Recent successes in natural language processing have led to the proliferation of large language models (LLMs) by multiple providers. Each LLM offering has different inference accuracy, monetary cost, and latency, and their accuracy further depends on the exact wording of the question (i.e., the specific prompt). At the same time, users often have a limit on monetary budget and latency to answer all their questions, and they do not know which LLMs to choose for each question to meet their accuracy and long-term budget requirements. To navigate this rich design space, we propose TREACLE (Thrifty Reasoning via Context-Aware LLM and Prompt Selection), a reinforcement learning policy that jointly selects the model and prompting scheme while respecting the user's monetary cost and latency constraints. TREACLE uses the problem context, including question text embeddings (reflecting the type or difficulty of a query) and the response history (reflecting the consistency of previous responses) to make smart decisions. Our evaluations on standard reasoning datasets (GSM8K, CSQA, and LLC ) with various LLMs and prompts show that TREACLE enables cost savings of up to 85% compared to baselines while maintaining high accuracy. Importantly, it provides the user with the ability to gracefully trade off accuracy for cost.
Physiological blood pressure changes in pregnancy are insufficiently defined. This paper describes the blood pressure changes across healthy pregnancies in a Southern Chinese population to present gestational - age - specific blood pressure ranges with smoothed centiles (3rd, 10th, 50th, 90th, and 97th). Antenatal blood pressure measurements [median (interquartile range) 9 (8 - 10) per woman] were repeated in 17, 776 women from a Southern China population. Multilevel cubic splines models were used to derive longitudinal reference ranges for systolic blood pressure (SBP) and diastolic blood pressure (DBP) from 6 to 42 weeks of gestation for the normal pregnancies (excluding chronic hypertension, preeclampsia, diabetic ones, and preterm birth et al.). Systolic and diastolic BP increased from 6 weeks of gestation: 50th centile (3rd - 97th centile) 106 (87 - 125); 61 (47 - 77) mm Hg to 12 weeks of gestation: 50th centile (3rd - 97th centile) 108 (88 - 129); 64 (49 - 81) mm Hg. Then, the lowest value of 107 (87 - 129); 62 (47 - 78) mm Hg was reached at 16 weeks and 20 weeks of gestation, respectively. Systolic and diastolic BP then rose to a maximum median (3rd - 97th centile) of 115 (96 - 135); 68 (53 - 85) mm Hg at 42 weeks of gestation. Additionally, the ascending tendency of SBP after 16 weeks of gestation was interrupted by two fluctuations that occurred at 24 weeks and 30 weeks of gestation. In summary, our study provides blood pressure reference values for Southern Chinese women with normal pregnancies. To identify gestational hypertension and hypotension, centiles for gestational - age - specific BP should be defined in healthy pregnancies. Understanding these changes in low risk pregnancies is essential to optimize maternal blood pressure management.
Abstract Background Currently, there are no effective tools to accurately assess acute biliary pancreatitis (ABP) risk in patients with gallstones. This study aimed to develop an ABP risk nomogram in patients with gallstones. Methods Data on 2102 patients with gallstones admitted to the Department of General Surgery of The First Affiliated Hospital of Harbin Medical University between January 6, 2009 and January 22, 2018 were retrospectively collected. Some patients were randomly divided into the training cohort (n=1470) for nomogram development; the others formed the validation cohort (n=632) to confirm the model’s performance. The chi-square test was used to optimize feature selection, and logistic regression analysis was applied to build a prediction model incorporating the selected features. The area under the curve (AUC), Hosmer-Lemeshow test, calibration curve, decision curve analysis (DCA) and internal validation were used to validate the model’s accuracy, calibration and clinical effectiveness. Results Predictors included sex (male), diabetes, gallbladder wall thickness ≤3 mm, gallbladder stone diameter <3 mm, coexisting CBD stone, CBD diameter ≤10 mm, AST≥53.6 U/L, GGT≥150 U/L, DBIL≥1.0 mg/dL, WBC≥10Í10 9 , and GRAN%≥80%. The model displayed good predictive power with AUCs of 0.850 (95% CI: 0.825~0.875) and 0.844 (95% CI: 0.825~0.875) in the training and validation cohorts, respectively. The DCA showed a 10-100% risk threshold. The Hosmer-Lemeshow test and calibration curve demonstrated the accuracy and effectiveness of this model, which could be applied in clinical practice. Conclusions The ABP risk nomogram incorporating 11 features is useful to predict ABP risk in gallstone patients.
Aim: To evaluate the efficacy and safety of first-line immunochemotherapy in the treatment of advanced esophageal squamous cell carcinoma (CRD42021287033). Methods: PubMed, Embase, Cochrane Library and Web of Science were systematically searched to obtain randomized controlled trials, and the outcome indicators of the reports were compared and analyzed. Results: A total of 3163 patients from five reported randomized controlled trials were included in the meta-analysis. The results showed the comprehensive benefits of toripalimab combined with chemotherapy, in terms of overall survival (hazard ratio: 0.59; 95% CI: 0.43-0.81) and progression-free survival (hazard ratio: 0.58; 95% CI: 0.46-0.73). Conclusion: Toripalimab combined with chemotherapy may be a better choice for first-line immunochemotherapy, although this needs to be verified by clinical studies.The treatment of cancer is an issue of importance to the general public. A number of drugs are available to treat cancer, including those that enhance the body's natural defense. Such drugs are also the first choice for cancer of the esophagus, which cannot be removed surgically. In this study, we analyzed five different first-choice drugs in different ways, including how long the patient survives and how long the patient lives without their disease getting worse. We found that toripalimab, which strengthens the body's natural defense, may be the best combination choice for use in combination with chemotherapy. Although further studies are needed to increase the reliability of the conclusions, we preliminarily consider that this drug is particularly promising.
Background: Fc gamma receptor 3A (FCGR3A) encodes a receptor for the Fc portion of immunoglobulin G, which plays a significant role in the immune response. However, the role of FCGR3A in cancers remains unclear. This study aimed to visualize the prognostic landscape of FCGR3A in pan-cancer and investigate the relationship between FCGR3A expression and tumor microenvironment. Method: Based on the TCGA database, GTEx database, and GDSC database, we analyzed the expression of FCGR3A in pan-cancers and adjacent normal tissues and its relationship with prognosis, immune cells infiltration, immune-related genes, DNA mismatch repair (MMR) genes, DNA methylation, and drugs sensitivity. The gene alteration frequency of FCGR3A was acquired on the cBioportal website. Moreover, we constructed PPI networks, performed GO and KEGG analysis to illustrate the function, and signaling pathways of FCGR3A-related genes, and conducted gene set enrichment analysis (GSEA) of FCGR3A to further explore its potential biological functions. Result: The differential analysis results of the publicly available databases showed that FCGR3A was generally highly expressed in pan-cancer. Survival analysis revealed that FCGR3A predominated as a risk prognostic factor in most cancers. Additionally, the expression of FCGR3A was confirmed to be associated with several immune cells infiltration, multiple immune checkpoint genes, and DNA mismatch repair genes expression in generalized carcinoma. We also identified a negative correlation between FCGR3A and DNA methylation levels. Through GO/KEGG and GESA, we found that FCGR3A was involved in many pathologic and physiological processes, and was most closely related to tumor immune-related pathways. Drug sensitivity analysis showed that higher FCGR3A expression predicts a low IC50 value for the vast majority of drugs. Conclusions: FCGR3A may be an immune-oncogenic molecule that correlates with tumor immune infiltration levels and affects drug sensitivity, thus it can be served as a promising biomarker for cancer detection, prognosis, therapeutic design, and follow-up.
Abstract Background Tertiary lymphoid structures (TLSs) affect the prognosis and efficacy of immunotherapy in patients with non‐small cell lung cancer (NSCLC), but the underlying mechanisms are not well understood. Methods TLSs were identified and categorized online from the Cancer Digital Slide Archive (CDSA). Overall survival (OS) and disease‐free survival (DFS) were analyzed. GSE111414 and GSE136961 datasets were downloaded from the GEO database. GSVA, GO and KEGG were used to explore the signaling pathways. Immune cell infiltration was analyzed by xCell, ssGSEA and MCP‐counter. The analysis of WGCNA, Lasso and multivariate cox regression were conducted to develop a gene risk score model based on the SU2C‐MARK cohort. Results TLS‐positive was a protective factor for OS according to multivariate cox regression analysis ( p = 0.029). Both the TLS‐positive and TLS‐mature groups exhibited genes enrichment in immune activation pathways. The TLS‐mature group showed more activated dendritic cell infiltration than the TLS‐immature group. We screened TLS‐related genes using WGCNA. Lasso and multivariate cox regression analysis were used to construct a five‐genes (RGS8, RUF4, HLA‐DQB2, THEMIS, and TRBV12‐5) risk score model, the progression free survival (PFS) and OS of patients in the low‐risk group were markedly superior to those in the high‐risk group ( p < 0.0001; p = 0.0015, respectively). Calibration and ROC curves indicated that the combined model with gene risk score and clinical features could predict the PFS of patients who have received immunotherapy more accurately than a single clinical factor. Conclusions Our data suggested a pivotal role of TLSs formation in survival outcome and immunotherapy response of NSCLC patients. Tumors with mature TLS formation showed more activated immune microenvironment. In addition, the model constructed by TLS‐related genes could predict the response to immunotherapy and is meaningful for clinical decision‐making.
Presently, a variety of policies and measures has implemented to enhance the scientific research and innovation ability of medical students, but in the process of practice, there are many problems, such as they lack of independent topic selection ability, weak scientific research skills, lack of autonomous learning ability, the research results are simple and ineffective, limited teacher guidance time and so on. This paper attempted to build an effective model for the promotion of medical students' scientific research and innovation ability, in order to establish an efficacy evaluation model of the "Medical students' Innovative Scientific Research Program." Undergraduates, graduate assistants, and tutors were interviewed with the Behavioral Event Interview technique, and a questionnaire of efficacy evaluation characteristics concluded from the interviews was formed. The questionnaire was conducted on medical students in the Medical students' Innovative Scientific Research Program, and the constructed model was analyzed using reliability analysis, validity analysis, and variation analysis. At the same time, the experimental teaching models are summarized and combed, and compared with other methods such as independent sample test. The results show the model could effectively evaluate the efficacy of the Medical students' Innovative Scientific Research Program and its teaching model is effective in cultivating medical students' learning and scientific research ability. It can provide theoretical support and practical reference for the evaluation and reform of the teaching modes related to the cultivation of scientific and innovative ability of medical students.
To investigate the expression and clinical significance of flotillin-2 (FLOT2) in cervical cancer (CC).We examined FLOT2 mRNA levels in 10 pairs of cervical cancer and adjacent normal tissues. Immunohistochemistry was performed to analyze FLOT2 protein expression in 115 archived cervical cancer samples. The association between FLOT2 levels, clinicopathologic factors and prognosis was analyzed statistically as well.The cancer tissues of CC patients had clearly increased expression of FLOT2 at mRNA level as compared to adjacent nontumorous tissues. Survival analysis of CC patients indicated that FLOT2 expression was significantly associated with poor overall and local recurrence-free survival (P = 0.025 and P = 0.028, respectively). Moreover, FLOT2 expression was significantly correlated with clinical stage, tumor differentiation, and lymph nodes metastasis. Multivariate analysis revealed that FLOT2 expression was an independent prognostic factor for overall survival in CC patients.FLOT2 may serve as an oncogene in the development of CC, and may serve as a clinicopathologic biomarker for prognosis in CC patients.
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