Miracle-dz/UniFAR-FTUs huggingface dataset:
Deciphering controversial results of cell proliferation on TiO2 nanotubes using machine learning

Abstract With the rapid development of biomedical sciences, contradictory results on the relationships between biological responses and material properties emerge continuously, adding to the challenge of interpreting the incomprehensible interfacial process. In the present paper, we use cell proliferation on titanium dioxide nanotubes (TNTs) as a case study and apply machine learning methodologies to decipher contradictory results in the literature. The gradient boosting decision tree model demonstrates that cell density has a higher impact on cell proliferation than other obtainable experimental features in most publications. Together with the variation of other essential features, the controversy of cell proliferation trends on various TNTs is understandable. By traversing all combinational experimental features and the corresponding forecast using an exhausted grid search strategy, we find that adjusting cell density and sterilization methods can simultaneously induce opposite cell proliferation trends on various TNTs diameter, which is further validated by experiments. This case study reveals that machine learning is a burgeoning tool in deciphering controversial results in biomedical researches, opening up an avenue to explore the structure–property relationships of biomaterials.
Influence of CDK5 Regulatory Subunit-Associated Protein 1-Like 1 Expression on the Survival of Patients with Non-Metastatic Nasopharyngeal Carcinoma

Background The aim of this study was to investigate the influence of CDK5 regulatory subunit-associated protein 1-like 1 (CDKAL1) expression on the survival of nasopharyngeal carcinoma (NPC) patients. Methods A total of 140 non-metastatic NPC patients were retrospectively analyzed. The expression of CDKAL1 was detected by immunohistochemistry. Results The CDKAL1-negative group exhibited better overall survival (OS) according to Kaplan–Meier curve analysis (p = 0.006), with 5-year OS rates for the CDKAL1-negative and -positive groups of 89.7% and 70.2%, respectively. The CDKAL1-negative group also exhibited a tendency toward a better progression-free survival (PFS) rate. Multivariate analysis showed that CDKAL1 expression was independently associated with both OS (p = 0.002) and PFS (p = 0.043). Conclusion CDKAL1 expression is an independent negative predictor of patient survival in non-metastatic NPC.
Identifying a novel biological mechanism for alcohol addiction associated with circRNA networks acting as potential miRNA sponges

Our lab and others have shown that chronic alcohol use leads to gene and miRNA expression changes across the mesocorticolimbic (MCL) system. Circular RNAs (circRNAs) are noncoding RNAs that form closed‐loop structures and are reported to alter gene expression through miRNA sequestration, thus providing a potentially novel neurobiological mechanism for the development of alcohol dependence (AD). Genome‐wide expression of circRNA was assessed in the nucleus accumbens (NAc) from 32 AD‐matched cases/controls. Significant circRNAs (unadj. p ≤ 0.05) were identified via regression and clustered in circRNA networks via weighted gene co‐expression network analysis (WGCNA). CircRNA interactions with previously generated mRNA and miRNA were detected via correlation and bioinformatic analyses. Significant circRNAs (N = 542) clustered in nine significant AD modules (FWER p ≤ 0.05), within which we identified 137 circRNA hubs. We detected 23 significant circRNA–miRNA–mRNA interactions (FDR ≤ 0.10). Among these, circRNA‐406742 and miR‐1200 significantly interact with the highest number of mRNA, including genes associated with neuronal functioning and alcohol addiction (HRAS, PRKCB, HOMER1, and PCLO). Finally, we integrate genotypic information that revealed 96 significant circRNA expression quantitative trait loci (eQTLs) (unadj. p ≤ 0.002) that showed significant enrichment within recent alcohol use disorder (AUD) and smoking genome‐wide association study (GWAS). To our knowledge, this is the first study to examine the role of circRNA in the neuropathology of AD. We show that circRNAs impact mRNA expression by interacting with miRNA in the NAc of AD subjects. More importantly, we provide indirect evidence for the clinical importance of circRNA in the development of AUD by detecting a significant enrichment of our circRNA eQTLs among GWAS of substance abuse.
Quality of life in adults with acute lymphoblastic leukemia in France: results from a French cross-sectional study

Abstract In recent years, treatment of acute lymphoblastic leukemia (ALL) has improved substantially, leading to longer survival. This has necessitated a greater focus on health-related quality of life (HRQoL), but data are lacking. In a part-prospective, part-retrospective study, we enrolled 219 adults with ALL in France to assess the impact of key disease and treatment characteristics on HRQoL. Overall HRQoL and most specific QoL domain scores were consistently better among patients receiving front-line therapy, those currently in complete remission, and those who had previously received hematopoietic stem-cell transplantation. Furthermore, HRQoL was consistently impaired in patients with minimal residual disease present (MRD+). In multivariate analyses, multiple lines of therapy, MRD+, leukopenia, comorbidities, and anemia were significantly associated with impaired HRQoL. This study provides real-world data on HRQoL in adults with ALL in France and shows the positive impact of MRD-negative status on HRQoL.
Application of Text Mining in Risk Assessment of Chemical Mixtures: A Case Study of Polycyclic Aromatic Hydrocarbons (PAHs)

Background: Cancer risk assessment of complex exposures, such as exposure to mixtures of polycyclic aromatic hydrocarbons (PAHs), is challenging due to the diverse biological activities of these compounds. With the help of text mining (TM), we have developed TM tools—the latest iteration of the Cancer Risk Assessment using Biomedical literature tool (CRAB3) and a Cancer Hallmarks Analytics Tool (CHAT)—that could be useful for automatic literature analyses in cancer risk assessment and research. Although CRAB3 analyses are based on carcinogenic modes of action (MOAs) and cover almost all the key characteristics of carcinogens, CHAT evaluates literature according to the hallmarks of cancer referring to the alterations in cellular behavior that characterize the cancer cell. Objectives: The objective was to evaluate the usefulness of these tools to support cancer risk assessment by performing a case study of 22 European Union and U.S. Environmental Protection Agency priority PAHs and diesel exhaust and a case study of PAH interactions with silica. Methods: We analyzed PubMed literature, comprising 57,498 references concerning priority PAHs and complex PAH mixtures, using CRAB3 and CHAT. Results: CRAB3 analyses correctly identified similarities and differences in genotoxic and nongenotoxic MOAs of the 22 priority PAHs and grouped them according to their known carcinogenic potential. CHAT had the same capacity and complemented the CRAB output when comparing, for example, benzo[a]pyrene and dibenzo[a,l]pyrene. Both CRAB3 and CHAT analyses highlighted potentially interacting mechanisms within and across complex PAH mixtures and mechanisms of possible importance for interactions with silica. Conclusion: These data suggest that our TM approach can be useful in the hazard identification of PAHs and mixtures including PAHs. The tools can assist in grouping chemicals and identifying similarities and differences in carcinogenic MOAs and their interactions. https://doi.org/10.1289/EHP6702
The Landscape of Perception: Racial Differences in How Disability Is Viewed Among Older-Adult Cancer Survivors

This paper compares disability perceptions of Black with white older cancer survivors’ to document racial disparities in these perceptions and the factors that contribute to them. The data are from a randomly selected tumor registry sample of 321 older adult cancer survivors from an NCI funded study. OLS regression models of disability perceptions, nested by race, examined the effects cancer and non-cancer health factors along with important covariates. Black older adult cancer survivors perceived themselves to be more disabled than did white survivors. Multivariate analyses showed a strong relationship between functional difficulties and disability perceptions for both Black and white survivors. However cancer-related factors such as continuing symptoms of the illness or treatment were relatively more important for Blacks. The findings suggest that race and cancer are both important factors in our understanding of disability in later life. These findings can then inform clinical best practices among minority older adults.
Effect of Vaccination on Household Transmission of SARS-CoV-2 in England

Vaccination against SARS-CoV-2 with either ChAdOx1 nCoV-19, produced by AstraZeneca, or BNT162b2, produced by Pfizer, has been shown to produce a robust antibody response (1,2), and is effective in both preventing cases and reducing the severity of COVID-19 in vaccinated individuals(3,4). While fewer cases will reduce disease burden, it is not yet clear whether these vaccinations will also reduce transmission in the minority who have been vaccinated but develop post-vaccination infection.
The Inverse Association of Body Mass Index with Lung Cancer: Exploring Residual Confounding, Metabolic Aberrations and Within-Person Variability in Smoking

Background: The inverse observational association between body mass index (BMI) and lung cancer risk remains unclear. We assessed whether the association is explained by metabolic aberrations, residual confounding, and within-person variability in smoking, and compared against other smoking-related cancers. Methods: We investigated the association between BMI, and its combination with a metabolic score (MS) of mid-blood pressure, glucose, and triglycerides, with lung cancer and other smoking-related cancers in 778,828 individuals. We used Cox regression, adjusted and corrected for within-person variability in smoking (status/pack-years), calculated from 600,201 measurements in 221,958 participants. Results: Over a median follow-up of 20 years, 20,242 smoking-related cancers (6,735 lung cancers) were recorded. Despite adjustment and correction for substantial within-person variability in smoking, BMI remained inversely associated with lung cancer [HR per standard deviation increase, 0.87 (95% confidence interval 0.85–0.89)]. Individuals with BMI less than 25 kg/m2 and high MS had the highest risk [HR 1.52 (1.44–1.60) vs. BMI ≥25 with low MS]. These associations were weaker and nonsignificant among nonsmokers. Similar associations were observed for head and neck cancers and esophageal squamous cell carcinoma, whereas for other smoking-related cancers, we generally observed positive associations with BMI. Conclusions: The increased lung cancer risk with low BMI and high MS is unlikely due to residual confounding and within-person variability in smoking. However, similar results for other cancers strongly related to smoking suggest a remaining, unknown, effect of smoking. Impact: Extensive smoking-adjustments may not capture all the effects of smoking on the relationship between obesity-related factors and risk of smoking-related cancers.
SARS-CoV-2 uses major endothelial integrin αvβ3 to cause vascular dysregulation in-vitro during COVID-19

The unprecedented global COVID-19 pandemic has prompted a desperate international effort to accelerate the development of anti-viral candidates. For unknown reasons, COVID-19 infections are associated with adverse cardiovascular complications, implicating that vascular endothelial cells are essential in viral propagation. The etiological pathogen, SARS-CoV-2, has a higher reproductive number and infection rate than its predecessors, indicating it possesses novel characteristics that infers enhanced transmissibility. A unique K403R spike protein substitution encodes an Arg-Gly-Asp (RGD) motif, introducing a potential role for RGD-binding host integrins. Integrin αVβ3 is widely expressed across the host, particularly in the endothelium, which acts as the final barrier before microbial entry into the bloodstream. This mutagenesis creates an additional binding site, which may be sufficient to increase SARS-CoV-2 pathogenicity. Here, we investigate how SARS-CoV-2 passes from the epithelium to endothelium, the effects of αVβ3 antagonist, Cilengitide, on viral adhesion, vasculature permeability and leakage, and also report on a simulated interaction between the viral and host protein in-silico.
LAMP3 deficiency affects surfactant homeostasis in mice

Lysosome-associated membrane glycoprotein 3 (LAMP3) is a type I transmembrane protein of the LAMP protein family with a cell-type-specific expression in alveolar type II cells in mice and hitherto unknown function. In type II pneumocytes, LAMP3 is localized in lamellar bodies, secretory organelles releasing pulmonary surfactant into the extracellular space to lower surface tension at the air/liquid interface. The physiological function of LAMP3, however, remains enigmatic. We generated Lamp3 knockout mice by CRISPR/Cas9. LAMP3 deficient mice are viable with an average life span and display regular lung function under basal conditions. The levels of a major hydrophobic protein component of pulmonary surfactant, SP-C, are strongly increased in the lung of Lamp3 knockout mice, and the lipid composition of the bronchoalveolar lavage shows mild but significant changes, resulting in alterations in surfactant functionality. In ovalbumin-induced experimental allergic asthma, the changes in lipid composition are aggravated, and LAMP3-deficient mice exert an increased airway resistance. Our data suggest a critical role of LAMP3 in the regulation of pulmonary surfactant homeostasis and normal lung function.
Effect of static knee joint flexion on vastus medialis obliquus fiber angle in patellofemoral pain syndrome: An ultrasonographic study

In patients with patellofemoral pain syndrome, the vastus medialis obliquus muscle fiber angle measured by ultrasound at knee extension was found to be different from that in healthy individuals. An important feature of patellofemoral pain syndrome is the increase in pain severity during activities that require knee flexion.
Quality indicators for systemic lupus erythematosus based on the 2019 EULAR recommendations: development and initial validation in a cohort of 220 patients

Background Quality of care is receiving increased attention in systemic lupus erythematosus (SLE). We developed quality indicators (QIs) for SLE based on the 2019 update of European League Against Rheumatism recommendations. Methods A total of 44 candidate QIs corresponding to diagnosis, monitoring and treatment, were independently rated for validity and feasibility by 12 experts and analysed by a modified Research and Development Corporation/University of California Los Angeles model. Adherence to the final set of QIs and correlation with disease outcomes (flares, hospitalisations and organ damage) was tested in a cohort of 220 SLE patients with a median monitoring of 2 years (IQR 2–4). Results The panel selected a total of 18 QIs as valid and feasible. On average, SLE patients received 54% (95% CI 52.3% to 56.2%) of recommended care, with adherence ranging from 44.7% (95% CI 40.8% to 48.6%) for diagnosis-related QIs to 84.3% (95% CI 80.6% to 87.5%) for treatment-related QIs. Sustained remission or low disease activity were achieved in 26.8% (95% CI 21.1% to 33.2%). Tapering of prednisone dose to less than 7.5 mg/day was achieved in 93.6% (95% CI 88.2% to 97.0%) while 73.5% (95% CI 66.6% to 79.6%) received the recommended hydroxychloroquine dose. Higher adherence to monitoring-related QIs was associated with reduced risk for a composite adverse outcome (flare, hospitalisation or damage accrual) during the last year of observation (OR 0.97 per 1% adherence rate, 95% CI 0.96 to 0.99). Conclusion We developed QIs for assessing and improving the care of SLE patients. Initial real-life data suggest face validity, but a variable degree of adherence and a need for further improvement.
Predictors of moral harassment in nursing work in critical care units.

OBJECTIVES to analyze the predictors of moral harassment in nursing work in critical care units. METHODS a cross-sectional study conducted in a public hospital in Fortaleza, Ceará, with 167 nursing professionals in 2016. Sociodemographic/occupational questionnaire and Negative Acts Questionnaire Revised were applied. The analysis included descriptive statistics, measures of central tendency and dispersion, as well as Mann-Whitney, Kruskal-Wallis and Conover Inman U-tests for multiple comparisons. RESULTS there was a 33% prevalence of self-perception of moral harassment, highlighting personal/professional disqualification and work-related harassment. The predictors of moral harassment included age, time working in the job and time in the unit, employment relationship and sector. CONCLUSIONS young professionals (< 30 years), cooperative, crowded in intensive care or emergency units, with less time working in the job (< 5 years) or greater time in the unit (above 10 years) are the biggest victims of moral harassment in the work of nursing in critical environments.
Dendrobium mixture attenuates renal damage in rats with diabetic nephropathy by inhibiting the PI3K/Akt/mTOR pathway

Dendrobium mixture (DMix) is a Traditional Chinese Medicine widely used for preventing and treating diabetic nephropathy (DN). Autophagy contributes to DN development and progression. The present study aimed to investigate the mechanism underlying the protective effects of DMix on the kidneys of rats with DN and to determine whether this involves autophagy. Herein, a high-sugar and high-fat diet, combined with the intra-abdominal injection of low-dose streptozocin, was used to induce DN in 40 Sprague-Dawley male rats. In total, 10 additional rats were used as controls. The rats with DN were then randomly divided into three groups and treated with DMix, gliquidone or saline via gastric administration for 8 weeks. Body weight, kidney weight, kidney index, fasting blood glucose (FBG), blood lipid, hemoglobin A1c (HbA1c), insulin, blood urea nitrogen and serum creatinine levels, as well as the 24-h urinary albumin excretion rate (UAER) were measured. H&E, Periodic Acid-Schiff and Masson staining were used to examine the renal pathology. The mRNA and protein expression levels of LC3 and Beclin-1 in renal tissues were measured using reverse transcription-quantitative PCR and immunohistochemistry, respectively. Western blotting was conducted to measure the protein expression levels of PI3K, phosphorylated (p)-PI3K, Akt, p-Akt, mTOR, p-mTOR, LC3 and Beclin-1 in renal tissues. It was found that DMix significantly reduced the FBG, blood lipids, HbA1c and insulin levels, kidney weight, kidney index and UAER in rats with DN, as well as improved renal function. Rats with DN showed notable glomerular hypertrophy, an increase in mesangial matrix content and renal interstitial fibrosis. Moreover, DMix notably reduced kidney damage. The results demonstrated that DMix inhibited the phosphorylation of PI3K, Akt and mTOR in the kidney tissues of rats with DN, and increased the protein and mRNA expression levels of LC3 and Beclin-1. Therefore, it was suggested that DMix has protective effects on the kidney of rats with DN, which may be associated with the inhibition of the PI3K/Akt/mTOR signaling pathway and activation of renal autophagy by this traditional medicine.
Impact of chronic obstructive pulmonary disease on immune checkpoint inhibitor efficacy in advanced lung cancer and the potential prognostic factors

Background The coexistence of chronic obstructive pulmonary disease (COPD) in lung cancer patients often correlates with a poor clinical outcome regardless of tumor stage, mainly due to older age, poor lung function, and complex comorbid disease. Emerging data suggest that the pathogenesis of both diseases involves aberrant immune functioning. We conducted this retrospective study to describe the impact of COPD on the clinical outcomes of lung cancer patients treated with immunotherapy and investigate the potential prognostic factors. Methods In total, 156 patients with advanced-stage lung cancer who received at least one administration of an anti-programmed cell death 1 (PD-1)/anti-programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitor (ICI) at any treatment line at Zhongshan Hospital Fudan University between May 2018 and December 2019 were enrolled in our study. Overall survival (OS) and progression-free survival (PFS) were analyzed according to the presence of COPD. We also evaluated the prognostic value of circulating cytokine levels for clinical outcome. Results We found that the presence of COPD (both spirometry-based COPD and physician-defined COPD) was significantly associated with longer PFS (316 vs. 186 days, P=0.018). Moderate and severe COPD tended to have a better impact on the survival of these patients. In the present study, we reported that patients with mixed ventilatory defects tended to have a better OS (P=0.043) and PFS (P=0.18) when treated with ICIs compared to the normal lung function group. We also found that low baseline plasma interleukin (IL)-8 and IL-2 receptor (IL-2R) levels were associated with longer PFS in patients with advanced-stage lung cancer who received ICI treatment. Furthermore, patients who had increased IL-2R levels had significantly poorer OS [hazard ratio (HR) =3.63; 95% confidence interval (CI), 0.98–13.44; P=0.040] and PFS (HR =3.241; 95% CI, 1.032–10.18; P=0.035) when treated with ICIs. Nomograms were established based on the independent prognostic factors derived from our final multivariate models. Conclusions COPD was associated with better survival in advanced-stage lung cancer patients treated with ICIs. Plasma IL-8 and IL-2R levels were potential prognostic factors for clinical outcome. The nomograms represent a possibly useful tool for predicting the clinical outcomes of immunotherapy.
Pseudouridines on Trypanosoma brucei mRNAs are developmentally regulated: Implications to mRNA stability and protein binding

The parasite Trypanosoma brucei cycles between an insect and a mammalian host and is the causative agent of sleeping sickness. Here, we performed high‐throughput mapping of pseudouridines (Ψs) on mRNA from two life stages of the parasite. The analysis revealed ~273 Ψs, including developmentally regulated Ψs that are guided by homologs of pseudouridine synthases (PUS1, 3, 5, and 7). Mutating the U that undergoes pseudouridylation in the 3′ UTR of valyl‐tRNA synthetase destabilized the mRNA level. To investigate the mechanism by which Ψ affects the stability of this mRNA, proteins that bind to the 3′ UTR were identified, including the RNA binding protein RBSR1. The binding of RBSR1 protein to the 3′ UTR was stronger when lacking Ψ compared to transcripts carrying the modification, suggesting that Ψ can inhibit the binding of proteins to their target and thus affect the stability of mRNAs. Consequently, Ψ modification on mRNA adds an additional level of regulation to the dominant post‐transcriptional control in these parasites.