SignificanceCarbohydrates hold an unprecedented capacity for altering biological function, but determining which glycans and underlying enzymes are crucial for a specific biological pathway is a major impediment to our understanding of this posttranslational modification. Here we demonstrate that the mRNA target networks of microRNA (miRNA), small noncoding RNA, identify glycosylation enzymes acting as regulatory elements within a biological pathway. Leveraging the miRNA-200 family (miR-200f), regulators of epithelial-to-mesenchymal transition (EMT), we identify multiple promesenchymal glycosylation enzymes. Silencing miR-200f–targeted glycogenes phenocopies the effect of miR-200f, inducing mesenchymal-to-epithelial transition. These enzymes are upregulated in TGF-β–induced EMT, suggesting tight integration within the signaling network. Our work indicates that miRNA networks can be used to identify crucial glycosylation enzymes driving disease states.

Background Cardiovascular disease remains a leading cause of death among women. Despite improvements in the management of patients with acute coronary syndrome ( ACS ), women with an ACS remain at higher risk. Methods and Results We performed a time‐dependent analysis of the management and outcomes of women admitted with ACS who enrolled in the prospective biennial ACS Israeli Surveys between 2000 and 2016. Surveys were divided into 3 time periods (2000‐2004, 2006‐2010, and 2013‐2016). Outcomes included 30‐day major adverse cardiac events (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularization) and 1‐year mortality. Overall, 3518 women were admitted with an ACS . Their mean age (70±12 years) was similar among the time periods. Over the time course of the study, more women were admitted with non– ST ‐elevation ACS (51.9%, 59.6%, and 66.1%, respectively; P <0.001), and statins and percutaneous coronary intervention were increasingly utilized (66%, 91%, 93%, and 42%, 60%, and 68%, respectively; P <0.001 for each). Among women with ST ‐segment–elevation myocardial infarction, more primary percutaneous coronary interventions were performed (48.5%, 84.7%, and 95.3%, respectively; P <0.001). The rate of 30‐day major adverse cardiac events has significantly decreased over the years (24.6%, 18.6%, and 13.5%, respectively; P <0.001). However, 1‐year mortality rates declined only from 2000 to 2004 (16.9%, 12.8%, and 12.3%; P =0.007 for the overall difference), and this change was not significant after propensity matching or multivariate analysis. Conclusions Over more than a decade, 30‐day major adverse cardiac events have decreased among women with ACS . Advances in pharmacological treatments and an early invasive approach may have accounted for this improvement. However, the lack of further reduction in 1‐year mortality rates among women suggests that more measures should be provided in this high‐risk population.

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Introduction: Vedolizumab is a monoclonal antibody used in ulcerative colitis and Crohn's disease, targeting the ɑ4b7 integrin receptor on T lymphocytes. Lymphoproliferative reactions have not been reported with Vedolizumab. We report a case of reversible T-cell lymphoproliferative disorder in a patient on vedolizumab. Case Description/Methods: A 44-year-old female presented in 2013 with bloody diarrhea and was diagnosed with ulcerative colitis (unclear extent). She was treated with mesalamine and then later with adalimumab. She had a secondary loss of response to adalimumab and was switched to vedolizumab in 2020. After the first vedolizumab infusion, she developed a pruritic skin rash that briefly improved with a course of prednisone. After completing the third infusion, the rash recurred along with symptoms of intense fatigue, joint pain, nausea, and vomiting. She had no fevers, chills, or night sweats. Labs showed a new leukocytosis (15,000/microliter) with significant elevation in lymphocytes (66% absolute lymphocyte count). Peripheral blood smear showed 10% atypical lymphocytes and LDH was elevated. A CT abdomen with contrast showed small lymph nodes in the perirectal area and splenomegaly of 17 cm. Findings were concerning a lymphoproliferative disorder and the patient was referred to hematology. Testing for EBV and CMV were negative. Peripheral blood flow cytometry was negative for tumor markers (negative CD7, CD16, and CD57) and bone marrow biopsy showed a normocellular bone marrow. Despite a thorough work-up, no other etiology for this lymphoproliferative disorder was found. Since there was a temporal relationship between the onset of systemic symptoms and the start of vedolizumab, vedolizumab was discontinued. Her systemic symptoms significantly improved within a few weeks of therapy cessation. Her lymphocytosis improved and resolved within 2 months. Repeat CT-scan at 3 months showed significant regression in spleen and lymph node size. The patient was subsequently started on infliximab monotherapy for her ulcerative colitis. Discussion: The enhanced risk of lymphoproliferative disorders in patients with inflammatory bowel disease on anti-TNFa agents is well documented. This phenomenon has not been reported with novel biologic therapies, such as vedolizumab. To our knowledge, this is the first case of vedolizumab-induced reversible lymphoproliferative disorder and highlights the importance of routine blood cell count monitoring while on this therapy.