RSPO4 is a potential risk gene of stages III–IV, grade C periodontitis through effects on innate immune response and oral barrier integrity

AIM: R-spondin 4 (RSPO4) is a suggestive risk gene of stage III–IV, grade C periodontitis and upregulated in gingiva of mice resistant to bacteria-induced alveolar bone loss. We aimed to replicate the association, identify and characterize the putative causal variant(s) and molecular effects, and understand the downstream effects of RSPO4 upregulation. MATERIALS AND METHODS: We performed a two-step association study for RSPO4 with imputed genotypes of a German–Dutch (896 stage III–IV, grade C periodontitis cases, 7104 controls) and Spanish sample (441 cases and 1141 controls). We analysed the allelic effects on transcription factor binding sites with reporter gene and antibody electrophoretic mobility shift assays. We used CRISPR/dCas9 activation and RNA sequencing to pinpoint RSPO4 as the target gene and to analyse downstream effects. RESULTS: RSPO4 was associated with periodontitis (rs6056178, p(meta) = 4.6 x 10(-5)). rs6056178 contains a GATA-binding motif. The rs6056178 T-allele abolished reporter activity (p = .004) and reduced GATA binding (−14.5%). CRISPRa of the associated region increased RSPO4 expression (25.8 ± 6.5-fold, p = .003). RSPO4 activation showed strongest induction of Gliomedin (439-fold) and Mucin 21 (178-fold) and of the gene set “response to interferon-alpha” (area under the curve [AUC] = 0.8, p < 5 x 10(-6)). The most repressed gene set was “extracellular matrix interactions” (AUC = 0.8, p(adj) = .00016). CONCLUSION: RSPO4 is a potential periodontitis risk gene and modifies host defence and barrier integrity

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Clinical Proton MR Spectroscopy in Central Nervous System Disorders.

A large body of published work shows that proton (hydrogen 1 [1H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of 1H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of 1H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which 1H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units

Risk assessment for major adverse cardiovascular events after noncardiac surgery using self-reported functional capacity: international prospective cohort study

Background Guidelines endorse self-reported functional capacity for preoperative cardiovascular assessment, although evidence for its predictive value is inconsistent. We hypothesised that self-reported effort tolerance improves prediction of major adverse cardiovascular events (MACEs) after noncardiac surgery. Methods This is an international prospective cohort study (June 2017 to April 2020) in patients undergoing elective noncardiac surgery at elevated cardiovascular risk. Exposures were (i) questionnaire-estimated effort tolerance in metabolic equivalents (METs), (ii) number of floors climbed without resting, (iii) self-perceived cardiopulmonary fitness compared with peers, and (iv) level of regularly performed physical activity. The primary endpoint was in-hospital MACE consisting of cardiovascular mortality, non-fatal cardiac arrest, acute myocardial infarction, stroke, and congestive heart failure requiring transfer to a higher unit of care or resulting in a prolongation of stay on ICU/intermediate care (≥24 h). Mixed-effects logistic regression models were calculated. Results In this study, 274 (1.8%) of 15 406 patients experienced MACE. Loss of follow-up was 2%. All self-reported functional capacity measures were independently associated with MACE but did not improve discrimination (area under the curve of receiver operating characteristic [ROC AUC]) over an internal clinical risk model (ROC AUCbaseline 0.74 [0.71–0.77], ROC AUCbaseline+4METs 0.74 [0.71–0.77], ROC AUCbaseline+floors climbed 0.75 [0.71–0.78], AUCbaseline+fitnessvspeers 0.74 [0.71–0.77], and AUCbaseline+physical activity 0.75 [0.72–0.78]). Conclusions Assessment of self-reported functional capacity expressed in METs or using the other measures assessed here did not improve prognostic accuracy compared with clinical risk factors. Caution is needed in the use of self-reported functional capacity to guide clinical decisions resulting from risk assessment in patients undergoing noncardiac surgery. Clinical trial registration: NCT03016936

Search for rare decays of the Z and Higgs bosons to a J/ψ or ψ(2S) meson and a photon in proton-proton collisions at s=13TeV

A search is presented for rare decays of the Image 1 and Higgs bosons to a photon and a Image 2 or a Image 3 meson, with the charmonium state subsequentially decaying to a pair of muons. The data set corresponds to an integrated luminosity of 123fb−1 of proton-proton collisions at a center-of-mass energy of 13 TeV collected with the CMS detector at the LHC. No evidence for branching fractions of these rare decay channels larger than predicted in the standard model is observed. Upper limits at 95% confidence level are set: Image 4, Image 5, Image 6, and Image 7. The ratio of the Higgs boson coupling modifiers Image 8 is constrained to be in the interval (−157,+199) at 95% confidence level. Assuming Image 9, this interval becomes (−166,+208)

Identification of low-momentum muons in the CMS detector using multivariate techniques in proton-proton collisions at √s = 13.6 TeV

"Soft"muons with a transverse momentum below 10 GeV are featured in many processes studied by the CMS experiment, such as decays of heavy-flavor hadrons or rare tau lepton decays. Maximizing the selection efficiency for these muons, while simultaneously suppressing backgrounds from long-lived light-flavor hadron decays, is therefore important for the success of the CMS physics program. Multivariate techniques have been shown to deliver better muon identification performance than traditional selection techniques. To take full advantage of the large data set currently being collected during Run 3 of the CERN LHC, a new multivariate classifier based on a gradient-boosted decision tree has been developed. It offers a significantly improved separation of signal and background muons compared to a similar classifier used for the analysis of the Run 2 data. The performance of the new classifier is evaluated on a data set collected with the CMS detector in 2022 and 2023, corresponding to an integrated luminosity of 62 fb-

Search for the Higgs boson decays to a ρ0, ϕ, or K⁎0 meson and a photon in proton-proton collisions at s=13TeV

Three rare decay processes of the Higgs boson to a ρ(770)0, ϕ(1020), or K⁎(892)0 meson and a photon are searched for using s=13TeV proton-proton collision data collected by the CMS experiment at the LHC. Events are selected assuming the mesons decay into a pair of charged pions, a pair of charged kaons, or a charged kaon and pion, respectively. Depending on the Higgs boson production mode, different triggering and reconstruction techniques are adopted. The analyzed data sets correspond to integrated luminosities up to 138fb−1, depending on the reconstructed final state. After combining various data sets and categories, no significant excess above the background expectations is observed. Upper limits at 95% confidence level on the Higgs boson branching fractions into ρ(770)0γ, ϕ(1020)γ, and K⁎(892)0γ are determined to be 3.7×10−4, 3.0×10−4, and 3.0×10−4, respectively. In case of the ρ(770)0γ and ϕ(1020)γ channels, these are the most stringent experimental limits to date