Clinical management of endometriosis is limited by the complex relationship between symptom severity, heterogeneous surgical presentation, and variability in clinical outcomes. As a complement to visual classification schemes, molecular profiles of disease activity may improve risk stratification to better inform treatment decisions and identify new approaches to targeted treatment. We use a network analysis of information flow within and between inflammatory cells to discern consensus behaviors characterizing patient subpopulations. Unsupervised multivariate analysis of cytokine profiles quantified by multiplex immunoassays identified a subset of patients with a shared "consensus signature" of 13 elevated cytokines that was associated with common clinical features of endometriosis, but was not observed among patient subpopulations defined by morphologic presentation alone. Enrichment analysis of consensus markers reinforced the primacy of peritoneal macrophage infiltration and activation, which was demonstrably elevated in ex vivo cultures. Although familiar targets of the nuclear factor κB family emerged among overrepresented transcriptional binding sites for consensus markers, our analysis provides evidence for an unexpected contribution from c-Jun, c-Fos, and AP-1 effectors of mitogen-associated kinase signaling. Their crucial involvement in propagation of macrophage-driven inflammatory networks was confirmed via targeted inhibition of upstream kinases. Collectively, these analyses suggest a clinically relevant inflammatory network that may serve as an objective measure for guiding treatment decisions for endometriosis management, and in the future may provide a mechanistic endpoint for assessing efficacy of new agents aimed at curtailing inflammatory mechanisms that drive disease progression.
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http://dx.doi.org/10.1126/scitranslmed.3007988 | DOI Listing |
GMS J Med Educ
November 2024
Heidelberg University Hospital, Department of General Medicine and Health Services Research, Heidelberg, Germany.
Objective: To aid the shortage of general practitioners (GPs) in Germany, since 2011 medical specialists from other fields may switch specialisation by undergoing a slim-lined training programme (lateral entry) into general practice (GP). Available published qualitative and quantitative data on lateral entrants (LEs) is scarce. Aim of the study was an explorative analysis of LEs in the competence centre for postgraduate medical education Baden-Wuerttemberg (KWBW).
View Article and Find Full Text PDFFront Neurol
December 2024
Optimax Access Ltd, Southampton, United Kingdom.
Background: Relapsing multiple sclerosis (RMS) is a chronic, inflammatory disease of the central nervous system. Ublituximab, an anti-CD20 monoclonal antibody (mAb), is indicated for the treatment of RMS. We performed a systematic literature review (SLR) to identify randomized trials reporting the clinical efficacy and tolerability of ublituximab or comparator disease-modifying therapies (DMTs) for treatment of RMS, and assessed their comparative effects using network meta-analysis (NMA).
View Article and Find Full Text PDFDigit Health
December 2024
School of Public Administration, Central South University, Changsha, Hunan, China.
Objective: To evaluate the service quality of integrated health and social care institutions for older adults in residential settings in China, addressing a critical gap in the theoretical and empirical understanding of service quality assurance in this rapidly expanding sector.
Methods: This study employs three machine learning algorithms-Backpropagation Neural Networks (BPNN), Feedforward Neural Networks (FNN), and Support Vector Machines (SVM)-to train and validate an evaluative item system. Comparative indices such as Mean Squared Error, Mean Absolute Error (MAE), Mean Absolute Percentage Error (MAPE), and predictive performance metrics were employed to assess the models.
Introduction: Idiopathic Intracranial Hypertension (IIH) presents an increasing health burden with changing demographic patterns. We studied nationwide trends in IIH epidemiology, treatment patterns, and associated outcomes using a large-scale database analysis within the United States (US).
Methods: We performed a retrospective analysis using the TriNetX US Collaborative Network database (1990-2024).
Ann Surg Open
December 2024
HPB and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
Background: The use of minimally invasive (laparoscopic and robotic) pancreatoduodenectomy (PD) is being increasingly adopted despite the lack of hard evidence to support its utilisation. With recent randomised controlled trials (RCTs) comparing open pancreatoduodenectomy (OPD) with robotic or laparoscopic pancreatoduodenectomy (RPD or LPD), we undertook a network meta-analysis (NMA) comparing all 3 approaches to evaluate comparative outcomes.
Methods: A systematic search of MEDLINE, EMBASE, and Cochrane CENTRAL was conducted up to May 2024 and relevant RCTs were identified.
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