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As a fundamental mechanism for gene expression regulation, post-transcriptional RNA methylation plays versatile roles in various biological processes and disease mechanisms. Recent advances in single-cell technology have enabled simultaneous profiling of transcriptome-wide RNA methylation in thousands of cells, holding the promise to provide deeper insights into the dynamics, functions, and regulation of RNA methylation. However, it remains a major challenge to determine how to best analyze single-cell epitranscriptomics data. In this study, we developed SigRM, a computational framework for effectively mining single-cell epitranscriptomics datasets with a large cell number, such as those produced by the scDART-seq technique from the SMART-seq2 platform. SigRM not only outperforms state-of-the-art models in RNA methylation site detection on both simulated and real datasets but also provides rigorous quantification metrics of RNA methylation levels. This facilitates various downstream analyses, including trajectory inference and regulatory network reconstruction concerning the dynamics of RNA methylation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Mixta calida , previously known as Pantoea calida , is an environmental bacterium rarely associated with human pathologies. Rare case reports mention sepsis, meningitis and implantable defibrillator infection., Case Presentation: A 67-year-old female with multiple comorbidities was referred to the emergency room for a comminuted fracture of both right tibial plateaus secondary to a fall and for which she benefited from an external fixator. After removal of the fixator, failure of osteosynthesis and placement of a new fixator, a skin necrosis appeared and a propeller distal anteromedial thigh perforator flap was performed. After 6 weeks, she presented a necrosis of the flap and an osteitis. The bone biopsy was positive with pure M. calida . The patient underwent an above-knee amputation, but 6 weeks later the wound was dehiscent and again positive with pure M. calida ., Conclusions: Serious infections due to M. calida are uncommon but can occur in immunocompromised patients. This case illustrates the first reported osteitis and skin necrosis due to M. calida ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Aims: To investigate the effect of tumor necrosis factor (TNF) on the growth of human periodontal ligament (PDL) cells, their osteogenic differentiation and modulation of their matrix secretion in vitro., Methods: The influence of 10 ng/ml TNF on proliferation and metabolic activity of PDL cells was analyzed by cell counting (DAPI [4',6-diamidino-2-phenylindole] staining) and the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. In addition, cells were cultured under control conditions and osteogenic conditions (media containing 10 mM β-glycerophosphate). Quantitative expression analysis of genes encoding the osteogenic markers alkaline phosphatase (ALP), collagen type I alpha 1 chain (COL1A1), osteoprotegerin (OPG), and osteopontin (OPN) was performed after 7 and 14 days of cultivation. Calcium deposits were stained with alizarin red., Results: Our studies showed that 10 ng/ml TNF did not affect the survival and metabolic activity of PDL cells. Quantitative expression analysis revealed that long-term cultures with TNF impaired osteogenic cell fate at early and late developmental stages. Furthermore, TNF significantly reduced matrix secretion in PDL cells., Conclusion: The present data confirm TNF as a regulatory factor of proinflammatory remodeling that influences the differentiation behavior but not the metabolism and cell proliferation of the periodontium. Therefore, TNF represents an interesting target for the regulation of orthodontic remodeling processes in the periodontium., (© 2024. The Author(s).)

Aim: To develop and employ machine learning (ML) algorithms to analyse electrocardiograms (ECGs) for the diagnosis of cardiac autonomic neuropathy (CAN)., Materials and Methods: We used motif and discord extraction techniques, alongside long short-term memory networks, to analyse 12-lead, 10-s ECG tracings to detect CAN in patients with diabetes. The performance of these methods with the support vector machine classification model was evaluated using 10-fold cross validation with the following metrics: accuracy, precision, recall, F1 score, and area under the receiver-operating characteristic curve (AUC)., Results: Among 205 patients (mean age 54 ± 17 years, 54% female), 100 were diagnosed with CAN, including 38 with definite or severe CAN (dsCAN) and 62 with early CAN (eCAN). The best model performance for dsCAN classification was achieved using both motifs and discords, with an accuracy of 0.92, an F1 score of 0.92, a recall at 0.94, a precision of 0.91, and an excellent AUC of 0.93 (95% confidence interval [CI] 0.91-0.94). For the detection of any stage of CAN, the approach combining motifs and discords yielded the best results, with an accuracy of 0.65, F1 score of 0.68, a recall of 0.75, a precision of 0.68, and an AUC of 0.68 (95% CI 0.54-0.81)., Conclusion: Our study highlights the potential of using ML techniques, particularly motifs and discords, to effectively detect dsCAN in patients with diabetes. This approach could be applied in large-scale screening of CAN, particularly to identify definite/severe CAN where cardiovascular risk factor modification may be initiated., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Lyme neuroborreliosis is a rare zoonosis which can be difficult to diagnose, in particular in low endemic areas. We here report the case of a 35-year-old man presenting with disabling back pain preceded by facial monoplegia, which was wrongly treated as Bell's palsy (paralysis a frigore) and then as post-traumatic lumbosciatica. The onset of facial diplegia allowed for a definitive diagnosis. The patient was treated with ceftriaxone and symptoms gradually improved., Competing Interests: Les auteurs ne déclarent aucun conflit d´intérêts., (Copyright: Sophie Collignon et al.)

Objectives: The aim of this study was to demonstrate the performance and added value of rapid glucose determination in cerebrospinal fluid using a connected glucometer., Design and Methods: Intra-assay and inter-assay accuracies were calculated using residual clinical samples. Accuracies were measured by comparing the results obtained with the glucometer to those from the central laboratory on a large routine chemistry platform., Results: The intra-assay coefficients of variation were between 6.1% and 6.2% for low values (18 mg/dL) and between 5.6% and 6.8% for high values (58 mg/dL). The inter-assay coefficients of variation were between 9.4% and 16.3% for the low values (18 mg/dL) and between 5.7% and 8.7% for the high values (pool; ±75 mg/dL). The regression equation by comparison to the central laboratory was y = 4.08 + 0.82 x, with a coefficient of determination (r 2 ) of 0.95., Conclusions: The measurement of glycorrhachia with a connected glucometer before the analysis in the central laboratory allows a rapid orientation in the deferential diagnosis of a meningitis of viral vs bacterial origin. The response time is fast (6 s) and requires only a small amount of fluid (1.2 μL), which is important in infants, especially since lumbar puncture is an integral part of the investigation of the origin of a fever in this population., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The reagents required for the precision evaluation were provided free of charge by Nova Biomedical. However, the study was conducted independently and without any conflict of interest., (© 2024 The Authors.)