Drugst.One - a plug-and-play solution for online systems medicine and network-based drug repurposing.

In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities. To tackle these challenges, we introduce Drugst.One, a platform that assists specialized computational medicine tools in becoming user-friendly, web-based utilities for drug repurposing. With just three lines of code, Drugst.One turns any systems biology software into an interactive web tool for modeling and analyzing complex protein-drug-disease networks. Demonstrating its broad adaptability, Drugst.One has been successfully integrated with 21 computational systems medicine tools. Available at https://drugst.one, Drugst.One has significant potential for streamlining the drug discovery process, allowing researchers to focus on essential aspects of pharmaceutical treatment research.

Inference of differential key regulatory networks and mechanistic drug repurposing candidates from scRNA-seq data with SCANet.

MOTIVATION: The reconstruction of small key regulatory networks that explain the differences in the development of cell (sub)types from single-cell RNA sequencing is a yet unresolved computational problem. RESULTS: To this end, we have developed SCANet, an all-in-one package for single-cell profiling that covers the whole differential mechanotyping workflow, from inference of trait/cell-type-specific gene co-expression modules, driver gene detection, and transcriptional gene regulatory network reconstruction to mechanistic drug repurposing candidate prediction. To illustrate the power of SCANet, we examined data from two studies. First, we identify the drivers of the mechanotype of a cytokine storm associated with increased mortality in patients with acute respiratory illness. Secondly, we find 20 drugs for eight potential pharmacological targets in cellular driver mechanisms in the intestinal stem cells of obese mice. AVAILABILITY AND IMPLEMENTATION: SCANet is a free, open-source, and user-friendly Python package that can be seamlessly integrated into single-cell-based systems medicine research and mechanistic drug discovery.

Cancer driver drug interaction explorer.

Cancer is a heterogeneous disease characterized by unregulated cell growth and promoted by mutations in cancer driver genes some of which encode suitable drug targets. Since the distinct set of cancer driver genes can vary between and within cancer types, evidence-based selection of drugs is crucial for targeted therapy following the precision medicine paradigm. However, many putative cancer driver genes can not be targeted directly, suggesting an indirect approach that considers alternative functionally related targets in the gene interaction network. Once potential drug targets have been identified, it is essential to consider all available drugs. Since tools that offer support for systematic discovery of drug repurposing candidates in oncology are lacking, we developed CADDIE, a web application integrating six human gene-gene and four drug-gene interaction databases, information regarding cancer driver genes, cancer-type specific mutation frequencies, gene expression information, genetically related diseases, and anticancer drugs. CADDIE offers access to various network algorithms for identifying drug targets and drug repurposing candidates. It guides users from the selection of seed genes to the identification of therapeutic targets or drug candidates, making network medicine algorithms accessible for clinical research. CADDIE is available at https://exbio.wzw.tum.de/caddie/ and programmatically via a python package at https://pypi.org/project/caddiepy/.

Percutaneous CT-Guided Abdominal and Pelvic Biopsies: Comparison of an Electromagnetic Navigation System and CT Fluoroscopy.

PURPOSE: To compare electromagnetic navigation (EMN) with computed tomography (CT) fluoroscopy for guiding percutaneous biopsies in the abdomen and pelvis. MATERIALS AND METHODS: A retrospective matched-cohort design was used to compare biopsies in the abdomen and pelvis performed with EMN (consecutive cases, n = 50; CT-Navigation; Imactis, Saint-Martin-d'Hères, France) with those performed with CT fluoroscopy (n = 100). Cases were matched 1:2 (EMN:CT fluoroscopy) for target organ and lesion size (±10 mm). RESULTS: The population was well-matched (age, 65 vs 65 years; target size, 2.0 vs 2.1 cm; skin-to-target distance, 11.4 vs 10.7 cm; P > .05, EMN vs CT fluoroscopy, respectively). Technical success (98% vs 100%), diagnostic yield (98% vs 95%), adverse events (2% vs 5%), and procedure time (33 minutes vs 31 minutes) were not statistically different (P > .05). Operator radiation dose was less with EMN than with CT fluoroscopy (0.04 vs 1.2 µGy; P < .001), but patient dose was greater (30.1 vs 9.6 mSv; P < .001) owing to more helical scans during EMN guidance (3.9 vs 2.1; P < .001). CT fluoroscopy was performed with a mean of 29.7 tap scans per case. In 3 (3%) cases, CT fluoroscopy was performed with gantry tilt, and the mean angle out of plane for EMN cases was 13.4°. CONCLUSIONS: Percutaneous biopsies guided by EMN and CT fluoroscopy were closely matched for technical success, diagnostic yield, procedure time, and adverse events in a matched cohort of patients. EMN cases were more likely to be performed outside of the gantry plane. Radiation dose to the operator was higher with CT fluoroscopy, and patient radiation dose was higher with EMN. Further study with a wider array of procedures and anatomic locations is warranted.

Percutaneous Lung Biopsy with Pleural and Parenchymal Blood Patching: Results and Complications from 1,112 Core Biopsies.

PURPOSE: To evaluate the outcomes of computed tomography (CT) fluoroscopy-guided core lung biopsies with emphasis on diagnostic yield, complications, and efficacy of parenchymal and pleural blood patching to avoid chest tube placement. METHODS: This is a single-center retrospective analysis of CT fluoroscopy-guided percutaneous core lung biopsies between 2006 and 2020. Parenchymal blood patching during introducer needle withdrawal was performed in 74% of cases as a preventive measure, and pleural blood patching was the primary salvage maneuver for symptomatic or growing pneumothorax in 60 of 83 (72.2%) applicable cases. RESULTS: A total of 1,029 patients underwent 1,112 biopsies (532 men; mean age, 66 years; 38.6%, history of emphysema; lesion size, 16.7 mm). The diagnostic yield was 93.6% (1,032/1,103). Fewer complications requiring intervention were observed in patients who underwent parenchymal blood patching (5.7% vs 14.2%, P < .001). Further intervention was required in 83 of 182 pneumothorax cases, which included the following: (a) pleural blood patch (5.4%, 60/1,112), (b) chest tube placement without a pleural blood patch attempt (1.5%, 17/1,112), and (c) simple aspiration (0.5%, 6/1,112). Pleural blood patch as monotherapy was successful in 83.3% (50/60) of cases without need for further intervention. The overall chest tube rate was 2.6% (29/1,112). Emphysema was the only significant risk factor for complications requiring intervention (P ≤ .001). CONCLUSIONS: Parenchymal blood patching during introducer needle withdrawal decreased complications requiring intervention. Salvage pleural blood patching reduced the frequency of chest tube placement for pneumothorax.

How to Create a Great Radiology Report.

The radiology report represents the sum of a radiologist's highest level of synthesis and insight into a patient's condition. It is the most important product that radiologists generate to help direct patient care. Despite the self-evident importance of clear and effective radiology reporting, radiologists usually receive little or no formal reporting education during training. Instead, it is learned in a piecemeal and often indirect fashion through occasional correction and imitating the reports of other radiologists. The audience of the radiology report extends far beyond the ordering provider and includes patients and their families, medical support staff, subspecialty providers, other radiologists, and research interests. Creating a report that fulfills the needs of this diverse group is a formidable if not quixotic ambition. However, there are certain key principles to reporting the imaging findings, impression, and recommendations that serve as a guide and promote careful consideration about how reports are understood. The findings section should emphasize short, informative, and factual observations while avoiding inappropriate interpretation, excessive use of terms of perception, and redundancy. The impression is the thoughtful synthesis of the meaning of the findings leading to a diagnosis, a differential diagnosis, and management recommendations. Creating a clear and impactful impression allows radiologists to provide the highest level of clinical care and direction but takes time and effort beyond simply restating the findings. The impression should use language that is understandable, memorable, and actionable. Reporting skills require ongoing attention and must adapt to the evolving practice patterns and communication styles in medicine. ©RSNA, 2020.

Safety and Efficacy of Minimally Invasive Acetabular Stabilization for Periacetabular Metastatic Disease with Thermal Ablation and Augmented Screw Fixation.

PURPOSE: To evaluate minimally invasive acetabular stabilization (MIAS) with thermal ablation and augmented screw fixation for impending or minimally displaced fractures of the acetabulum secondary to metastatic disease. MATERIALS AND METHODS: Between February 2011 and July 2014, 13 consecutive patients underwent thermal ablation, percutaneous screw fixation, and polymethyl methacrylate augmentation for impending or nondisplaced fractures of the acetabulum secondary to metastatic disease. Functional outcomes were evaluated before and after the procedure using the Musculoskeletal Tumor Society (MSTS) scoring system. Complications, hospital length of stay, and eligibility for chemotherapy and radiation therapy were assessed. RESULTS: All procedures were technically successful with no major periprocedural complications. The mean total MSTS score improved from 23% ± 11 before MIAS to 51% ± 21 after MIAS (P < .05). The mean MSTS pain scores improved from 0% (all) to 32% ± 22 after MIAS (P < .05). The mean MSTS walking ability score improved from 22% ± 19 to 55% ± 26 after MIAS (P < .05). Two complications occurred; a patient had a minimally displaced fracture of the superior pubic ramus at the site of repair but remained ambulatory, and septic arthritis was diagnosed in another patient 12 months after repair. The average length of hospital stay was 2 days ± 3.6; six patients were discharged within 24 hours of the procedure. All patients were eligible for chemotherapy and radiation therapy immediately after the procedure. CONCLUSIONS: MIAS is feasible, improves pain and mobility, and offers a minimally invasive alternative to open surgical reconstruction.

UVC Irradiation as a Surface Treatment of Polycarbonate to Generate Adhesion to Liquid Silicone Rubber in an Overmolding Process.

This study investigates the adhesion properties of polycarbonate (PC) and liquid silicone rubbers (LSR) through surface activation using ultraviolet C (UVC) radiation. While self-adhesive LSRs adhere easily to certain thermoplastic composites such as polybutylene terephthalate (PBT) and polyamides (PAs), bonding to PC typically requires surface treatment due to the lack of compatible functional groups. Previous methods like plasma or flame treatment have been effective, but the use of UVC radiation for surface activation remains unexplored. Through experiments, it was found that UVC surface activation, particularly with ozone-generating lamps, significantly enhances the peel strength between PC and self-adhesive LSRs. The study evaluates the impact of different irradiation times and lamp configurations on peel resistance, surface energy, and composite stability. Results show that UVC/ozone (wavelengths 254 nm and 185 nm) activation increases peel resistance, with distinct differences observed between LSR types. Additionally, the study examines the stability of UVC activation over time and under various storage conditions, highlighting its effectiveness for up to 36 months at room temperature. Furthermore, the relationship between surface energy and peel strength is analyzed, finding that UVC/ozone activation increases surface energy but does not consistently correlate with improved adhesion. The study concludes with a comparison of UVC/ozone activation to alternative surface treatment methods, emphasizing its advantages such as cost-effectiveness and stability while considering limitations regarding substrate compatibility and occupational safety aspects. Overall, UVC/ozone surface activation presents a promising approach for enhancing adhesion in PC-LSR composite systems and holds potential for applications across various industries.

CODEX: exploration of semantic changes between ontology versions.

Life science ontologies substantially change over time to meet the requirements of their users and to include the newest domain knowledge. Thus, an important task is to know what has been modified between two versions of an ontology (diff). This diff should contain all performed changes as compact and understandable as possible. We present CODEX (Complex Ontology Diff Explorer), a tool that allows determining semantic changes between two versions of an ontology, which users can interactively analyze in multiple ways.

Impact of ontology evolution on functional analyses.

MOTIVATION: Ontologies are used in the annotation and analysis of biological data. As knowledge accumulates, ontologies and annotation undergo constant modifications to reflect this new knowledge. These modifications may influence the results of statistical applications such as functional enrichment analyses that describe experimental data in terms of ontological groupings. Here, we investigate to what degree modifications of the Gene Ontology (GO) impact these statistical analyses for both experimental and simulated data. The analysis is based on new measures for the stability of result sets and considers different ontology and annotation changes. RESULTS: Our results show that past changes in the GO are non-uniformly distributed over different branches of the ontology. Considering the semantic relatedness of significant categories in analysis results allows a more realistic stability assessment for functional enrichment studies. We observe that the results of term-enrichment analyses tend to be surprisingly stable despite changes in ontology and annotation.

MRI for acute chest pain: current state of the art.

This article reviews the magnetic resonance imaging (MRI) and angiography (MRA) techniques, imaging findings, and evidence for evaluating patients with acute chest pain due to acute pulmonary embolus (PE), aortic dissection (AD), and myocardial infarction (MI). When computed tomographic angiography (CTA) is contraindicated, MRI and MRA are important alternative imaging modalities for diagnosis and management of patients with acute PE, AD, and MI. Familiarity with the techniques, imaging findings, and evidence is critical to safely and appropriately managing patients presenting with acute chest pain.

COnto-Diff: generation of complex evolution mappings for life science ontologies.

Life science ontologies evolve frequently to meet new requirements or to better reflect the current domain knowledge. The development and adaptation of large and complex ontologies is typically performed collaboratively by several curators. To effectively manage the evolution of ontologies it is essential to identify the difference (Diff) between ontology versions. Such a Diff supports the synchronization of changes in collaborative curation, the adaptation of dependent data such as annotations, and ontology version management. We propose a novel approach COnto-Diff to determine an expressive and invertible diff evolution mapping between given versions of an ontology. Our approach first matches the ontology versions and determines an initial evolution mapping consisting of basic change operations (insert/update/delete). To semantically enrich the evolution mapping we adopt a rule-based approach to transform the basic change operations into a smaller set of more complex change operations, such as merge, split, or changes of entire subgraphs. The proposed algorithm is customizable in different ways to meet the requirements of diverse ontologies and application scenarios. We evaluate the proposed approach for large life science ontologies including the Gene Ontology and the NCI Thesaurus and compare it with PromptDiff. We further show how the Diff results can be used for version management and annotation migration in collaborative curation.

Weathering of a Polyurethane-Based Gel Electrolyte.

A recently described flexible polyurethane electrolyte was artificially weathered at 25/50 °C and 50% r.h. in air and at 25 °C in a dry nitrogen atmosphere, each with and without UV irradiation. Different formulations and the polymer matrix, used as a reference, were weathered in order to investigate the influence of the amount of conductive lithium salt and the solvent propylene carbonate. The complete loss of the solvent at a standard climate was already observed after a few days, strongly influencing the conductivity and mechanical properties. The essential degradation mechanism appears to be the photo-oxidative degradation of the polyol's ether bonds, which leads to chain scission, oxidation products and negative changes in the mechanical and optical properties. A higher salt content has no effect on the degradation; however, the presence of propylene carbonate intensifies the degradation.

MC-Injection Molding with Liquid Silicone Rubber (LSR) and Acrylonitrile Butadiene Styrene (ABS) for Medical Technology.

The multicomponent injection molding of liquid silicone rubbers (LSR) with thermoplastics, such as polybutylene terephthalate (PBT) or polyamide (PA), is a state-of-the-art technique and is used in the manufacturing process for many components in the automotive industry and in the field of sanitary engineering. Standard thermoplastics, such as acrylonitrile butadiene styrene (ABS), cannot be bonded with silicone rubbers in injection molding because of their low heat deflection temperature. In this study, we investigated ABS grades approved for medical applications to show how dynamic mold heating and various pretreatment methods for thermoplastic surfaces can be used to produce ABS-LSR test specimens. In addition, such components' sterilization effect on the adhesive bond will be shown.

The Influence of Thermal and Mechanical Stress on the Electrical Conductivity of ITO-Coated Polycarbonate Films.

The influence of thermomechanical stress on the conductivity of indium tin oxide (ITO)-coated polycarbonate (PC) films was investigated. PC is the industry's standard material for window panes. ITO coatings on polyethylene terephthalate (PET) films are the main commercially available option; as such, most investigations refer to this combination. The investigations in this study aim to investigate the critical crack initiation strain at different temperatures and crack initiation temperatures for two different coating thicknesses and for a commercially available PET/ITO film for validation purposes. Additionally, the cyclic load was investigated. The results show the comparatively sensitive behavior of the PC/ITO films, with a crack initiation strain at room temperature of 0.3-0.4% and critical temperatures of 58 °C and 83 °C, with high variation depending on the film's thickness. Under thermomechanical loading, the crack initiation strain decreases with increasing temperatures.

Flexible Electrochromic Device on Polycarbonate Substrate with PEDOT:PSS and Color-Neutral TiO2 as Ion Storage Layer.

Electrochromic (EC) windows on glass for thermal and glare protection in buildings, often referred to as smart (dimmable) windows, are commercially available, along with rearview mirrors or windows in aircraft cabins. Plastic-based applications, such as ski goggles, visors and car windows, that require lightweight, three-dimensional (3D) geometry and high-throughput manufacturing are still under development. To produce such EC devices (ECDs), a flexible EC film could be integrated into a back injection molding process, where the films are processed into compact 3D geometries in a single automized step at a low processing time. Polycarbonate (PC) as a substrate is a lightweight and robust alternative to glass due to its outstanding optical and mechanical properties. In this study, an EC film on a PC substrate was fabricated and characterized for the first time. To achieve a highly transmissive and colorless bright state, poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) was used as the working electrode, while titanium dioxide (TiO2) was used as the counter electrode material. They were deposited onto ITO-coated PC films using dip- and slot-die coating, respectively. The electrodes were optically and electrochemically characterized. An ECD with a polyurethane containing gel electrolyte was investigated with regard to optical properties, switching speed and cycling behavior. The ECD exhibits a color-neutral and highly transmissive bright state with a visible light transmittance of 74% and a bluish-colored state of 64%, a fast switching speed (7 s/4 s for bleaching/coloring) and a moderately stable cycling behavior over 500 cycles with a decrease in transmittance change from 10%to 7%.

CT without borders: Comparison of diagnoses for abdominal pain from a teaching hospital in rural Kenya and a US academic medical center.

PURPOSE: Radiology global health opportunities are expanding as more hospitals in low- and middle-income countries utilize CT. This creates opportunities for global health program building, education, service, and research. This study determines the diagnostic yield and variety of abdominopelvic CT diagnoses for abdominal pain in a US academic medical center (UW) compared to a rural Kenyan teaching hospital (Tenwek). METHODS: A retrospective, cross-sectional sequential sample of 750 adults from both hospitals who underwent abdominopelvic CT for abdominal pain from February 2019 through July 2020 was obtained. Exclusion criteria were trauma, cancer staging, and recent hospitalization or surgery. Patient age, sex, comparison studies, use of contrast, known cancer diagnosis, and CT diagnoses were compared. Negative exam rate, acute abdomen diagnosis, and new cancer diagnosis were recorded. Statistical analysis was performed using R. RESULTS: 750 UW patients met inclusion criteria (mean age 53.3 ± 20 years; 442 women) and 750 Tenwek patients met inclusion criteria (mean age 52.5 ± 18 years; 394 women). 72% of UW patients had comparison imaging compared to 6% of Tenwek patients. 11% (83/750) of UW patients had a known cancer diagnosis compared to 1% (10/750) of Tenwek patients. 39% of UW patients had a negative exam compared to 23% of Tenwek patients (p < 0.001). 58% of UW patients had an acute abdomen diagnosis compared to 38% of Tenwek patients (p < 0.001). 10 of the 15 top acute abdomen diagnoses were shared, but in different order of frequency. Diagnoses unique to UW were diverticulitis, constipation, stercoral colitis, and epiploic appendagitis. Diagnoses unique to Tenwek were tuberculosis and hydatidosis. 3% of UW patients received a new cancer diagnosis (7/19 metastatic), compared to 40% of Tenwek patients (153/303 metastatic) (p < 0.001). CONCLUSION: For adults undergoing CT for abdominal pain, there are differences in the prevalence of abdominal pain diagnoses, new cancer diagnosis, and negative exam rate between the rural Kenyan teaching hospital and the US academic medical center.

Drugst.One - A plug-and-play solution for online systems medicine and network-based drug repurposing.

In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities. To tackle these challenges, we introduce Drugst.One, a platform that assists specialized computational medicine tools in becoming user-friendly, web-based utilities for drug repurposing. With just three lines of code, Drugst.One turns any systems biology software into an interactive web tool for modeling and analyzing complex protein-drug-disease networks. Demonstrating its broad adaptability, Drugst.One has been successfully integrated with 21 computational systems medicine tools. Available at https://drugst.one, Drugst.One has significant potential for streamlining the drug discovery process, allowing researchers to focus on essential aspects of pharmaceutical treatment research.