Chemical Space Mimicry for Drug Discovery

We describe a new library generation method, Machine-based Identification of Molecules Inside Characterized Space (MIMICS), that generates sets of molecules inspired by a text-based input. MIMICS-generated libraries were found to preserve distributions of properties while simultaneously increasing structural diversity. Newly identified MIMICS-generated compounds were found to be bioactive as inhibitors of specific components of the unfolded protein response (UPR) and the VEGFR2 pathway in cell-based assays, thus confirming the applicability of this methodology toward drug design applications. Wider application of MIMICS could facilitate the efficient utilization of chemical space

Proportion and associated risk ratio of complication classes for the young compared to old adult with ARDS.

Proportion and associated risk ratio of complication classes for the young compared to old adult with ARDS.</p

Number and percentage of patients per Elixhauser comorbidities for young adult patients with ARDS and non severe young adult patients.

Risk ratio associated in uni-variable analysis for the sub population which had previous hospital visits and considering only the ICD code related to those previous visits (one year and– 14 before the admission). (DOCX)</p

Flow chart.

Distribution of patients per group (y.o. = years old).</p

Name, city, country, number of hospitals per HS, number of beds and inpatient discharges/year per HS.

Name, city, country, number of hospitals per HS, number of beds and inpatient discharges/year per HS.</p

Number and percentage of patients per age groups, per sex, per Elixhauser comorbidities for all groups.

(DOCX)</p

Elixhauser comorbidities.

(DOCX)</p

Number and percentage of patients per age groups, per sex, per Elixhauser comorbidities for young adult patients with ARDS and non severe young adult patients.

Risk ratio associated in uni- and multivariable analysis.</p

Descriptions of the parent category ICD-10 diagnosis codes mapped to each condition of the Elixhauser Comorbidity Index.

Notes: 1. Complicated and uncomplicated diabetes were combined as one condition. Likewise, complicated and uncomplicated hypertension were combined as one condition. 2. ICD-10 descriptions were curated using the icd R package [1]. Supplemental Citation 1. Wasey JO, Frank SM, Rehman MA. icd: Efficient Computation of Comorbidities from ICD Codes Using Sparse Matrix Multiplication in R. Journal of Statistical Software. 2018. Available: https://jackwasey.github.io/icd/articles/efficiency-prebuilt.pdf (PDF)</p

Study Population Characteristics.

Few studies examining the patient outcomes of concurrent neurological manifestations during acute COVID-19 leveraged multinational cohorts of adults and children or distinguished between central and peripheral nervous system (CNS vs. PNS) involvement. Using a federated multinational network in which local clinicians and informatics experts curated the electronic health records data, we evaluated the risk of prolonged hospitalization and mortality in hospitalized COVID-19 patients from 21 healthcare systems across 7 countries. For adults, we used a federated learning approach whereby we ran Cox proportional hazard models locally at each healthcare system and performed a meta-analysis on the aggregated results to estimate the overall risk of adverse outcomes across our geographically diverse populations. For children, we reported descriptive statistics separately due to their low frequency of neurological involvement and poor outcomes. Among the 106,229 hospitalized COVID-19 patients (104,031 patients ≥18 years; 2,198 patients </div