The cognitive mechanisms involved in the “DEGREE ADVERB + PROPER NAME” construction: Evaluating proposals from Construction Grammar and Formal Semantics

There are broad disagreements between existing models regarding the mental representations and processes involved in the "DEGREE ADVERB + PROPER NAME" construction, including disagreements regarding the semantics of the degree device, the category status of the proper name, the construction’s expressed meaning and its (non-)compositionality, and, crucially, the operation that holds between the degree device and the proper name. Our corpus-based investigation into two competing models from Construction Grammar and Formal Semantics shows that these models collectively make useful contributions to the scientific understanding of this construction, but neither is empirically adequate. Most importantly, we find that the construction participates in several non-predicted expressed meanings; multivariate analyses show that the three amenable to statistical analysis cluster with different semantic usage-features. We argue that the best way to account for the construction’s semantics-pragmatics is via a previously-dismissed cognitive mechanism: an enrichment-/strengthening-type operation whereby a pragmatically-supplied scale is added to the message.

Blood cholesterol-to-lymphocyte ratio as a novel prognostic marker to predict postoperative overall survival in patients with colorectal cancer

Background Lipid disequilibrium and systemic inflammation are reported to correlate with tumorigenesis and development of colorectal cancer (CRC). We construct the novel biomarker cholesterol-to-lymphocyte ratio (CLR) to reflect the synergistic effect of cholesterol metabolism and inflammation on CRC outcomes. This study aims to investigate the clinical significance of CLR and establish a prognostic model for CRC. Methods Our study retrospectively enrolled 223 CRC patients who underwent curative surgical resection. The Kaplan-Meier method was employed to estimate the overall survival (OS) rates, and the association between serological biomarkers and survival was assessed with a log-rank test. Cox proportional hazard regression was applied in the univariate and multivariate analyses to identify independent prognostic factors, which were then used to develop a predictive nomogram model for OS in CRC. The nomogram was evaluated by the C-index, receiver operator characteristic curve (ROC) analysis, and calibration plot. All cases were grouped into three stratifications according to the total risk points calculated from the nomogram, and the difference in OS between them was assessed with the Kaplan-Meier method. Results At the end of the study, death occurred in 47 (21%) cases. Patients with low CLR (< 3.23) had significantly prolonged survival (P < 0.001). Multivariate analyses revealed that N stage (P < 0.001), harvested lymph nodes (P = 0.021), and CLR (P = 0.005) were independent prognostic factors for OS and a prognostic nomogram was established based on these variables. The nomogram showed good calibration and predictive performance with a superior C-index than TNM stage (0.755 (0.719–0.791) vs. 0.663 (0.629–0.697), P = 0.001). Patients of different risk stratifications based on the total score of nomogram showed distinct survival (P < 0.001). Conclusions The nomogram based on CLR and other clinical features can be used as a potentially convenient and reliable tool in predicting survival in patients with CRC.

Ventilator-Free Days in Neonatal Ventilator-Associated Pneumonia

Objective To compare the ventilator-free days (VFDs) at day 28 and the short-term outcomes in neonates with and without ventilator-associated pneumonia (VAP and non-VAP groups). Study Design We performed a cohort study in a Thai neonatal intensive care unit between 2014 and 2020 to identify the VFDs in VAP and non-VAP neonates. Univariate and multivariate analyses were performed. Results The incidences of VAP rates were 5.76% (67/1,163 neonates) and 10.86 per 1,000 (92/8,469) ventilator days. The medians (interquartile ranges) of gestational age and birth weight in the VAP vs non-VAP groups were 31 (27–35) vs 34 (30–38) weeks, and 1,495 (813–2,593) vs 2,220 (1,405–2,940) grams (p < 0.001 both), respectively. The medians (interquartile ranges) of VFDs at 28 days in the VAP and non-VAP groups were 5 (0–16) and 24 (20–26) days (<i>p</i> < 0.001). From the univariate analysis, the lower VFDs, longer ventilator days, and higher rates of moderate to severe bronchopulmonary dysplasia (BPD), postnatal steroids for BPD, length of stay, and daily hospital cost in the VAP group were significantly higher than in the non-VAP group. From the multivariate analysis, the VAP group had significantly lower VFDs (regression coefficient = -10.99, standard error = 1.11, <i>p</i> < 0.001) and higher BPD (adjusted risk ratio 18.70; 95% confidence interval 9.17–39.5, <i>p</i> < 0.001) than the non-VAP group. <b>Conclusion</b> Neonatal VAP lead to lower VFDs and a higher frequency of BPD. A multimodal strategy with a VAP prevention bundle care should be used in indicated cases to reduce the occurrence of neonatal VAP.

Clinical Relevance of Soluble Forms of Immune Checkpoint Molecules sPD-1, sPD-L1, and sCTLA-4 in the Diagnosis and Prognosis of Ovarian Cancer

It is crucial to find new diagnostic and prognostic biomarkers. A total of 80 patients were enrolled in the study. The study group consisted of 37 patients with epithelial ovarian cancer, and the control group consisted of 43 patients with benign ovarian cystic lesions. Three proteins involved in the immune response were studied: PD-1, PD-L1, and CTLA-4. The study material was serum and peritoneal fluid. The ROC curve was plotted, and the area under the curve was calculated to characterize the sensitivity and specificity of the studied parameters. Univariate and multivariate analyses were performed simultaneously using the Cox regression model. The cut-off level of CTLA-4 was 0.595 pg/mL, with the sensitivity and specificity of 70.3% and 90.7% (p = 0.000004). Unfavorable prognostic factors determined in serum were: PD-L1 (for PFS: HR 1.18, 95% CI 1.11–1.21, p = 0.016; for OS: HR 1.17, 95% CI 1.14–1.19, p = 0.048) and PD-1 (for PFS: HR 1.01, 95% CI 0.91–1.06, p = 0.035). Unfavorable prognostic factors determined in peritoneal fluid were: PD-L1 (for PFS: HR 1.08, 95% CI 1.01–1.11, p = 0.049; for OS: HR 1.14, 95% CI 1.10–1.17, p = 0.045) and PD-1 (for PFS: HR 1.21, 95% CI 1.19–1.26, p = 0.044). We conclude that CTLA-4 should be considered as a potential biomarker in the diagnosis of ovarian cancer. PD-L1 and PD-1 concentrations are unfavorable prognostic factors for ovarian cancer.

Upper extremity deep vein thrombosis in COVID-19: Incidence and correlated risk factors in a cohort of non-ICU patients

Background Venous thromboembolism is a frequent complication of COVID-19 infection. Less than 50% of pulmonary embolism (PE) is associated with the evidence of deep venous thrombosis (DVT) of the lower extremities. DVT may also occur in the venous system of the upper limbs especially if provoking conditions are present such as continuous positive airway pressure (CPAP). The aim of this study was to evaluate the incidence of UEDVT in patients affected by moderate-severe COVID-19 infection and to identify potential associated risk factors for its occurrence. Methods We performed a retrospective analysis of all patients affected by moderate-severe COVID-19 infection admitted to our unit. In accordance with the local protocol, all patients had undergone a systematic screening for the diagnosis of UEDVT, by vein compression ultrasonography (CUS). All the patients were receiving pharmacological thromboprophylaxis according to international guidelines recommendations. Univariate and multivariate analyses were used to identify risk factors associated with UEDVT. Results 257 patients were included in the study, 28 patients were affected by UEDVT with an incidence of 10.9% (95% CI, 7.1–14.7). At univariate analysis UEDVT appeared to be significantly associated (p< 0.05) with pneumonia, ARDS, PaO2/FiO2, D-dimer value higher than the age adjusted cut off value and need for CPAP ventilation. Multivariate analysis showed a significant association between UEDVT and the need for CPAP ventilation (OR 5.95; 95% IC 1.33–26.58). Increased mortality was found in patients affected by UEDVT compared to those who were not (OR 3.71; 95% CI, 1.41–9.78). Conclusions UEDVT can occur in COVID-19 patients despite adequate prophylaxis especially in patients undergoing helmet CPAP ventilation. Further studies are needed to identify the correct strategy to prevent DVT in these patients.

In-Silico Multi-Omics Analysis of the Functional Significance of Calmodulin 1 in Multiple Cancers

Aberrant activation of calmodulin 1 (CALM1) has been reported in human cancers. However, comprehensive understanding of the role of CALM1 in most cancer types has remained unclear. We systematically analyzed the expression landscape, DNA methylation, gene alteration, immune infiltration, clinical relevance, and molecular pathway of CALM1 in multiple cancers using various online tools, including The Cancer Genome Atlas, cBioPortal and the Human Protein Atlas databases. Kaplan–Meier and receiver operating characteristic (ROC) curves were plotted to explore the prognostic and diagnostic potential of CALM1 expression. Multivariate analyses were used to evaluate whether the CALM1 expression could be an independent risk factor. A nomogram predicting the overall survival (OS) of patients was developed, evaluated, and compared with the traditional Tumor-Node-Metastasis (TNM) model using decision curve analysis. R language was employed as the main tool for analysis and visualization. Results revealed CALM1 to be highly expressed in most cancers, its expression being regulated by DNA methylation in multiple cancers. CALM1 had a low mutation frequency (within 3%) and was associated with immune infiltration. We observed a substantial positive correlation between CALM1 expression and macrophage and neutrophil infiltration levels in multiple cancers. Different mutational forms of CALM1 hampered immune cell infiltration. Additionally, CALM1 expression had high diagnostic and prognostic potential. Multivariate analyses revealed CALM1 expression to be an independent risk factor for OS. Therefore, our newly developed nomogram had a higher clinical value than the TNM model. The concordance index, calibration curve, and time-dependent ROC curves of the nomogram exhibited excellent performance in terms of predicting the survival rate of patients. Moreover, elevated CALM1 expression contributes to the activation of cancer-related pathways, such as the WNT and MAPK pathways. Overall, our findings improved our understanding of the function of CALM1 in human cancers.

A Scoring Tool to Predict Pulmonary Complications in Severe Leptospirosis with Kidney Failure

Rapid identification of patients likely to develop pulmonary complications in severe leptospirosis is crucial to prompt aggressive management and improve survival. The following article is a cohort study of leptospirosis patients admitted at the National Kidney and Transplant Institute (NKTI). Logistic regression was used to predict pulmonary complications and obtain a scoring tool. The Kaplan–Meir method was used to describe survival rates. Among 380 patients with severe leptospirosis and kidney failure, the overall mortality was 14%, with pulmonary hemorrhage as the most common cause. In total, there were 85 (22.4%) individuals who developed pulmonary complications, the majority (95.3%) were observed within three days of admission. Among the patients with pulmonary complications, 56.5% died. Patients placed on mechanical ventilation had an 82.1% mortality rate. Multivariate analyses showed that dyspnea (OR = 28.76, p < 0.0001), hemoptysis (OR = 20.73, p < 0.0001), diabetes (OR = 10.21, p < 0.0001), renal replacement therapy (RRT) requirement (OR = 6.25, p < 0.0001), thrombocytopenia (OR = 3.54, p < 0.0029), and oliguria/anuria (OR = 3.15, p < 0.0108) were significantly associated with pulmonary complications. A scoring index was developed termed THe-RADS score (Thrombocytopenia, Hemoptysis, RRT, Anuria, Diabetes, Shortness of breath). The odds of developing pulmonary complications were 13.90 times higher among patients with a score >2 (63% sensitivity, 88% specificity). Pulmonary complications in severe leptospirosis with kidney failure have high mortality and warrant timely and aggressive management.

Defense Budget Growth and Inflation: A Wavelet-Based Study of the U.S. and Britain

Despite the extensive theoretical connections between defense budget growth and inflation, empirical findings based on traditional time-domain methods have been inconclusive. This study reexamines the issue from a time–frequency perspective. Applying continuous wavelet analysis to the U.S. and Britain, it shows empirical evidence in support of positive bilateral effects in both cases. In the bivariate context, U.S. defense budget growth promoted inflation at 2- to 4-year cycles in the 1840s and at 8- to 24-year cycles between 1825 and 1940. Conversely, inflation accelerated defense spending growth at 5- to 7-year cycles in the 1830s and at 25- to 64-year cycles between 1825 and 1940. Similarly, British defense budget growth spurred inflation at 8- to 48-year cycles between 1890 and 1940 and at 50- to 65-year cycles between 1790 and 1860. Inflation fueled the growth of defense spending at 7- to 20-year cycles between 1840 and 1870, in the 1940s, and in the 1980s. Preliminary results from multivariate analyses are also supportive, though there is a need for further research that is contingent on advancements in the wavelet method in the direction of simulation-based significance tests.