Synthetic Oligodeoxynucleotide CpG Motifs Activate Human Complement through Their Backbone Structure and Induce Complement-Dependent Cytokine Release.

Bacterial and mitochondrial DNA, sharing an evolutionary origin, act as danger-associated molecular patterns in infectious and sterile inflammation. They both contain immunomodulatory CpG motifs. Interactions between CpG motifs and the complement system are sparsely described, and mechanisms of complement activation by CpG remain unclear. Lepirudin-anticoagulated human whole blood and plasma were incubated with increasing concentrations of three classes of synthetic CpGs: CpG-A, -B, and -C oligodeoxynucleotides and their GpC sequence controls. Complement activation products were analyzed by immunoassays. Cytokine levels were determined via 27-plex beads-based immunoassay, and CpG interactions with individual complement proteins were evaluated using magnetic beads coated with CpG-B. In whole blood and plasma, CpG-B and CpG-C (p < 0.05 for both), but not CpG-A (p > 0.8 for all), led to time- and dose-dependent increase of soluble C5b-9, the alternative complement convertase C3bBbP, and the C3 cleavage product C3bc. GpC-A, -B, and -C changed soluble fluid-phase C5b-9, C3bBbP, and C3bc to the same extent as CpG-A, -B, and -C, indicating a DNA backbone-dependent effect. Dose-dependent CpG-B binding was found to C1q (r = 0.83; p = 0.006) and factor H (r = 0.93; p < 0.001). The stimulatory complement effect was partly preserved in C2-deficient plasma and completely preserved in MASP-2-deficient serum. CpG-B increased levels of IL-1ß, IL-2, IL-6, IL-8, MCP-1, and TNF in whole blood, which were completely abolished by inhibition of C5 and C5aR1 (p < 0.05 for all). In conclusion, synthetic analogs of bacterial and mitochondrial DNA activate the complement system via the DNA backbone. We suggest that CpG-B interacts directly with classical and alternative pathway components, resulting in complement-C5aR1-dependent cytokine release.

deepSimDEF: deep neural embeddings of gene products and gene ontology terms for functional analysis of genes.

MOTIVATION: There is a plethora of measures to evaluate functional similarity (FS) of genes based on their co-expression, protein-protein interactions and sequence similarity. These measures are typically derived from hand-engineered and application-specific metrics to quantify the degree of shared information between two genes using their Gene Ontology (GO) annotations. RESULTS: We introduce deepSimDEF, a deep learning method to automatically learn FS estimation of gene pairs given a set of genes and their GO annotations. deepSimDEF's key novelty is its ability to learn low-dimensional embedding vector representations of GO terms and gene products and then calculate FS using these learned vectors. We show that deepSimDEF can predict the FS of new genes using their annotations: it outperformed all other FS measures by >5-10% on yeast and human reference datasets on protein-protein interactions, gene co-expression and sequence homology tasks. Thus, deepSimDEF offers a powerful and adaptable deep neural architecture that can benefit a wide range of problems in genomics and proteomics, and its architecture is flexible enough to support its extension to any organism. AVAILABILITY AND IMPLEMENTATION: Source code and data are available at https://github.com/ahmadpgh/deepSimDEF. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients.

Respiratory failure in the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is hypothesized to be driven by an overreacting innate immune response, where the complement system is a key player. In this prospective cohort study of 39 hospitalized coronavirus disease COVID-19 patients, we describe systemic complement activation and its association with development of respiratory failure. Clinical data and biological samples were obtained at admission, days 3 to 5, and days 7 to 10. Respiratory failure was defined as PO2/FiO2 ratio of ≤40 kPa. Complement activation products covering the classical/lectin (C4d), alternative (C3bBbP) and common pathway (C3bc, C5a, and sC5b-9), the lectin pathway recognition molecule MBL, and antibody serology were analyzed by enzyme-immunoassays; viral load by PCR. Controls comprised healthy blood donors. Consistently increased systemic complement activation was observed in the majority of COVID-19 patients during hospital stay. At admission, sC5b-9 and C4d were significantly higher in patients with than without respiratory failure (P = 0.008 and P = 0.034). Logistic regression showed increasing odds of respiratory failure with sC5b-9 (odds ratio 31.9, 95% CI 1.4 to 746, P = 0.03) and need for oxygen therapy with C4d (11.7, 1.1 to 130, P = 0.045). Admission sC5b-9 and C4d correlated significantly to ferritin (r = 0.64, P < 0.001; r = 0.69, P < 0.001). C4d, sC5b-9, and C5a correlated with antiviral antibodies, but not with viral load. Systemic complement activation is associated with respiratory failure in COVID-19 patients and provides a rationale for investigating complement inhibitors in future clinical trials.

Photochemical synthesis of pink silver and its use for monitoring peptide nitration via surface enhanced Raman spectroscopy (SERS).

Oxidative stress may cause extended tyrosine posttranslational modifications of peptides and proteins. The 3-nitro-L-tyrosine (Nit), which is typically formed, affects protein behavior during neurodegenerative processes, such as Alzheimer's and Parkinson's diseases. Such metabolic products may be conveniently detected at very low concentrations by surface enhanced Raman spectroscopy (SERS). Previously, we have explored the SERS detection of the Nit NO2 bending vibrational bands in a presence of hydrogen chloride (Niederhafner et al., Amino Acids 53:517-532, 2021, ibid). In this article, we describe performance of a new SERS substrate, "pink silver", synthesized photochemically. It provides SERS even without the HCl induction, and the acid further decreases the detection limit about 9 times. Strong SERS bands were observed in the asymmetric (1550-1475 cm-1) and symmetric (1360-1290 cm-1) NO stretching in the NO2 group. The bending vibration was relatively weak, but appeared stronger when HCl was added. The band assignments were supported by density functional theory modeling.

Solvent Extraction and Conformation Rigidity: Actinide(IV) and Actinide(VI) Come Together.

The first comprehensive structural and extraction study of a 2,2'-bipyridine-6,6'-dicarboxamide (L diamide) extractant for U, Np, Pu, Th, Am, and Eu ions showed great potential for actinide separation due to steric hindrance of the amidic side phenyl ring of the given compound. The study of the complexes of An(VI) and Th(IV) with 2,2'-bipyridyldicarboxamide-type extractants demonstrated the structure of the extraction species for the first time. Investigation of the extraction properties with the radiometric and millimolar quantities of actinides showed similar extraction trends. For the first time, a metal-ion-induced phenyl-ring rotation restriction was found for the U, Th, and Eu complexes by employing temperature-dependent dynamic NMR. A study of the solution behavior of the complexes accompanied by density functional theory modeling studies elucidated the mechanism of the unusual C-N bond rotation restriction induced by metal coordination.

Secondary Role of Aliphatic and Heterocyclic Amines in the Formation of Low-Temperature Amine-Bearing U, Np, and Pu(VI) Chromates.

Uranyl compounds with tetrahedral oxoanions demonstrate a significant structural and topological diversity. Complexes of transuranium elements with such anions are not equally well-represented in the literature. To answer the question about the structural similarity in a series of An6+ complexes with XO42- anions, we synthesized and studied 10 new U, Np, and Pu chromates with outer-sphere organic cations. The structural analysis and comparison with the literature data shows that the Np and Pu complexes are generally based on the same structural blocks as the uranyl compounds. Moreover, the chromate anion does not show any unique structural role as compared to the sulfate and selenate ions. As a result, the neptunium and plutonium chromates contain 1D and 2D structural units similar to those found in the uranyl sulfates and selenates. The templating role of the outer-sphere cations in the actinyl complexes with tetrahedral oxoanions is also not evident, and there is no clear correlation between the nature of the outer-sphere cations and the topology of the structural units.

Perrhenate and Pertechnetate Complexes of U(IV), Np(IV), and Pu(IV) with Dimethyl Sulfoxide as an O-Donor Ligand.

A series of new dimethyl-sulfoxide-containing pertechnetates and perrhenates of tetravalent U, Np, and Pu were synthesized and structurally characterized by the X-ray diffractometry. In all the synthesized compounds, the actinide atoms were coordinated by eight DMSO molecules with or without an extra XO4- anion in the coordination sphere. This resulted in the square antiprismatic or capped square antiprismatic coordination of An atoms. Three or four XO4- anions play the role of outer-sphere anions. The electron and IR spectra of the compounds correlated with their crystal structure.

NLRP3 Inflammasome: A Novel Player in Metabolically Induced Inflammation-Potential Influence on the Myocardium.

Metabolic and immune systems are among the most fundamental requirements for survival. Many metabolic and immune response pathways or nutrient- and pathogen-sensing systems are evolutionarily conserved throughout species. As a result, the immune response and metabolic regulation are highly integrated and the proper function of each is dependent on the other. This interaction between metabolic disturbances and the immune system has been most extensively studied in disorders related to obesity such as insulin resistance, type 2 diabetes, and nonalcoholic fatty liver disease. Metabolically induced inflammation seems also to play a role in the development and progression of atherosclerosis including its complications such as myocardial infarction (MI) and post-MI remodeling. There are several lines of evidence suggesting that NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a sensor of metabolic stress linking metabolic disturbances to inflammation. Here, we will discuss the role of the NLRP3 inflammasome in the pathogenesis of obesity and diabetes, 2 important risk factors for atherosclerosis and MI. We will also discuss the role of NLRP3 inflammasome in the interaction between metabolic disturbances and myocardial inflammation during MI and during metabolically induced myocardial remodeling.

NLRP3 inflammasome mediates oxidative stress-induced pancreatic islet dysfunction.

Inflammasomes are multiprotein inflammatory platforms that induce caspase-1 activation and subsequently interleukin (IL)-1ß and IL-18 processing. The NLRP3 inflammasome is activated by different forms of oxidative stress, and, based on the central role of IL-1ß in the destruction of pancreatic islets, it could be related to the development of diabetes. We therefore investigated responses in wild-type C57Bl/6 (WT) mice, NLRP3-/- mice, and mice deficient in apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) after exposing islets to short-term hypoxia or alloxan-induced islet damage. NLRP3-deficient islets compared with WT islets had preserved function ex vivo and were protected against hypoxia-induced cell death. Furthermore, NLRP3 and ASC-deficient mice were protected against oxidative stress-induced diabetes caused by repetitive low-dose alloxan administration, and this was associated with reduced ß-cell death and reduced macrophage infiltration. This suggests that the beneficial effect of NLRP3 inflammasome deficiency on oxidative stress-mediated ß-cell damage could involve reduced macrophage infiltration and activation. To support the role of macrophage activation in alloxan-induced diabetes, we injected WT mice with liposomal clodronate, which causes macrophage depletion before induction of a diabetic phenotype by alloxan treatment, resulting in improved glucose homeostasis in WT mice. We show here that the NLRP3 inflammasome acts as a mediator of hypoxia and oxidative stress in insulin-producing cells, suggesting that inhibition of the NLRP3 inflammasome could have beneficial effects on ß-cell preservation.

Muscle dysmorphia: detection of the use-abuse of anabolic adrogenic steroids in a Spanish sample. / Dismorfia Muscular: detección del uso-abuso de esteroides anabolizantes androgénicos en una muestra española.

Due to a distortion in the body image, the people who suffer from muscle dysmorphia have the self-perception of being less muscular than they currently are. With the aim of increasing their muscular development, they resort to the use of AAS. The purpose of the present study is to know the prevalence of the use of AAS in a Spanish sample affected by muscle dysmorphia. 562 male and 172 female bodybuilders and weightlifters were provided with different questionnaires in order to know, firstly, if they suffered from this disorder and, secondly, the percentage of the participants affected who use these substances. Decision trees and regression was applied to create explanatory models for muscle dysmorphia (R = 0.78 and R2 = 0.62). The results show that almost 50% of the participants, male and female, affected by this disorder use this kind of drugs.

Las personas que padecen Dismorfia Muscular (DM) debido a una distorsión en la imagen corporal, se perciben menos musculosas de lo que son en realidad. Para paliar este problema y con el fin de aumentar su musculatura, algunas de estas personas hacen uso de hormonas ilegales, como son los esteroides anabolizantes androgénicos (EAA), cuya función principal es aumentar la musculatura. El objetivo de este estudio es conocer la prevalencia del uso de EAA en personas afectadas por Dismorfia Muscular. La muestra de este estudio estaba compuesta de 562 hombres y 172 mujeres fisicoculturistas y levantadores de pesas, a los que se le administraron medidas antropométricas, la ecuación Fat-Free Mass Index, el cuestionario Escala de Satisfacción Muscular y el test informatizado Somatomorphic Matrix. Como resultado se crearon diferentes modelos de regresión de la DM, empleando las técnicas estadísticas de árboles de decisión (R = .78 y R2 = .62) de minería de datos. La principal conclusión es que el 50% de participantes afectados por este trastorno usa EAA.

Palmitate promotes inflammatory responses and cellular senescence in cardiac fibroblasts.

Palmitate triggers inflammatory responses in several cell types, but its effects on cardiac fibroblasts are at present unknown. The aims of the study were to (1) assess the potential of palmitate to promote inflammatory signaling in cardiac fibroblasts through TLR4 and the NLRP3 inflammasome and (2) characterize the cellular phenotype of cardiac fibroblasts exposed to palmitate. We examined whether palmitate induces inflammatory responses in cardiac fibroblasts from WT, NLRP3-/- and ASC-/-mice (C57BL/6 background). Exposure to palmitate caused production of TNF, IL-6 and CXCL2 via TLR4 activation. NLRP3 inflammasomes are activated in a two-step manner. Whereas palmitate did not prime the NLRP3 inflammasome, it induced activation in LPS-primed cardiac fibroblasts as indicated by IL-1ß, IL-18 production and NLRP3-ASC co-localization. Palmitate-induced NLRP3 inflammasome activation in LPS-primed cardiac fibroblasts was associated with reduced AMPK activity, mitochondrial reactive oxygen species production and mitochondrial dysfunction. The cardiac fibroblast phenotype caused by palmitate, in an LPS and NLRP3 independent manner, was characterized by decreased cellular proliferation, contractility, collagen and MMP-2 expression, as well as increased senescence-associated ß-galactosidase activity, and consistent with a state of cellular senescence. This study establishes that in vitro palmitate exposure of cardiac fibroblasts provides inflammatory responses via TLR4 and NLRP3 inflammasome activation. Palmitate also modulates cardiac fibroblast functionality, in a NLRP3 independent manner, resulting in a phenotype related to cellular senescence. These effects of palmitate could be of importance for myocardial dysfunction in obese and diabetic patients.

simDEF: definition-based semantic similarity measure of gene ontology terms for functional similarity analysis of genes.

MOTIVATION: Measures of protein functional similarity are essential tools for function prediction, evaluation of protein-protein interactions (PPIs) and other applications. Several existing methods perform comparisons between proteins based on the semantic similarity of their GO terms; however, these measures are highly sensitive to modifications in the topological structure of GO, tend to be focused on specific analytical tasks and concentrate on the GO terms themselves rather than considering their textual definitions. RESULTS: We introduce simDEF, an efficient method for measuring semantic similarity of GO terms using their GO definitions, which is based on the Gloss Vector measure commonly used in natural language processing. The simDEF approach builds optimized definition vectors for all relevant GO terms, and expresses the similarity of a pair of proteins as the cosine of the angle between their definition vectors. Relative to existing similarity measures, when validated on a yeast reference database, simDEF improves correlation with sequence homology by up to 50%, shows a correlation improvement >4% with gene expression in the biological process hierarchy of GO and increases PPI predictability by > 2.5% in F1 score for molecular function hierarchy. AVAILABILITY AND IMPLEMENTATION: Datasets, results and source code are available at http://kiwi.cs.dal.ca/Software/simDEF CONTACT: ahmad.pgh@dal.ca or beiko@cs.dal.ca SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Microencapsulation of mildronate in biodegradable and non-biodegradable polymers.

The extremely high hygroscopicity (solubility in water ≥2 g/ml) of the pharmaceutical preparation mildronate defines specific requirements to both packaging material and storage conditions. To overcome the above mentioned inconveniences, microencapsulated form of mildronate was developed using polystyrene (PS) and poly (lactic acid) (PLA) as watertight coating materials. Drug/polymer interaction as well as influence of the microencapsulation process variables on microparticle properties was studied in detail. Water-in-oil-in-water double emulsion technique was adapted and applied for the preparation of PS/mildronate microparticles with total drug load up to 77 %wt and PLA/mildronate microparticles with total drug load up to 80 %wt. The repeatability of the microencapsulation process was ±4% and the encapsulation efficiency of the active ingredient reached 60 %wt. The drug release kinetics from the obtained microparticles was evaluated and it was found that drug release in vivo could be successfully sustained if polystyrene matrix has been used.

Can anonymous posters on medical forums be reidentified?

BACKGROUND: Participants in medical forums often reveal personal health information about themselves in their online postings. To feel comfortable revealing sensitive personal health information, some participants may hide their identity by posting anonymously. They can do this by using fake identities, nicknames, or pseudonyms that cannot readily be traced back to them. However, individual writing styles have unique features and it may be possible to determine the true identity of an anonymous user through author attribution analysis. Although there has been previous work on the authorship attribution problem, there has been a dearth of research on automated authorship attribution on medical forums. The focus of the paper is to demonstrate that character-based author attribution works better than word-based methods in medical forums. OBJECTIVE: The goal was to build a system that accurately attributes authorship of messages posted on medical forums. The Authorship Attributor system uses text analysis techniques to crawl medical forums and automatically correlate messages written by the same authors. Authorship Attributor processes unstructured texts regardless of the document type, context, and content. METHODS: The messages were labeled by nicknames of the forum participants. We evaluated the system's performance through its accuracy on 6000 messages gathered from 2 medical forums on an in vitro fertilization (IVF) support website. RESULTS: Given 2 lists of candidate authors (30 and 50 candidates, respectively), we obtained an F score accuracy in detecting authors of 75% to 80% on messages containing 100 to 150 words on average, and 97.9% on longer messages containing at least 300 words. CONCLUSIONS: Authorship can be successfully detected in short free-form messages posted on medical forums. This raises a concern about the meaningfulness of anonymous posting on such medical forums. Authorship attribution tools can be used to warn consumers wishing to post anonymously about the likelihood of their identity being determined.

Lateral inhibition in accumulative computation and fuzzy sets for human fall pattern recognition in colour and infrared imagery.

Fall detection is an emergent problem in pattern recognition. In this paper, a novel approach which enables to identify a type of a fall and reconstruct its characteristics is presented. The features detected include the position previous to a fall, the direction and velocity of a fall, and the postfall inactivity. Video sequences containing a possible fall are analysed image by image using the lateral inhibition in accumulative computation method. With this aim, the region of interest of human figures is examined in each image, and geometrical and kinematic characteristics for the sequence are calculated. The approach is valid in colour and in infrared video.

P2P watch: personal health information detection in peer-to-peer file-sharing networks.

BACKGROUND: Users of peer-to-peer (P2P) file-sharing networks risk the inadvertent disclosure of personal health information (PHI). In addition to potentially causing harm to the affected individuals, this can heighten the risk of data breaches for health information custodians. Automated PHI detection tools that crawl the P2P networks can identify PHI and alert custodians. While there has been previous work on the detection of personal information in electronic health records, there has been a dearth of research on the automated detection of PHI in heterogeneous user files. OBJECTIVE: To build a system that accurately detects PHI in files sent through P2P file-sharing networks. The system, which we call P2P Watch, uses a pipeline of text processing techniques to automatically detect PHI in files exchanged through P2P networks. P2P Watch processes unstructured texts regardless of the file format, document type, and content. METHODS: We developed P2P Watch to extract and analyze PHI in text files exchanged on P2P networks. We labeled texts as PHI if they contained identifiable information about a person (eg, name and date of birth) and specifics of the person's health (eg, diagnosis, prescriptions, and medical procedures). We evaluated the system's performance through its efficiency and effectiveness on 3924 files gathered from three P2P networks. RESULTS: P2P Watch successfully processed 3924 P2P files of unknown content. A manual examination of 1578 randomly selected files marked by the system as non-PHI confirmed that these files indeed did not contain PHI, making the false-negative detection rate equal to zero. Of 57 files marked by the system as PHI, all contained both personally identifiable information and health information: 11 files were PHI disclosures, and 46 files contained organizational materials such as unfilled insurance forms, job applications by medical professionals, and essays. CONCLUSIONS: PHI can be successfully detected in free-form textual files exchanged through P2P networks. Once the files with PHI are detected, affected individuals or data custodians can be alerted to take remedial action.

Targeting the Inflammasome in Cardiovascular Disease.

The pathogenesis of cardiovascular disease (CVD) is complex and multifactorial, and inflammation plays a central role. Inflammasomes are multimeric protein complexes that are activated in a 2-step manner in response to infection or tissue damage. Upon activation the proinflammatory cytokines, interleukins-1ß and -18 are released. In the last decade, the evidence that inflammasome activation plays an important role in CVD development became stronger. We discuss the role of different inflammasomes in the pathogenesis of CVD, focusing on atherosclerosis and heart failure. This review also provides an overview of existing experimental studies and clinical trials on inflammasome inhibition as a therapeutic target in these disorders.

Vitamin C, Hydrocortisone, and the Combination Thereof Significantly Inhibited Two of Nine Inflammatory Markers Induced by Escherichia Coli But Not by Staphylococcus Aureus - When Incubated in Human Whole Blood.

ABSTRACT: Vitamin C combined with hydrocortisone is increasingly being used to treat septic patients, even though this treatment regimen is based on questionable evidence. When used, a marked effect on key players of innate immunity would be expected, as sepsis is featured by a dysregulated immune response.Here, we explored the effect of vitamin C and hydrocortisone alone and combined, in an ex vivo human whole-blood model of Escherichia coli- or Staphylococcus aureus-induced inflammation. Inflammatory markers for activation of complement (terminal C5b-9 complement complex [TCC]), granulocytes (myeloperoxidase), platelets (ß-thromboglobulin), cytokines (tumor necrosis factor [TNF], IL-1ß, IL6, and IL-8), and leukocytes (CD11b and oxidative burst) were quantified, by enzyme-linked immunosorbent assay, multiplex technology, and flow cytometry.In E. coli- and S. aureus-stimulated whole blood, a broad dose-titration of vitamin C and hydrocortisone alone did not lead to dose-response effects for the central innate immune mediators TCC and IL-6. Hence, the clinically relevant doses were used further. Compared to the untreated control sample, two of the nine biomarkers induced by E. coli were reduced by hydrocortisone and/or vitamin C. TNF was reduced by hydrocortisone alone (19%, P = 0.01) and by the combination (31%, P = 0.01). The oxidative burst of monocytes and granulocytes was reduced for both drugs alone and their combination, (ranging 8-19%, P < 0.05). Using S. aureus, neither of the drugs, alone nor in combination, had any effects on the nine biomarkers.In conclusion, despite the limitation of the ex vivo model, the effect of vitamin C and hydrocortisone on bacteria-induced inflammatory response in human whole blood is limited and following the clinical data.

Development and Validation of a Protein Array for Detection of Antibodies against the Tick-Borne Pathogen Borrelia miyamotoi.

Current serological tests for the emerging tick-borne pathogen Borrelia miyamotoi lack diagnostic accuracy. To improve serodiagnosis, we investigated a protein array simultaneously screening for IgM and IgG reactivity against multiple recombinant B. miyamotoi antigens. The array included six B. miyamotoi antigens: glycerophosphodiester phosphodiesterase (GlpQ), multiple variable major proteins (Vmps), and flagellin. Sera included samples from cases of PCR-proven Borrelia miyamotoi disease (BMD), multiple potentially cross-reactive control groups (including patients with culture-proven Lyme borreliosis, confirmed Epstein-Barr virus, cytomegalovirus, or other spirochetal infections), and several healthy control groups from regions where Ixodes is endemic and regions where it is nonendemic. Based on receiver operating characteristic (ROC) analyses, the cutoff for reactivity per antigen was set at 5 µg/mL for IgM and IgG. The individual antigens demonstrated high sensitivity but relatively low specificity for both IgM and IgG. The best-performing single antigen (GlpQ) showed a sensitivity of 88.0% (95% confidence interval [CI], 78.9 to 93.5) and a specificity of 94.2% (95% CI, 92.7 to 95.6) for IgM/IgG. Applying the previous published diagnostic algorithm-defining seroreactivity as reactivity against GlpQ and any Vmp-revealed a significantly higher specificity of 98.5% (95% CI, 97.6 to 99.2) but a significantly lower sensitivity of 79.5% (95% CI, 69.3 to 87.0) for IgM/IgG compared to GlpQ alone. Therefore, we propose to define seroreactivity as reactivity against GlpQ and any Vmp or flagellin which resulted in a comparable sensitivity of 84.3% (95% CI, 74.7 to 90.8) and a significantly higher specificity of 97.9% (95% CI, 96.9 to 98.7) for IgM/IgG compared to GlpQ alone. In conclusion, we have developed and validated a novel serological tool to diagnose BMD that could be implemented in clinical practice and epidemiological studies. IMPORTANCE This paper describes the protein array as a novel serological test for the diagnosis of Borrelia miyamotoi disease (BMD), by reporting the methodology, the development of a diagnostic algorithm, and its extensive validation. With rising numbers of ticks and tick bites, tick-borne diseases, such as BMD, urgently deserve further societal and medical attention. B. miyamotoi is prevalent in Ixodes ticks across the northern hemisphere. Humans are exposed to, and infected by, B. miyamotoi and develop BMD in Asia, in North America, and to a lesser extent in Europe. However, the burden of infection and disease remains largely unknown, due to the noncharacteristic clinical presentation, together with the lack of awareness and availability of diagnostic tools. With this paper, we offer a novel diagnostic tool which will assist in assessing the burden of disease and could be implemented in clinical care.

Specialists, Scientists, and Sentiments: Word2Vec and Doc2Vec in Analysis of Scientific and Medical Texts.

Analyze performance of unsupervised embedding algorithms in sentiment analysis of knowledge-rich data sets. We apply state-of-the-art embedding algorithms Word2Vec and Doc2Vec as the learning techniques. The algorithms build word and document embeddings in an unsupervised manner. To assess the algorithms' performance, we define sentiment metrics and use a semantic lexicon SentiWordNet (SWN) to establish the benchmark measures. Our empirical results are obtained on the Obesity data set from i2b2 clinical discharge summaries and the Reuters Science dataset. We use the Welch's test to analyze the obtained sentiment evaluation. On the Obesity data, the Welch's test found significant difference between the SWN evaluation of the most positive and most negative texts. On the same data, the Word2Vec results support the SWN results, whereas the Doc2Vec results partially correspond to the Word2Vec and the SWN results. On the Reuters data, the Welch's test did not find significant difference between the SWN evaluation of the most positive and most negative texts. On the same data, Word2Vec and Doc2Vec results only in part correspond to the SWN results. In unsupervised sentiment analysis of medical and scientific texts, the Word2Vec sentiment analysis has been more consistent with the SentiWordNet sentiment assessment than the Doc2Vec sentiment analysis. The Welch's test of the SentiWordNet results has been a strong indicator of future correspondence between Word2Vec and SentiWordNet results.