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Background: Torsional malalignment of the femur and/or tibia is associated with patellar maltracking, and torsional osteotomies have shown to improve clinical symptoms. In patients with severe torsional malalignment, a double-level torsional osteotomy may be necessary. Indications: Symptomatic torsional malalignment leading to patellofemoral maltracking associated with anterior knee pain and/or patellofemoral instability. Technique Description: A double-level torsional osteotomy correcting both increased internal femoral torsion and increased external tibial torsion, is described. Meticulous preoperative deformity analysis and planning of the osteotomy is mandatory. An arthroscopy of the knee is performed first to evaluate the patellofemoral joint and patellar tracking. Tibial torsional correction is performed by a lateral approach. A biplanar osteotomy is performed, and the amount of torsional correction is controlled by 2 Schanz screws. Osteosynthesis can be done via a bended 5-hole DC-Plate or an angle-stable plate. The femoral osteotomy is performed by a medial approach. A uniplanar osteotomy is performed perpendicular to the mechanical axis of the femur. The amount of torsional correction is controlled by 2 Schanz screws. Osteosynthesis is achieved by an angle-stable plate. Results: Double-level torsional osteotomy has been shown to be an effective treatment for patients with patellar dislocation or subluxation associated with severe torsional malalignment. In a series of 18 patients, double-level osteotomy led to improved patellofemoral stability, decreased pain, and increases subjective outcome scores. Discussion/Conclusion: In patients with patellofemoral problems caused by a combined increased tibial external torsion and increased femoral internal torsion, a double-level torsional osteotomy is able to correct torsional angles to normal. Available clinical data on this procedure are promising. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Abstract Artificial intelligence's (AI) accelerating progress demands rigorous evaluation standards to ensure safe, effective integration into healthcare's high‐stakes decisions. As AI increasingly enables prediction, analysis and judgement capabilities relevant to medicine, proper evaluation and interpretation are indispensable. Erroneous AI could endanger patients; thus, developing, validating and deploying medical AI demands adhering to strict, transparent standards centred on safety, ethics and responsible oversight. Core considerations include assessing performance on diverse real‐world data, collaborating with domain experts, confirming model reliability and limitations, and advancing interpretability. Thoughtful selection of evaluation metrics suited to the clinical context along with testing on diverse data sets representing different populations improves generalisability. Partnering software engineers, data scientists and medical practitioners ground assessment in real needs. Journals must uphold reporting standards matching AI's societal impacts. With rigorous, holistic evaluation frameworks, AI can progress towards expanding healthcare access and quality. Level of Evidence Level V.

Abstract Recent advances in artificial intelligence (AI) present a broad range of possibilities in medical research. However, orthopaedic researchers aiming to participate in research projects implementing AI‐based techniques require a sound understanding of the technical fundamentals of this rapidly developing field. Initial sections of this technical primer provide an overview of the general and the more detailed taxonomy of AI methods. Researchers are presented with the technical basics of the most frequently performed machine learning (ML) tasks, such as classification, regression, clustering and dimensionality reduction. Additionally, the spectrum of supervision in ML including the domains of supervised, unsupervised, semisupervised and self‐supervised learning will be explored. Recent advances in neural networks (NNs) and deep learning (DL) architectures have rendered them essential tools for the analysis of complex medical data, which warrants a rudimentary technical introduction to orthopaedic researchers. Furthermore, the capability of natural language processing (NLP) to interpret patterns in human language is discussed and may offer several potential applications in medical text classification, patient sentiment analysis and clinical decision support. The technical discussion concludes with the transformative potential of generative AI and large language models (LLMs) on AI research. Consequently, this second article of the series aims to equip orthopaedic researchers with the fundamental technical knowledge required to engage in interdisciplinary collaboration in AI‐driven orthopaedic research. Level of Evidence Level IV.

The central nervous system momentarily activates a set of specific muscle synergies to maintain balance when external mechanical perturbations induce walking instability, which is critically involved in preventing falls. The activation patterns and composition of the muscle synergies recruited in the perturbed leg have not been fully characterized, and even less so for the recovery step. Here, we addressed this research gap by measuring the surface electromyographic data of the relevant muscles during a backward-pitched perturbed walk, and then extracting muscle synergy-related parameters using a non-negative matrix factorization algorithm. Our findings indicated that 1) a common set of four muscle synergies was activated in normal, perturbated and first recovery steps; 2) a specific muscle synergy controlled hip movement was recruited in the first recovery step; and 3) the main temporal activation phases of several muscle synergies were prolonged in the perturbed or the first recovery step. These results emphasize the potential significance of exploring the neurological control strategies of muscle synergy in fall prevention.

Abstract Purpose Refixation of acute anterior cruciate ligament (ACL) tears represents an increasingly popular treatment option. Systematic evaluations of various suture technique parameters are still pending. We therefore aimed to evaluate the mechanical pull‐out outcomes of various suture methods for optimization of ACL refixation. Methods Sixty fresh knees from mature domestic pigs were dissected and the femoral attachment of the ACL was peeled off. The 60 knees were divided in 10 groups and sutured as follows: (A) one suture (1, 2, 4 and 6 passes), (B) two sutures (2, 4 and 6 passes each; sutures knotted together as a loop) and (C) two sutures (2, 4 and 6 passes each, sutures knotted separately). The pull‐out test was conducted using a validated electrodynamic testing machine. First occurrence of failure, maximum pull‐out load and stiffness were measured. Suture failure was defined as pull‐out of the ACL. Results Two‐point fixation, using two sutures, with at least two passes, showed the most favourable biomechanical stability. The maximum pull‐out load was significantly higher with two sutures (529.5 N) used compared to one (310.4 N), p

Purpose: The goal of this systematic review is to offer a detailed summary of the present status of robotic-assisted surgery for adult spinal deformity. Methods: This review is based on articles systematically searched in PubMed, Medline, and Web of Science Core Collection databases on robotic-assisted surgery for adult spinal deformity. Differences in the precision of pedicle screw placement, duration of surgery, and incidence of complications between robotic-assisted surgery and the conventional open surgery were considered. Results: A total of 172 articles were retrieved from the literature search. A total of 168 articles were excluded. Therefore, this systematic review included the remaining four original articles, including accuracy of pedicle screw placement, operative time, radiation exposure, intraoperative and postoperative complications, respectively. The overall level of evidence in the studies was moderate to low. Conclusion: Robotic-assisted surgery for adult spinal deformity demonstrates the potential to enhance the precision of screw placement, possibly reduce intraoperative and postoperative complications, and decrease radiation exposure. However, the impact on operation duration requires further investigation.

Abstract Background Perturbation-based balance training on a treadmill is an emerging method of gait stability training with a characteristic task nature that has had positive and sustained effects on balance recovery strategies and fall reduction. Little is known about the effects produced by shod and barefoot walking. We aimed to investigate which is more appropriate, shod or barefoot walking, for perturbation-based balance training in older adults. Methods Fourteen healthy older adults (age: 68.29 ± 3.41 years; body height: 1.76 ± 0.10 m; body mass: 81.14 ± 14.52 kg) performed normal and trip-like perturbed walking trials, shod and barefoot, on a treadmill of the Gait Real-time Analysis Interactive Lab. The marker trajectories data were processed by Human Body Model software embedded in the Gait Offline Analysis Tool. The outcomes of stride length variability, stride time variability, step width variability, and swing time variability were computed and statistically analyzed by a two-way repeated-measures analysis of variance (ANOVA) based on gait pattern (normal gait versus perturbed recovery gait) and footwear condition (shod versus barefoot). Results Footwear condition effect (p = 0.0310) and gait pattern by footwear condition interaction effect (p = 0.0055) were only observed in swing time variability. Gait pattern effects were detected in all four outcomes of gait variability. Conclusions Swing time variability, independent of gait speed, could be a valid indicator to differentiate between footwear conditions. The lower swing time variability in perturbed recovery gait suggests that barefoot walking may be superior to shod walking for perturbation-based balance training in older adults.

Abstract Background The lower extremity may play a crucial role in compensating for gait perturbations. The study aimed to explore the mechanism of perturbation compensation by investigating the gait characteristics and lower extremity joint moment effects in young (YS) and older subjects (OS) during the first recovery gait following slipping (slipping_Rec1) and stumbling (stumbling_Rec1). Method An automatic perturbation-triggered program was developed using D-Flow software based on the Gait Real-time Analysis Interactive Lab to induce the two aforementioned perturbations. Marker trajectories and ground reaction forces were recorded from 15 healthy YS (age: 26.53 ± 3.04 years; body height: 1.73 ± 0.07 m; body mass: 66.81 ± 11.44 kg) and 15 healthy OS (age: 68.33 ± 3.29 years; body height: 1.76 ± 0.10 m; body mass: 81.13 ± 13.99 kg). The Human Body Model was used to compute the variables of interest. One-way analysis of variance and independent samples t-test statistical analyses were performed. Results In slipping_Rec1 and stumbling_Rec1, the change in gait pattern was mainly reflected in a significant increase in step width, no alterations in step length and stance/swing ratio were revealed. Based on perturbed task specificity, lower extremity joint moments increased or decreased at specific phases of the gait cycle in both YS and OS in slipping_Rec1 and stumbling_Rec1 compared to normal gait. The two perturbed gaits reflected the respective compensatory requirements for the lower extremity joints, with both sagittal and frontal joint moments producing compensatory effects. The aging effect was not reflected in the gait pattern, but rather in the hip extension moment during the initial stance of slipping_Rec1. Conclusions Slipping appears to be more demanding for gait recovery than stumbling. Gait perturbation compensatory mechanisms for OS should concentrate on ankle strategy in the frontal plane and counter-rotation strategy around the hip.

Abstract Purpose To examine a series of papers from top ranked orthopaedic journals with respect to the number of citations over a 10‐year observation period to identify factors that lead to high citation rates. Methods The Web of Science database was consulted to identify all published papers from the first‐year term of 2010 (January‐May) from four top orthopaedic journals: AJSM, Arthroscopy, JBJS Am and KSSTA. The database was used to analyze and compare the papers with respect to their characteristics and citations up to 2019. Basic information for each paper was collected including the author, country, study type and average citations per year (ACY). The most (Top20%) and least (Bottom20%) frequently cited papers were identified and differences were extracted. Results Five hundred sixteen papers were included with a total of 19,261 citations. Most of the published papers were from the United States (n = 245). On average, a paper received 37.3 citations over the 10‐year observation period. The most cited paper was cited 322 times. The most cited study type was randomized controlled trial (RCT) (Ø80.8). The Top20% papers were cited 37 times more often than the Bottom20%. Among the Top20%, the largest group was cohort study (n = 20) followed by case series (n = 19). Among others, the number of authors, the number of keywords and the number of references significantly correlated with the number of citations (p

Abstract Artificial intelligence (AI) has the potential to transform medical research by improving disease diagnosis, clinical decision‐making, and outcome prediction. Despite the rapid adoption of AI and machine learning (ML) in other domains and industry, deployment in medical research and clinical practice poses several challenges due to the inherent characteristics and barriers of the healthcare sector. Therefore, researchers aiming to perform AI‐intensive studies require a fundamental understanding of the key concepts, biases, and clinical safety concerns associated with the use of AI. Through the analysis of large, multimodal datasets, AI has the potential to revolutionize orthopaedic research, with new insights regarding the optimal diagnosis and management of patients affected musculoskeletal injury and disease. The article is the first in a series introducing fundamental concepts and best practices to guide healthcare professionals and researcher interested in performing AI‐intensive orthopaedic research studies. The vast potential of AI in orthopaedics is illustrated through examples involving disease‐ or injury‐specific outcome prediction, medical image analysis, clinical decision support systems and digital twin technology. Furthermore, it is essential to address the role of human involvement in training unbiased, generalizable AI models, their explainability in high‐risk clinical settings and the implementation of expert oversight and clinical safety measures for failure. In conclusion, the opportunities and challenges of AI in medicine are presented to ensure the safe and ethical deployment of AI models for orthopaedic research and clinical application. Level of evidence IV

Background: Functional impairment of the knee joint affected by osteoarthritis and loss of muscle strength leads to a significant increase in the number of falls. Nevertheless, little is known about strategies for coping with gait perturbations in patients with knee osteoarthritis (KOA). Thus, this study aimed to examine the compensatory strategies of patients with KOA in response to a backward slip perturbation compared with healthy older adults.Methods: An automated perturbation program was developed by using D-Flow software based on the Gait Real-time Analysis Interactive Lab, and an induced backward slip perturbation was implemented on nine patients with severe KOA (68.89 ± 3.59 years) and 15 age-matched healthy older adults (68.33 ± 3.29 years). Step length, gait speed, range of motion, vertical ground reaction forces, lower extremity joint angles, and joint moments were computed and analyzed.Results: Compared with older adults, patients with KOA had significantly lower step length, gait speed, and vertical ground reaction forces in both normal walking and the first recovery step following backward slip perturbations. Inadequate flexion and extension of joint angles and insufficient generation of joint moments predispose patients with KOA to fall. Hip extension angle and flexion moment, knee range of motion, and vertical ground reaction forces are key monitoring variables.Conclusion: The risk of falls for patients with KOA in response to backward slip perturbations is higher. Patients with KOA should focus not only on quadriceps muscle strength related to knee range of motion but also on improving hip extensor strength and activation through specific exercises. Targeted resistance training and perturbation-based gait training could be better options.

Background: Closed finger flexor tendon pulley injuries occur most frequently in rock climbing but also during other heavy finger strength work or exercises. While single pulley injuries receive a conservative therapy, multiple pulley injuries often require a surgical repair, as otherwise they will lead to contracture and loss of range of motion and functionality. While established surgical techniques, which use bone encircling tendon graft techniques, were found to produce osteonecrosis of the phalanx, our new transosseous technique avoids this problem. Indications: All triple pulley injuries (A2,3,4) (grade-4b injuries) and double pulley injuries (A2,3 or A3,4) (grade-4a injuries) are indicated, if the injury is older than 10 days at the point of therapy start or the flexor tendons bowstringing is either not redressable in the ultrasound or extended. Also, grade-4a injuries are indicated, if a secondary contracture starts to build. Technique Description: Standard palmar-sided incision, followed by debridement of the tendon sheath, pulley flap, and, if applicable, scare tissue in between the flexor tendons and the bone is performed. Wire-guided 3.0-mm drill holes at the base phalanx at the level of the former distal portion of the A2 pulley are completed. Passing of the palmaris longus tendon through the drill hole and interlacing it as a “loop and a half” follows. Distal continuation through lacing the transplant through the remaining rims of the former pulleys and the flexor tendon sheath is then performed. Securing the repair after tendon gliding control to itself is completed. Postsurgically, the splint is immobilized for 2 weeks, followed by the use of a thermoplastic pulley support ring for 4 weeks with active mobilization. Results: No complications occurred during or after the surgery. In few cases, a restricted range of motion in the proximal interphalangeal (PIP) joint of the respective finger of up to 3 to 5 grade occurred. One patient, who had a presurgical PIP extension deficit of 30°, which was released during the surgery, developed over time again a 20° extension deficit. The functional outcome score ranged between good and excellent, with one case being only satisfactory. The sport-specific outcome score was either good or excellent for all patients, with one patient with contracture where it was satisfactory. No osteonecrosis of the phalanx was recorded. Discussion: For multiple pulley ruptures, various surgical techniques are described. We favored a modified “loop and a half” technique with a distal continuation to the A3 pulley. This combines the advantages of the “loop and a half” technique, as the strongest, and the Weilby repair, as the most functional repair. We recently noticed some cases with osseous necrosis of the phalanx following this repair, likely due to the high pressure of the circulation of the tendon graft onto the bone and its blood vessels. Therefore, we have modified our procedure into a transosseous repair, which is presented in this article. This approach was first evaluated in a cadaver study to exclude a potential risk of osseous failure (fracture) during stress caused by the drill hole. After ruling out this risk, the transosseous technique became our standard approach, as it combines the advantages of the “loop and a half” technique with those of the Weilby repair and decreases the pressure onto the dorsal cortex of the fingers base phalanx and thus the risk of osteonecrosis.

Abstract Purpose The aim of this systematic review was to update the knowledge on risk factors and prevention strategies for shoulder injuries in overhead sports with special emphasis on methodological quality. Methods All methodological procedures were performed in line with a previous systematic review by Asker et al. (2018). The literature search was conducted in the PubMed, Google Scholar, Cochrane, and SPORT‐Discuss databases. Due to the risk of bias assessment, only studies with at least an acceptable methodological quality were included. A best‐evidence synthesis was performed to clarify the evidence and direction of the risk factors and prevention strategies. Results A total of nine studies were included in the data extraction process. One study had a high and eight studies had an acceptable methodological quality. Seven cohort studies investigated risk factors and two randomised controlled trails evaluated prevention strategies. Moderate evidence was found for two non‐modifiable (playing position, gender) and three modifiable factors (shoulder rotational strength, scapular dyskinesia, shoulder prevention programme) that were associated with the shoulder injury risk. All further risk factors had moderate and no association with risk (shoulder rotational ROM, joint position sense) or limited (history of shoulder/elbow pain, age, training experience, training volume, school grade, playing level), and conflicting evidence (setting). Conclusions There is moderate evidence for two non‐modifiable (playing position, gender) and three modifiable factors (shoulder rotational strength, scapular dyskinesia, shoulder prevention programme) being associated with the shoulder injury risk in overhead sports.

Background: Lower extremity alignment-correcting procedures for unicompartmental osteoarthritis are experiencing a rapid rise. Medial open-wedge high tibial osteotomy (MOW-HTO) thereby represents the most common technique among osteotomies but is limited in cases of severe malalignment. Some cases make a double-level osteotomy necessary. Indications: If planning of malalignment correction using a MOW-HTO results in a mechanical medial proximal tibial angle (mMPTA) of more than 93° (causing an oblique joint line), double-level osteotomy is indicated to avoid nonphysiological knee kinematics. Technique Description: After clinical examination and detailed analysis of malalignment (full-weight-bearing long-leg radiograph: hip-knee-angle [HKA], mMPTA, mechanical lateral distal femoral angle [mLDFA], joint line convergence angle [JLCA]), as well as individualized planning of the correction, the surgical procedure starts with an arthroscopy to evaluate the cartilage conditions and eventually treat intraarticular pathologies. Then, the femoral supracondylar correction is performed (closed wedge, biplanar osteotomy [ to increase bony healing ]) according to the presurgical planning by resecting the osteotomy wedge with the measured length. K-wires are placed to check the correction. An angle-stable plate is used for osteosynthesis. The wedge taken out will be used as bone stock for the MOW-HTO afterward. The biplanar open-wedge tibial osteotomy is then performed subsequently using a medial tibial approach and an angle-stable plate. Opening of the osteotomy is then performed and double checked with intraoperative fluoroscopy using an alignment rod. Postoperative partial weight bearing for 6 weeks is recommended. Results: In recent literature, only few publications report on results of double-level osteotomies. Babis et al reports that it is a valuable procedure for patients with large varus deformity. Nakayama et al noted a significant improvement in patient-registered clinical outcomes in early postoperative evaluation of 20 patients. Schröter et al reports on 37 knees and findings include good clinical results, despite progressive osteoarthritis. Discussion/Conclusion: In cases of severe malalignment, adequate axis correction may require a double-level osteotomy. Exact preoperative planning is essential. Results reported in recent publications are promising. By splitting 1 large correction into 2 smaller ones, complications like hinge fracture and delayed bone healing are lowered.

During the spindle assembly checkpoint, the activity of the anaphase promoting complex/cyclosome (APC/C) is repressed, yet cyclin A2 evades the checkpoint and is targeted for degradation. Here, the authors define the underlying mechanism and reveal that cyclin A2 engages the APC/C in multiple binding modes.

Abstract Background Post-operative limb swelling may negatively affect the outcome of arthroscopic surgery and prolong rehabilitation. The aim of this pilot study was to evaluate the effect of compression stockings versus no compression on post-operative swelling and pain in the early post-operative phase. Methods A single-centre, randomised controlled trial was performed. Patients who underwent minor knee arthroscopy were randomised to wear class II compression stockings (23-32 mmHg) (CS) or no compression stockings (NCS) immediately post-operatively for ten days. All patients received low molecular weight heparin (LMWH) at prophylactic dosage. The primary outcome variable was post-operative swelling of the limb, quantified by using an optical 3D measurement system (Bodytronic© 600). Pain was rated on a visual analogue scale (VAS). From a total of 76 patients assessed, 19 patients were eligible for final analysis. The trial followed the CONSORT criteria, was registered at clinicaltrial.gov and approved by the local ethics committee. Results The circumference at the middle thigh (cF) was significantly different between groups at day 10 (p = 0.032; circumference − 1.35 ± 2.15% (CS) and + 0.79 ± 3.71% (NCS)). Significant differences were also noted around the knee (cD) at day 10 (p = 0.026) and a significant trend at cD and at the mid lower leg (cB1) at day 4. The volume of the thigh was also different with marked difference between days 1 and 4 between the two groups (p = 0.021; volume + 0.54 ± 2.03% (CS) and + 4.17 ± 4.67 (NCS)). Pain was lower in compression group (not statistically significant). Conclusions Post-operative limb swelling can be reduced significantly by wearing compression stockings in the early post-operative phase when compared to not wearing stockings. This may improve the rehabilitation process after arthroscopic surgery. The optimal duration of compression therapy seems to be between three and ten days. Trial registration clinicaltrials.gov (NCT02096562, date of registration 11.11.2013).

Over the past few decades, more and more articles about platelet-rich plasma (PRP) use in regenerative medicine have been published. The aim of this study was to determine which articles have been most influential in this field by identifying and analyzing the characteristics of the 100 most cited articles. Articles on the use of PRP in regenerative medicine were identified via the Thomson ISI Web of Science database. A majority of the articles originated from the USA (36%). The top journal in terms of number of articles was American Journal of Sports Medicine (12%). Musculoskeletal system and orthopedics (54%) were the most popular fields of applications. Preclinical studies were the most represented study type, from which only 8 from 46 (17.4%) provided a complete numerical description of the injected product. Analysis showed a time-dependent trend of increasing quality of the clinical studies (p = 0.004), although none of them provided a complete biological characterization of the injected PRP. This study demonstrated that the use of PRP in regenerative medicine is a growing and popular area of research, mainly focused on orthopedic applications. Studies on PRP-derived exosomes, biological characterization, and correlation with clinical results might be areas of future trends.

Background: Microfracture is an established technique for cartilage regeneration but is limited by many factors such as small defect size, intralesional osteophytes, and lower quality of cartilage regeneration. Therefore, methods to improve results after microfracture like additional matrix augmentation or autologous cell addition are promising techniques. An all-arthroscopic surgical technique for matrix-augmented bone marrow stimulation will be presented here. Indications: Cartilage lesions of moderate size (>1 cm 2 ) that appear too large or unsuitable for pure microfracture but do not yet meet the criteria for autologous cartilage transplantation (>2.5 cm 2 ). The exact size of suitable lesions is currently evolving with only few evidence-based data available. Technique Description: The arthroscopic procedure largely follows the standard microfracture technique. First, the cartilage defect is extensively debrided with removal of calcific cartilage layer. Stable cartilage margins have to be created with removal of all unstable fragments. The resulting well-defined defect is then measured with the use of a marking probe. The subchondral bone is then penetrated and opened using a microfracture awl. Next, the matrix based on hyaluronic acid (Hyalofast) is cut to the appropriate size. All joint fluid is removed, and the matrix is inserted through a previously placed canula and modeled into the defect with the probe. When the defect is well contained, no other fixation material is necessary. Otherwise, the matrix can be additionally fixed using fibrin clue. Cell application (dependent on regulatory issues) can be performed. Before closure, the joint should be moved to ensure safe fixation of the matrix. Results: Currently, there are only insufficient data to exactly define the defect size for microfracture or matrix-assisted bone marrow stimulation. Some studies show an advantage of using biomaterials compared with microfracture alone, but further studies are necessary. Discussion/Conclusion: The presented arthroscopic matrix-assisted bone marrow stimulation is a technically simple, inexpensive way of treating cartilage defects and should therefore be considered when treating affected patients. It can be used in a variety of joints. An additional combination with bone marrow–derived mesenchymal stem cells might be promising but is subject to country-specific regulatory issues.

Summary: The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that controls cell cycle transitions. Its regulation by the spindle assembly checkpoint (SAC) is coordinated with the attachment of sister chromatids to the mitotic spindle. APC/C SUMOylation on APC4 ensures timely anaphase onset and chromosome segregation. To understand the structural and functional consequences of APC/C SUMOylation, we reconstituted SUMOylated APC/C for electron cryo-microscopy and biochemical analyses. SUMOylation of the APC/C causes a substantial rearrangement of the WHB domain of APC/C’s cullin subunit (APC2WHB). Although APC/CCdc20 SUMOylation results in a modest impact on normal APC/CCdc20 activity, repositioning APC2WHB reduces the affinity of APC/CCdc20 for the mitotic checkpoint complex (MCC), the effector of the SAC. This attenuates MCC-mediated suppression of APC/CCdc20 activity, allowing for more efficient ubiquitination of APC/CCdc20 substrates in the presence of the MCC. Thus, SUMOylation stimulates the reactivation of APC/CCdc20 when the SAC is silenced, contributing to timely anaphase onset.

Abstract Purpose Injuries are common in sports and can have significant physical, psychological and financial consequences. Machine learning (ML) methods could be used to improve injury prediction and allow proper approaches to injury prevention. The aim of our study was therefore to perform a systematic review of ML methods in sport injury prediction and prevention. Methods A search of the PubMed database was performed on March 24th 2020. Eligible articles included original studies investigating the role of ML for sport injury prediction and prevention. Two independent reviewers screened articles, assessed eligibility, risk of bias and extracted data. Methodological quality and risk of bias were determined by the Newcastle–Ottawa Scale. Study quality was evaluated using the GRADE working group methodology. Results Eleven out of 249 studies met inclusion/exclusion criteria. Different ML methods were used (tree‐based ensemble methods (n = 9), Support Vector Machines (n = 4), Artificial Neural Networks (n = 2)). The classification methods were facilitated by preprocessing steps (n = 5) and optimized using over‐ and undersampling methods (n = 6), hyperparameter tuning (n = 4), feature selection (n = 3) and dimensionality reduction (n = 1). Injury predictive performance ranged from poor (Accuracy = 52%, AUC = 0.52) to strong (AUC = 0.87, f1‐score = 85%). Conclusions Current ML methods can be used to identify athletes at high injury risk and be helpful to detect the most important injury risk factors. Methodological quality of the analyses was sufficient in general, but could be further improved. More effort should be put in the interpretation of the ML models.

Abstract Background Animal fracture models, primarily performed in rats, are crucial to investigate normal and pathological bone healing. However, results of biomechanical testing representing a major outcome measure show high standard deviations often precluding statistical significance. Therefore, the aim of our study was a systematical examination of biomechanical characteristics of rat femurs during three-point bending. Furthermore, we tried to reduce variation of results by individually adapting the span of bearing and loading areas to the bone’s length. Methods We examined 40 paired femurs of male Wistar-rats by DXA (BMD and BMC of the whole femur) and pQCT-scans at the levels of bearing and loading areas of the subsequent biomechanical three-point bending test. Individual adjustment of bearing and loading bars was done respecting the length of each specimen. Subgroups of light ( 400 g, n = 18) animals were formed and analysed separately. We furthermore compared the results of the individualised bending-setting to 20 femurs tested with a fix span of 15 mm. Results Femurs showed a length range of 34 to 46 mm. The failure loads ranged from 116 to 251 N (mean 175.4 ± 45.2 N; heavy animals mean 221 ± 18.9 N; light animals mean 138.1 ± 16.4 N) and stiffness ranged from 185 N/mm to 426 N/mm (mean 315.6 ± 63 N/mm; heavy animals mean 358.1 ± 34.64 N/mm; light animals mean 280.8 ± 59.85 N/mm). The correlation of densitometric techniques and failure loads was high (DXA R2 = 0.89 and pQCT R2 = 0.88). In comparison to femurs tested with a fix span, individual adaptation of biomechanical testing homogenized our data significantly. Most notably, the standard deviation of failure loads (221 ± 18.95 N individualized setting vs. 205.5 ± 30.36 N fixed) and stiffness (358.1 ± 34.64 N/mm individualized setting vs. 498.5 ± 104.8 N/mm fixed) was reduced by at least one third. Conclusions Total variation observed in any trait reflects biological and methodological variation. Precision of the method hence affects the statistical power of the study. By simply adapting the setting of the biomechanical testing, interindividual variation could be reduced, which improves the precision of the method significantly.

Abstract Objectives Rat fracture models are extensively used to characterize normal and pathological bone healing. Despite, systematic research on inter- and intra-individual differences of common rat bones examined is surprisingly not available. Thus, we studied the biomechanical behaviour and radiological characteristics of the humerus, the tibia and the femur of the male Wistar rat—all of which are potentially available in the experimental situation—to identify useful or detrimental biomechanical properties of each bone and to facilitate sample size calculations. Methods 40 paired femura, tibiae and humeri of male Wistar rats (10–38 weeks, weight between 240 and 720 g) were analysed by DXA, pQCT scan and three-point-bending. Bearing and loading bars of the biomechanical setup were adapted percentually to the bone’s length. Subgroups of light (skeletal immature) rats under 400 g (N = 11, 22 specimens of each bone) and heavy (mature) rats over 400 g (N = 9, 18 specimens of each bone) were formed and evaluated separately. Results Radiologically, neither significant differences between left and right bones, nor a specific side preference was evident. Mean side differences of the BMC were relatively small (1–3% measured by DXA and 2.5–5% by pQCT). Over all, bone mineral content (BMC) assessed by DXA and pQCT (TOT CNT, CORT CNT) showed high correlations between each other (BMC vs. TOT and CORT CNT: R 2 = 0.94–0.99). The load–displacement diagram showed a typical, reproducible curve for each type of bone. Tibiae were the longest bones (mean 41.8 ± 4.12 mm) followed by femurs (mean 38.9 ± 4.12 mm) and humeri (mean 29.88 ± 3.33 mm). Failure loads and stiffness ranged from 175.4 ± 45.23 N / 315.6 ± 63.00 N/mm for the femurs, 124.6 ± 41.13 N / 260.5 ± 59.97 N/mm for the humeri to 117.1 ± 33.94 N / 143.8 ± 36.99 N/mm for the tibiae. Smallest interindividual differences were observed in failure loads of the femurs (CV% 8.6) and tibiae (CV% 10.7) of heavy animals, light animals showed good consistency in failure loads of the humeri (CV% 7.7). Most consistent results of both sides (left vs. right) in failure loads were provided by the femurs of light animals (mean difference 4.0 ± 2.8%); concerning stiffness, humeri of heavy animals were most consistent (mean difference of 6.2 ± 5%). In general, the failure loads showed strong correlations to the BMC (R 2 = 0.85–0.88) whereas stiffness correlated only moderate, except for the humerus (BMC vs. stiffness: R 2 = 0.79). Discussion Altogether, the rat’s femur of mature specimens showed the most accurate and consistent radiological and biomechanical results. In synopsis with the common experimental use enabling comparison among different studies, this bone offers ideal biomechanical conditions for three point bending experiments. This can be explained by the combination of a superior aspect ratio and a round and long, straight morphology, which satisfies the beam criteria more than other bones tested.

Abstract Background A high percentage of closed femur fractures have slight comminution. Using micro-CT (μCT), multiple fragment segmentation is much more difficult than segmentation of unfractured or osteotomied bone. Manual or semi-automated segmentation has been performed to date. However, such segmentation is extremely laborious, time-consuming and error-prone. Our aim was to therefore apply a fully automated segmentation algorithm to determine μCT parameters and examine their association with biomechanics. Methods The femura of 64 rats taken after randomised inhibitory or neutral medication, in terms of the effect on fracture healing, and controls were closed fractured after a Kirschner wire was inserted. After 21 days, μCT and biomechanical parameters were determined by a fully automated method and correlated (Pearson’s correlation). Results The fully automated segmentation algorithm automatically detected bone and simultaneously separated cortical bone from callus without requiring ROI selection for each single bony structure. We found an association of structural callus parameters obtained by μCT to the biomechanical properties. However, results were only explicable by additionally considering the callus location. Conclusions A large number of slightly comminuted fractures in combination with therapies that influence the callus qualitatively and/or quantitatively considerably affects the association between μCT and biomechanics. In the future, contrast-enhanced μCT imaging of the callus cartilage might provide more information to improve the non-destructive and non-invasive prediction of callus mechanical properties. As studies evaluating such important drugs increase, fully automated segmentation appears to be clinically important.

The assembly and functionality of the mitotic spindle depends on the coordinated activities of microtubule-associated motor proteins of the dynein and kinesin superfamily. Our current understanding of the function of motor proteins is significantly shaped by studies using Xenopus laevis egg extract as its open structure allows complex experimental manipulations hardly feasible in other model systems. Yet, the Kinesin-8 orthologue of human Kif18A has not been described in Xenopus laevis so far. Here, we report the cloning and characterization of Xenopus laevis (Xl) Kif18A. Xenopus Kif18A is expressed during oocyte maturation and its depletion from meiotic egg extract results in severe spindle defects. These defects can be rescued by wild-type Kif18A, but not Kif18A lacking motor activity or the C-terminus. Single-molecule microscopy assays revealed that Xl_Kif18A possesses high processivity, which depends on an additional C-terminal microtubule-binding site. Human tissue culture cells depleted of endogenous Kif18A display mitotic defects, which can be rescued by wild-type, but not tail-less Xl_Kif18A. Thus, Xl_Kif18A is the functional orthologue of human Kif18A whose activity is essential for the correct function of meiotic spindles in Xenopus oocytes.

Summary: Mammalian oocytes are stored in the ovary, where they are arrested in prophase for prolonged periods. The mechanisms that abrogate the prophase arrest in mammalian oocytes and reinitiate meiosis are not well understood. Here, we identify and characterize an essential pathway for the resumption of meiosis that relies on the protein phosphatase DUSP7. DUSP7-depleted oocytes either fail to resume meiosis or resume meiosis with a significant delay. In the absence of DUSP7, Cdk1/CycB activity drops below the critical level required to reinitiate meiosis, precluding or delaying nuclear envelope breakdown. Our data suggest that DUSP7 drives meiotic resumption by dephosphorylating and thereby inactivating cPKC isoforms. In addition to controlling meiotic resumption, DUSP7 has a second function in chromosome segregation: DUSP7-depleted oocytes that enter meiosis show severe chromosome alignment defects and progress into anaphase prematurely. Altogether, these findings establish the phosphatase DUSP7 as an essential regulator of multiple steps in oocyte meiosis. : Tischer and Schuh study how oocytes resume meiosis after a prolonged prophase arrest. They show that the phosphatase DUSP7 drives meiotic resumption by dephosphorylating and inactivating conventional protein kinase C (cPKC) isoforms. Hyperactivation of cPKC isoforms in the absence of DUSP7 causes a decrease in the activity of the cell-cycle-regulating kinase Cdk1/Cyclin B, preventing meiotic resumption. Keywords: mouse oocytes, meiosis, DUSP7, phosphatase, PKC, chromosome segregation, prophase arrest

The global platinum market has been in downturn and unstable for five consecutive years, and thus market participants are demanding effective quantitative risk management tools. Since platinum is so widely used and serves as an important investment vehicle, the importance of risk management of platinum spot returns cannot be understated. In this paper, we take advantage of a very popular econometric model, the generalized autoregressive conditional heteroscedasticity (GARCH) model, for platinum returns. We received two important findings by using the conventional GARCH models in explain daily platinum spot returns. First, it is crucial to introduce heavy-tailed distribution to explain conditional heavy tails; and second, the NRIG distribution performs better than the most widely-used heavy-tailed distribution, the Student’s t distribution.