On optimal comparability editing with applications to molecular diagnostics

<p>Abstract</p> <p>Background</p> <p>The C<smcaps>OMPARABILITY</smcaps> E<smcaps>DITING</smcaps> problem appears in the context of hierarchical disease classification based on noisy data. We are given a directed graph <it>G </it>representing hierarchical relationships between patient subgroups. The task is to identify the minimum number of edge insertions or deletions to transform <it>G </it>into a transitive graph, that is, if edges (<it>u</it>, <it>v</it>) and (<it>v</it>, <it>w</it>) are present then edge (<it>u</it>, <it>w</it>) must be present, too.</p> <p>Results</p> <p>We present two new approaches for the problem based on fixed-parameter algorithmics and integer linear programming. In contrast to previously used heuristics, our approaches compute provably optimal solutions.</p> <p>Conclusion</p> <p>Our computational results demonstrate that our exact algorithms are by far more efficient in practice than a previously used heuristic approach. In addition to the superior running time performance, our algorithms are capable of enumerating all optimal solutions, and naturally solve the weighted version of the problem.</p

SOM-based Peptide Prototyping for Mass Spectrometry Peak Intensity Prediction

In todays bioinformatics, Mass spectrometry (MS) is the key technique for the identification of proteins. A prediction of spectrum peak intensities from pre computed molecular features would pave the way to better understanding of spectrometry data and improved spectrum evaluation. We propose a neural network architecture of Local Linear Map (LLM)-type based on Self-Organizing Maps (SOMs) for peptide prototyping and learning locally tuned regression functions for peak intensity prediction in MALDI-TOF mass spectra. We obtain results comparable to those obtained by nu-Support Vector Regression and show how the SOM learning architecture provides a basis for peptide feature profiling and visualisation

Targeting of Rad51-dependent homologous recombination: implications for the radiation sensitivity of human lung cancer cell lines

The aim of the present work was to study the role of Rad51-dependent homologous recombination in the radiation response of non-small-cell lung cancer (NSCLC) cell lines. A dose- and time-dependent increase in the formation of Rad51 and γ-H2AX foci with a maximum at about 4 and 1 h after irradiation, followed by a decrease, has been found. The relative fraction of cells with persisting Rad51 foci was 20–30% in radioresistant and 60–80% in radiosensitive cell lines. In comparison, a higher fraction of residual Dsb was evident in cell lines with nonfunctional p53. Transfection with As-Rad51 significantly downregulates radiation-induced formation of Rad51 foci and increases apoptosis, but did not influence the rejoining of DNA double-strand breaks. Interestingly, wortmannin, a well-known inhibitor of nonhomologous end-joining, also inhibits Rad51 foci formation. In general, there was no correlation between the clonogenic survival at 2 Gy and the percentage of initial Rad51 or γ-H2AX foci after ionising radiation (IR). The most reliable predictive factor for radiosensitivity of NSCLC cell lines was the relative fraction of Rad51 foci remaining at 24 h after IR. Although most of the Rad51 foci are co-localised with γ-H2AX foci, no correlation of the relative fraction of persisting γ-H2AX foci and SF2 is evident

High prevalence of missed information related on bone health in orthogeriatric patients with fragility fractures of the pelvis-an institutional register-based analysis

This is the first study that highlighted the amount of missed information related on bone health in orthogeriatric patients suffering fragility fractures of the pelvis and also evaluated its prevalence and differing etiology in the assessed patients, regarding osteoporosis and/or osteomalacia, based on laboratory and instrumental measurements. This evaluation should become a standardized procedure in the treatment of orthogeriatric patients presenting with a FFP. INTRODUCTION Fragility fractures of the pelvis (FFP) are common in orthogeriatric patients. Secondary fracture prevention regarding evaluation and treatment of an underlying osteoporosis or osteomalacia is still often neglected. The purpose of this study was to evaluate the amount of missed information related on bone health in older adult FFP patients, the prevalence of vitamin D deficiency in assessed patients, and if fracture type-dependent distribution patterns could be observed. METHODS A retrospective analysis of prospectively collected data of an institutional register was performed. Patients aged 80~years and older (n = 456) admitted with a FFP from 01/2003 until 12/2019 to a level I trauma center were included. RESULTS In 456 patients, FFP type II were leading (66.7%). Diagnostics were conducted in 37.1% of the patients regarding measurement of vitamin D levels and 21.7% regarding DXA measurements; vitamin D deficiency was observed in 62.7%, indicators for an underlying osteomalacia in 45.8%, and an osteoporosis in 46.5% of the assessed patients. CONCLUSION Although FFP are common and will increase, there is still a lack of secondary fracture prevention, starting with information related on bone health. In the assessed patients, a high prevalence of vitamin D deficiency was present, but no significant correlation between vitamin D level and type of fracture was observed. Ongoing education for varying etiology and specific treatment of these fractures is necessary, as surgical treatment was unified, but drug therapy remains different

SOM-based Peptide Prototyping for Mass Spectrometry Peak Intensity Prediction

In todays bioinformatics, Mass spectrometry (MS) is the key technique for the identification of proteins. A prediction of spectrum peak intensities from pre computed molecular features would pave the way to better understanding of spectrometry data and improved spectrum evaluation. We propose a neural network architecture of Local Linear Map (LLM)-type based on Self-Organizing Maps (SOMs) for peptide prototyping and learning locally tuned regression functions for peak intensity prediction in MALDI-TOF mass spectra. We obtain results comparable to those obtained by nu-Support Vector Regression and show how the SOM learning architecture provides a basis for peptide feature profiling and visualisation

Eradication of Acinetobacter baumannii/Enterobacter cloacae complex in an open proximal tibial fracture and closed drop foot correction with a multidisciplinary approach using the Taylor Spatial Frame®

Background Multi-drug-resistant bacteria (e.g. Carbapenem-resistant Acinetobacter baumannii, extended-spectrum betalactamase or carbapenemase-producing enterobacteriaceae) are emerging in early-onset infections. So far, there is no report describing the eradication of these bacteria in a osseous infection of an open proximal tibial fracture in combination with the hexapod technology to address both osseous consolidation and closed drop foot correction. Case presentation After sustaining a proximal tibial fracture (Gustilo 3B), a 41-year-old man was primarily treated with open reduction and internal fixation by a locking plate and split-thickness skin graft in the home country. At the time of admission to our hospital there was a significant anterolateral soft tissue defect covered with an already-necrotic split-thickness graft and suspicious secretion. CAT and MRI scans revealed no signs of osseous healing, intramedullary distinctive osteomyelitis, as well as a large abscess zone in the dorsal compartment. Multiple wound smears showed multi-drug-resistant bacteria: Acinetobacter baumannii (Carbapenem resistant) as well as Enterobacter cloacae complex (AmpC overexpression). After implant removal, excessive osseous and intramedullary debridements using the Reamer Irrigator Aspirator (RIA®) as well as initial negative pressure wound therapy were performed. Colistin hand-modelled chains and sticks were applied topically as well as an adjusted systemic antibiotic scheme was applied. After repetitive surgical interventions, the smears showed bacterial eradication and the patient underwent soft tissue reconstruction with a free vascularized latissimus dorsi muscle flap. External fixation was converted to a hexapod fixator (TSF®) to correct primary varus displacement, axial assignment and secure osseous healing. A second ring was mounted to address the fixed drop foot in a closed fashion without further intervention. At final follow-up, 12 months after trauma, the patient showed good functional recovery with osseous healing, intact soft tissue with satisfactory cosmetics and no signs of reinfection. Conclusions A multidisciplinary approach with orthopaedic surgeons for debridement, planning and establishing osseous and joint correction and consolidation, plastic surgeons for microvascular muscle flaps for soft tissue defect coverage as well as clinical microbiologists for the optimized anti-infective treatment is essential in these challenging rare cases

Cancellous allogenic and autologous bone grafting ensure comparable tunnel filling results in two-staged revision ACL surgery

Objectives!#!Patients with recurrent instability after anterior cruciate ligament (ACL) reconstruction often present with enlarged or misplaced tunnels and bone grafting is required prior to the actual revision reconstruction. Autologous bone grafting features limited quantity and donor site morbidity. These problems may be eliminated utilizing cancellous bone allografts, but their efficiency and reliability have not been investigated systematically. The aim of the present study was to compare tunnel filling rates attained by utilizing either allogenic or autologous cancellous bone grafts.!##!Materials and methods!#!A total of 103 consecutive patients were enrolled retrospectively. All patients suffered from recurrent instability and underwent either allogenic or autologous cancellous bone grafting. Computed tomography (CT) was carried out before and after the bone grafting procedure. Based on preoperative CT scans, positioning and maximum diameter of the femoral and tibial tunnels were determined. Tunnel filling rates were calculated as a ratio of pre- and postoperative tunnel volumes. Primary outcome was the tibial tunnel filling rate. Femoral filling rates and density of the grafted bone were assessed secondarily.!##!Results!#!Preoperative CT scans revealed no significant differences between the two groups regarding distribution of misplacement and widening of the femoral or tibial tunnel. Postoperative CT scans were conducted after an interval of 5.2 months. Tunnel filling rates of 74.5% (± 14.3) femoral and 85.3% (± 10.3) tibial were achieved in the allogenic compared to 74.3% (± 15.9) femoral and 84.9% (± 9.4) tibial in the autologous group. With p values of 0.85 at the femur and 0.83 at the tibia, there were no significant differences between the groups. The density of the grafted bone revealed significantly higher values in the allogenic group.!##!Conclusions!#!Utilizing cancellous bone allografts in two-staged revision ACL surgery provides for sufficient and reproducible filling of enlarged or misplaced tunnels. The filling rates are comparable to those achieved with autologous bone grafting. Advantages of allografts are the unrestricted quantity and the absence of any harvesting procedure