Gypsum-DL: an open-source program for preparing small-molecule libraries for structure-based virtual screening

Computational techniques such as structure-based virtual screening require carefully prepared 3D models of potential small-molecule ligands. Though powerful, existing commercial programs for virtual-library preparation have restrictive and/or expensive licenses. Freely available alternatives, though often effective, do not fully account for all possible ionization, tautomeric, and ring-conformational variants. We here present Gypsum-DL, a free, robust open-source program that addresses these challenges. As input, Gypsum-DL accepts virtual compound libraries in SMILES or flat SDF formats. For each molecule in the virtual library, it enumerates appropriate ionization, tautomeric, chiral, cis/trans isomeric, and ring-conformational forms. As output, Gypsum-DL produces an SDF file containing each molecular form, with 3D coordinates assigned. To demonstrate its utility, we processed 1558 molecules taken from the NCI Diversity Set VI and 56,608 molecules taken from a Distributed Drug Discovery (D3) combinatorial virtual library. We also used 4463 high-quality protein-ligand complexes from the PDBBind database to show that Gypsum-DL processing can improve virtual-screening pose prediction. Gypsum-DL is available free of charge under the terms of the Apache License, Version 2.0

Variation of the cochlear anatomy and cochlea duct length: analysis with a new tablet-based software

PURPOSE In cochlear implantation, thorough preoperative planning together with measurement of the cochlear duct length (CDL) assists in choosing the correct electrode length. For measuring the CDL, different techniques have been introduced in the past century along with the then available technology. A tablet-based software offers an easy and intuitive way to visualize and analyze the anatomy of the temporal bone, its proportions and measure the CDL. Therefore, we investigated the calculation technique of the CDL via a tablet-based software on our own cohort retrospectively. METHODS One hundred and eight preoperative computed tomography scans of the temporal bone (slice thickness < 0.7~mm) of already implanted FLEX28™ and FLEXSOFT™ patients were found eligible for analysis with the OTOPLAN software. Measurements were performed by two trained investigators independently. CDL, angular insertion depth (AID), and cochlear coverage were calculated and compared between groups of electrode types, sex, sides, and age. RESULTS Mean CDL was 36.2 ± 1.8~mm with significant differences between sex (female: 35.8 ± 0.3~mm; male: 36.5 ± 0.2~mm; p = 0.037), but none concerning side or age. Differences in mean AID (FLEX28: 525.4 ± 46.4°; FLEXSOFT: 615.4 ± 47.6°), and cochlear coverage (FLEX28: 63.9 ± 5.6%; FLEXSOFT: 75.8 ± 4.3%) were significant (p < 0.001). CONCLUSION A broad range of CDL was observed with significant larger values in male, but no significant differences concerning side or age. Almost every cochlea was measured longer than 31.0~mm. Preoperative assessment aids in prevention of complications (incomplete insertion, kinking, tipfoldover), attempt of atraumatic insertion, and addressing individual necessities (hearing preservation, cochlear malformation). The preferred AID of 720° (two turns of the cochlea) was never reached, opening the discussion for the requirement of longer CI-electrodes versus a debatable audiological benefit for the patient in his/her everyday life

Benefit of postoperative radiotherapy for early tumors with single ipsilateral lymph node metastasis

Objectives/Hypothesis Indication for postoperative radiotherapy in patients with locally circumscribed tumors (pT1–pT2) and a single ipsilateral lymph node metastasis (pN1) is debatable. The aim of this study was to evaluate the oncological long‐term outcome of patients with pT1‐pT2 pN1 squamous cell carcinoma (SCC) of the oral cavity, the oropharynx, and the hypopharynx without extracapsular spread (ECS) after a margin‐negative surgical resection, who either received or did not receive postoperative (chemo)radiotherapy. Study Design Retrospective case series. Methods The oncological outcome of patients with pT1‐pT2 pN1 SCC without ECS was evaluated retrospectively. All patients underwent primary tumor resection that included transoral laser microsurgery and neck dissection at an academic tertiary referral center. Results Of 65 identified patients treated between 1986 and 2015 (18 oral cavity, 30 oropharynx, 17 hypopharynx), 21 (32%) received postoperative radiotherapy, and 44 (68%) were treated by surgery alone. The group of patients receiving postoperative treatment showed a significantly superior 5‐year disease‐specific (94.4% vs. 73.2%, P = .029) and recurrence‐free survival (85.2% vs. 43.2%, P = .002), as well as a higher local control rate (90.2% vs. 64.9%, P = .042). The overall survival was 71.4% vs. 62.6% (P = .53). The mean follow‐up was 80.7 months. Conclusions Patients with locally circumscribed carcinomas and a single ipsilateral ECS‐negative lymph node metastasis seem to benefit from postoperative radiotherapy. Level of Evidence 4 Laryngoscope, 130:E530–E538, 202

Prognostic impact of additional HPV diagnostics in 102 patients with p16-stratified advanced oropharyngeal squamous cell carcinoma

Purpose!#!p16 overexpression was considered as surrogate marker to identify human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCCs).!##!Methods!#!102 patients with advanced stage OPSCCs treated primarily by transoral lasermicrosurgery were included. Prognostic associations of p16- and HPV-status were analyzed separately and combined.!##!Results!#!In contrast to p16, the HPV-status resulted in no significant survival discrepancies (5-year overall survival (OS) HPV-positive 64.9%, HPV-negative 78.7%). Combining both markers, p16-positive (p16-positive/HPV-positive, p16-positive/HPV-negative) and p16-negative/HPV-negative groups demonstrated comparable high survival (OS 78.1% vs. 85.6% vs. 73.6%). Lowest survival was observed for patients with p16-negative/HPV-positive OPSCCs (OS 40.8%). Never smoking patients with p16-positive OPSCCs demonstrated the highest survival, whereas within former/current smokers with p16-positive and p16-negative disease it was comparable low (OS 90.0% vs. 63.0% vs. 57.4%).!##!Conclusions!#!p16- and HPV-status should not be considered as equivalent markers for a better prognosis. Furthermore, they should not generally predominate patient associated factors like smoking