Miracle-dz/UniFAR-FTUs huggingface dataset:
A nomogram for predicting brain metastases of EGFR-mutated lung adenocarcinoma patients and estimating the efficacy of therapeutic strategies

Background To establish a nomogram for predicting the outcome of EGFR-mutated lung adenocarcinoma patients with brain metastases (BMs) and to estimate the efficacy of different therapeutic strategies. Methods The data of 129 cases with BM from the period between January 1st 2011 and December 31st 2014 were collected, and all of the cases were pathologically confirmed to be lung adenocarcinoma, stages I–IV and with 19 and/or 21 exon mutations of EGFR. Cox regression analysis and log-rank test were used for data analysis. The nomogram was used to establish the progression models. Results In the univariate analysis, the stage, ECOG score, interval between the diagnosis of lung cancer and BM, the number of brain metastatic lesions, and the diameter of the maximal brain metastatic lesion correlated well with overall survival (OS). In multivariate Cox proportional hazard analysis, the ECOG score, interval between the diagnosis of lung cancer and BM, and the number of brain metastatic lesions correlated well with the OS. Patients were divided into the poor prognostic group and the good prognostic group based on the nomogram prognostic model score. Subgroup analysis showed that in the poor prognostic group, the OS of patients who received radiotherapy was better than that of the patients who did not receive radiotherapy as the first-line treatment (30 vs. 19 months, P<0.05). The OS was 30 months in the TKI subgroup and 21 months in the no TKI subgroup, but no statistical difference was found (P>0.05). Patients in the good prognostic group who received radiotherapy had a better 3-y OS rate than the patients who received no radiotherapy as the first-line treatment (91.2% vs. 58.1%, P<0.05). The 3-y OS rate was 87.6% in the TKI subgroup and 67.8% in the no TKI group (P<0.05). Conclusions We established an effective nomogram model to predict the progression of EGFR-mutated lung adenocarcinoma patients with BM and the therapeutic effect of the individual treatments. Radiotherapy was beneficial for the patients of both the poor and good prognostic groups, but TKI may be better suited for treating the patients with good prognosis.
Neutrophil-to-lymphocyte ratio is associated with malnutrition risk estimated by the Royal Free Hospital-Nutritional Prioritizing Tool in hospitalized cirrhosis.

BACKGROUND Liver cirrhosis is characterized by immune dysfunction contributing to malnutrition. We previously revealed neutrophil-to-lymphocyte ratio (NLR) as an indicator of disordered immune system. Herein we aimed to i) determine the optimal NLR cut-off that best predicts malnutrition risk; ii) clarify the association between NLR and nutritional status. METHODS A total of 135 hospitalized cirrhotics were included. Immune dysfunction was evaluated by levels of serum C-reactive protein (CRP), NLR and other parameters. Malnutrition was screened by a risk score referring to Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT). ROC curve was implemented to determine the best NLR cut-off which predicts malnutrition risk. Correlation between NLR and indicators of hepatic and physical function (handgrip strength) were also examined. Multivariable logistic regression was used to assess the association between NLR and malnutrition risk. RESULTS ROC curve revealed that the optimum cut-off to predict malnutrition risk was NLR > 4.2 with a sensitivity of 47.2%, specificity of 81.0%, NPV of 58.0% and PPV of 74.5%, respectively. Patients with NLR > 4.2 exhibited higher RFH-NPT score, higher serum platelet-to-lymphocyte ratio, and CRP. A positive correlation was found between NLR values and CTP (r = 0.22, p = 0.010), MELD (r = 0.36, p < 0.001) and RFH-NPT score (r = 0.31, p < 0.001). NLR was a risk factor for malnutrition independently of alcoholic liver disease and presence of ascites. CONCLUSIONS Immune dysfunction measured by NLR was associated with malnutrition risk estimated by RFH-NPT in cirrhosis. This article is protected by copyright. All rights reserved.
Treatment challenges in clinically amyopathic dermatomyositis: A case series and review of new therapeutic options for skin involvement

The term clinically amyopathic dermatomyositis (CADM) is used to represent a subgroup of patients with the typical cutaneous features of dermatomyositis (DM) in the absence of muscle involvement. Similar to classic DM, CADM can be associated with other connective tissue disorders and systemic manifestations such as interstitial lung disease and malignancy. Owing to the frequent discordance between muscle response and skin disease, the therapeutic approach to CADM represents a challenge. The current literature suggests that CADM treatment should follow a specific protocol, influenced by visceral involvement and the expression of certain myositis‐specific antibodies, and different from the recommendation in the presence of myositis. Here, we present five new cases of CADM. We describe the available therapeutic options for skin manifestations in this type of DM, and we propose a step‐by‐step therapeutic scheme, using the cutaneous dermatomyositis disease area and severity index to assess response. Our literature review establishes mycophenolate mofetil and intravenous immunoglobulin as the most frequently successful therapies in refractory skin disease.
Investigation of urinary components in rat model of ketamine-induced bladder fibrosis based on metabolomics

Background Ketamine abuse has been linked to the system's damage, presenting with lower urinary tract symptoms (LUTS). While the pathogenesis of ketamine-induced urinary damage is not fully understood, fibrosis is believed to be a potential mechanism. A metabolomic investigation of the urinary metabolites in ketamine abuse was conducted to gain insights into its pathogenesis. Methods A rat model of ketamine induced bladder fibrosis was established through tail vein injection of ketamine hydrochloride and control group was established through tail vein injection of the equivalent normal saline. Hematoxylin and eosin (H&E) staining and Masson trichrome staining were performed to evaluated bladder pathology. Urinary components were detected based on a metabolomic approach using ultra-high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOFMS platform). Orthogonal projections analyzed the data to latent structures discriminant analysis (OPLS-DA) and bioinformatics analysis. Results The rat model of ketamine induced bladder fibrosis was confirmed through H&E and Masson trichrome staining. There were marked differences in the urinary metabolites between the experimental group and the control group. Compared to the control group, 16 kinds of differential metabolites were up-regulated and 102 differential metabolites were down-regulated in the urine samples of the ketamine group. Bioinformatics analysis revealed the related metabolic pathways. Conclusions Using a ketamine-induced bladder fibrosis rat model, this study identified the differential urinary metabolites expressed following ketamine treatment. These results provide vital clues for exploring the pathogenesis of ketamine-induced LUTS and may further contribute to the disease's diagnosis and treatment.
Water-Soluble Organic Aerosol material and the light-absorption characteristics of aqueous extracts measured over the Southeastern United States

Abstract. Light absorption of fine particle (PM2.5) aqueous extracts between wavelengths of 200 and 800 nm were investigated from two data sets: 24-h Federal Reference Method (FRM) filter extracts from 15 Southeastern US monitoring sites over the year of 2007 (900 filters), and online measurements from a Particle-Into-Liquid Sampler deployed from July to mid-August 2009 in Atlanta, Georgia. Three main sources of soluble chromophores were identified: biomass burning, mobile source emissions, and compounds linked to secondary organic aerosol (SOA) formation. Absorption spectra of aerosol solutions from filter extracts were similar for different sources. Angstrom exponents were ~7±1 for biomass burning and non-biomass burning-impacted 24-h filter samples (delineated by a levoglucosan concentration of 50 ng m−3) at both rural and urban sites. The absorption coefficient from measurements averaged between wavelength 360 and 370 nm (Abs365, in units m−1) was used as a measure of overall brown carbon light absorption. Biomass-burning-impacted samples were highest during winter months and Abs365 was correlated with levoglucosan at all sites. During periods of little biomass burning in summer, light absorbing compounds were still ubiquitous and correlated with fine particle Water-Soluble Organic Carbon (WSOC), but comprised a much smaller fraction of the WSOC, where Abs365/WSOC (i.e., mass absorption efficiency) was typically ~3 times higher in biomass burning-impacted samples. Factor analysis attributed 50% of the yearly average Abs365 to biomass burning sources. Brown carbon from primary urban emissions (mobile sources) was also observed and accounted for ~10% of the regional yearly average Abs365. Summertime diurnal profiles of Abs365 and WSOC showed that morning to midday increases in WSOC from photochemical production were associated with a decrease in Abs365/WSOC. After noon, this ratio substantially increased, indicating that either some fraction of the non-light absorbing fresh SOA was rapidly (within hours) converted to chromophores heterogeneously, or that SOA from gas-particle partitioning later in the day was more light-absorbing. Factor analysis on the 24-h integrated filter data associated ~20 to 30% of Abs365 over 2007 with a secondary source that was highest in summer and also the main source for oxalate, suggesting that aqueous phase reactions may account for the light-absorbing fraction of WSOC observed throughout the Southeastern US in summer.
The Role of Racial and Developmental Experience on Emotional Adaptive Coding in Autism Spectrum Disorder

ABSTRACT Sensitivity to emotional face aids in rapid detection and evaluation of others, such that by school-age, children and youth exhibit adult-like patterns when the prolonged viewing of an emotional face distorts the perception of a subsequent face. However, the developmental considerations of this phenomenon (known as emotional adaptive coding) are unclear given ongoing maturational and experiential changes, including the influence of own-race experiences or the lack of face expertise, as is evident in autism spectrum disorder (ASD). This study addressed whether emotional adaptive coding is sensitive to factors of face perception expertise, specifically self-race and developmental experience, in adults (age 19–28 years) and youth (age 10–16 years). Emotional adaptive coding was not influenced by race expertise (i.e., other versus same race identity) in White and Asian adults. Emotional adaptation coding during childhood and adolescence is consistent with adults, though youth with ASD exhibited stronger adaptor after-effects in response to other-race faces, relative to TD youth and adults. By extending prior work to examine the integration of race and emotional adaptive coding in ASD, we discovered that the strength of response in ASD is atypical when viewing other-race faces, which clarifies the role of racial and facial experience on emotional face adaption.
Relationship between de novo lipogenesis and serum sex hormone binding globulin in humans

Obesity and liver fat are associated with decreased levels of serum sex hormone binding globulin (SHBG). Laboratory studies suggest that hepatic de novo lipogenesis (DNL) is involved in the downregulation of SHBG synthesis. The aim of the present study was to address the role of DNL on serum SHBG in humans.
Factor VIII levels and bleeding according to factor 8 (F8) mutation in pregnant carriers of haemophilia A: a multicentre retrospective cohort study

This retrospective cohort study investigated the association between factor 8 (F8) genotype severity and factor VIII (FVIII) levels during pregnancy for 52 women (64 pregnancies) who were heterozygous carriers of mild, moderate or severe haemophilia A. There were no significant differences in FVIII levels for carriers of mild, moderate or severe haemophilia A at baseline [mean (SD) level: mild, 0·78 (0·22); moderate, 0·83 (0·33); severe, 0·70 (0·25) iu/ml; P = 0·81] or in the third trimester [mean (SD) level: mild, 1·42 (0·28); moderate, 1·47 (0·41); severe, 1·37 (0·49) iu/ml; P = 0·80). Post‐partum haemorrhage rates were higher for carriers of severe haemophilia A (13/24; 54·2%) compared to carriers of mild haemophilia A (four of 14; 28·6%).
An In Vitro Study on the Effects of Selected Natural Dietary Fiber from Salad Vegetables for Lowering Intestinal Glucose and Lipid Absorption.

BACKGROUND Salad vegetables are good sources of dietary fiber and are becoming increasingly popular among consumers. Therefore, these plants have the potential to be developed as functional foods. OBJECTIVE Using an in vitro model, this study investigated the physical properties and intestinal glucose and lipid absorption capacities of dry dietary fiber from vegetables typically consumed in salads (types of lettuce, including red oak, red coral, green oak, butterhead, and cos). METHOD Fiber was prepared from each type of lettuce using an enzymatic method and then characterized. Physical properties, including solubility and water-binding, swelling, cation-exchange, and oil-binding capacities, and antihyperglycemic and antihypercholesterolemic effects of fiber were investigated. RESULTS The hydration capacity of total dietary fiber and insoluble fiber from the majority of sources was significantly different from that of cellulose. Adsorption and diffusion of glucose were directly proportional to incubation time, and the diffusion rate was significantly lower in the treatments containing fiber compared to the cellulose control. Fiber from these vegetables also inhibited amylase and alpha-glucosidase activities. Moreover, fiber from all sources exhibited significantly higher sodium cholate and cholesterol-binding capacity compared to cellulose, and also retarded pancreatic cholesterol esterase activity in a concentration-dependent manner. CONCLUSION This study demonstrates that natural dietary fiber from salad vegetables can reduce glucose and lipid absorption and breakdown rates, thus preventing increases in postprandial blood glucose and cholesterol levels, which can be beneficial to human health.
S-Nitrosylation of Histone Deacetylase 2 by Neuronal Nitric Oxide Synthase as a Mechanism of Diastolic Dysfunction

Supplemental Digital Content is available in the text. Background: Although the clinical importance of heart failure with preserved ejection fraction has been extensively explored, most therapeutic regimens, including nitric oxide (NO) donors, lack therapeutic benefit. Although the clinical characteristics of heart failure with preserved ejection fraction are somewhat heterogeneous, diastolic dysfunction (DD) is one of the most important features. Here we report that neuronal NO synthase (nNOS) induces DD by S-nitrosylation of HDAC2 (histone deacetylase 2). Methods: Two animal models of DD—SAUNA (SAlty drinking water/Unilateral Nephrectomy/Aldosterone) and mild transverse aortic constriction mice—as well as human heart samples from patients with left ventricular hypertrophy were used. Genetically modified mice that were either nNOS-ablated or HDAC2 S-nitrosylation–resistant were also challenged. N(ω)-propyl-L-arginine, an nNOS selective inhibitor, and dimethyl fumarate, an NRF2 (nuclear factor erythroid 2–related factor 2) inducer, were used. Molecular events were further checked in human left ventricle specimens. Results: SAUNA or mild transverse aortic constriction stress impaired diastolic function and exercise tolerance without overt systolic failure. Among the posttranslational modifications tested, S-nitrosylation was most dramatically increased in both models. Utilizing heart samples from both mice and humans, we observed increases in nNOS expression and NO production. N(ω)-propyl-L-arginine alleviated the development of DD in vivo. Similarly, nNOS knockout mice were resistant to SAUNA stress. nNOS-induced S-nitrosylation of HDAC2 was relayed by transnitrosylation of GAPDH. HDAC2 S-nitrosylation was confirmed in both DD mouse and human left ventricular hypertrophy. S-nitrosylation of HDAC2 took place at C262 and C274. When DD was induced, HDAC2 S-nitrosylation was detected in wild-type mouse, but not in HDAC2 knock-in mouse heart that expressed HDAC2 C262A/C274A. In addition, HDAC2 C262A/C274A mice maintained normal diastolic function under DD stimuli. Gene delivery with adenovirus-associated virus 9 (AAV9)–NRF2, a putative denitrosylase of HDAC2, or pharmacological intervention by dimethyl fumarate successfully induced HDAC2 denitrosylation and mitigated DD in vivo. Conclusions: Our observations are the first to demonstrate a new mechanism underlying DD pathophysiology. Our results provide theoretical and experimental evidence to explain the ineffectiveness of conventional NO enhancement trials for improving DD with heart failure symptoms. More important, our results suggest that reduction of NO or denitrosylation of HDAC2 may provide a new therapeutic platform for the treatment of refractory heart failure with preserved ejection fraction.
Development of Voltammetric Sensor for Determination of Tryptophan Using MWCNTs‐modified Sol‐gel Electrode

In the present work, an electrochemical sensor was developed for simple and sensitive determination of tryptophan (Trp) using multi-walled carbon nanotubes modified sol-gel electrode (MWCNTs/SGE). The electrocatalytic oxidation of tryptophan was investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). It was found that the oxidation peak current of Trp at the MWCNTs/SGE was greatly improved compared with that of the bare SGE. Furthermore, at the MWCNTs/SGE, the anodic peak potential of Trp is shifted about 220 mV to more negative value indicated that modified electrode has better electrocatalytic activity for electro-oxidation of Trp. The anodic peak currents increased linearly with the concentration of tryptophan in the range of 0.2 x 10(-6) to 15 x 10(-6) M with a detection limit of 0.139 x 10(-6) M (at an S/N = 3).
PMMA-based composite materials with reactive ceramic fillers. Part1.—Chemical modification and characterisation of ceramicparticles

Polymerisable organic silane molecules [3-(trimethoxysilyl)propyl methacrylate, γ-MPS] have been grafted onto the surface of ceramic oxide powders (Al 2 O 3 , ZrO 2 , TiO 2 ), via hydroxy groups of the latter oxides, in order to obtain organic–inorganic hybrid ‘macromonomers’. Densities of surface hydroxy groups have been determined using thermogravimetry (TG) and chemical titration. Quantification of γ-MPS grafting has been determined by FTIR spectroscopy, elemental analysis and TG. Typical grafting yields up to 6 µmol m -2 were obtained. The influence of the relative amount of silane used has been studied. Silane multilayers and/or aggregates are formed as observed in 29 Si CP MAS NMR spectroscopy.
Associations between lifetime classic psychedelic use and markers of physical health

Background: In recent years, there has been significant research on the mental health effects of classic psychedelic use, but there is very little evidence on how classic psychedelics might influence physical health. Aims: The purpose of the present study was to investigate the associations between lifetime classic psychedelic use and markers of physical health. Methods: Using data from the National Survey on Drug Use and Health (2015-2018) with 171,766 (unweighted) adults aged 18 or above in the United States, the current study examined the associations between lifetime classic psychedelic use and three markers of physical health (self-reported overall health, body mass index, and heart condition and/or cancer in the past 12 months) while controlling for a range of covariates. Results: Respondents who reported having tried a classic psychedelic at least once in their lifetime had significantly higher odds of greater self-reported overall health and significantly lower odds of being overweight or obese versus having a normal weight. The association between lifetime classic psychedelic use and having a heart condition and/or cancer in the past 12 months approached conventional levels of significance, with lower odds of having a heart condition and/or cancer in the past 12 months for respondents who had tried a classic psychedelic at least once. Conclusion: The results of the present study suggest that classic psychedelics may be beneficial to physical health. Future research should investigate the causal effects of classic psychedelics on physical health and evaluate possible mechanisms.
Mucin 4 mutation is associated with tumor mutation burden and promotes antitumor immunity in colon cancer patients

At present, immunotherapy is widely used for different mismatch repair (dMMR) or highly microsatellite instability (MSI-H) colorectal cancer patients, and tumor mutation burden (TMB) is a valuable independent predictor of response to immunotherapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immune cells in colon cancer remains unclear. In the present study, we analyzed somatic mutation data of colon cancer from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets, and found that 17 frequently mutated genes were occurred in both cohorts, including APC, TP53, TNN, KRAS, MUC16, MUC4 (mucin 4), SYNE1, FLG, FAT4, OBSCN, FAT3, RYR2, PIK3CA, FBXW7, DNAH11, MUC5B and ZFHX4. Interestingly, only MUC4 mutation was associated with higher TMB and patient clinical prognosis among the 17 mutated genes. Moreover, according to gene set enrichment analysis (GSEA) and the CIBERSORT algorithm, we revealed that MUC4 mutation activated signaling pathways involved in the immune system and enhanced the antitumor immune response. In conclusion, MUC4 may have important clinical implications for immune therapy of colon cancer.
Proteomic/transcriptomic analysis of erythropoiesis

Purpose of review Erythropoiesis is a hierarchical process by which hematopoietic stem cells give rise to red blood cells through gradual cell fate restriction and maturation. Deciphering this process requires the establishment of dynamic gene regulatory networks (GRNs) that predict the response of hematopoietic cells to signals from the environment. Although GRNs have historically been derived from transcriptomic data, recent proteomic studies have revealed a major role for posttranscriptional mechanisms in regulating gene expression during erythropoiesis. These new findings highlight the need to integrate proteomic data into GRNs for a refined understanding of erythropoiesis. Recent findings Here, we review recent proteomic studies that have furthered our understanding of erythropoiesis with a focus on quantitative mass spectrometry approaches to measure the abundance of transcription factors and cofactors during differentiation. Furthermore, we highlight challenges that remain in integrating transcriptomic, proteomic, and other omics data into a predictive model of erythropoiesis, and discuss the future prospect of single-cell proteomics. Summary Recent proteomic studies have considerably expanded our knowledge of erythropoiesis beyond the traditional transcriptomic-centric perspective. These findings have both opened up new avenues of research to increase our understanding of erythroid differentiation, while at the same time presenting new challenges in integrating multiple layers of information into a comprehensive gene regulatory model.