Miracle-dz/UniFAR-FTUs huggingface dataset:
Text mining for modeling of protein complexes enhanced by machine learning

MOTIVATION Procedures for structural modeling of protein-protein complexes (protein docking) produce a number of models which need to be further analyzed and scored. Scoring can be based on independently determined constraints on the structure of the complex, such as knowledge of amino acids essential for the protein interaction. Previously, we showed that text mining of residues in freely available PubMed abstracts of papers on studies of protein-protein interactions may generate such constraints. However, absence of post-processing of the spotted residues reduced usability of the constraints, as a significant number of the residues were not relevant for the binding of the specific proteins. RESULTS We explored filtering of the irrelevant residues by two machine learning approaches, Deep Recursive Neural Network (DRNN) and Support Vector Machine (SVM) models with different training/testing schemes. The results showed that the DRNN model is superior to the SVM model when training is performed on the PMC-OA full-text articles and applied to classification (interface or non-interface) of the residues spotted in the PubMed abstracts. When both training and testing is performed on full-text articles or on abstracts, the performance of these models is similar. Thus, in such cases, there is no need to utilize computationally demanding DRNN approach, which is computationally expensive especially at the training stage. The reason is that SVM success is often determined by the similarity in data/text patterns in the training and the testing sets, whereas the sentence structures in the abstracts are, in general, different from those in the full text articles. AVAILABILITY The code and the datasets generated in this study are available at https://gitlab.ku. edu/vakser-lab-public/text-mining/-/tree/2020-09-04. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Preventive Triple Gene Therapy Reduces the Negative Consequences of Ischemia-Induced Brain Injury after Modelling Stroke in a Rat

Currently, the main fundamental and clinical interest for stroke therapy is focused on developing a neuroprotective treatment of a penumbra region within the therapeutic window. The development of treatments for ischemic stroke in at-risk patients is of particular interest. Preventive gene therapy may significantly reduce the negative consequences of ischemia-induced brain injury. In the present study, we suggest the approach of preventive gene therapy for stroke. Adenoviral vectors carrying genes encoding vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF) and neural cell adhesion molecule (NCAM) or gene engineered umbilical cord blood mononuclear cells (UCB-MC) overexpressing recombinant VEGF, GDNF, and NCAM were intrathecally injected before distal occlusion of the middle cerebral artery in rats. Post-ischemic brain recovery was investigated 21 days after stroke modelling. Morphometric and immunofluorescent analysis revealed a reduction of infarction volume accompanied with a lower number of apoptotic cells and decreased expression of Hsp70 in the peri-infarct region in gene-treated animals. The lower immunopositive areas for astrocytes and microglial cells markers, higher number of oligodendrocytes and increased expression of synaptic proteins suggest the inhibition of astrogliosis, supporting the corresponding myelination and functional recovery of neurons in animals receiving preventive gene therapy. In this study, for the first time, we provide evidence of the beneficial effects of preventive triple gene therapy by an adenoviral- or UCB-MC-mediated intrathecal simultaneous delivery combination of vegf165, gdnf, and ncam1 on the preservation and recovery of the brain in rats with subsequent modelling of stroke.
Iris: Interactive all‐in‐one graphical validation of 3D protein model iterations

Iris validation is a Python package created to represent comprehensive per‐residue validation metrics for entire protein chains in a compact, readable and interactive view. These metrics can either be calculated by Iris, or by a third‐party program such as MolProbity. We show that those parts of a protein model requiring attention may generate ripples across the metrics on the diagram, immediately catching the modeler's attention. Iris can run as a standalone tool, or be plugged into existing structural biology software to display per‐chain model quality at a glance, with a particular emphasis on evaluating incremental changes resulting from the iterative nature of model building and refinement. Finally, the integration of Iris into the CCP4i2 graphical user interface is provided as a showcase of its pluggable design.
Juniperonic Acid Biosynthesis is Essential in Caenorhabditis elegans Lacking Δ6 Desaturase (fat-3) and Generates New ω-3 Endocannabinoids

In eukaryotes, the C20:4 polyunsaturated fatty acid arachidonic acid (AA) plays important roles as a phospholipid component, signaling molecule and precursor of the endocannabinoid-prostanoid axis. Accordingly, the absence of AA causes detrimental effects. Here, compensatory mechanisms involved in AA deficiency in Caenorhabditis elegans were investigated. We show that the ω-3 C20:4 polyunsaturated fatty acid juniperonic acid (JuA) is generated in the C. elegans fat-3(wa22) mutant, which lacks Δ6 desaturase activity and cannot generate AA and ω-3 AA. JuA partially rescued the loss of function of AA in growth and development. Additionally, we observed that supplementation of AA and ω-3 AA modulates lifespan of fat-3(wa22) mutants. We described a feasible biosynthetic pathway that leads to the generation of JuA from α-linoleic acid (ALA) via elongases ELO-1/2 and Δ5 desaturase which is rate-limiting. Employing liquid chromatography mass spectrometry (LC-MS/MS), we identified endocannabinoid-like ethanolamine and glycerol derivatives of JuA and ω-3 AA. Like classical endocannabinoids, these lipids exhibited binding interactions with NPR-32, a G protein coupled receptor (GPCR) shown to act as endocannabinoid receptor in C. elegans. Our study suggests that the eicosatetraenoic acids AA, ω-3 AA and JuA share similar biological functions. This biosynthetic plasticity of eicosatetraenoic acids observed in C. elegans uncovers a possible biological role of JuA and associated ω-3 endocannabinoids in Δ6 desaturase deficiencies, highlighting the importance of ALA.
Controlled Release of Pyrimidine Compound Using Polymeric Coated ZIF-8 Metal-Organic Framework as Glucagon-Like Peptide-1 Receptor Agonist Carrier

This work demonstrates synthetic strategies for the incorporation of a synthesized pyrimidine glucagon-like peptide-1 (GLP-1) agonist into alginate-coated ZIF-8. The prepared pyrimidine GLP-1 agonist used for the treatment of diabetes type II, was trapped inside polymer coated ZIF-8. The encapsulation of the GLP-1 agonist was confirmed by UV-visible and FT-IR spectroscopies. Furthermore, the release kinetics of GLP-1 agonist drug from alginate-coated ZIF-8 were investigated in phosphate-buffered saline at 37 °C at pH 8 and 1.5. The alginate-coated ZIF-8 exhibited much faster drug release at basic pH than at pH 1.5, indicating the potential of the alginate-coated ZIF-8 system to overcome the fast degradation at acidic pH of the stomach and improve the drug’s activity. This study may open the way for the synthesis of new metal organic frameworks (MOFs) to enhance drug delivery systems.
Food Habits of Older Australians Living Alone in the Australian Capital Territory

The link between adequate nutrition and quality of life for older persons is well established. With the proportion of older adults increasing, policy regarding support and care for the ageing has shifted emphasis to keeping older adults in their homes for as long as possible. Risk of malnutrition is an issue of importance for this population and, while this risk is well researched within the hospital setting, it is still relatively under-researched within the community-dwelling elderly, particularly with respect to the lived experience. This qualitative study (underpinned by interpretative phenomenology philosophy) explores how the lived experiences of community-dwelling older people living in one-person households in the Australian Capital Territory (ACT) influences dietary patterns, food choices and perceptions about food availability. Using purposeful and snowballing sampling, older people (65 years and over) living alone in the community participated in focus group discussions triangulated with their family/carers. Data were thematically analysed using a previously established approach. Participants (n = 22) were interviewed in three focus groups. Three themes were identified: active and meaningful community connectedness; eating well and behaviours to promote dietary resilience. Of these, community connectedness was pivotal in driving food patterns and choices and was a central component influencing behaviours to eating well and maintaining dietary resilience.
Effects of Glycyrrhizin on Multi-Drug Resistant Pseudomonas aeruginosa

The effects of glycyrrhizin (GLY) on multi-drug resistant (MDR) systemic (MDR9) vs. ocular (B1045) Pseudomonas aeruginosa clinical isolates were determined. Proteomes of each isolate with/without GLY treatment were profiled using liquid chromatography mass spectrometry (LC-MS/MS). The effect of GLY on adherence of MDR isolates to immortalized human (HCET) and mouse (MCEC) corneal epithelial cells, and biofilm and dispersal was tested. Both isolates were treated with GLY (0.25 minimum inhibitory concentration (MIC), 10 mg/mL for MDR9 and 3.75 mg/mL for B1045) and subjected to proteomic analysis. MDR9 had a greater response to GLY (51% of identified proteins affected vs. <1% in B1045). In MDR9 vs. controls, GLY decreased the abundance of proteins for: antibiotic resistance, biofilm formation, and type III secretion. Further, antibiotic resistance and type III secretion proteins had higher control abundances in MDR9 vs. B1045. GLY (5 and 10 mg/mL) significantly reduced binding of both isolates to MCEC, and B1045 to HCET. MDR9 binding to HCET was only reduced at 10 mg/mL GLY. GLY (5 and 10 mg/mL) enhanced dispersal for both isolates, at early (6.5 h) but not later times (24–72 h). This study provides evidence that GLY has a greater effect on the proteome of MDR9 vs. B1045, yet it was equally effective at disrupting adherence and early biofilm dispersal.
Is Extreme in the Eye of the Beholder? An Experimental Assessment of Extremist Cognitions

Scholars have extensively discussed the topic of “online radicalization,” often seeking to understand the form and function of online extremist material. However, this work has neglected to examine the role that the Internet plays alongside individual personality factors in the process through which someone develops violent extremist cognitions. This article aims to extend the understanding of the role of personality differences in the effect of exposure to extremist material online. In this study, we experimentally measure the short-term psychological consequences of exposure to extremist material on extremist cognitions. We use a between-group experimental design in which participants are shown extremist propaganda with either pre- or post-counter messages. Our results indicate that trait personality, and specifically aggression, may be more influential than exposure to extremist propaganda in influencing extremist cognitions. We discuss the implications of these results in the context of future research directions.
A Comparison of Fitness-Related Traits in the Coleopteran Parasitoid Dastarcus helophoroides (Coleoptera: Bothrideridae) Reared on Two Factitious Hosts

Abstract The coleopteran parasitoid Dastarcus helophoroides (Fairmaire) (Coleoptera: Bothrideridae) is considered an efficient preventative method against the damage caused by a large number of cerambycid pests in China and other East Asian countries. Mass rearing of this parasitoid depends on screening appropriate factitious hosts. In this paper, the fitness-related traits of this parasitic beetle were explored using pupae of the two tenebrionid beetles, Tenebrio molitor Linnaeus and Zophobas morio Fabricius (Coleoptera: Tenebrionidae) as factitious hosts. The results showed that in dual-choice trials, D. helophoroides larvae preferred to attack Z. morio pupae. In no-choice trials, D. helophoroides reared on Z. morio pupae displayed significantly higher pupation and emergence rate, longer developmental duration of larval and larval–pupal stages, larger adult body size, shorter preoviposition period, more egg masses and egg production, and higher relative expected reproduction than those reared on T. molitor pupae. These results demonstrate that Z. morio is a more suitable factitious host for mass rearing of D. helophoroides.
Onset of the climacteric phase by the mid-forties associated with impaired insulin sensitivity: a birth cohort study

Supplemental Digital Content is available in the text Abstract Objective: To investigate whether the early-onset menopausal transition is associated with deteriorated glucose tolerance in women in their mid-forties. Methods: A cross-sectional analysis of a cohort study including 2,632 women of the Northern Finland Birth Cohort 1966. The participants were divided into two groups by their menstrual history and follicle-stimulating hormone values at age 46: climacteric and preclimacteric women. Glucose and insulin parameters, as well as mathematical indices derived from them to evaluate insulin sensitivity, were compared between the groups. The results were adjusted for measured body mass index and smoking. The possible effect of hormone therapy was investigated in subanalyses excluding hormone therapy users. Results: Climacteric women (n = 379) were more often current smokers at age 46 (P = 0.008), and their body mass indices increased more from 31 to 46 years (P = 0.013), compared to preclimacteric women (n = 2,253). In a multivariable generalized linear model, being climacteric at age 46 was associated with several findings suggesting decreased insulin sensitivity: increased glycated hemoglobin (P < 0.001), 2-hour oral glucose tolerance test 30- and 60-minute insulin (P = 0.040 and 0.006, respectively), and area under the insulin curve (P = 0.005). Being climacteric also was associated with a decreased the McAuley (P = 0.024) and Belfiore indices (P = 0.027) and glucose tolerance test 60-minute glucose (P = 0.015). In subanalyses excluding hormone therapy users (n = 94), the results did not change significantly. Conclusions: Earlier onset of climacteric transition is associated with impaired insulin sensitivity in middle-aged women. Video Summary:http://links.lww. com/MENO/A648.
Data-Driven Molecular Dynamics: A Multifaceted Challenge

The big data concept is currently revolutionizing several fields of science including drug discovery and development. While opening up new perspectives for better drug design and related strategies, big data analysis strongly challenges our current ability to manage and exploit an extraordinarily large and possibly diverse amount of information. The recent renewal of machine learning (ML)-based algorithms is key in providing the proper framework for addressing this issue. In this respect, the impact on the exploitation of molecular dynamics (MD) simulations, which have recently reached mainstream status in computational drug discovery, can be remarkable. Here, we review the recent progress in the use of ML methods coupled to biomolecular simulations with potentially relevant implications for drug design. Specifically, we show how different ML-based strategies can be applied to the outcome of MD simulations for gaining knowledge and enhancing sampling. Finally, we discuss how intrinsic limitations of MD in accurately modeling biomolecular systems can be alleviated by including information coming from experimental data.
Dose‐dependent association of proton pump inhibitors use with gastric intestinal metaplasia among Helicobacter pylori‐positive patients

Abstract Background Gastric intestinal metaplasia is a pre‐cancerous condition associated with multiple factors. Objective We evaluated whether cumulative proton pump inhibitor dose is associated with the diagnosis of gastric intestinal metaplasia while controlling for multiple variables. Methods We retrospectively identified patients who underwent upper endoscopy with gastric biopsy between 2005 and 2014. Covariate data retrieved included age, sex, ethnicity, smoking status, Helicobacter pylori status (based on clarithromycin‐amoxicillin‐proton pump inhibitor issued), cumulative proton pump inhibitor issued within 10 years (quartiles [PPI‐Q1–4] of daily drug dose), anti‐parietal cell antibodies, body mass index and comorbidity index. Results Of the 14,147 included patients (median age 63.4 years; women 54.4%; Helicobacter pylori‐positive 29.0%), 1244 (8.8%) had gastric intestinal metaplasia. Increasing age, Helicobacter pylori infection, smoking, anti‐parietal cell antibodies and proton pump inhibitor use were all associated with the diagnosis of gastric intestinal metaplasia. Upper quartiles of cumulative proton pump inhibitor doses (PPI‐Q4 and PPI‐Q3 vs. PPI‐Q1) were associated with the diagnosis of gastric intestinal metaplasia: adjusted odds ratios 1.32 (95% confidence interval [CI] 1.111.57) and 1.27 (95% CI 1.07–1.52), respectively, for the whole cohort (Ptotal 0.007, Ptrend 0.013), 1.69 (95% CI 1.23–2.33) and 1.40 (95% CI 1.04–1.89), respectively, for Helicobacter pylori‐positive patients (Ptotal 0.004, Ptrend 0.005) and 1.21 (95% CI 0.98–1.49) and 1.20 (95% CI 0.96–1.49), respectively, for Helicobacter pylori‐negative patients (Ptotal 0.288, Ptrend 0.018). Upper quartiles of proton pump inhibitor dose were associated with a 5–10‐fold increased risk of low‐grade dysplasia. Conclusions Among Helicobacter pylori‐positive patients, proton pump inhibitor use appears to be associated with a dose‐dependent increased likelihood of gastric intestinal metaplasia.
A Multi-Omics Approach Reveals New Signatures in Obese Allergic Asthmatic Children

Background: Asthma is a multifactorial condition where patients with identical clinical diagnoses do not have the same clinical history or respond to treatment. This clinical heterogeneity is reflected in the definition of two main endotypes. We aimed to explore the metabolic and microbiota signatures that characterize the clinical allergic asthma phenotype in obese children. Methods: We used a multi-omics approach combining clinical data, plasma and fecal inflammatory biomarkers, metagenomics, and metabolomics data in a cohort of allergic asthmatic children. Results: We observed that the obese allergic asthmatic phenotype was markedly associated with higher levels of leptin and lower relative proportions of plasma acetate and a member from the Clostridiales order. Moreover, allergic children with a worse asthma outcome showed higher levels of large unstained cells, fecal D lactate and D/L lactate ratio, and with a higher relative proportion of plasma creatinine and an unclassified family member from the RF39 order belonging to the Mollicutes class. Otherwise, children with persistent asthma presented lower levels of plasma citrate and dimethylsulfone. Conclusion: Our integrative approach shows the molecular heterogeneity of the allergic asthma phenotype while highlighting the use of omics technologies to examine the clinical phenotype at a more holistic level.
Infectious or Recovered? Optimizing the Infectious Disease Detection Process for Epidemic Control and Prevention Based on Social Media

Detecting the period of a disease is of great importance to building information management capacity in disease control and prevention. This paper aims to optimize the disease surveillance process by further identifying the infectious or recovered period of flu cases through social media. Specifically, this paper explores the potential of using public sentiment to detect flu periods at word level. At text level, we constructed a deep learning method to classify the flu period and improve the classification result with sentiment polarity. Three important findings are revealed. Firstly, bloggers in different periods express significantly different sentiments. Blogger sentiments in the recovered period are more positive than in the infectious period when measured by the interclass distance. Secondly, the optimized disease detection process can substantially improve the classification accuracy of flu periods from 0.876 to 0.926. Thirdly, our experimental results confirm that sentiment classification plays a crucial role in accuracy improvement. Precise identification of disease periods enhances the channels for the disease surveillance processes. Therefore, a disease outbreak can be predicted credibly when a larger population is monitored. The research method proposed in our work also provides decision making reference for proactive and effective epidemic control and prevention in real time.
The Prognostic Impact of Body Mass Index in Patients with Diffuse Large B-Cell Lymphoma: A Meta-Analysis

Abstract Objective Some studies on the relation between body mass index (BMI) and outcome of diffuse large B-cell lymphoma (DLBCL) remain controversial. We performed a meta-analysis to evaluate the overall survival (OS) and progression-free survival (PFS) of DLBCL in overweight (≥25 to <30 kg/m2), obese (≥30 kg/m2) and underweight (<18.5 kg/m2) individuals compared with normal weight patients (≥18.5 to <25 kg/m2). Methods PubMed, Web of Science, EMBASE and the Cochrane Library databases were searched to identify relevant studies before February 20, 2020. The summary hazard ratio (HR) and 95% confidence interval (CI) were used for analyzing survival outcomes. Results Fourteen articles involving 8,753 subjects were included. The pooled analysis indicated that OS of overweight group (HR = 0.86, 95% CI: 0.78–0.95, P = 0.002) was better than of normal weight group, but no association was found in obese patients (HR = 1.11, 95% CI: 0.81–1.53, P = 0.501). Similarly, obese and overweight status had no significant impact on PFS in DLBCL. Underweight patients had poorer OS (HR = 1.99, 95% CI: 1.45–2.74, P < 0.001) and PFS (HR = 1.78, 95% CI: 1.12–2.83, P = 0.014) compared with normal weight group. Conclusion Overweight patients have a better survival than normal weight patients, while underweight patients have a poorer survival in DLBCL.
Antisense Oligonucleotide (AS‐ODN) Technology: Principle, Mechanism and Challenges

Recently, there is a hopefully tremendous interest in antisense therapeutics for clinical purposes. Single‐stranded synthetic antisense oligonucleotides (As‐ODNs) with monomers of chemically modified 18–21 deoxynucleotides complement the mRNA sequence in target gene. The target gene expression can be blocked because of created cleavage or disability of the mRNA by binding the As‐ODNs to cognate mRNA sequences via sequence‐specific hybridization. The idea of antisense therapy has become particular concerning that any sequence longer than a minimal number of nucleotides (17 for DNA and 13 for RNA) can be observed only once within the human genome. The mRNA is omnipresent more probably to manipulate compared to DNA, which results in multiple in vitro and in vivo applications for As‐ODNs in the field of regulatory mechanisms of biological processes, cancer, viral infections and hereditary impairments. Although, there are uncertain clinical outcomes on the ability of this approach in treatment procedures despite achieving promising findings based on previous investigations. Accordingly, the efficacy, off‐target effects, delivery are issues that should be investigated to obtain satisfactory results. In this review, we will explain the mechanism of action of As‐ODNs and various types of modifications and their therapeutic purposes.