26e cm (90% C.L.) [1, 2], by experiments using ultracold neutrons (UCN). We plan to improve this limit by an order of magnitude or more with PanEDM, the first experiment exploiting the ILL's new UCN source SuperSUN. SuperSUN is expected to provide a high density of UCN with energies below 80 neV, implying extended statistical reach with respect to existing sources, for experiments that rely on long storage or spin-precession times. Systematic errors in PanEDM are strongly suppressed by passive magnetic shielding, with magnetic field and gradient drifts at the single fT level. A holding-field homogeneity on the order of 10−4 is achieved in low residual fields, via a high static damping factor and built-in coil system. No comagnetometer is needed for the first order-of-magnitude improvement in dn, thanks to high magnetic stability and an assortment of sensors outside the UCN storage volumes. PanEDM will be commissioned and upgraded in parallel with SuperSUN, to take full advantage of the source's output in each phase. Commissioning is ongoing in 2019, and a new limit in the mid 10−27e cm range should be possible with two full reactor cycles of data in the commissioned apparatus.

Background: Vitamin A plays a key role in lung development, but there is no consensus regarding the optimal vitamin A dose and administration route in extremely low birthweight (ELBW) infants. We aimed to assess whether early postnatal additional high-dose fat-soluble enteral vitamin A supplementation versus placebo would lower the rate of moderate or severe bronchopulmonary dysplasia or death in ELBW infants receiving recommended basic enteral vitamin A supplementation., Methods: This prospective, multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial conducted at 29 neonatal intensive care units in Austria and Germany assessed early high-dose enteral vitamin A supplementation (5000 international units [IU]/kg per day) or placebo (peanut oil) for 28 days in ELBW infants. Eligible infants had a birthweight of more than 400 g and less than 1000 g; gestational age at birth of 32 +0 weeks postmenstrual age or younger; and the need for mechanical ventilation, non-invasive respiratory support, or supplemental oxygen within the first 72 h of postnatal age after admission to the neonatal intensive care unit. Participants were randomly assigned by block randomisation with variable block sizes (two and four). All participants received basic vitamin A supplementation (1000 IU/kg per day). The composite primary endpoint was moderate or severe bronchopulmonary dysplasia or death at 36 weeks postmenstrual age, analysed in the intention-to-treat population. This trial was registered with EudraCT, 2013-001998-24., Findings: Between March 2, 2015, and Feb 27, 2022, 3066 infants were screened for eligibility at the participating centres. 915 infants were included and randomly assigned to the high-dose vitamin A group (n=449) or the control group (n=466). Mean gestational age was 26·5 weeks (SD 2·0) and mean birthweight was 765 g (162). Moderate or severe bronchopulmonary dysplasia or death occurred in 171 (38%) of 449 infants in the high-dose vitamin A group versus 178 (38%) of 466 infants in the control group (adjusted odds ratio 0·99, 95% CI 0·73-1·55). The number of participants with at least one adverse event was similar between groups (256 [57%] of 449 in the high-dose vitamin A group and 281 [60%] of 466 in the control group). Serum retinol concentrations at baseline, at the end of intervention, and at 36 weeks postmenstrual age were similar in the two groups., Interpretation: Early postnatal high-dose fat-soluble enteral vitamin A supplementation in ELBW infants was safe, but did not change the rate of moderate or severe bronchopulmonary dysplasia or death and did not substantially increase serum retinol concentrations., Funding: Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN)., Competing Interests: Declaration of interests We declare no competing interests. The vitamin A study medication and placebo were provided by Aristo Pharma, Berlin, Germany. Aristo Pharma had no influence on study protocol, data compilation, and data analysis., (Copyright © 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Open heart surgery is often an unavoidable procedure for the treatment of coronary artery disease. The procedure-associated reperfusion injury affects postoperative cardiac performance and long-term outcomes. We addressed here whether cardioplegia essential for cardiopulmonary bypass surgery activates Nrf2, a transcription factor regulating the expression of antioxidant and detoxification genes. With commonly used cardioplegic solutions, high K + , low K + , Del Nido (DN), histidine-tryptophan-ketoglutarate (HTK), and Celsior (CS), we found that DN caused a significant increase of Nrf2 protein in AC16 human cardiomyocytes. Tracing the ingredients in DN led to the discovery of KCl at the concentration of 20-60 mM capable of significant Nrf2 protein induction. The antioxidant response element (ARE) luciferase reporter assays confirmed Nrf2 activation by DN or KCl. Transcriptomic profiling using RNA-seq revealed that oxidation-reduction as a main gene ontology group affected by KCl. KCl indeed elevated the expression of classical Nrf2 downstream targets, including TXNRD1, AKR1C, AKR1B1, SRXN1, and G6PD. DN or KCl-induced Nrf2 elevation is Ca 2+ concentration dependent. We found that KCl decreased Nrf2 protein ubiquitination and extended the half-life of Nrf2 from 17.8 to 25.1 mins. Knocking out Keap1 blocked Nrf2 induction by K + . Nrf2 induction by DN or KCl correlates with the protection against reactive oxygen species generation or loss of viability by H 2 O 2 treatment. Our data support that high K + concentration in DN cardioplegic solution can induce Nrf2 protein and protect cardiomyocytes against oxidative damage. NEW & NOTEWORTHY Open heart surgery is often an unavoidable procedure for the treatment of coronary artery disease. The procedure-associated reperfusion injury affects postoperative cardiac performance and long-term outcomes. We report here that Del Nido cardioplegic solution or potassium is an effective inducer of Nrf2 transcription factor, which controls the antioxidant and detoxification response. This indicates that Del Nido solution is not only essential for open heart surgery but also exhibits cardiac protective activity.

Introduction: Fetal magnetocardiography (fMCG) is considered the best technique for diagnosis of fetal arrhythmia. It is superior to more widely used methods such as fetal, fetal electrocardiography, and cardiotocography for evaluation of fetal rhythm. The combination of fMCG and fetal echocardiography can provide a more comprehensive evaluation of fetal cardiac rhythm and function than is currently possible. In this study, we demonstrate a practical fMCG system based on optically pumped magnetometers (OPMs)., Methods: Seven pregnant women with uncomplicated pregnancies underwent fMCG at 26-36 weeks' gestation. The recordings were made using an OPM-based fMCG system and a person-sized magnetic shield. The shield is much smaller than a shielded room and provides easy access with a large opening that allows the pregnant woman to lie comfortably in a prone position., Results: The data show no significant loss of quality compared to data acquired in a shielded room. Measurements of standard cardiac time intervals yielded the following results: PR = 104 ± 6 ms, QRS = 52.6 ± 1.5 ms, and QTc = 387 ± 19 ms. These results are compatible with those from prior studies performed using superconducting quantum interference device (SQUID) fMCG systems., Conclusions: To our knowledge, this is the first European fMCG device with OPM technology commissioned for basic research in a pediatric cardiology unit. We demonstrated a patient-friendly, comfortable, and open fMCG system. The data yielded consistent cardiac intervals, measured from time-averaged waveforms, compatible with published SQUID and OPM data. This is an important step toward making the method widely accessible.

Nrf2 encodes a transcription factor best known for regulating the expression of antioxidant and detoxification genes. Recent evidence suggested that Nrf2 mediates metabolic reprogramming in cancer cells. However, the role of Nrf2 in the biochemical metabolism of cardiac cells has not been studied. Using LC-MS/MS-based metabolomics, we addressed whether knocking out the Nrf2 gene in AC16 human cardiomyocytes affects metabolic reprogramming by oxidative stress. Profiling the basal level metabolites showed an elevated pentose phosphate pathway and increased levels of sugar alcohols, sorbitol, L-arabitol, xylitol and xylonic acid, in Nrf2 KO cells. With sublethal levels of oxidative stress, depletion of NAD, an increase of GDP and elevation of sugar alcohols, sorbitol and dulcitol, were detected in parent wild type (WT) cells. Knocking out Nrf2 did not affect these changes. Biochemical assays confirmed depletion of NAD in WT and Nrf2 KO cells due to H 2 O 2 treatment. These data support that although Nrf2 deficiency caused baseline activation of the pentose phosphate pathway and sugar alcohol synthesis, a brief exposure to none-lethal doses of H 2 O 2 caused NAD depletion in an Nrf2 independent manner. Loss of NAD may contribute to oxidative stress associated cell degeneration as observed with aging, diabetes and heart failure., (Copyright © 2022. Published by Elsevier Inc.)

Type 1 diabetes (T1D) is a known risk factor for fractures, but the underlying pathophysiology is still not fully understood. This study aims to define age peaks and frequent fracture sites of children and young adults with T1D. Additionally, associations of fractures with metabolic and lifestyle factors as well as with additional complications in individuals with T1D were analyzed. A total of 750 individuals with T1D aged ≤25 years with fractures were matched to 3750 patients with T1D without fractures by demographics and insulin regimen. Hemoglobin A1c (HbA1c) values were compared using linear regression, and logistic regression was used to calculate odds ratios (OR) for fractures in individuals with acute complications and diseases. Median (Q1-Q3) age was 12.7 (9.9 to 14.9) years in individuals with fractures and 16.3 (12.6 to 17.8) years in the entire control group with 65% versus 53% males. Peak age for fractures was 7 to <15 years in males and 9 to <11 years in females, which is earlier than reported for the general population. HbA1c (%) was significantly higher in individuals with fractures than in controls (difference of estimated means: 0.26%; 95% confidence interval [CI] 0.07-0.46), especially in postpubertal females (0.68; 0.10-1.26). Significantly higher odds for fractures were observed in individuals with severe hypoglycemia (OR = 1.90; 95% CI 1.47-2.47), especially in prepubertal females (OR = 2.81; 1.21-6.52]) and postpubertal males (2.44; 1.11-5.38), celiac disease (2.02; 1.67-2.45), and with a history of smoking (1.38; 1.02-1.88). The age peak of fractures seems to be earlier in T1D than in the general population. Poor glycemic control is related to fractures, even before puberty. Associations of HbA1c and severe hypoglycemia with fractures highly depend on age and sex. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Ultralight bosons such as axion-like particles are viable candidates for dark matter. They can form stable, macroscopic field configurations in the form of topological defects that could concentrate the dark matter density into many distinct, compact spatial regions that are small compared with the Galaxy but much larger than the Earth. Here we report the results of the search for transient signals from the domain walls of axion-like particles by using the global network of optical magnetometers for exotic (GNOME) physics searches. We search the data, consisting of correlated measurements from optical atomic magnetometers located in laboratories all over the world, for patterns of signals propagating through the network consistent with domain walls. The analysis of these data from a continuous month-long operation of GNOME finds no statistically significant signals, thus placing experimental constraints on such dark matter scenarios., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2021.)

To test the association between bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD) and long-term clinical outcome and to identify risk factors for severe outcomes, a dataset comprising 504 patients from the international registry study ARegPKD was analyzed for characteristics and complications of patients with very early (≤ 3 months; VEBNE) and early (4-15 months; EBNE) bilateral nephrectomies. Patients with very early dialysis (VED, onset ≤ 3 months) without bilateral nephrectomies and patients with total kidney volumes (TKV) comparable to VEBNE infants served as additional control groups. We identified 19 children with VEBNE, 9 with EBNE, 12 with VED and 11 in the TKV control group. VEBNE patients suffered more frequently from severe neurological complications in comparison to all control patients. Very early bilateral nephrectomies and documentation of severe hypotensive episodes were independent risk factors for severe neurological complications. Bilateral nephrectomies within the first 3 months of life are associated with a risk of severe neurological complications later in life. Our data support a very cautious indication of very early bilateral nephrectomies in ARPKD, especially in patients with residual kidney function, and emphasize the importance of avoiding severe hypotensive episodes in this at-risk cohort.