Algorithm for the Pruning of Synthesis Graphs.

Synthesis route planning is in the core of chemical intelligence that will power the autonomous chemistry platforms. In this task, we rely on algorithms to generate possible synthesis routes with the help of retro- and forward-synthetic approaches. Generated synthesis routes can be merged into a synthesis graph which represents theoretical pathways to the target molecule. However, it is often required to modify a synthesis graph due to typical constraints. These constraints might include "undesirable substances", e.g., an intermediate that the chemist does not favor or substances that might be toxic. Consequently, we need to prune the synthesis graph by the elimination of such undesirable substances. Synthesis graphs can be represented as directed (not necessarily acyclic) bipartite graphs, and the pruning of such graphs in the light of a set of undesirable substances has been an open question. In this study, we present the Synthesis Graph Pruning (SGP) algorithm that addresses this question. The input to the SGP algorithm is a synthesis graph and a set of undesirable substances. Furthermore, information for substances is provided as metadata regarding their availability from the inventory. The SGP algorithm operates with a simple local rule set, in order to determine which nodes and edges need to be eliminated from the synthesis graph. In this study, we present the SGP algorithm in detail and provide several case studies that demonstrate the operation of the SGP algorithm. We believe that the SGP algorithm will be an essential component of computer aided synthesis planning.

A Workflow of Integrated Resources to Catalyze Network Pharmacology Driven COVID-19 Research.

In the event of an outbreak due to an emerging pathogen, time is of the essence to contain or to mitigate the spread of the disease. Drug repositioning is one of the strategies that has the potential to deliver therapeutics relatively quickly. The SARS-CoV-2 pandemic has shown that integrating critical data resources to drive drug-repositioning studies, involving host-host, host-pathogen, and drug-target interactions, remains a time-consuming effort that translates to a delay in the development and delivery of a life-saving therapy. Here, we describe a workflow we designed for a semiautomated integration of rapidly emerging data sets that can be generally adopted in a broad network pharmacology research setting. The workflow was used to construct a COVID-19 focused multimodal network that integrates 487 host-pathogen, 63 278 host-host protein, and 1221 drug-target interactions. The resultant Neo4j graph database named "Neo4COVID19" is made publicly accessible via a web interface and via API calls based on the Bolt protocol. Details for accessing the database are provided on a landing page (https://neo4covid19.ncats.io/). We believe that our Neo4COVID19 database will be a valuable asset to the research community and will catalyze the discovery of therapeutics to fight COVID-19.

A Workflow of Integrated Resources to Catalyze Network Pharmacology Driven COVID-19 Research.

MOTIVATION: In the event of an outbreak due to an emerging pathogen, time is of the essence to contain or to mitigate the spread of the disease. Drug repositioning is one of the strategies that has the potential to deliver therapeutics relatively quickly. The SARS-CoV-2 pandemic has shown that integrating critical data resources to drive drug-repositioning studies, involving host-host, hostpathogen and drug-target interactions, remains a time-consuming effort that translates to a delay in the development and delivery of a life-saving therapy. RESULTS: Here, we describe a workflow we designed for a semi-automated integration of rapidly emerging datasets that can be generally adopted in a broad network pharmacology research setting. The workflow was used to construct a COVID-19 focused multimodal network that integrates 487 host-pathogen, 74,805 host-host protein and 1,265 drug-target interactions. The resultant Neo4j graph database named "Neo4COVID19" is accessible via a web interface and via API calls based on the Bolt protocol. We believe that our Neo4COVID19 database will be a valuable asset to the research community and will catalyze the discovery of therapeutics to fight COVID-19. AVAILABILITY: https://neo4covid19.ncats.io.

Penile pyoderma gangrenosum.

A 70-year-old man presented with indurated penile ulcers of 1-month duration. Initial biopsy was reported as chronic ulcer. A repeat biopsy done due to inadequate response to doxycycline showed features of pyoderma gangrenosum. The ulcer healed with a course of steroids and has not recurred till date.

Psychosocial outcomes following electroconvulsive therapy in a community setting: retrospective chart review with 2-year follow-up.

OBJECTIVE: Electroconvulsive therapy (ECT) continues to be one of the most effective biological therapies for patients with mood disorders. Numerous studies address clinical response; however, few have examined psychosocial or occupational outcomes following ECT, especially in community settings. This study aimed to examine these outcomes in short- and long-term naturalistic follow-up of ECT conducted in a community hospital. METHODS: A retrospective chart review was conducted of all patients who received ECT at Ridge Meadows Hospital in Maple Ridge, British Columbia, between January 1997 and December 2003. Charts were evaluated with the Clinical Global Impression (CGI), Global Assessment of Functioning, and Social and Occupational Functioning Assessment Scales prior to ECT and at 6 months, 1 year, and 2 years post-ECT. RESULTS: A total of 90 patients with mood disorders underwent ECT; 86.5% were rated on the CGI as "markedly ill" to "among the most extremely ill" at baseline. All clinical ratings improved at every follow-up point, and by the end of 24 months, 56.6% of patients were rated as "much improved" or "very much improved" on the CGI. Similarly, the measures of psychosocial functioning also showed significant improvement throughout the follow-up period. CONCLUSIONS: These findings show that substantial and meaningful improvement occurred in clinical and psychosocial outcomes after ECT conducted in a community hospital. These changes were robust and stable over the 2-year follow-up period. Limitations of the study include the retrospective ratings, the open-label use of ECT, and the naturalistic treatment in follow-up.

Anatomic and hemodynamic imaging using a new vector phased-array intracardiac catheter.

BACKGROUND: We used a new vector, phased-array intracardiac catheter (AcuNav) with complete 2-dimensional imaging and Doppler capabilities to describe a systematic approach for a detailed anatomic and hemodynamic cardiac assessment. METHODS: In 14 dogs, the intracardiac echocardiographic catheter was inserted through an 11F venous access and placed in the right side of the heart to perform a comprehensive ultrasound examination of the heart. RESULTS: Imaging was successful in all dogs. All 4 cardiac chambers and valves were imaged clearly in multiple orientations. Additional structures seen included the vena cavae, coronary sinus, right and left appendages, interarterial septum, coronary arteries, and all 4 pulmonary veins. Intra-abdominal structures, such as the aorta, liver, and hepatic veins were also visualized. A complete Doppler examination of intracardiac and paracardiac flows was also possible. CONCLUSION: AcuNav is a unique intracardiac imaging device, which allows comprehensive structural and functional cardiac assessment.