Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of the polarization states of the alveolar macrophages in chronic obstructive pulmonary disease samples based on miRNA-mRNA network signatures

Background Multiple gene expression studies have been performed to investigate the biomarkers of chronic obstructive pulmonary disease (COPD). However, few studies have related COPD to macrophage cells. Methods The gene expression levels of clinical samples of COPD smokers (COPD; n=6), healthy smokers (Smoke; n=11), and never smokers (Never; n=4) were downloaded from the Gene Expression Omnibus (GEO) repository of GSE124180. The expression levels of messenger RNAs (mRNAs) and microRNAs (miRNAs) in macrophage cells of M0 (n=7), M1 (n=7), and M2 (n=7) were downloaded from the GEO repository of GSE46903 and GSE51307. Differentially expressed (DE) mRNAs (DEmRNAs) were identified by edgeR and GEO2R, with an adjusted P value <0.05 and |log2fold change (FC)| ≥1 chosen as the cut-off threshold. The potential target genes of miRNA were identified using miRanda (v3.3a) and TargetScan (v6.0) with default settings. Gene Ontology (GO) and Reactome pathway analyses were performed. Results The composition of macrophages was quite different between COPD, Never, and Smoke samples. The proportion of M1 cells was lower than that of M0 and M2 cells in Smokers and COPD samples. Most of the genes specifically up-regulated in M1 are related to inflammation/immunity. The expression levels of miR-30a-5p, miR-200c-3p, miR-20b-5p, miR-199b-5p, and miR-301b-3p in M1 macrophages were all lower than that of M0. Their expression levels in M2 macrophages compared with M1 varied, with higher expression in miR-30a-5p, miR-20b-5p, and lower expression in miR-200c-3p, and miR-301b-3p. The mRNAs of the fms related receptor tyrosine kinase 1 (FLT1), cardiotrophin like cytokine factor 1 (CLCF1), phosphodiesterase 4D (PDE4D), coagulation factor III, and tissue factor (F3) were dysregulated in COPD and macrophage cells. Conclusions The present study mined the miRNA-mRNA signature which might play an essential role in COPD and macrophage polarization.
An automated tool for comparing phonetic transcriptions

ABSTRACT Many computerized tools for comparing phonetic transcriptions have been proposed and shared in the past; however, previous tools are relatively difficult to access and incorporate into clinical and research practice, or require users to learn additional phonetic symbol systems. The purpose of this project was to develop and test a readily available web-based application for quantitatively comparing phonetic transcriptions that are input using International Phonetic Alphabet (IPA) symbols. A web-based computer application was developed to allow for IPA phonetic transcription comparison. A point-and-click keyboard was developed to provide support for character input of the full IPA, as well as most symbols in the extIPA set. The application compares phonetic transcriptions using a modified edit distance algorithm following phonologically informed alignment. Visualizations of the algorithm’s optimal alignment and scoring operations are shown for each comparison input by a user. The application, named the Automated Phonetic Transcription Comparison Tool (APTct), was thoroughly tested for accurate implementation of the algorithm principles. Validity tests through two sample use cases were also performed by comparison of hand calculations to APTct calculations. In function testing, the APTct showed excellent agreement with an expert’s hand scoring using the same algorithm principles. In a validity test, only minor differences between the APTct and hand calculations were observed, primarily due to errors inputting the transcriptions into the APTct. The web-based APTct is a validated and versatile tool for quantitatively comparing even complex IPA phonetic transcriptions. It is freely available to clinicians and researchers, who may find it useful for a variety of potential scenarios. We invite researchers, clinicians, and other individuals to use the tool in their clinical and research work. The permalink for the website is as follows: https://aptct.auburn. edu
A process-based model for ammonia emission from urine patches, GAG (Generation of Ammonia from Grazing): description and sensitivity analysis

Abstract. In this paper a new process-based, weather-driven model for ammonia (NH3) emission from a urine patch has been developed and its sensitivity to various factors assessed. The GAG model (Generation of Ammonia from Grazing) is capable of simulating the TAN (total ammoniacal nitrogen) and the water content of the soil under a urine patch and also soil pH dynamics. The model tests suggest that ammonia volatilization from a urine patch can be affected by the possible restart of urea hydrolysis after a rain event as well as CO2 emission from the soil. The vital role of temperature in NH3 exchange is supported by our model results; however, the GAG model provides only a modest overall temperature dependence in total NH3 emission compared with the literature. This, according to our findings, can be explained by the higher sensitivity to temperature close to urine application than in the later stages and may depend on interactions with other nitrogen cycling processes. In addition, we found that wind speed and relative humidity are also significant influencing factors. Considering that all the input parameters can be obtained for larger scales, GAG is potentially suitable for field and regional scale application, serving as a tool for further investigation of the effects of climate change on ammonia emissions and deposition.
An immune-related gene expression signature predicts brain metastasis in lung adenocarcinoma patients after surgery: gene expression profile and immunohistochemical analyses

Background Lung adenocarcinoma (LUAD) with brain metastasis (BM) occurs frequently and has a poor prognosis. In this study, we aimed to assess the correlation between gene expression signatures and the development of BM after surgical resection of LUAD. Methods We analyzed the immune-related gene expression profiles of 72 LUADs with and without BM after surgery and verified them using NanoString method and immunohistochemistry (IHC). We matched the Tumor, Node, Metastasis (TNM) stage in the groups with and without BM to minimize the effect of TNM stage. Pathway enrichment studies were also performed. Results In the NanoString results, we identified 11 upregulated immune-related gene signature that correlated specifically with BM in the discovery and validation sets [area under the curve (AUC) =0.750 and 0.787, respectively]. The discovery set achieved 94% sensitivity and 62% specificity and the validation set displayed 100% sensitivity and 50% specificity. Eight out of the 11 genes were verified by IHC and had profiles similar to the gene expression profile results (AUC =0.844 for the discovery set and AUC =0.795 for the validation set). Subgroup analysis revealed that 11 immune-related gene signature enabled prediction of BM at all TNM stages. There were no differences in the 11 immune-related gene expression signatures between the primary LUAD samples and the matched brain samples. Pathway enrichment analysis revealed that the cytokine-cytokine receptor interaction pathway was closely correlated with BM. Conclusions The 11 identified immune-related gene expression signatures may be potentially clinically useful predictors for BM and can provide patient-specific treatment options.
Acute pancreatitis in COVID-19 patients: true risk?

Abstract Background A relation between coronavirus disease 2019 (COVID-19) and acute pancreatitis has been suggested. However, the incidence and clinical relevance of this relation remain unclear. Objective We aimed to investigate the incidence, severity and clinical impact of acute pancreatitis in patients with COVID-19. Methods This is a cross-sectional study of a prospective, observational cohort concerning all COVID-19 patients admitted to two Dutch university hospitals between 4 March 2020 and 26 May 2020. Primary outcome was acute pancreatitis potentially related to COVD-19 infection. Acute pancreatitis was defined according to the revised Atlanta Classification. Potential relation with COVID-19 was defined as the absence of a clear aetiology of acute pancreatitis. Results Among 433 patients with COVID-19, five (1.2%) had potentially related acute pancreatitis according to the revised Atlanta Classification. These five patients suffered from severe COVID-19 infection; all had (multiple) organ failure and 60% died. None of the patients developed necrotizing pancreatitis. Moreover, development of acute pancreatitis did not lead to major treatment consequences. Conclusions In contrast with previous research, our study demonstrated that COVID-19 related acute pancreatitis is rare and of little clinical impact. It is therefore debatable if acute pancreatitis in COVID-19 patients requires specific screening. We hypothesize that acute pancreatitis occurs in patients with severe illness due to COVID-19 infection as a result of transient hypoperfusion and pancreatic ischemia, not as a direct result of the virus.
Computer Methods and Programs in Biomedicine

Background and Objective: The capability of deep learning radiomics (DLR) to extract high-level medical imaging features has promoted the use of computer-aided diagnosis of breast mass detected on ultrasound. Recently, generative adversarial network (GAN) has aided in tackling a general issue in DLR, i.e., obtaining a suﬃcient number of medical images. However, GAN methods require a pair of input and labeled images, which require an exhaustive human annotation process that is very time-consuming. The aim of this paper is to develop a radiomics model based on a semi-supervised GAN method to perform data augmentation in breast ultrasound images. Methods: A total of 1447 ultrasound images, including 767 benign masses and 680 malignant masses were acquired from a tertiary hospital. A semi-supervised GAN model was developed to augment the breast ultrasound images. The synthesized images were subsequently used to classify breast masses using a convolutional neural network (CNN). The model was validated using a 5-fold cross-validation method. Results: The proposed GAN architecture generated high-quality breast ultrasound images, veriﬁed by two experienced radiologists. The improved performance of semi-supervised learning increased the quality of the synthetic data produced in comparison to the baseline method. We achieved more accurate breast mass classiﬁcation results (accuracy 90.41%, sensitivity 87.94%, speciﬁcity 85.86%) with our synthetic data augmentation compared to other state-of-the-art methods. Conclusion: The proposed radiomics model has demonstrated a promising potential to synthesize and classify breast masses on ultrasound in a semi-supervised manner.
Do Montmorillonite Surfaces Promote Methane Hydrate Formation? Monte Carlo and Molecular Dynamics Simulations

Recent laboratory experiments on methane hydrate formation in the presence of Na-montmorillonite, a clay mineral found coexistently with hydrates in oceanic sediments, suggest that clay surfaces may facilitate methane hydrate crystallization from aqueous solution. Monte Carlo and molecular dynamics simulations were carried out to determine whether stable methane clathrates could in principle form in the interlayers of hydrated Na-montmorillonite in equilibrium with seawater under ambient conditions. Stable interlayer methane clathrate structures were indeed found to occur under pressures as low as 10 atm and at temperatures as high as 300 K in simulations of a three-layer hydrate of Na-montmorillonite containing 0.5 CH4 per clay mineral unit cell. This result is consistent with a “thermodynamic promotion effect” of clay mineral surfaces on hydrate formation. Visualization of local methane clathrate structure in the 0.5 CH4 per unit cell system revealed that the methane molecule is nested on a hexagonal ri.
Facile and large-scale synthesis and characterization of carbon nanotube/silver nanocrystal nanohybrids

A facile and efficient aqueous phase-based strategy to synthesize carbon nanotube (CNT)/silver nanocrystal nanohybrids at room temperature is reported. In the presence of carboxyl group functionalized or poly(acrylic acid)- (PAA-) grafted CNTs, silver nanoparticles were in situ generated from AgNO3 aqueous solution, without any additional reducing agent or irradiation treatment, and readily attached to the CNT convex surfaces, leading to the CNT/Ag nanohybrids. The produced silver nanoparticles were determined to be face-centred cubic silver nanocrystals by scanning transmission electron microscopy (STEM), electron diffraction (ED) and x-ray powder diffraction (XRD) analyses. Detailed experiments showed that this strategy can also be applied to different CNTs, including single-walled carbon nanotubes (SWNTs), double-walled carbon nanotubes (DWNTs), multiwalled carbon nanotubes (MWNTs), and polymer-functionalized CNTs. The nanoparticle sizes can be controlled from 2 nm to 10–20 nm and the amount of metal deposited on CNT surfaces can be as high as 82 wt%. Furthermore, large-scale (10 g or more) CNT/Ag nanohybrids can be prepared via this approach without the decrease of efficiency and quality. This approach can also be extended to prepare Au single crystals by CNTs. The facile, efficient and large-scale availability of the nanohybrids makes their tremendous potential realizable and developable.
Exon 20 YVMA insertion is associated with high incidence of brain metastasis and inferior outcome of chemotherapy in advanced non-small cell lung cancer patients with HER2 kinase domain mutations

Background Chemotherapy remains the standard care for HER2 mutated advanced non-small cell lung cancer (NSCLC) even though several targeted drugs showed promising results in preliminary stages. This study aimed to investigate the association of mutation variants with clinical features and the efficacy of chemotherapy in patients with HER2 mutated advanced NSCLC. Methods ARMS-PCR was used to identify HER2 mutation in patients without common oncogenic alterations. Patients with detailed information were further enrolled for analysis of clinical features and efficacy of first line chemotherapy. Survival data was analyzed by Kaplan-Meier method and compared by log-rank test. Brain metastasis incidence was analyzed and compared by Gray’s test. Results YVMA insertion accounted for the majority (68.4%, 67/98) of HER2 mutation, and associated with significantly higher incidence of baseline extrathoracic metastasis (P=0.009), notably brain metastasis (P=0.004). Among 82 patients those received first line chemotherapy, YVMA insertion remarkably associated with inferior treatment outcomes, namely, a significantly shorter median progression free survival (PFS) and lower objective response rate (ORR) both in total patients (PFS: 5.2 vs. 7.7 m, P=0.038; ORR: 30.9% vs. 51.9%, P=0.09) and pemetrexed subgroup (PFS: 5.2 vs. 6.5 m, P=0.022; ORR: 31.8% vs. 60.0%, P=0.054). Multivariate analysis further established YVMA insertion as prognostic factor of worse PFS both for total patients (HR =1.578, 95% CI, 0.956–2.606) and patients received pemetrexed-based chemotherapy (HR =1.789, 95% CI, 1.013–3.160). In addition, YVMA insertion associated with higher incidence of lifetime brain metastasis (P=0.002) compared by Gray’s test, with estimated 12-month brain metastasis incidence as 40.2% compared with 3.6% in the non-YVMA group. Conclusions YVMA insertion is associated with a higher incidence of brain metastasis, and inferior outcomes to chemotherapy than non-YVMA variants in patients with advanced NSCLC and HER2 kinase domain mutations, which emphasized the unmet need of more potent anti-cancer therapies with high blood-brain barrier (BBB) penetration capacity for patients with YVMA insertion.
In silico prediction, molecular docking and binding studies of acetaminophen and dexamethasone to Enterococcus faecalis diaminopimelate epimerase

Enterococcus faecalis (E. faecalis) is a Gram‐positive coccoid, non‐sporulating, facultative anaerobic, multidrug resistance bacterium responsible for almost 65% to 80% of all enterococcal nosocomial infections. It usually causes infective endocarditis, urinary tract and surgical wound infections. The increase in E. faecalis resistance to conventionally available antibiotic has rekindled intense interest in developing useful antibacterial drugs. In E. faecalis, diaminopimelate epimerase (DapF) is involved in the lysine biosynthetic pathway. The product of this pathway is precursors of peptidoglycan synthesis, which is a component of bacterial cell wall. Also, because mammals lack this enzyme, consequently E. faecalis diaminopimelate epimerase (EfDapF) represents a potential target for developing novel class of antibiotics. In this regard, we have successfully cloned, overexpressed the gene encoding DapF in BL‐21(DE3) and purified with Ni‐NTA Agarose resin. In addition to this, binding studies were performed using fluorescence spectroscopy in order to confirm the bindings of the identified lead compounds (acetaminophen and dexamethasone) with EfDapF. Docking studies revealed that acetaminophen found to make hydrogen bonds with Asn72 and Asn13 while dexamethasone interacted by forming hydrogen bonds with Asn205 and Glu223. Thus, biochemical studies indicated acetaminophen and dexamethasone, as potential inhibitors of EfDapF and eventually can reduce the catalytic activity of EfDapF.
Exercise test in patients with asymptomatic aortic stenosis - clinically useful or not?

INTRODUCTION Aortic valve replacement (AVR) is recommended for symptomatic patients (pts) with severe aortic stenosis (AS). In asymptomatic AS (AAS) exercise testing (ET) is recommended but is controversial and varies among practicing clinicians. OBJECTIVES The aim of our study was to assess the importance of ET in AAS pts. PATIENTS AND METHODS 89 pts with AAS (53 men; age 59.5 yrs) underwent 244 symptoms-limited ET. RESULTS All ET were clinically negative. During median follow-up 22(12) months 39 pts (22 men) became symptomatic - AVRgroup. This group was compared with the asymptomatic nonAVR 50 pts. In multivariable Cox analysis presence of maximal HR<85% (THR<85%) during ET was significantly related with AVR (p=0.01). After adjustment for the use of beta-blockers (BB) this was not statistically significant (p=0.08). In BB subgroup THR<85% was significantly related with AVR in univariable Cox analysis hazard ratio 2.2 (1.07-4.9) p=0.03 and after adjusting for age (p=0.047). This relationship was not observed in the group not treated with BB. CONCLUSION In patients with asymptomatic AS exercise test is safe but in our group of patients the results were not crucial in decision of AVR. Patients treated with beta-blockers who did not achieve 85% of predicted maximal heart rate had a higher probability of AVR. The influence of beta blockers treatment on the decision of AVR in this small group of patients need further revision.
Genetics-Based Approach to Identify Novel Genes Regulated by the Aryl Hydrocarbon Receptor (AHR) in Mice Liver.

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor in the PAS superfamily of environmental sensors that is linked to several metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). Much remains unknown regarding the impact of genetic variation in AHR-driven disease, as past studies have focused on a small number of inbred strains. Recently, the presence of a wide-range of interindividual variability amongst humans was reported in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the prototypical ligand of the AHR. In this study, a panel of 14 diverse mouse strains were exposed to TCDD for 10 days to characterize the AHR-mediated response across genetic backgrounds. In this study, responses to TCDD are heavily-dependent on genetic background. While mice carry one of four Ahr alleles known to impact the affinity to AHR-ligands, we observed significant intra-allelic variability suggesting the presence of novel genetic modifiers of AHR signaling. A regression-based approach was used to scan for genes regulated by the AHR and/or associated with TCDD-induced phenotypes. The approach identified seven genes, two of which are novel, that are likely regulated by the AHR based on association with hepatic TCDD burden (p ≤ 0.05). Finally, we identified one gene, Dio1, which was associated with change in percent body fat across the diverse set of strains (p ≤ 0.05). Overall, the results in this study exemplify the power of genetics-based approaches in identifying novel genes that are putatively regulated by the AHR.
Friction reduction mechanism of glycerol monooleate-containing lubricants at elevated temperature - transition from physisorption to chemisorption

The friction reduction mechanism of glycerol monooleate (GMO) was investigated under boundary lubrication with elevated temperature. Tribological performances were tested using reciprocating test rig by adding 5 wt. % GMO into Poly-alpha Olefin (PAO) base oil. Friction coefficient and wear were recorded during experiments. The used oil was evaluated by infrared detection after experiments. Results show that GMO could reduce friction coefficient at both low and high temperature. At elevated temperature, the friction coefficient of PAO-GMO blend climb up gradually, followed by a decrease tendency, and the wear increase gradually with temperature. The results of Quartz Crystal Microbalance show that the physical adsorption film plays the main role in friction reduction at low temperature. While at high temperature, the Infrared Spectrum and X-Ray Photoelectron Spectrum show that the GMO involves into the chemisorption with friction surface, producing Fe(OH)O and Fe3O4. The friction reduction mechanism of GMO transferred from physisorption to chemisorption, which reduced friction coefficient at both low and high temperature.
Extracellular buffer choice influences acid-base responses and gastrointestinal symptoms

ABSTRACT To compare the bicarbonate kinetics and gastrointestinal (GI) symptom responses between an equal dose of sodium bicarbonate and sodium citrate using delayed-release capsules. Thirteen active males (age 20.5 ± 2.1 y, height 1.8 ± 0.1 m and body mass [BM] 76.5 ± 9.6 kg) consumed either 0.3 g.kg−1 BM sodium bicarbonate, sodium citrate or a placebo, using a double-blind, randomized crossover design. Blood bicarbonate ion (HCO3 −) concentration, pH and GI symptoms were measured pre-consumption and every 10 min for 180 min post-consumption. Blood HCO3 − concentration (P < 0.001) and pH (P = 0.040) were significantly higher in the sodium bicarbonate condition compared with sodium citrate condition up to 3 h post-consumption. Peak blood HCO3 – concentration was significantly higher with the sodium bicarbonate compared with citrate (P < 0.001). Mean GI symptom scores were lower (P = 0.037) for sodium citrate (1.5 ± 1.8 AU) than bicarbonate (2.6 ± 3.1 AU), with considerable inter-individual variability. No GI symptoms were reported following consumption of the placebo. Both substances increase HCO3 − values significantly, with sodium bicarbonate causing significantly higher pH and HCO3 − values than the same dose of sodium citrate, but results in slightly more severe GI symptoms.