Partial RNA design.

MOTIVATION: RNA design is a key technique to achieve new functionality in fields like synthetic biology or biotechnology. Computational tools could help to find such RNA sequences but they are often limited in their formulation of the search space. RESULTS: In this work, we propose partial RNA design, a novel RNA design paradigm that addresses the limitations of current RNA design formulations. Partial RNA design describes the problem of designing RNAs from arbitrary RNA sequences and structure motifs with multiple design goals. By separating the design space from the objectives, our formulation enables the design of RNAs with variable lengths and desired properties, while still allowing precise control over sequence and structure constraints at individual positions. Based on this formulation, we introduce a new algorithm, libLEARNA, capable of efficiently solving different constraint RNA design tasks. A comprehensive analysis of various problems, including a realistic riboswitch design task, reveals the outstanding performance of libLEARNA and its robustness. AVAILABILITY AND IMPLEMENTATION: libLEARNA is open-source and publicly available at: https://github.com/automl/learna_tools.

High-Precision Visual Servoing for the Neutron Diffractometer STRESS-SPEC at MLZ.

With neutron diffraction, the local stress and texture of metallic components can be analyzed non-destructively. For both, highly accurate positioning of the sample is essential, requiring the measurement at the same sample location from different directions. Current sample-positioning systems in neutron diffraction instruments combine XYZ tables and Eulerian cradles to enable the accurate six-degree-of-freedom (6DoF) handling of samples. However, these systems are not flexible enough. The choice of the rotation center and their range of motion are limited. Industrial six-axis robots have the necessary flexibility, but they lack the required absolute accuracy. This paper proposes a visual servoing system consisting of an industrial six-axis robot enhanced with a high-precision multi-camera tracking system. Its goal is to achieve an absolute positioning accuracy of better than 50µm. A digital twin integrates various data sources from the instrument and the sample in order to enable a fully automatic measurement procedure. This system is also highly relevant for other kinds of processes that require the accurate and flexible handling of objects and tools, e.g., robotic surgery or industrial printing on 3D surfaces.

Can artificial intelligence support or even replace physicians in measuring sagittal balance? A validation study on preoperative and postoperative full spine images of 170 patients.

PURPOSE: Sagittal balance (SB) plays an important role in the surgical treatment of spinal disorders. The aim of this research study is to provide a detailed evaluation of a new, fully automated algorithm based on artificial intelligence (AI) for the determination of SB parameters on a large number of patients with and without instrumentation. METHODS: Pre- and postoperative sagittal full body radiographs of 170 patients were measured by two human raters, twice by one rater and by the AI algorithm which determined: pelvic incidence, pelvic tilt, sacral slope, L1-S1 lordosis, T4-T12 thoracic kyphosis (TK) and the spino-sacral angle (SSA). To evaluate the agreement between human raters and AI, the mean error (95% confidence interval (CI)), standard deviation and an intra- and inter-rater reliability was conducted using intra-class correlation (ICC) coefficients. RESULTS: ICC values for the assessment of the intra- (range: 0.88-0.97) and inter-rater (0.86-0.97) reliability of human raters are excellent. The algorithm is able to determine all parameters in 95% of all pre- and in 91% of all postoperative images with excellent ICC values (PreOP-range: 0.83-0.91, PostOP: 0.72-0.89). Mean errors are smallest for the SSA (PreOP: -0.1° (95%-CI: -0.9°-0.6°); PostOP: -0.5° (-1.4°-0.4°)) and largest for TK (7.0° (6.1°-7.8°); 7.1° (6.1°-8.1°)). CONCLUSION: A new, fully automated algorithm that determines SB parameters has excellent reliability and agreement with human raters, particularly on preoperative full spine images. The presented solution will relieve physicians from time-consuming routine work of measuring SB parameters and allow the analysis of large databases efficiently.

SPINE20 recommendations 2021: spine care for people's health and prosperity.

PURPOSE: The focus of SPINE20 is to develop evidence-based policy recommendations for the G20 countries to work with governments to reduce the burden of spine disease, and disability. METHODS: On September 17-18, 2021, SPINE20 held its annual meeting in Rome, Italy. Prior to the meeting, the SPINE20 created six proposed recommendations. These recommendations were uploaded to the SPINE20 website 10 days before the meeting and opened to the public for comments. The recommendations were discussed at the meeting allowing the participants to object and provide comments. RESULTS: In total, 27 societies endorsed the following recommendations. SPINE20 calls upon the G20 countries: (1) to expand telehealth for the access to spine care, especially in light of the current situation with COVID-19. (2) To adopt value-based interprofessional spine care as an approach to improve patient outcomes and reduce disability. (3) To facilitate access and invest in the development of a competent rehabilitation workforce to reduce the burden of disability related to spine disorders. (4) To adopt a strategy to promote daily physical activity and exercises among the elderly population to maintain an active and independent life with a healthy spine, particularly after COVID-19 pandemic. (5) To engage in capacity building with emerging countries and underserved communities for the benefit of spine patients. (6) To promote strategies to transfer evidence-based advances into patient benefit through effective implementation processes. CONCLUSIONS: SPINE20's initiatives will make governments and decision makers aware of efforts to reduce needless suffering from disabling spine pain through education that can be instituted across the globe.

Artificial Intelligence-Based Assistance System for Visual Inspection of X-ray Scatter Grids.

Convolutional neural network (CNN)-based approaches have recently led to major performance steps in visual recognition tasks. However, only a few industrial applications are described in the literature. In this paper, an object detection application for visual quality evaluation of X-ray scatter grids is described and evaluated. To detect the small defects on the 4K input images, a sliding window approach is chosen. A special characteristic of the selected approach is the aggregation of overlapping prediction results by applying a 2D scalar field. The final system is able to detect 90% of the relevant defects, taking a precision score of 25% into account. A practical examination of the effectiveness elaborates the potential of the approach, improving the detection results of the inspection process by over 13%.

Effects of a multimodal exercise intervention on physical and cognitive functions in patients with chronic low back pain (MultiMove): study protocol for a randomized controlled trial.

BACKGROUND: Chronic low back pain (CLBP) is a common medical condition in adults over the age of 50. It is associated with severe disability, ranging from physical impairments to psychosocial distress. Since current treatments provide only small to moderate short-term effects, alternative interventions are required, whereby guidelines recommended multimodal approaches. Dancing can be considered as an inherently multimodal approach, as it requires a combination of physical and cognitive functions. Furthermore, it has already been applied effectively in neurorehabilitation. Therefore, it seems promising to merge a dance-therapeutic component together with motor-cognitive, strength and flexibility exercises in a novel multimodal treatment (MultiMove) to target the impaired everyday mobility and cognition of CLBP patients. The aim of this study is to analyse specific physical, cognitive and psychosocial effects of MultiMove in CLBP patients. METHODS: A prospective, two-arm, single-blinded, randomized controlled trial will be conducted with an estimated sample size of 100 CLBP patients, assigned to either the MultiMove group or a control group. The intervention group will receive MultiMove twice a week for 60 min each over a period of 12 weeks. The primary outcome will be the mobility and function of the lower extremities assessed by the Timed Up-and-Go Test. Secondary outcomes comprise further physical and physiological functions (e.g. gait variability and haemodynamic response in the prefrontal cortex during motor-cognitive dual tasks), subjective health state (e.g. disability in daily life), executive functions (e.g. cognitive flexibility) and psychosocial aspects (e.g. kinesiophobia). Measures will be taken at baseline, after the intervention and at a 12-week follow-up. It is assumed that MultiMove improves the mentioned outcome parameters. DISCUSSION: The combined assessment of changes in physical and cognitive functions as well as neuropsychological aspects in response to MultiMove will allow a better understanding of the motor-cognitive adaptations induced by multimodal exercises in CLBP patients. The specific conclusions will lead to recommendations for the conservative treatment approach in this clinically relevant patient group. TRIAL REGISTRATION: German Clinical Trial Register (ID: DRKS00021696 / 10.07.2020), https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021696.

A Wireless Angle and Position Tracking Concept for Live Data Control of Advanced, Semi-Automated Manufacturing Processes.

Despite recent industrial automation advances, small series production still requires a considerable amount of manual work, and training,and monitoring of workers is consuming a significant amount of time and manpower. Adopting live monitoring of the stages in manual production, along with the comprehensive representation of production steps, may help resolve this problem. For ergonomic live support, the overall system presented in this paper combines localization, torque control, and a rotation counter in a novel approach to monitor of semi-automated manufacturing processes. A major challenge in this context is tracking, especially hand-guided tools, without the disruptions and restrictions necessary with rigid position encoders. In this paper, a promising measurement concept involving wireless wave-based sensors for close-range position tracking in industrial surroundings is proposed. By using simple beacons, the major share of processing is transferred to fixed nodes, allowing for reduced hardware size and power consumption for the wireless mobile units. This requires designated localization approaches relying on only relative phase information, similar to the proposed Kalman-filter-based-beam-tracking approach. Measurement results show a beam-tracking accuracy of about 0.58 ∘ in azimuth and 0.89 ∘ in elevation, resulting in an overall tracking accuracy of about 3.18 cm.

The appropriate management of persisting pain after spine surgery: a European panel study with recommendations based on the RAND/UCLA method.

PURPOSE: Management of patients with persisting pain after spine surgery (PPSS) shows significant variability, and there is limited evidence from clinical studies to support treatment choice in daily practice. This study aimed to develop patient-specific recommendations on the management of PPSS. METHODS: Using the RAND/UCLA appropriateness method (RUAM), an international panel of 6 neurosurgeons, 6 pain specialists, and 6 orthopaedic surgeons assessed the appropriateness of 4 treatment options (conservative, minimally invasive, neurostimulation, and re-operation) for 210 clinical scenarios. These scenarios were unique combinations of patient characteristics considered relevant to treatment choice. Appropriateness had to be expressed on a 9-point scale (1 = extremely inappropriate, 9 = extremely appropriate). A treatment was considered appropriate if the median score was ≥ 7 in the absence of disagreement (≥ 1/3 of ratings in each of the opposite sections 1-3 and 7-9). RESULTS: Appropriateness outcomes showed clear and specific patterns. In 48% of the scenarios, exclusively one of the 4 treatments was appropriate. Conservative treatment was usually considered appropriate for patients without clear anatomic abnormalities and for those with new pain differing from the original symptoms. Neurostimulation was considered appropriate in the case of (predominant) neuropathic leg pain in the absence of conditions that may require surgical intervention. Re-operation could be considered for patients with recurrent disc, spinal/foraminal stenosis, or spinal instability. CONCLUSIONS: Using the RUAM, an international multidisciplinary panel established criteria for appropriate treatment choice in patients with PPSS. These may be helpful to educate physicians and to improve consistency and quality of care. These slides can be retrieved under Electronic Supplementary Material.

Applications of Metals for Bone Regeneration.

The regeneration of bone tissue is the main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP)-based substitute materials based on natural (allo- and xenografts) and synthetic origins (alloplastic materials) are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, as well as resorb in the time frame needed for complete regeneration up to the condition of restitution ad integrum. In this context, the modes of action of CaP-based substitute materials have been frequently investigated, where it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also osteoclastic resorption due to different physicochemical properties of the materials. However, the material characteristics needed for the required ratio between new bone tissue formation and material degradation has not been found, until now. The addition of different substances such as collagen or growth factors and also of different cell types has already been tested but did not allow for sufficient or prompt application. Moreover, metals or metal ions are used differently as a basis or as supplement for different materials in the field of bone regeneration. Moreover, it has already been shown that different metal ions are integral components of bone tissue, playing functional roles in the physiological cellular environment as well as in the course of bone healing. The present review focuses on frequently used metals as integral parts of materials designed for bone regeneration, with the aim to provide an overview of currently existing knowledge about the effects of metals in the field of bone regeneration.

Approach for the production chain of printed polymer optical waveguides-an overview.

Research for new production chains in the field of waveguide fabrication is a challenging task. Realizing a cost efficient manufacturing process allows integrating optical data communication in arbitrary structures, for example, the wing of an airplane or the body of a car. The production chain described in this paper contains the design, simulation, and fabrication process of printed polymer optical waveguides (POWs).

Burden of disease of reoperations in instrumental spinal surgeries in Germany.

PURPOSE: To estimate the incidence of instrumental spinal surgeries (ISS) and consecutive reoperations and to calculate the related resource utilization and costs. METHODS: ISS and subsequent reoperations were identified retrospectively using surgery codes in claims data. The study period included January 01, 2009 to December 31, 2011. The reoperation rate was calculated for 1 year after the primary ISS. Resource utilization and costs were analyzed by group comparison. RESULTS: A total of 3316 incident ISS patients were identified in 2010 with an annual reoperation rate of 9.98% (95% CI 8.98-11.02%). Mean costs per patient were €11,331 per ISS and €11,370 per reoperation, with €8432 directly attributed to the reoperation and €2938 to additional resources. CONCLUSIONS: Costs of ISS and subsequent reoperations have a significant impact on health insurances budgets. The annual cost of reoperations exceeds the direct cost of the primary surgery driven by the need for further inpatient and outpatient care.

Maverick total disc replacement in a real-world patient population: a prospective, multicentre, observational study.

PURPOSE: Controlled trials have shown that total disc replacement (TDR) can provide pain and disability relief to patients with degenerative disc disease; however, whether these outcomes can also be achieved for patients treated in normal surgical practice has not been well documented. METHODS: This prospective, international study observed changes in disability and back pain in 134 patients who were implanted with Maverick TDR within the framework of routine clinical practice and followed for 2 years post-surgery. Primary and secondary outcomes were the differences from baseline to 6 months post-surgery in the means of the Oswestry Disability Index and the change in back pain intensity assessed on a 10-cm visual analogue scale, respectively. Mean patient age at surgery was 43 years, but ranged up to 65 years. RESULTS: One hundred twenty-three patients had an implant at one level, 10 patients at two levels, and one patient at three levels. Statistically significant improvements in mean disability (-25.4) and low back pain intensity (-4.0) scores were observed at 6 months postoperatively (P < 0.0001 for both) in the hands of experienced surgeons (>10 TDRs per centre). During the study, 56 patients (42 %) experienced a complication or adverse event. CONCLUSIONS: This is the first international observational study to report outcomes of TDR in real-world clinical settings. We showed statistically significant improvements in disability and pain scores at 6 months following Maverick TDR, which were maintained for 2 years alongside an acceptable rate of perioperative complications. The safety and tolerability shown in this observational study were comparable to those from controlled trials.

Synergistic toxicity of gentamicin- and nanosilver-doped polymethylmethacrylate bone cement on primary human osteoclasts.

Bacterial colonization of implant surfaces is a feared complication in surgery and orthopedics. Due to the increasing number of periprosthetic infections caused by multidrug-resistant microorganisms, new antibacterial coatings for biomaterials must be developed. The excellent antibacterial properties of silver nanoparticles (AgNPs) against multidrug-resistant bacteria, for example, have been repeatedly described. For this reason, we tested a nanosilver-doped polymethylmethacrylate (PMMA) bone cement and a nanosilver-coated titanium alloy regarding their influence on osteoclastogenesis of primary human peripheral blood mononuclear cells. Both implant variants did not inhibit osteoclast differentiation. Excellent cell attachment and unaltered podosomal structures were confirmed. Additionally, no induction of oxidative or endoplasmic reticulum stress could be observed. However, PMMA loaded with gentamicin and nanosilver inhibited preosteoclast fusion and further osteoclastogenesis. The material also led to decreased clathrin-dependent endocytosis as well as decreased levels of endoplasmic reticulum stress. Therefore, biomaterial functionalization with AgNPs did not disturb osteoclastogenesis, while addition of gentamicin reduced the cytocompatibility of nanosilver-doped materials towards human osteoclasts.

A Dataset of Electrical Components for Mesh Segmentation and Computational Geometry Research.

Data quality is of crucial importance in the field of automated or digitally assisted assembly. This paper presents a comprehensive data set of triangle meshes representing electrical and electronic components obtained by scraping Computer Aided Design (CAD) models from the Internet. Consisting of a total of 234 triangle meshes with labelled vertices, this data set was specifically created for segmentation tasks. Its versatility for multimodal tasks is underscored by the presence of various labels, including vertex labels, categories, and subcategories. This paper presents the data set and provides a thorough statistical analysis, including measures of shape, size, distribution, and inter-rater reliability. In addition, the paper suggests several approaches for using the data set, considering its multimodal characteristics. The data set and related findings presented in this paper are intended to encourage further research and advancement in the field of manufacturing automation, specifically spatial assembly.

Assessment of the Suitability of Selected Linear Actuators for the Implementation of the Load-Adaptive Biological Principle of Redundant Motion Generation.

The load-adaptive behavior of the muscles in the human musculoskeletal system offers great potential for minimizing resource and energy requirements in many technical systems, especially in drive technology and robotics. However, the lack of knowledge about suitable technical linear actuators that can reproduce the load-adaptive behavior of biological muscles in technology is a major reason for the lack of successful implementation of this biological principle. In this paper, therefore, the different types of linear actuators are investigated. The focus is particularly on artificial muscles and rope pulls. The study is based on literature, on the one hand, and on two physical demonstrators in the form of articulated robots, on the other hand. The studies show that ropes are currently the best way to imitate the load-adaptive behavior of the biological model in technology. This is especially illustrated in the context of this paper by the discussion of different advantages and disadvantages of the technical linear actuators, where ropes, among other things, have a good mechanical and control behavior, which is very advantageous for use in an adaptive system. Finally, the next steps for future research are outlined to conclude how ropes can be used as linear actuators to transfer load-adaptive lightweight design into technical applications.

Influence of the sagittal spinal profile type on the long-term outcome of patients with symptomatic lumbar spinal stenosis after microsurgical decompression.

OBJECTIVE: Microsurgical decompression for patients with symptomatic lumbar spinal stenosis (LSS) has demonstrated long-term improvement concerning pain and function. Nonetheless, a considerable proportion of these patients do not experience satisfactory alleviation of symptoms. Previous studies have not found a direct influence of single sagittal parameters on patient outcomes. However, recent research indicates that a composite of parameters, presented in specific sagittal profile types (SPTs) that were defined by Roussouly and colleagues, may affect these outcomes. This study aims to investigate the impact of SPT on long-term outcomes of patients with LSS following microsurgical decompression. METHODS: This study is a prospective clinical observation. Patients with symptomatic LSS, who underwent microsurgical treatment and had long-term follow-up data for at least 36 months, were included. Patients with spinal deformity, fractures, or significant instability were excluded. Outcomes were measured using the numeric rating scale for pain, 36-Item Short Form Health Survey for quality of life, walking distance, Oswestry Disability Index, Roland-Morris Disability Questionnaire, and Odom's criteria. SPT was determined in blinded fashion by using preoperative long standing radiographs. RESULTS: The initial population of this observational study consisted of 128 patients, with long-term results available for 87 individuals, including 24 patients with SPT1, 20 with SPT2, 27 with SPT3, and 16 with SPT4. The average age was 70 years, with a slight male majority (56.3%) and a mean BMI of 27.9 kg/m2. After a median follow-up of 48 months, all groups showed significant improvement in walking distance, leg pain, and disability. Overall, 75% reported satisfaction with the surgery. However, patients with SPT1, which is characterized by low sacral slope and specific spinal curvatures, experienced significantly less improvement in back pain (p = 0.018) and related disability (p = 0.030), and lower satisfaction compared to other SPT groups (p = 0.008). CONCLUSIONS: The sagittal spinal type is influencing the long-term outcome of patients suffering from symptomatic LSS. Patients with a combination of a flat sacral slope and a low overall lumbar lordosis with a high lordosis in the lower lumbar spine (i.e., spinal SPT1) showed worse outcome concerning back pain and had decreased satisfaction with surgery than comparable subjects from other SPT groups. Consequently, the authors recommend the assessment of sagittal spinal types in patients diagnosed with symptomatic spinal stenosis prior to decompression surgery. Inclusion of SPT in the preoperative consultation process can provide valuable insights, potentially guiding practitioners to more tailored patient counseling.

ModE-RA: a global monthly paleo-reanalysis of the modern era 1421 to 2008.

The Modern Era Reanalysis (ModE-RA) is a global monthly paleo-reanalysis covering the period between 1421 and 2008. To reconstruct past climate fields an offline data assimilation approach is used, blending together information from an ensemble of transient atmospheric model simulations and observations. In the early period, ModE-RA utilizes natural proxies and documentary data, while from the 17th century onward instrumental measurements are also assimilated. The impact of each observation on the reconstruction is stored in the observation feedback archive, which provides additional information on the input data such as preprocessing steps and the regression-based forward models. The monthly resolved reconstructions include estimates of the most important climate fields. Furthermore, we provide a reconstruction, ModE-RAclim, which together with ModE-RA and the model simulations allows to disentangle the role of observations and model forcings. ModE-RA is best suited to study intra-annual to multi-decadal climate variability and to analyze the causes and mechanisms of past extreme climate events.

Randomized Trial of Augmented Pelvic Fixation in Patients Undergoing Thoracolumbar Fusion for Adult Spine Deformity: Initial Results from a Multicenter Randomized Trial.

BACKGROUND: The optimal configuration for spinopelvic fixation during multilevel spine fusion surgery for adult spine deformity remains unclear. Postoperative sacroiliac (SI) joint pain, S2AI screw loosening and implant breakage could be related to continued motion of the SI joint with use of only a single point of fixation across the SI joint. METHODS: Prospective, international, multicenter randomized controlled trial of 222 patients with adult spine deformity scheduled for multilevel (4 or more levels) spine fusion surgery with pelvic fixation. Subjects were randomized to sacroalar (S2) iliac (S2AI) screws alone for pelvic fixation or S2AI + triangular titanium implants placed cephalad to S2AI screws. Quad rod techniques were not allowed or used. Baseline spinal deformity measures were read by an independent radiologist. Site-reported perioperative adverse events were reviewed by a clinical events committee. Quality of life questionnaires and other clinical outcomes are in process with planned 2-year follow-up. RESULTS: One hundred thirteen participants were assigned to S2AI and 109 to S2AI + titanium triangular implants (TTI). 35/222 (16%) of all subjects had a history of SI joint pain or were diagnosed with SI joint pain during preoperative workup. Three-month follow-up was available in all but 4 subjects. TTI placement was successful in 106 of 109 (98%) subjects assigned to TTI. In 2 cases, TTI could not be placed due to anatomical considerations. Three TTI ventral iliac breaches were observed, all of which were managed non-surgically. One TTI subject had a transverse sacral fracture and 1 TTI subject had malposition of the implant requiring removal. CONCLUSIONS: SI joint pain is common in patients with adult spinal deformity who are candidates for multilevel spine fusion surgery. Concurrent placement of TTI parallel to S2AI screws during multilevel spine fusion surgery is feasible and safe. Further follow-up will help to determine the clinical value of this approach to augment pelvic fixation.

Calcineurin inhibitor dose-finding before kidney transplantation in HIV patients.

Kidney transplantation in HIV-infected patients is associated with a higher rate of graft rejection as well as an increased toxicity of the immunosuppressive therapy. Specifically, the use of the calcineurin inhibitor tacrolimus is problematic because of a narrow therapeutic range, a high interindividual variability of trough levels, and multiple interactions with combination antiretroviral therapy (cART). Our objective was to establish the optimal individual immunosuppressive dose for the time after kidney transplantation. We administered a temporary course of immunosuppressive therapy in three HIV-infected patients with end-stage renal disease (ESRD) after wait-listing and prior to transplantation for deceased donor kidney transplantation. Starting with a tacrolimus dose of 1 mg twice daily, the dose was titrated to reach a tacrolimus trough level of 8-12 ng/ml. HIV had been diagnosed 7-14 years prior. All patients had no detectable HIV-1 RNA while on cART. All three patients had been on chronic dialysis for 4, 7, and 10 years. In two patients, the intended tacrolimus trough levels of 8-12 ng/ml were achieved within a month. The required tacrolimus dose ranged from 0.5 mg thrice weekly to 10 mg daily. In one case, ventricular tachycardia occurred, so the immunosuppressive therapy was switched to cyclosporine A. So far, two patients have been transplanted successfully. In summary, dose-finding of immunosuppressive therapy with tacrolimus in patients on cART before renal transplantation is feasible and appears useful to minimize immunosuppressive therapy-related complications in the post-transplantation period.