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We investigated room-temperature metal and ligand K-edge X-ray absorption (XAS) spectra of a complete redox series of cubane-type iron-sulfur clusters. The Fe K-edge position provides a qualitative but convenient alternative to the traditional spectroscopic descriptors used to identify oxidation states in these systems, which we demonstrate by providing a calibration curve based on two analytic methods. Furthermore, high energy resolution fluorescence detected XAS (HERFD-XAS) at the S K-edge was used to measure Fe-S bond covalencies and record their variation with the average valence of the Fe atoms. While the Fe-S(thiolate) covalency evolves linearly, gaining 11 ± 0.4% per bond and hole, the Fe-S(μ 3 ) covalency evolves asystematically, reflecting changes in the magnetic exchange mechanism. A strong discontinuity manifested for superoxidation to the all-ferric state, distinguishing its electronic structure and its potential (bio)chemical role from those of its redox congeners. We highlight the functional implications of these trends for the reactivity of iron-sulfur cubanes., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Abdominal venous thromboses are rare thrombotic events with heterogeneous etiologies. They are related to myeloproliferative neoplasms (MPNs) in some patients and can occur as first signs of the disease. MPNs are characterized by mutations in the genes of Janus kinase 2 (JAK2), myeloproliferative leukemia virus oncogene (MPL), and calreticulin (CALR)., Methods: Within the prospective trial "Prevalence of JAK2 mutations in patients with abdominal venous thromboses" (JAK2 MV study; German Clinical Trials Register: DRKS00026943), the peripheral blood of patients with abdominal venous thromboses in Mecklenburg-West Pomerania, a federal state located in north-east Germany, was analyzed by next-generation ultradeep sequencing for MPN-associated mutations. Clinical characteristics and blood cell counts were also of interest. The primary endpoint was the detection of the mutation JAK2 p.V617F. Secondary endpoints were the detection of other acquired variants of JAK2, as well as MPL and CALR., Results: A total of 68 patients with abdominal venous thromboses were included from February 2017 to January 2021, with splanchnic veins affected in 65 patients. The mutation JAK2 p.V617F was present in 13 patients (19%), with four patients showing low variant allele frequencies (VAF 0.1% to 1.9%). The time interval from the thrombotic event to analysis was longer for patients with the mutation. The mutation MPL p.W515R was detected in three cases, all of them with low VAF. One patient among them had a concurrent mutation of JAK2 p.V617F. The mutations CALR type I or type II were not found., Discussion: By analyzing peripheral blood for the mutation JAK2 p.V617F, an important cause of these rare thrombotic events can be identified. The development of a diagnostic workup with next-generation ultradeep sequencing for the analysis of the JAK2 p.V617F mutation and further mutations has the potential to better understand the etiology of abdominal venous thromboses in individual patients in regional clinical care, as abdominal venous thromboses are diagnosed by various medical disciplines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Henze, Grunwald, Felser, Witte, Grosse-Thie, Roolf, Murua Escobar and Junghanss.)

Synthetic iron-sulfur cubanes are models for biological cofactors, which are essential to delineate oxidation states in the more complex enzymatic systems. However, a complete series of [Fe 4 S 4 ] n complexes spanning all redox states accessible by 1-electron transformations of the individual iron atoms ( n = 0-4+) has never been prepared, deterring the methodical comparison of structure and spectroscopic signature. Here, we demonstrate that the use of a bulky arylthiolate ligand promoting the encapsulation of alkali-metal cations in the vicinity of the cubane enables the synthesis of such a series. Characterization by EPR, 57 Fe Mössbauer spectroscopy, UV-visible electronic absorption, variable-temperature X-ray diffraction analysis, and cyclic voltammetry reveals key trends for the geometry of the Fe 4 S 4 core as well as for the Mössbauer isomer shift, which both correlate systematically with oxidation state. Furthermore, we confirm the S = 4 electronic ground state of the most reduced member of the series, [Fe 4 S 4 ] 0 , and provide electrochemical evidence that it is accessible within 0.82 V from the [Fe 4 S 4 ] 2+ state, highlighting its relevance as a mimic of the nitrogenase iron protein cluster.

Rationale & Objective: Health-impeding social determinants of health-including reduced access to care-contribute to racial and socioeconomic disparities in chronic kidney disease (CKD). The Military Health System (MHS) provides an opportunity to assess a large, diverse population for CKD disparities in the context of universal health care., Study Design: Cross-sectional study., Setting & Participants: MHS beneficiaries aged 18 to 64 years receiving care between October 1, 2015, and September 30, 2018., Predictors: Race, sponsor's rank (a proxy for socioeconomic status and social class), median household income by sponsor's zip code, and marital status., Outcome: CKD prevalence, defined by International Classification of Diseases, Tenth Revision codes and/or a validated, laboratory value-based electronic phenotype., Analytical Approach: Multivariable logistic regression compared CKD prevalence by predictors, controlling separately for confounders (age, sex, active-duty status, sponsor's service branch, and depression) and mediators (hypertension, diabetes, HIV, and body mass index)., Results: Of 3,330,893 beneficiaries, 105,504 (3.2%) had CKD. In confounder-adjusted models, the CKD prevalence was higher in Black versus White beneficiaries (OR, 1.67; 95% CI, 1.64-1.70), but lower in single versus married beneficiaries (OR, 0.77; 95% CI, 0.76-0.79). The prevalence of CKD was increased among those with a lower military rank and among those with a lower median household income in a nearly dose-response fashion ( P  < 0.0001). Associations were attenuated when further adjusting for suspected mediators., Limitations: The cross-sectional design prevents causal inferences. We may have underestimated the CKD prevalence, given a lack of data for laboratory tests conducted outside the MHS and the use of a specific CKD definition. The transient nature of the MHS population may limit the accuracy of zip code-level median household income data., Conclusions: Racial and socioeconomic CKD disparities exist in the MHS despite universal health care coverage. The existence of CKD disparities by rank and median household income suggests that social risks may contribute to both racial and socioeconomic disparities despite access to universal health care coverage.

Rationale & Objective: Chronic kidney disease (CKD) is common but often goes unrecorded., Study Design: Cross-sectional., Setting & Participants: Military Health System (MHS) beneficiaries aged 18 to 64 years who received care during fiscal years 2016 to 2018., Predictors: Age, sex, active duty status, race, diabetes, hypertension, and numbers of kidney test results., Outcomes: We defined CKD by International Classification of Diseases, Tenth Revision ( ICD-10 ) code and/or a positive result on a validated electronic phenotype that uses estimated glomerular filtration rate and measures of proteinuria with evidence of chronicity. We defined coded CKD by the presence of an  ICD-10 code. We defined uncoded CKD by a positive e-phenotype result without an ICD-10 code., Analytical Approach: We compared coded and uncoded populations using 2-tailed t tests (continuous variables) and Pearson χ 2 test for independence (categorical variables)., Results: The MHS population included 3,330,893 beneficiaries. Prevalence of CKD was 3.2%, based on ICD code and/or positive e-phenotype result. Of those identified with CKD, 63% were uncoded. Compared with beneficiaries with coded CKD, those with uncoded CKD were younger (aged 45 ± 13 vs 52 ± 11 years), more often women (54.4% vs 37.6%) and active duty (20.2% vs 12.5%), and less often of Black race (18.5% vs 31.5%) or with diabetes (23.5% vs 43.5%) or hypertension (46.6% vs 77.1%; P  < 0.001). Beneficiaries with coded (vs uncoded) CKD had greater numbers of kidney test results ( P  < 0.001)., Limitations: Use of cross-sectional administrative data prevents inferences about causality. The CKD e-phenotype may fail to capture CKD in individuals without laboratory data and may underestimate CKD., Conclusions: The prevalence of CKD in the MHS is ~3.2%. Beneficiaries with well-known CKD risk factors, such as older age, male sex, Black race, diabetes, and hypertension, were more likely to be coded, suggesting that clinicians may be missing CKD in groups traditionally considered lower risk, potentially resulting in suboptimal care.

Pseudomonas syringae is a Gram-negative and model pathogenic bacterium that causes plant diseases worldwide. Here, we set out to identify binding motifs for all 301 annotated transcription factors (TFs) of P. syringae using HT-SELEX. We successfully identify binding motifs for 100 TFs. We map functional interactions between the TFs and their targets in virulence-associated pathways, and validate many of these interactions and functions using additional methods such as ChIP-seq, electrophoretic mobility shift assay (EMSA), RT-qPCR, and reporter assays. Our work identifies 25 virulence-associated master regulators, 14 of which had not been characterized as TFs before.

Homonuclear decoupling sequences in solid-state nuclear magnetic resonance (NMR) under magic-angle spinning (MAS) show experimentally significantly larger residual line width than expected from Floquet theory to second order. We present an in-depth theoretical and experimental analysis of the origin of the residual line width under decoupling based on frequency-switched Lee-Goldburg (FSLG) sequences. We analyze the effect of experimental pulse-shape errors (e.g., pulse transients and B 1 -field inhomogeneities) and use a Floquet-theory-based description of higher-order error terms that arise from the interference between the MAS rotation and the pulse sequence. It is shown that the magnitude of the third-order auto term of a single homo- or heteronuclear coupled spin pair is important and leads to significant line broadening under FSLG decoupling. Furthermore, we show the dependence of these third-order error terms on the angle of the effective field with the B 0 field. An analysis of second-order cross terms is presented that shows that the influence of three-spin terms is small since they are averaged by the pulse sequence. The importance of the inhomogeneity of the radio-frequency (rf) field is discussed and shown to be the main source of residual line broadening while pulse transients do not seem to play an important role. Experimentally, the influence of the combination of these error terms is shown by using restricted samples and pulse-transient compensation. The results show that all terms are additive but the major contribution to the residual line width comes from the rf-field inhomogeneity for the standard implementation of FSLG sequences, which is significant even for samples with a restricted volume., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2020 Johannes Hellwagner et al.)

Highlights: Sanitizers and disinfectants (biocides) are essential for food safety assurance. Concerns have been raised about theoretical risk of biocide-induced antimicrobial resistance. In vitro studies provide weak causal evidence to attribute antimicrobial resistance to biocide usage. GMPs, proper biocide usage, and avoidance of biofilms mitigate risk of antimicrobial resistance.

Myocardial revascularization and implantation of the automatic implantable cardioverter defibrillator (AICD) have individually been shown to improve survival in patients after sudden cardiac death. Their combined role has not been well defined. Twenty-three survivors of sudden death underwent revascularization and AICD implantation at an average age of 59 years. The initial arrest was caused by ventricular fibrillation in 15 and ventricular tachycardia in 8. Exercise stress tests, ambulatory ECGs, and electrophysiological monitoring with programmed electrical stimulation were done preoperatively and postoperatively. Follow-up averaged 24 months with a two-year survival of 91%. Eight patients (35%) required AICD resuscitation an average of 8 months postoperatively, and electrophysiological testing did not accurately predict arrhythmia recurrence. The addition of AICD implantation to revascularization substantially improves survival of patients with sudden cardiac death.