Association between neutrophil-lymphocyte ratio and lymph node metastasis in gastric cancer : a meta-analysis

Introduction and Aim: The prognostic role of neutrophil to lymphocyte ratio (NLR) has been explored extensively in the literature. The aim of this meta-analysis was to evaluate the link between NLR and lymph node metastasis in gastric cancer. A method for increasing specificity and sensitivity of pre-treatment staging has implications on treatment algorithms and survival. Search Strategy: The relevant databases were searched as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart. After selection, 12 full text articles that met the inclusion criteria were included for quantitative analysis. 2 x 2 squares were generated using lymph node positive/negative, and NLR high/low data. The effect size for each study was calculated using the DerSimonian-Laird random effects model. P values were calculated using the chi-square method. Finally publication bias was evaluated. All statistics were calculated using R Studio. Results: Meta-analysis showed a 1.90 times (odds ratio, with 95% CI 1.52-2.38) increase in risk of positive lymph node status with high neutrophil to lymphocyte ratio. This has significant implications for cancer screening and staging, as NLR is a highly reproducible, cost-effective, and widely available prognostic factor for gastric cancer patients. Additionally, high or low NLR values may have implications for management pathways. Patients with lymph node metastasis can be offered neo adjuvant chemotherapy, avoiding salvage therapy in the form of adjuvant chemoradiotherapy, which is poorly tolerated. Conclusion: This meta-analysis shows an association between NLR and positive lymph node status in gastric cancer patients with implications for staging, as well as preoperative personalisation of therapy

Intravenous meloxicam for the treatment of moderate to severe acute pain: a pooled analysis of safety and opioid-reducing effects.

BACKGROUND AND OBJECTIVES: To describe the safety and tolerability of intravenous meloxicam compared with placebo across all phase II/III clinical trials. METHODS: Safety data and opioid use from subjects with moderate to severe postoperative pain who received ≥1 dose of intravenous meloxicam (5-60 mg) or placebo in 1 of 7 studies (4 phase II; 3 phase III) were pooled. Data from intravenous meloxicam 5 mg, 7.5 mg and 15 mg groups were combined (low-dose subset). RESULTS: A total of 1426 adults (86.6% white; mean age: 45.8 years) received ≥1 dose of meloxicam IV; 517 (77.6% white; mean age: 46.7 years) received placebo. The incidence of treatment-emergent adverse events (TEAEs) in intravenous meloxicam and placebo-treated subjects was 47% and 57%, respectively. The most commonly reported TEAEs across treatment groups (intravenous meloxicam 5-15 mg, 30 mg, 60 mg and placebo, respectively) were nausea (4.3%, 20.8%, 5.8% and 25.3%), headache (1.5%, 5.6%, 1.6% and 10.4%), vomiting (2.8%, 4.6%, 1.6% and 7.4%) and dizziness (0%, 3.5%, 1.1% and 4.8%). TEAE incidence was generally similar in subjects aged \u3e65 years with impaired renal function and the general population. Similar rates of cardiovascular events were reported between treatment groups. One death was reported (placebo group; unrelated to study drug). There were 35 serious adverse events (SAEs); intravenous meloxicam 15 mg (n=5), intravenous meloxicam 30 mg (n=15) and placebo (n=15). The SAEs in meloxicam-treated subjects were determined to be unrelated to study medication. Six subjects withdrew due to TEAEs, including three treated with intravenous meloxicam (rash, localized edema and postprocedural pulmonary embolism). In trials where opioid use was monitored, meloxicam reduced postoperative rescue opioid use. CONCLUSIONS: Intravenous meloxicam was generally well tolerated in subjects with moderate to severe postoperative pain. TRIAL REGISTRATION NUMBERS: NCT01436032, NCT00945763, NCT01084161, NCT02540265, NCT02678286, NCT02675907 and NCT02720692

Generative AI for Education (GAIED): Advances, Opportunities, and Challenges

This survey article has grown out of the GAIED (pronounced "guide") workshop organized by the authors at the NeurIPS 2023 conference. We organized the GAIED workshop as part of a community-building effort to bring together researchers, educators, and practitioners to explore the potential of generative AI for enhancing education. This article aims to provide an overview of the workshop activities and highlight several future research directions in the area of GAIED

Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling

Following endocytosis into the endosomal network, integral membrane proteins undergo sorting for lysosomal degradation or are retrieved and recycled back to the cell surface. Here we describe the discovery of an ancient and conserved multiprotein complex that orchestrates cargo retrieval and recycling and, importantly, is biochemically and functionally distinct from the established retromer pathway. We have called this complex 'retriever'; it is a heterotrimer composed of DSCR3, C16orf62 and VPS29, and bears striking similarity to retromer. We establish that retriever associates with the cargo adaptor sorting nexin 17 (SNX17) and couples to CCC (CCDC93, CCDC22, COMMD) and WASH complexes to prevent lysosomal degradation and promote cell surface recycling of α5β1 integrin. Through quantitative proteomic analysis, we identify over 120 cell surface proteins, including numerous integrins, signalling receptors and solute transporters, that require SNX17-retriever to maintain their surface levels. Our\ua0identification of retriever establishes a major endosomal retrieval and recycling pathway