We present a new open-source software, called OpenGrowth, which aims to create de novo ligands by connecting small organic fragments in the active site of proteins. Molecule growth is biased to produce structures that statistically resemble drugs in an input training database. Consequently, the produced molecules have superior synthetic accessibility and pharmacokinetic properties compared with randomly grown molecules. The growth process can take into account the flexibility of the target protein and can be started from a seed to mimic R-group strategy or fragment-based drug discovery. Primary applications of the software on the HIV-1 protease allowed us to quickly identify new inhibitors with a predicted Kd as low as 18 nM. We also present a graphical user interface that allows a user to select easily the fragments to include in the growth process. OpenGrowth is released under the GNU GPL license and is available free of charge on the authors' website and at http://opengrowth.sourceforge.net/ .

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The rate of operative fixation for completely displaced mid-shaft clavicle fractures in adolescents has been increasing yearly over the last decade, largely driven by studies of adult populations, in whom the rate of nonunion is approximately 15% with non-operative treatment. However, nonunion and symptomatic malunion in younger populations remain rare. Recent studies suggest that functional outcomes are similar between conservative management and operative fixation in adolescents, with higher rates of complications and slightly decreased time to return to sport with operative fixation. Implant-related symptoms after surgery remains an important consideration, due to potential for reoperation for implant removal. Additionally, the cost of operative fixation is significantly higher than that of non-operative management. The aim of this review is to summarize the salient historical and more recent literature regarding displaced mid-shaft clavicle fractures in order to better understand treatment considerations and the natural history of these fractures in the adolescent.

Background:Controversy remains regarding optimal treatment of clavicular fractures, despite evidence touting lower nonunion rates for operative interventions. Given increasing evidence supporting operative treatment, the goal of this study was to observe trends in operative versus nonoperative treatment over a 15-year period. Methods:One thousand and eighty nine patients with any clavicular fracture (AO Foundation/Orthopaedic Trauma Association 15A to 15AC) between 2004 and 2018 were identified. Patient records were queried for demographic information, injuries to the head or chest, and treatment modality (operative vs. nonoperative). Independent sample t-tests, Fisher exact, or chi-square tests were used for analysis, with P less than 0.05 representing significance. Results:Of the 1089 qualified patients, the average age was 47.5 yr and 70.7% were men. Two hundred forty-two patients (20.2%) were managed operatively. Two hundred seventy-one patients (24.8%) had isolated injuries. Operative clavicle management increased from 6.4% of patients in 2004 and 2005 to 31.5% in 2018 (P < 0.001). During this time, both patient age and chest-injury rates increased (both P < 0.01). Patients with head injuries had a fixation rate of 4.8%, compared with 45.5% in patients with chest injuries. Those fixation rates differed from the rate for isolated clavicular fractures (30.9%) and those polytraumatized patients who had both chest and head injuries (18.8%) (P = 0.026). Conclusions:Our data indicated that from 2004 to 2018, there was a five-fold increase in the rate of operative management of clavicular fractures. This rise in fixation rates may substantially influence the rate of complications, secondary surgeries, and cost of additional healthcare utilization. It is important to counsel patients individually to limit unnecessary surgery.