Rapidly progressive interstitial lung disease risk prediction in anti-MDA5 positive dermatomyositis: the CROSS model.

Background: The prognosis of anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+DM) is poor and heterogeneous. Rapidly progressive interstitial lung disease (RP-ILD) is these patients' leading cause of death. We sought to develop prediction models for RP-ILD risk in anti-MDA5+DM patients. Methods: Patients with anti-MDA5+DM were enrolled in two cohorts: 170 patients from the southern region of Jiangsu province (discovery cohort) and 85 patients from the northern region of Jiangsu province (validation cohort). Cox proportional hazards models were used to identify risk factors of RP-ILD. RP-ILD risk prediction models were developed and validated by testing every independent prognostic risk factor derived from the Cox model. Results: There are no significant differences in baseline clinical parameters and prognosis between discovery and validation cohorts. Among all 255 anti-MDA5+DM patients, with a median follow-up of 12 months, the incidence of RP-ILD was 36.86%. Using the discovery cohort, four variables were included in the final risk prediction model for RP-ILD: C-reactive protein (CRP) levels, anti-Ro52 antibody positivity, short disease duration, and male sex. A point scoring system was used to classify anti-MDA5+DM patients into moderate, high, and very high risk of RP-ILD. After one-year follow-up, the incidence of RP-ILD in the very high risk group was 71.3% and 85.71%, significantly higher than those in the high-risk group (35.19%, 41.69%) and moderate-risk group (9.54%, 6.67%) in both cohorts. Conclusions: The CROSS model is an easy-to-use prediction classification system for RP-ILD risk in anti-MDA5+DM patients. It has great application prospect in disease management.

Annotation of cell types (ACT): a convenient web server for cell type annotation.

BACKGROUND: The advancement of single-cell sequencing has progressed our ability to solve biological questions. Cell type annotation is of vital importance to this process, allowing for the analysis and interpretation of enormous single-cell datasets. At present, however, manual cell annotation which is the predominant approach remains limited by both speed and the requirement of expert knowledge. METHODS: To address these challenges, we constructed a hierarchically organized marker map through manually curating over 26,000 cell marker entries from about 7000 publications. We then developed WISE, a weighted and integrated gene set enrichment method, to integrate the prevalence of canonical markers and ordered differentially expressed genes of specific cell types in the marker map. Benchmarking analysis suggested that our method outperformed state-of-the-art methods. RESULTS: By integrating the marker map and WISE, we developed a user-friendly and convenient web server, ACT ( http://xteam.xbio.top/ACT/ or http://biocc.hrbmu.edu.cn/ACT/ ), which only takes a simple list of upregulated genes as input and provides interactive hierarchy maps, together with well-designed charts and statistical information, to accelerate the assignment of cell identities and made the results comparable to expert manual annotation. Besides, a pan-tissue marker map was constructed to assist in cell assignments in less-studied tissues. Applying ACT to three case studies showed that all cell clusters were quickly and accurately annotated, and multi-level and more refined cell types were identified. CONCLUSIONS: We developed a knowledge-based resource and a corresponding method, together with an intuitive graphical web interface, for cell type annotation. We believe that ACT, emerging as a powerful tool for cell type annotation, would be widely used in single-cell research and considerably accelerate the process of cell type identification.

EZ-InSAR: An easy-to-use open-source toolbox for mapping ground surface deformation using satellite interferometric synthetic aperture radar.

Satellite Interferometric Synthetic Aperture Radar (InSAR) is a space-borne geodetic technique that can map ground displacement at millimetre accuracy. Via the new era for InSAR applications provided by the Copernicus Sentinel-1 SAR satellites, several open-source software packages exist for processing SAR data. These packages enable one to obtain high-quality ground deformation maps, but still require a deep understanding of InSAR theory and the related computational tools, especially when dealing with a large stack of images. Here we present an open-source toolbox, EZ-InSAR (easy-to-use InSAR), for a user-friendly implementation of InSAR displacement time series analysis with multi-temporal SAR images. EZ-InSAR integrates the three most popular and renowned open-source tools (i.e., ISCE, StaMPS, and MintPy), to generate interferograms and displacement time series by using these state-of-art algorithms within a seamless Graphical User Interface. EZ-InSAR reduces the user's workload by automatically downloading the Sentinel-1 SAR imagery and the digital elevation model data for the user's area of interest, and by streamlining preparation of input data stacks for the time series InSAR analysis. We illustrate the EZ-InSAR processing capabilities by mapping recent ground deformation at Campi Flegrei (> 100 mm·yr-1) and Long Valley (~ 10 mm·yr-1) calderas with both Persistent Scatterer InSAR and Small-Baseline Subset approaches. We also validate the test results by comparing the InSAR displacements with Global Navigation Satellite System measurements at those volcanoes. Our tests indicate that the EZ-InSAR toolbox provided here can serve as a valuable contribution to the community for ground deformation monitoring and geohazard evaluation, as well as for disseminating bespoke InSAR observations for all.

Automated and Rapid Easy-to-Use Magnetic Solid-Phase Extraction System for Five Heavy Metals in Cereals and Feeds.

A rapid, accurate, and ecofriendly pretreatment plays an extremely important role prior to ICP-MS for heavy metal analysis. In order to improve the pretreatment efficiency, a high-throughput and automatic magnetic solid-phase extraction of five heavy metals (Cd, Pb, Mn, Cu, and Zn) was carried out by a magnet-controlled pretreatment system with an ecofriendly diluted acid as an extracting agent and carboxyl-functionalized magnetic beads as a pretreatment material. Key conditions, including the pH, adsorption time, and eluent solution, were optimized. The time for purification and enrichment was only 8 min. The adsorption capacities of the carboxyl-functionalized magnetic beads were in the range of 152~426 mg g-1. The preconcentration factor of Cu was 40, and others were 200. In the optimal conditions, the limits of detection for Mn, Zn, Cd, Cu, and Pb by ICP-MS were 3.84, 2.71, 0.16, 11.54, and 6.01 ng L-1, respectively. The percentage recoveries were in the range of 80~110%, and the relative standard deviations were less than 3%. The developed method was in good agreement with traditional standard microwave digestion. Additionally, the designed system could simultaneously process up to 24 samples within 22 min, reducing the time to less than 1 min/sample. Thus, the proposed auto-MSPE-ICP-MS method was successfully applied to analyze five heavy metals in cereals and feeds with a simple operation and high precision, safety, and reliability.

What the Phage: a scalable workflow for the identification and analysis of phage sequences.

Phages are among the most abundant and diverse biological entities on earth. Phage prediction from sequence data is a crucial first step to understanding their impact on the environment. A variety of bacteriophage prediction tools have been developed over the years. They differ in algorithmic approach, results, and ease of use. We, therefore, developed "What the Phage" (WtP), an easy-to-use and parallel multitool approach for phage prediction combined with an annotation and classification downstream strategy, thus supporting the user's decision-making process by summarizing the results of the different prediction tools in charts and tables. WtP is reproducible and scales to thousands of datasets through a workflow manager (Nextflow). WtP is freely available under a GPL-3.0 license (https://github.com/replikation/What_the_Phage).

Safety-Stock: Predicting the demand for supplies in Brazilian hospitals during the COVID-19 pandemic.

Many challenges lie ahead when dealing with COVID-19, not only related to the acceleration of the pandemic, but also to the prediction of personal protective equipment sets consumption to accommodate the explosive demand. Due to this situation of uncertainty, hospital administration encourages the excess stock of these materials, over-stocking products in some hospitals, and provoking shortages in others. The number of available personal protective equipment sets is one of the three main factors that limit the number of patients at a hospital, as well as the number of available beds and the number of professionals per shift. In this scenario, we developed an easy-to-use expert system to predict the demand for personal protective equipment sets in hospitals during the COVID-19 pandemic, which can be updated in real-time for short term planning. For this system, we propose a naive statistical modeling which combines historical data of the consumption of personal protective equipment sets by hospitals, current protocols for their uses and epidemiological data related to the disease, to build predictive models for the demand for personal protective equipment in Brazilian hospitals during the pandemic. We then embed this modeling in the free Safety-Stock system, which provides useful information for the hospital, especially the safety-stock level and the prediction of consumption/demand for each personal protective equipment set over time. Considering our predictions, a hospital may have its needs related to specific personal protective equipment sets estimated, taking into account its historical stock levels and possible scheduled purchases. The tool allows for adopting strategies to control and keep the stock at safety levels to the demand, mitigating the risk of stock-out. As a direct consequence, it also enables the interchange and cooperation between hospitals, aiming to maximize the availability of equipment during the pandemic.

[Risk communication for protection against hazardous substances in the workplace]. / Risikokommunikation zum Schutz vor Gefahrstoffen am Arbeitsplatz.

Hazardous substances are ubiquitous in the world of work. Employees from all sectors are exposed to different risks when working with hazardous substances. This also applies to people who do not directly handle hazardous substances (bystanders). Risk communication in occupational safety and health takes place at different levels. The spectrum ranges from large to small companies, safety experts, company physicians, works and staff council representatives to employees and the general public. Risk communication in occupational safety and health along the supply chain aims to create risk awareness among manufacturers, employers and employees to reduce risky behaviour and to encourage risk-reducing behaviour.Instruments of risk communication are explained in this article and considered with regard to their effectiveness. This affects binding instruments in the European internal market such as the hazard label or the safety data sheet (SDS). At the level of the Hazardous Substances Ordinance, they are the Technical Rules for Hazardous Substances (TRGS), limit values, the Easy-to-use Workplace Control Scheme for Hazardous Substances (EMKG) and, as a creative instrument, objects of the "DASA Working World Exhibition" in Dortmund, Germany. The results of the paper show that an adaptation of the instruments is necessary, especially for small and micro-enterprises, in order to find the appropriate entry point into risk assessment. Often, the existing instruments are not known, too extensive or difficult to understand. Recommendations for action are necessary that make it easy to get started with risk assessment. Existing scientific studies tend to focus on the deficits in risk assessment rather than on the development of efficient ways to communicate risks. Further analyses of the needs of the different target groups are necessary for appropriate risk communication.

A New, Quick, and Simple Protocol to Evaluate Microalgae Polysaccharide Composition.

In this work, a new methodological approach, relying on the high specificity of enzymes in a complex mixture, was developed to estimate the composition of bioactive polysaccharides produced by microalgae, directly in algal cultures. The objective was to set up a protocol to target oligomers commonly known to be associated with exopolysaccharides' (EPS) nutraceutical and pharmaceutical activities (i.e., rhamnose, fucose, acidic sugars, etc.) without the constraints classically associated with chromatographic methods, while maintaining a resolution sufficiently high to enable their monitoring in the culture system. Determination of the monosaccharide content required the application of acid hydrolysis (2 M trifluoroacetic acid) followed by NaOH (2 M) neutralization. Quantification was then carried out directly on the fresh hydrolysate using enzyme kits corresponding to the main monosaccharides in a pre-determined composition of the polysaccharides under analysis. Initial results showed that the enzymes were not sensitive to the presence of TFA and NaOH, so the methodology could be carried out on fresh hydrolysate. The limits of quantification of the method were estimated as being in the order of the log of nanograms of monosaccharides per well, thus positioning it among the chromatographic methods in terms of analytical performance. A comparative analysis of the results obtained by the enzymatic method with a reference method (high-performance anion-exchange chromatography) confirmed good recovery rates, thus validating the closeness of the protocol. Finally, analyses of raw culture media were carried out and compared to the results obtained in miliQ water; no differences were observed. The new approach is a quick, functional analysis method allowing routine monitoring of the quality of bioactive polysaccharides in algal cultures grown in photobioreactors.

Whole blood ristocetin-induced platelet impedance aggregometry does not reflect clinical severity in patients with type 1 von Willebrand disease.

BACKGROUND: The haemorrhagic phenotype in patients with von Willebrand disease (VWD) is heterogeneous, and assays of von Willebrand factor ristocetin cofactor activity (VWF:RCo) do not always reflect clinical severity, especially in those individuals classed as type 1 VWD. Recent studies have shown that whole blood ristocetin-induced platelet agglutination (WB-RIPA) using an easy-to-use analyzer, Multiplate® platelet impedance technique, could be informative as a diagnostic test in VWD, although inconsistencies were evident in patients with the type 1 disorder, possibly associated with clinical symptoms. AIM: To investigate the relationship between WB-RIPA, bleeding scores (BS) and VWF-related measurements in type 1 VWD. METHODS: WB-RIPA assay using the Multiplate® was performed using whole blood from 55 patients with type 1 VWD. BS was determined using a standardized questionnaire. RESULTS: WB-RIPA values were significantly lower in type 1 VWD than in healthy controls (P < 0.0001). Weak correlations were apparent between WB-RIPA and VWF:RCo or VWF antigen (VWF:Ag; r = 0.22 or 0.28, respectively). There were significant differences in VWF:RCo (P = 0.036) and VWF:Ag (P = 0.0013) between patients with BS ≥4 (defined as abnormal bleeding tendency) and BS <4 (defined as no abnormal bleeding tendency), respectively. However, no significant difference was observed in WB-RIPA between the BS ≥4 group and BS <4 group. Overall, VWD patients with a WB-RIPA level >70 U did not seem to have an abnormal bleeding tendency, but low levels of WB-RIPA did not correlate with BS. CONCLUSION: WB-RIPA did not reflect clinical severity in type 1 VWD patients.

Patient preference for a maintenance inhaler in chronic obstructive pulmonary disease: a comparison of Breezhaler and Respimat.

BACKGROUND: Good compliance in chronic obstructive pulmonary disease (COPD) is of 'paramount importance' in reducing the occurrence of acute exacerbations, hospitalisation and mortality and in improving quality of life. However, a number of studies have confirmed that long-term compliance is low and often associated with difficulties in handling maintenance inhalers. Therefore, the easier an inhaler is to use, the more likely the patient will comply with handling instructions and so, optimise control of the condition. A research study was undertaken comparing the maintenance inhalers BreezhalerTM (BH-available in combination with Ultibro, Seebri and Onbrez from Novartis) and RespimatTM (RM-available in combination with Spiriva, Spiolto and Striverdi from Boehringer Ingelheim). METHODS: The research was conducted among 240 maintenance inhaler-naive participants who before handling the inhalers were asked to indicate how important they felt it was that an inhaler offered each of a list of 22 handling-related attributes. They then handled each inhaler on three separate occasions familiarising themselves with the correct handling procedure by consulting respective 'Instructions for use' and short training videos. Following the handling process, participants rated the individual inhaler against each of the 22 attributes and finally expressed their preference between the two on a number of key handling-related attributes and indicated which they preferred overall. RESULTS: A significant majority of participants preferred BH to RM overall. BH was rated statistically superior on 20 of the 22 handling-related attributes particularly those participants rated most highly including dosing confidence, 'easy to use' and 'easy to learn'. CONCLUSIONS: Significantly more participants were confident that BH would deliver a full dose of medication and was easier to learn and use. These attributes are crucial for achieving improved patient compliance. As a result, BH offers an opportunity for improved symptom control in the maintenance treatment of COPD.

Long-Lasting and Easy-to-Use Rewritable Paper Fabricated by Printing Technology.

Nowadays, urged by the high demand to reduce paper consumption, rewritable paper receives more and more attention. However, it is a great challenge to conveniently fabricate the rewritable paper which has long legible time of information and is easy to use simultaneously. Here, we report a new type of long-lasting rewritable paper based on color-memorizing thermochromic dye and photothermal-converting toner, which is fabricated by a two-step printing process. The rewritable paper demonstrates excellent rewriting performances (legible time > 6 months and reversibility > 100 times). The thermochromic effect is based on a temperature-driven phase change mechanism, accompanied by a lactone ring tautomerism of crystal violet lactone. The color of the rewritable paper rapidly changes from blue to colorlessness when the temperature is higher than 65 °C, and the colorless state can be maintained at room temperature. The color returns to blue when the temperature is lower than -10 °C. By using an electrothermal pen, a thermal printer, and near infrared (NIR) light, characters and images with high resolution can be handwritten, thermal-printed, and photoprinted on the rewritable paper. The written/printed information can be cleaned under lower temperature or can be quickly erased by NIR light. This rewritable paper is easy for large-scale production and will have promising opportunities in practical applications, such as long-lasting information recording and reading, rewritable label, reprintable displays, and so on.

Bringing Human Diversity into Design Processes Through Empathic Modelling.

Most products are developed while adapting to requirements from industrial production and logistics. To break that trend and design for people, we suggest focusing on those who put the strongest demands on the final solution. They cannot compensate for bad design solutions and are thereby, like sniffing dogs, guiding designers to meet peoples' needs. We always use a combination of empathic modelling and involvement of people with reduced functions to find new solutions to the problems a product is supposed to solve. We have used this method in the teaching of Universal design at different universities for more than ten years. The students find the exercises to be a very entertaining eye-opener leading to development of empathy for human diversity all while the level of innovation in their design work increase. To constantly make design students understand barriers that can occur due to bad design solutions we utilize a toolbox simulating different kinds of functional ability. It also includes a handbook that describes workshops, evaluation methods and design processes that can be performed using the tools. The goal is to guide efficient, innovative and inclusive design processes. By simulating diversity among people, the designer can interpret the needs of different users and use that as a starting point and for evaluating design solutions during the creative process.

Construction of an easy-to-use CRISPR-Cas9 system by patching a newly designed EXIT circuit.

BACKGROUND: Plasmid-borne genetic editing tools, including the widely used CRISPR-Cas9 system, have greatly facilitated bacterial programming to obtain novel functionalities. However, the lack of effective post-editing plasmid elimination methods impedes follow-up genetic manipulation or application. Conventional strategies including exposure to physical and chemical treatments, or exploiting temperature-sensitive replication origins have several drawbacks (e.g., they are limited for efficiency and are time-consuming). Therefore, the demand is apparent for easy and rapid elimination of the tool plasmids from their bacterial hosts after genetic manipulation. RESULTS: To bridge this gap, we designed a novel EXIT circuit with the homing endonuclease, which can be exploited for rapid and efficient elimination of various plasmids with diverse replication origins. As a proof of concept, we validated the EXIT circuit in Escherichia coli by harnessing homing endonuclease I-SceI and its cleavage site. When integrated into multiple plasmids with different origins, the EXIT circuit allowed them to be eliminated from the host cells, simultaneously. By combining the widely used plasmid-borne CRISPR-Cas9 system and the EXIT circuit, we constructed an easy-to-use CRISPR-Cas9 system that eliminated the Cas9- and the single-guide RNA (sgRNA)-encoding plasmids in one-step. Within 3 days, we successfully constructed an atrazine-degrading E. coli strain, thus further demonstrating the advantage of this new CRISPR-Cas9 system for bacterial genome editing. CONCLUSIONS: Our novel EXIT circuit, which exploits the homing endonuclease I-SceI, enables plasmid(s) with different replication origins to be eliminated from their host cells rapidly and efficiently. We also developed an easy-to-use CRISPR-Cas9 system with the EXIT circuit, and this new system can be widely applied to bacterial genome editing.

An easy-to-use scoring index to determine severity of mitral regurgitation by 2D echocardiography in clinical practice.

PURPOSE: Mitral regurgitation (MR) grading by two-dimensional transthoracic echocardiography is challenging, but important to determine the best treatment strategy in patients with MR. Current guidelines advocate an integrative approach, although no recommendation is provided on how to do so. An easy-to-use index will be helpful for standardized and reproducible MR grading. METHODS: Eleven echocardiographic parameters were retrospectively evaluated in 145 patients with moderate or severe MR. Parameters were scored positive or negative for severe MR, where expert panel consensus reading was considered as the reference standard. Logistic regression was performed, and adjusted coefficients were used to create a risk score for severe MR per patient (ROSE-index). The best cutoff with corresponding predictive values was determined. RESULTS: Eighty-two percent of all parameters could be determined. Multivariable analysis revealed five parameters that remained significant predictors for severe MR: morphology, jet characteristics, vena contracta, systolic reversal, and left ventricular dimensions. With different weighing, a total score of 8 could be obtained. Median total ROSE-index score for moderate (2.0) and severe MR (5.0) did significantly differ. The cutoff score (≥4) revealed sensitivity 0.84 and specificity 0.83 to diagnose severe MR. Negative predictive value was 100% for score 0 and 1; score 6-8 showed a 100% positive predictive value. Inter- and intra-observer agreements were excellent (K-values >0.80). CONCLUSION: Here, we propose an easy-to-use tool for integrated analysis of guideline parameters to assess MR severity. Using this so-called ROSE-index revealed reliable and reproducible assessment of severe MR (cutoff≥4) that may be helpful for clinical decision making.

Development and validation of the short version of the diabetes obstacles questionnaire (DOQ-30) in six European countries.

BACKGROUND: Patients with type 2 diabetes reveal different obstacles in living with the disease. The EGPRN initiated a qualitative research EUROBSTACLE to create a broadly conceptualized diabetes-related quality of life (DR-QoL) instrument. It led to the development of the diabetes obstacle questionnaire (DOQ), a five-point Likert-scaled measure, consisting of 78 items in eight scales. OBJECTIVES: To develop and validate a short, easy-to-use version of the DOQ. METHODS: A cross-sectional study with the DOQ was carried out. Participants answered the DOQ and GPs added some clinical data from their medical records. Data of 853 patients from Belgium, France, Estonia, Serbia, Slovenia, and Turkey were included in the analysis. The selection of items for the short version of the DOQ was achieved with exploratory factor analysis (EFA). Construct validity was proved with EFA and Pearson correlations between the DOQ and the new DOQ-30. Internal reliability was established with Cronbach's alpha. RESULTS: DOQ-30 resulted in 30 items in nine subscales. It explained 49.8% of items' variance. It shows a considerable good internal reliability and construct validity. CONCLUSION: The DOQ-30 is a five-point Likert-scaled broadly conceptualized measure of DR-QoL. It addresses a variety of obstacles, such as social, psychological, cognitive and behavioural. The DOQ-30 is ready for implementation in general practice and research in Europe as a valuable instrument to assess DR-QoL.

Easy-to-use rapid gene amplification method for direct detection of RNA and DNA viruses in sera and feces from various animals.

The development of rapid and simple gene amplification tests is required for detection of pathogens to prevent transmission of infectious diseases between animals or from animals to humans. An easy-to-use rapid gene amplification method that can directly detect RNA and DNA viruses in clinical samples was developed. This method is based on combining loop-mediated isothermal amplification (LAMP) or reverse transcription-LAMP (RT-LAMP) and RNA GEM Tissue, a thermophilic enzyme that extracts nucleic acid by quickly digesting proteins and ribonucleases. The authors named these methods GEM LAMP and GEM RT-LAMP. These methods were able to detect viral DNA and RNA within 70 min in a single tube using only a water bath. The detection capacities were 10-100-fold more sensitive than those of previously established LAMP and RT-LAMP methods. The GEM LAMP and GEM RT-LAMP methods were used to detect macroscopically the presence of DNA and RNA viruses in sera or fecal samples from cattle, pigs, horses, dolphins, penguins, and sea lions using SYBR green I. The GEM LAMP and GEM RT-LAMP methods thus have considerable versatility as tools for detecting pathogens and are applicable to basic human and veterinary medicine, environmental hygiene, and point-of-care-testing.