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Motivation Accurate estimation of false discovery rate (FDR) of spectral identification is a central problem in mass spectrometry-based proteomics. Over the past two decades, target-decoy approaches (TDAs) and decoy-free approaches (DFAs) have been widely used to estimate FDR. TDAs use a database of decoy species to faithfully model score distributions of incorrect peptide-spectrum matches (PSMs). DFAs, on the other hand, fit two-component mixture models to learn the parameters of correct and incorrect PSM score distributions. While conceptually straightforward, both approaches lead to problems in practice, particularly in experiments that push instrumentation to the limit and generate low fragmentation-efficiency and low signal-to-noise-ratio spectra. Results We introduce a new decoy-free framework for FDR estimation that generalizes present DFAs while exploiting more search data in a manner similar to TDAs. Our approach relies on multi-component mixtures, in which score distributions corresponding to the correct PSMs, best incorrect PSMs and second-best incorrect PSMs are modeled by the skew normal family. We derive EM algorithms to estimate parameters of these distributions from the scores of best and second-best PSMs associated with each experimental spectrum. We evaluate our models on multiple proteomics datasets and a HeLa cell digest case study consisting of more than a million spectra in total. We provide evidence of improved performance over existing DFAs and improved stability and speed over TDAs without any performance degradation. We propose that the new strategy has the potential to extend beyond peptide identification and reduce the need for TDA on all analytical platforms. Availabilityand implementation https://github.com/shawn-peng/FDR-estimation. Supplementary information Supplementary data are available at Bioinformatics online.

BACKGROUND: The Nottingham Clavicle Score (NCS) has been recently described for functional outcome assessment after injuries to clavicle and the Acromioclavicular joint. However; validity and responsiveness are context specific psychometric terms and the NCS has not been previously described in surgically treated clavicle shaft fractures. Aim of the present study was to investigate validity and responsiveness of the NCS in clavicle fractures treated with titanium flexible nailing. METHODS: This prospective study was undertaken on consecutively operated clavicle shaft fractures treated with titanium elastic nail from November 2013 to August 2016. Functional assessment using NCS was done at two and six months postoperatively. Construct validity was also evaluated by formulating the null hypothesis that there would be no difference in NCS at six months after open and closed reduction and in 15B1 and 15B2 fracture sub-types. The above two hypotheses were formulated based on previous studies that used Constant score and DASH score. Pre-specified hypothesis and results in accordance with the hypotheses suggest satisfactory construct validity. Responsiveness was evaluated using standardized response mean (SRM) and Effect size (ES). ES and SRM values ≥0.80 suggest satisfactory responsiveness. The proportion of patients having the least possible score of 0 points (floor effect) and the highest possible score of 100 points (ceiling effect) was evaluated at two and six months postoperatively. Floor and ceiling effect of

Accurately estimating performance accuracy of machine learning classifiers is of fundamental importance in biomedical research with potentially societal consequences upon the deployment of best-performing tools in everyday life. Although classification has been extensively studied over the past decades, there remain understudied problems when the training data violate the main statistical assumptions relied upon for accurate learning and model characterization. This particularly holds true in the open world setting where observations of a phenomenon generally guarantee its presence but the absence of such evidence cannot be interpreted as the evidence of its absence. Learning from such data is often referred to as positive-unlabeled learning, a form of semi-supervised learning where all labeled data belong to one (say, positive) class. To improve the best practices in the field, we here study the quality of estimated performance in positive-unlabeled learning in the biomedical domain. We provide evidence that such estimates can be wildly inaccurate, depending on the fraction of positive examples in the unlabeled data and the fraction of negative examples mislabeled as positives in the labeled data. We then present correction methods for four such measures and demonstrate that the knowledge or accurate estimates of class priors in the unlabeled data and noise in the labeled data are sufficient for the recovery of true classification performance. We provide theoretical support as well as empirical evidence for the efficacy of the new performance estimation methods.

Background Pulpotomy is the treatment for cariously exposed vital primary molars. UsingfFormocresol as a pulpotomy agent is been in controversy, which has triggered the search for better alternatives. The product like 'Myristica fragrans (MF)-Nutmeg gel, Terminalia chebula (TC)-Myrobolan gel is gaining popularity as herbal pulpotomy agents. Aim To evaluate and compare clinical and radiographical success of herbal gels Myristica fragrans (MF)-Nutmeg, and Terminalia chebula (TC)-Myrobolan as pulpotomy medicaments in primary teeth. Materials and methods Twenty participants (n = 20), each with at least two primary molars requiring pulpotomy, were selected and divided into two test groups. In 10 children Terminalia chebula gel was placed in one side and Formocresol on another side. Rest 10 children were treated with Myristica fragrans gel on one side and another side with formocresol. The treated teeth selected for clinical and radiographic evaluation were monitored periodically for 3, 6 and 12 months. Results With the follow-up of 12 months there was no significant difference in efficacy of all three pulpotomy medicaments, i.e. Nutmeg, Myrobolan, and Formocresol, respectively was found. Conclusion Herbal gels have a promising role in dentistry having the proper knowledge, and their effects on teeth would prove them as a successful dental therapeutic agent. How to cite this article Mali S, Singla S, Sharma A, Gautam A, Niranjan B, Jain S. Efficacy of Myristica fragrans and Terminalia chebula as Pulpotomy Agents in Primary Teeth: A Clinical Study. Int J Clin Pediatr Dent, 2018;11(6):505-509.

Intraosseous ganglion cyst is a rare bone tumor and the lesion could often be missed. The diagnosis could be delayed so proper radiologic investigation and index of suspicion is necessary .Differential diagnoses of painful cystic radiolucent carpal lesion are osteoid osteoma, osteoblastoma and intraosseous ganglion. Curettage of the scaphoid lesion and filling of void with bone graft provides good functional outcomes. The cyst contains mucoid viscous material without epithelial or synovial lining. We present a case of 30 years old male with intraosseous ganglion cyst of scaphoid which was treated with curettage and bone grafting. Rarely ganglion cyst is found in small bones of hand and should be considered as differential diagnosis of chronic radial wrist pain.

Elucidating the precise molecular events altered by disease-causing genetic variants represents a major challenge in translational bioinformatics. To this end, many studies have investigated the structural and functional impact of amino acid substitutions. Most of these studies were however limited in scope to either individual molecular functions or were concerned with functional effects (e.g. deleterious vs. neutral) without specifically considering possible molecular alterations. The recent growth of structural, molecular and genetic data presents an opportunity for more comprehensive studies to consider the structural environment of a residue of interest, to hypothesize specific molecular effects of sequence variants and to statistically associate these effects with genetic disease. In this study, we analyzed data sets of disease-causing and putatively neutral human variants mapped to protein 3D structures as part of a systematic study of the loss and gain of various types of functional attribute potentially underlying pathogenic molecular alterations. We first propose a formal model to assess probabilistically function-impacting variants. We then develop an array of structure-based functional residue predictors, evaluate their performance, and use them to quantify the impact of disease-causing amino acid substitutions on catalytic activity, metal binding, macromolecular binding, ligand binding, allosteric regulation and post-translational modifications. We show that our methodology generates actionable biological hypotheses for up to 41% of disease-causing genetic variants mapped to protein structures suggesting that it can be reliably used to guide experimental validation. Our results suggest that a significant fraction of disease-causing human variants mapping to protein structures are function-altering both in the presence and absence of stability disruption., Author Summary Identifying the molecular changes caused by mutations is a major challenge in understanding and treating human genetic disease. To address this problem, we have developed a wide range of profiling tools designed to predict specific types of functional site from protein 3D structures. We then apply these tools to data sets of inherited disease-associated and putatively neutral amino acid substitutions and estimate the relative contribution of the loss and gain of functional residues in disease. Our results suggest that alterations of molecular function are involved in a significant number of cases of human genetic disease and are over-represented as compared to putatively neutral variants. Additionally, we use experimental data to show that it is possible to computationally identify the loss of specific functional events in disease pathogenesis. Finally, our methodology can be used to reliably identify the potential molecular consequences of disease-causing genetic variants and hence prioritize experimental validation.

Hoffa’s fracture is coronal oriented fracture of distal femur with the fracture line extending through the femoral condyles. Hoffa’s fracture is rarely associated with ipsilateral femur and tibia fractures. Proper clinical examination and radiographic evaluation is necessary to diagnose associated injuries around the knee joint with Hoffa’s fracture. Closed reduction of dislocated patella in emergency room and field triage should be avoided to prevent patellar tendon incarcenation, patellar tendon rupture and osteochondral damage. We report a rare case of Hoffa’s fracture with irreducible patellar dislocation and tibial intercondylar eminence fracture following road traffic accident.