Association between ICW/TBW ratio and cancer prognosis: Subanalysis of a population-based retrospective multicenter study.

BACKGROUND & AIMS: Disease burden is known to alter cellular integrity and water balance. Therefore, the intracellular water/total body water (ICW/TBW) ratio is used as an adjunctive indicator to predict disease severity and prognosis. The ICW/TBW ratio of patients with cancer, who typically present with low muscle mass, poor nutritional status, and high inflammatory response, reportedly differs from that of the healthy population. Herein, we aimed to evaluate the effect of the ICW/TBW ratio on the prognosis of different subgroups of patients with cancer. METHODS: This multicenter cohort study included 2787 patients with malignancies between June 2014 and December 2018. The association between covariates and overall survival (OS) was assessed using restricted cubic spline models. The multivariate Cox regression model included variables demonstrating a statistical significance in the univariate Cox regression analysis (P < 0.05) without multicollinearity. The generated nomogram used the C-index and calibration curves to validate the predictive accuracy of the scoring system. RESULTS: The optimal cut-off value for the ICW/TBW ratio was 0.61. The ICW/TBW ratio was an independent prognostic factor (hazard ratio [HR]: 0.621; 95 % confidence interval [CI]: 0.537-0.719, P < 0.001). Moreover, the ICW/TBW ratio had a greater impact on the prognosis of patients receiving chemoradiotherapy than on those receiving chemotherapy alone (chemoradiotherapy: HR = 0.495, P = 0.005 vs. chemotherapy: HR = 0.646, P < 0.001). Multivariate Cox regression analysis showed that sex, age, tumor stage, body mass index, neutrophil-to-lymphocyte ratio (NLR), and ICW/TBW ratio were associated with OS. Subsequently, a nomogram was developed incorporating these variables and yielded a C-index of 0.743. CONCLUSIONS: The ICW/TBW ratio was associated with muscle mass, nutritional status, and inflammation. A low ICW/TBW ratio is an independent risk factor for poor prognosis in patients with cancer, especially when they are female, have advanced cancer stage, have sarcopenia, and are receiving radiotherapy.

Identification and Characterization of a Nerol Synthase in Fungi.

Nerol, a linear monoterpenoid, is naturally found in essential oils of various plants and is widely used in the fragrance, food, and cosmetic industries. Nerol synthase, essential for nerol biosynthesis, has previously been identified only in plants that use NPP as the precursor. In this study, a novel fungal nerol synthase, named PgfB, was cloned and characterized from Penicillium griseofulvum. In vitro enzymatic assays showed that PgfB could directly convert the substrate GPP into nerol. Furthermore, the successful expression of PgfB and its homologous protein in Saccharomyces cerevisiae resulted in the heterologous production of nerol. Finally, crucial amino acid residues for PgfB's catalytic activity were identified through site-directed mutagenesis. This research broadens our understanding of fungal monoterpene synthases and presents precious gene resources for the industrial production of nerol.

Two Directions for Clinical Data Generation with Large Language Models: Data-to-Label and Label-to-Data.

Large language models (LLMs) can generate natural language texts for various domains and tasks, but their potential for clinical text mining, a domain with scarce, sensitive, and imbalanced medical data, is under-explored. We investigate whether LLMs can augment clinical data for detecting Alzheimer's Disease (AD)-related signs and symptoms from electronic health records (EHRs), a challenging task that requires high expertise. We create a novel pragmatic taxonomy for AD sign and symptom progression based on expert knowledge and generated three datasets: (1) a gold dataset annotated by human experts on longitudinal EHRs of AD patients; (2) a silver dataset created by the data-to-label method, which labels sentences from a public EHR collection with AD-related signs and symptoms; and (3) a bronze dataset created by the label-to-data method which generates sentences with AD-related signs and symptoms based on the label definition. We train a system to detect AD-related signs and symptoms from EHRs. We find that the silver and bronze datasets improves the system performance, outperforming the system using only the gold dataset. This shows that LLMs can generate synthetic clinical data for a complex task by incorporating expert knowledge, and our label-to-data method can produce datasets that are free of sensitive information, while maintaining acceptable quality.

Feasibility and long-term outcomes of post-chemotherapy-based consolidation radiotherapy in extensive stage small-cell lung cancer.

Background: The target definition of consolidation radiotherapy (RT) for extensive stage small-cell lung cancer (ES-SCLC) has not been standardized. This study aimed to demonstrate the feasibility of post-chemotherapy based consolidation RT in ES-SCLC. Methods: All ES-SCLC patients without initial brain metastases who completed ≥ 4 cycles of systemic therapy at Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University from 2012 to 2021 were included in this retrospective study. We correlated the site of first recurrence to the post-chemotherapy-based radiation volume (small-field). Relapse pattern, progression-free survival (PFS) and overall survival (OS) were compared between those received and did not receive consolidation RT. Results: A total of 152 patients were followed up for a median of 31.7 months (interquartile range [IQR], 23.9-39.6 months). The median PFS and OS of the cohort were 8.3 months (IQR, 6.1-11.2 months) and 16.2 months (IQR, 9.9-24.9 months), respectively. Thoracic consolidation RT served not only as an independent prognostic factor for improved PFS in the entire cohort, but also significantly prolonged OS in the subgroup without synchronous liver metastases. Small-field consolidation RT markedly reduced in-field recurrences (hazard ratio [HR], 0.28 [95% CI, 0.12-0.38]; P < 0.001) without increasing out-of-field recurrences (HR, 0.40 [95% CI, 0.13-1.16]; P = 0.080). No relapse was observed at the margin of the targets. Treatment-related toxicities were moderate, with grade 3 acute radiation pneumonia, radiation esophagitis, and bone marrow suppression rates of 8.3%, 3.1%, and 12.5%, respectively. No grade 5 toxicity occurred. Conclusion: Small-field consolidation RT based on post-chemotherapy volume is safe and can significantly improve local control in ES-SCLC.