Miracle-dz/UniFAR-FTUs huggingface dataset:
Binding of omeprazole to protein targets identified by monoclonal antibodies

Omeprazole is the most commonly used proton pump inhibitor (PPI), a class of medications whose therapeutic mechanism of action involves formation of a disulfide linkage to cysteine residues in the H+/K+ ATPase pump on gastric secretory cells. Covalent linkage between the sole sulfur group of omeprazole and selected cysteine residues of the pump protein results in inhibition of acid secretion in the stomach, an effect that ameliorates gastroesophageal reflux and peptic ulcer disease. PPIs, though useful for specific conditions when used transiently, are associated with diverse untoward effects when used long term. The mechanisms underlying these potential off-target effects remain unclear. PPIs may, in fact, interact with non-canonical target proteins (non-pump molecules) resulting in unexpected pathophysiological effects, but few studies describe off-target PPI binding. Here, we describe successful cloning of monoclonal antibodies against protein-bound omeprazole. We developed and used monoclonal antibodies to characterize the protein target range of omeprazole, stability of omeprazole-bound proteins, and the involvement of cysteines in binding of omeprazole to targets. We demonstrate that a wide range of diverse proteins are targeted by omeprazole. Protein complexes, detected by Western blotting, are resistant to heat, detergents, and reducing agents. Reaction of omeprazole occurs with cysteine-free proteins, is not fully inhibited by cysteine alkylation, occurs at neutral pH, and induces protein multimerization. At least two other clinically used PPIs, rabeprazole and tenatoprazole, are capable of binding to proteins in a similar fashion. We conclude that omeprazole binds to multiple proteins and is capable of forming highly stable complexes that are not dependent on disulfide linkages between the drug and protein targets. Further studies made possible by these antibodies may shed light on whether PPI-protein complexes underlie off-target untoward effects of chronic PPI use.
High Prevalence of Rickettsia raoultii and Associated Pathogens in Canine Ticks, South Korea

We studied the prevalence of tickborne pathogens in canine ticks, South Korea, during 2010–2015. Results revealed a high prevalence of the emerging pathogen Rickettsia raoultii. Dog ticks may be maintenance hosts for tickborne pathogens, suggesting the need to continually evaluate the potential public health threat posed by R. raoultii–infected ticks.
HCV Glycoprotein Structure and Implications for B-Cell Vaccine Development

Despite the approval of highly efficient direct-acting antivirals in the last decade Hepatitis C virus (HCV) remains a global health burden and the development of a vaccine would constitute an important step towards the control of HCV. The high genetic variability of the viral glycoproteins E1 and E2, which carry the main neutralizing determinants, together with their intrinsic structural flexibility, the high level of glycosylation that shields conserved neutralization epitopes and immune evasion using decoy epitopes renders the design of an efficient vaccine challenging. Recent structural and functional analyses have highlighted the role of the CD81 receptor binding site on E2, which overlaps with those neutralization epitopes within E2 that have been structurally characterized to date. This CD81 binding site consists of three distinct segments including “epitope I”, “epitope II” and the “CD81 binding loop”. In this review we summarize the structural features of the HCV glycoproteins that have been derived from X-ray structures of neutralizing and non-neutralizing antibody fragments complexed with either recombinant E2 or epitope-derived linear peptides. We focus on the current understanding how neutralizing antibodies interact with their cognate antigen, the structural features of the respective neutralization epitopes targeted by nAbs and discuss the implications for informed vaccine design.
Differentiating High-Grade Gliomas from Brain Metastases at Magnetic Resonance: The Role of Texture Analysis of the Peritumoral Zone

High-grade gliomas (HGGs) and solitary brain metastases (BMs) have similar imaging appearances, which often leads to misclassification. In HGGs, the surrounding tissues show malignant invasion, while BMs tend to displace the adjacent area. The surrounding edema produced by the two cannot be differentiated by conventional magnetic resonance (MRI) examinations. Forty-two patients with pathology-proven brain tumors who underwent conventional pretreatment MRIs were retrospectively included (HGGs, n = 16; BMs, n = 26). Texture analysis of the peritumoral zone was performed on the T2-weighted sequence using dedicated software. The most discriminative texture features were selected using the Fisher and the probability of classification error and average correlation coefficients. The ability of texture parameters to distinguish between HGGs and BMs was evaluated through univariate, receiver operating, and multivariate analyses. The first percentile and wavelet energy texture parameters were independent predictors of HGGs (75–87.5% sensitivity, 53.85–88.46% specificity). The prediction model consisting of all parameters that showed statistically significant results at the univariate analysis was able to identify HGGs with 100% sensitivity and 66.7% specificity. Texture analysis can provide a quantitative description of the peritumoral zone encountered in solitary brain tumors, that can provide adequate differentiation between HGGs and BMs.
Relationship between Physicochemical Characteristics and Pathogenic Leptospira in Urban Slum Waters

Leptospirosis, a zoonosis caused by pathogenic Leptospira, primarily affects tropical, developing regions, especially communities without adequate sanitation. Outbreaks of leptospirosis have been linked with the presence of pathogenic Leptospira in water. In this study, we measured the physicochemical characteristics (temperature, pH, salinity, turbidity, electrical conductivity, and total dissolved solids (TDS)) of surface waters from an urban slum in Salvador, Brazil, and analyzed their associations with the presence and concentration of pathogenic Leptospira reported previously. We built logistic and linear regression models to determine the strength of association between physicochemical parameters and the presence and concentration of Leptospira. We found that salinity, TDS, pH, and type of water were strongly associated with the presence of Leptospira. In contrast, only pH was associated with the concentration of the pathogen in water. The study of physico-chemical markers can contribute to a better understanding of the occurrence of Leptospira in water and to the identification of sources of risk in urban slum environments.
Increased awareness and decreased acceptance of genome-editing technology: The impact of the Chinese twin babies

Genome-editing technology has become increasingly known in recent years, and the 2018 news of genome-edited twins in China had a particularly significant impact on public awareness. In the present study we investigate the effect of Japanese media coverage on public opinions of this technology. To identify the effects we employ a questionnaire survey method on a pre-registered sample from online research company Macromill. Our repeated survey from 2016 through 2019 reveal a generally supportive attitude toward the medical application of genome-editing methods. To see this we employed a multinomial logit analysis examining the determinants of negative and positive impressions of the technology. Results show that although editing for medical purposes remained mostly acceptable, its use in fertilizing human eggs was increasingly rejected, especially in 2019, the most recent sample year. The suggestion is that while genome-editing applications in general medical fields are publicly accepted, its use in human functionality enhancement is heavily increasingly resisted. News of the twin babies in China did raise public awareness of the methods but also damaged their reputation. It therefore is important for genome researchers to hold such concerns in mind, keeping the public informed of changing technology fundamentals. As a related question we inquire into the public acceptability of genome editing for animal and plant breeding, such as in agriculture and fisheries, as well. We find the Japanese public views the medical and breeding applications of this technology to be unconnected with each other, despite that awareness of both has risen significantly in recent years.
Influences of Successive Exposure to Bleaching and Fluoride Preparations on the Surface Hardness and Roughness of the Aged Resin Composite Restoratives

Background and Objectives: Surfaces of composite restorations are adversely affected upon bleaching and topical fluoride application. Such a procedure is normally carried out in the presence of restorations already serving in a different oral environment, although previous in vitro studies only considered the freshly-prepared composite specimens for assessment. The current study accordingly aimed to evaluate both the surface hardness and roughness of aged composite restoratives following their successive exposure to bleaching and topical fluoride preparations. Materials and Methods: Disc specimens were prepared from micro-hybrid, nano-filled, flowable and bulk-fill resin composites (groups 1–4, n = 60 each). All specimens were subjected to artificial aging before their intermittent exposure to surface treatment with: none (control), bleach or topical fluoride (subgroups 1–3, n = 20). All surface treatments were interrupted with two periods of 5000 thermal cycles. Specimens’ surfaces were then tested for both surface hardness (Vickers hardness number (VHN), n = 10) and roughness (Ra, n = 10). The collected VHNs and Ras were statistically analyzed using two-way ANOVA and Tukey’s comparisons at α = 0.05 to confirm the significance of differences between subgroups. Results: None of the tested composites showed differences in surface hardness and roughness between the bleached and the non-treated specimens (p > 0.05), but the bleached flowable composite specimens only were rougher than their control (p < 0.000126). In comparison to the control, fluoride treatment not only reduced the surface hardness of both micro-hybrid (p = 0.000129) and flowable (p = 0.0029) composites, but also increased the surface roughness of all tested composites (p < 0.05). Conclusion: Aged composite restoratives provide minimal surface alterations on successive bleaching and fluoride applications. Flowable resin composite is the most affected by such procedures. Although bleaching seems safe for other types of composites, the successive fluoride application could deteriorate the aged surfaces of the tested resin composites.
Early improvement of daily physical activity after catheter ablation for atrial fibrillation in an accelerometer assessment: A prospective pilot study

Catheter ablation improves physical activity in patients with atrial fibrillation (AF). However, continuous daily evaluation and time course of improvement in physical activity after ablation have not been fully assessed. This prospective study was conducted to evaluate the daily physical activities and changes in the physical performance in patients undergoing catheter ablation for AF by continuous monitoring of a portable accelerometer.
The intestinal microbiome is a co-determinant of the postprandial plasma glucose response

Elevated postprandial plasma glucose is a risk factor for development of type 2 diabetes and cardiovascular disease. We hypothesized that the inter-individual postprandial plasma glucose response varies partly depending on the intestinal microbiome composition and function. We analyzed data from Danish adults (n = 106), who were self-reported healthy and attended the baseline visit of two previously reported randomized controlled cross-over trials within the Gut, Grain and Greens project. Plasma glucose concentrations at five time points were measured before and during three hours after a standardized breakfast. Based on these data, we devised machine learning algorithms integrating bio-clinical, as well as shotgun-sequencing-derived taxa and functional potentials of the intestinal microbiome to predict individual postprandial glucose excursions. In this post hoc study, we found microbial and clinical features, which predicted up to 48% of the inter-individual variance of postprandial plasma glucose responses (Pearson correlation coefficient of measured vs. predicted values, R = 0.69, 95% CI: 0.45 to 0.84, p<0.001). The features were age, fasting serum triglycerides, systolic blood pressure, BMI, fasting total serum cholesterol, abundance of Bifidobacterium genus, richness of metagenomics species and abundance of a metagenomic species annotated to Clostridiales at order level. A model based only on microbial features predicted up to 14% of the variance in postprandial plasma glucose excursions (R = 0.37, 95% CI: 0.02 to 0.64, p = 0.04). Adding fasting glycaemic measures to the model including microbial and bio-clinical features increased the predictive power to R = 0.78 (95% CI: 0.59 to 0.89, p<0.001), explaining more than 60% of the inter-individual variance of postprandial plasma glucose concentrations. The outcome of the study points to a potential role of the taxa and functional potentials of the intestinal microbiome. If validated in larger studies our findings may be included in future algorithms attempting to develop personalized nutrition, especially for prediction of individual blood glucose excursions in dys-glycaemic individuals.
Effect of Shade on Photosynthesis, Specific Leaf Weight, Leaf Chlorophyll Content, and Morphology of Young Peach Trees

One-year-old peach [Prunus persica (L.) Batsch cv. Redhaven] trees were grown outdoors under 4 different shade levels (100%, 36%, 21%, and 9% of full sun). Shoot length, internode length, and node number were unaffected by shade, but heavy shade (9% full sun) reduced stem diameter 24%. Compared to those in full sun, average leaf areas were increased 18%, 30%, and 20% by 36%, 21%, and 9% shade, respectively. Shading caused a more horizontal leaf orientation and lower specific leaf weight. Both average and maximum photosynthetic rate per unit area or per mg chlorophyll decreased with shading, but increased with shading when expressed per unit dry weight. Chlorophyll content per unit leaf area increased with shading, but stomatal resistance was unaffected. Leaves from shade treatments became light-saturated between 400 and 600 µEs-1m-2; full-sun leaves became light-saturated at 700-900 µEs-1m-2.
Evaluation of Plasma Biomarker Utility for the Gastrointestinal Acute Radiation Syndrome in Non-human Primates after Partial Body Irradiation with Minimal Bone Marrow Sparing through Correlation with Tissue and Histological Analyses

Supplemental digital content is available in the text. Abstract Exposure to total- and partial-body irradiation following a nuclear or radiological incident result in the potentially lethal acute radiation syndromes of the gastrointestinal and hematopoietic systems in a dose- and time-dependent manner. Radiation-induced damage to the gastrointestinal tract is observed within days to weeks post-irradiation. Our objective in this study was to evaluate plasma biomarker utility for the gastrointestinal acute radiation syndrome in non-human primates after partial body irradiation with minimal bone marrow sparing through correlation with tissue and histological analyses. Plasma and jejunum samples from non-human primates exposed to partial body irradiation of 12 Gy with bone marrow sparing of 2.5% were evaluated at various time points from day 0 to day 21 as part of a natural history study. Additionally, longitudinal plasma samples from non-human primates exposed to 10 Gy partial body irradiation with 2.5% bone marrow sparing were evaluated at timepoints out to 180 d post-irradiation. Plasma and jejunum metabolites were quantified via liquid chromatography–tandem mass spectrometry and histological analysis consisted of corrected crypt number, an established metric to assess radiation-induced gastrointestinal damage. A positive correlation of metabolite levels in jejunum and plasma was observed for citrulline, serotonin, acylcarnitine, and multiple species of phosphatidylcholines. Citrulline levels also correlated with injury and regeneration of crypts in the small intestine. These results expand the characterization of the natural history of gastrointestinal acute radiation syndrome in non-human primates exposed to partial body irradiation with minimal bone marrow sparing and also provide additional data toward the correlation of citrulline with histological endpoints.
Sequential Acquisition of Human Papillomavirus Infection at Genital and Anal Sites, Liuzhou, China

Little is known about the risk for acquiring a concordant human papillomavirus (HPV) infection in a genital (or anal) site after an anal (or genital) HPV infection. We collected 3 sets of anogenital specimens at 6-month intervals from 2,309 men and 2,378 women in Liuzhou, China, and tested these specimens for HPV. The risk for sequential anal HPV infection in participants with a previous genital HPV infection was higher than for participants without an infection (hazard ratio [HR] 4.4, 95% CI 3.4–5.8 for women and HR 2.6, 95% CI 1.4–4.6 for men). For sequential genital HPV infection, women with a previous anal infection had a higher risk (HR 1.9, 95% CI 1.2–3.1), but no major difference was found for men (HR 0.7, 95% CI 0.2–1.9). Our study indicates that autoinoculation might play a major role in anogenital HPV transmission, in addition to direct sexual intercourse, especially for anal infection in women.
Norepinephrine Leads to More Cardiopulmonary Toxicities than Epinephrine by Catecholamine Overdose in Rats

While catecholamines like epinephrine (E) and norepinephrine (NE) are commonly used in emergency medicine, limited studies have discussed the harm of exogenously induced catecholamine overdose. We investigated the possible toxic effects of excessive catecholamine administration on cardiopulmonary function and structure via continuous 6 h intravenous injection of E and/or NE in rats. Heart rate, echocardiography, and ventricular pressure were measured throughout administration. Cardiopulmonary structure was also assessed by examining heart and lung tissue. Consecutive catecholamine injections induced severe tachycardia. Echocardiography results showed NE caused worse dysfunction than E. Simultaneously, both E and NE led to higher expression of Troponin T and connexin43 in the whole ventricles, which increased further with E+NE administration. The NE and E+NE groups showed severe pulmonary edema while all catecholamine-administering groups demonstrated reduced expression of receptor for advanced glycation end products and increased connexin43 levels in lung tissue. The right ventricle was more vulnerable to catecholamine overdose than the left. Rats injected with NE had a lower survival rate than those injected with E within 6 h. Catecholamine overdose induces acute lung injuries and ventricular cardiomyopathy, and E+NE is associated with a more severe outcome. The similarities of the results between the NE and E+NE groups may indicate a predominant role of NE in determining the overall cardiopulmonary damage. The results provide important clinical insights into the pathogenesis of catecholamine storm.
Transcriptomic and clonal characterization of T cells in the human central nervous system

We have profiled cerebrospinal fluid T cells in healthy individuals and patients with MS using single-cell RNA and TCR sequencing. Cerebrospinal fluid snapshot The central nervous system (CNS) features mechanisms to protect against untoward inflammation yet allowing immune surveillance for pathogens. Pappalardo et al. profiled T cells in the cerebrospinal fluid (CSF) of healthy individuals and patients with multiple sclerosis (MS) using single-cell RNA and TCR sequences to define CNS immune homeostasis in both healthy donors and patients with MS. In healthy individuals, clonally expanded CSF T cells are largely distinct from those found in the blood with effector, IFNγ, and tissue adaptation signatures, whereas CSF T cells from patients with MS differ from healthy controls with a gene expression signature consistent with elevated activation and cytotoxicity. These findings provide insight into the unique immune environment in the CSF under normal and disease-associated conditions. T cells provide critical immune surveillance to the central nervous system (CNS), and the cerebrospinal fluid (CSF) is thought to be a main route for their entry. Further characterization of the state of T cells in the CSF in healthy individuals is important for understanding how T cells provide protective immune surveillance without damaging the delicate environment of the CNS and providing tissue-specific context for understanding immune dysfunction in neuroinflammatory disease. Here, we have profiled T cells in the CSF of healthy human donors and have identified signatures related to cytotoxic capacity and tissue adaptation that are further exemplified in clonally expanded CSF T cells. By comparing profiles of clonally expanded T cells obtained from the CSF of patients with multiple sclerosis (MS) and healthy donors, we report that clonally expanded T cells from the CSF of patients with MS have heightened expression of genes related to T cell activation and cytotoxicity.
Towards Interpretable Arrhythmia Classification With Human-Machine Collaborative Knowledge Representation

Arrhythmia detection and classification is a crucial step for diagnosing cardiovascular diseases. However, deep learning models that are commonly used and trained in end-to-end fashion are not able to provide good interpretability. In this paper, we address this deficiency by proposing the first novel interpretable arrhythmia classification approach based on a human-machine collaborative knowledge representation. Our approach first employs an AutoEncoder to encode electrocardiogram signals into two parts: hand-encoding knowledge and machine-encoding knowledge. A classifier then takes as input the encoded knowledge to classify arrhythmia heartbeats with or without human in the loop (HIL). Experiments and evaluation on the MIT-BIH Arrhythmia Database demonstrate that our new approach not only can effectively classify arrhythmia while offering interpretability, but also can improve the classification accuracy by adjusting the hand-encoding knowledge with our HIL mechanism.